John Munkhaugen

• Getz, Vilde; Pleym, Karin; Dammen, Toril; Husebye, Einar; Sverre, Elise Christine Bjørkholen & Peersen, Kari [Show all 9 contributors for this article] (2026). Patient and healthcare system factors associated with participation in municipal smoking cessation programs after hospitalization for atherosclerotic vascular disease in Norway: A prespecified analysis of two randomized controlled trials. Tobacco Prevention & Cessation. 12(61), p. 1–13. doi: 10.18332/tpc/236282. Full text in Research Archive Show summary

  Introduction: Persistent smoking after hospitalization for an atherosclerotic vascular event remains common, and only a small proportion attend cardiac rehabilitation or community-based lifestyle support, including smoking cessation programs. This study aimed to identify patient and healthcare...

• Caglar, Harun; Holmager, Therese; Kristensen, Anna Meta Dyrvig; Bakken, Arnhild; Rykind-Eriksen, Frida & Deeg, Peter Stefan [Show all 12 contributors for this article] (2026). Risk-Score Guided Estimation of Absolute Benefit From Beta-blockers after Myocardial Infarction in Patients Without Heart Failure. European Heart Journal - Quality of Care and Clinical Outcomes. ISSN 2058-5225. doi: 10.1093/ehjqcco/qcag142. Full text in Research Archive Show summary

  Abstract Aims To assess whether a modified clinical risk-score can stratify baseline risk and estimate expected absolute benefit from beta-blocker therapy in post-MI (myocardial infarction) patients with LVEF (left ventricular ejection fraction) ≥40%. Methods This substudy of the BETAMI-DANBLOCK trial included patients with a recent MI and LVEF ≥40% who were randomized to beta-blocker or no beta-blocker therapy. A modified Thrombolysis in Myocardial Infarction Risk Score for Secondary Prevention (TRS-2P) was constructed, and patients were categorized as low-, intermediate-, or high-risk. The primary outcome was a composite of all-cause mortality, new-MI, unplanned coronary revascularization, ischemic stroke, heart failure, or malignant ventricular arrhythmia. Treatment effects across TRS-2P strata were estimated using Cox proportional hazards and Fine-Gray subdistribution hazard models. Three-year absolute risk reduction (ARR) and number needed to treat (NNT) were calculated for each risk stratum. Results Among 5558 patients, 38.4% were classified as low-risk, 52.8% as intermediate-risk, and 8.8% as high-risk. Event rates increased stepwise with higher modified TRS-2P, with no evidence of heterogeneity in the relative treatment effects across risk-strata (hazard ratios: 0.88, 0.81 and 0.88, respectively). However, the score translated the modest relative effects into clinically distinct absolute benefits: Three-year ARR was 1.4% (NNT=72 [95% CI: 41 to 361]) in low-risk, 2.1% (NNT=47 [95% CI: 27 to 239]) in intermediate-risk, and 3.6% (NNT=28 [95% CI: 16 to 140]) in high-risk patients. Conclusions The modified TRS-2P stratified baseline risk and provided estimates of absolute beta-blocker benefit, supporting further evaluation of individualized, risk-guided treatment after MI in patients with LVEF ≥40%.

• Singstad, Bjørn-Jostein; Turan, Bangin; Ravn, Jesper; Sovershaev, Timofey; Eek, Christian & Aksnes, Tonje Amb [Show all 12 contributors for this article] (2026). Artificial intelligence-enabled electrocardiographic detection of acute occlusive myocardial infarction. Research Square. ISSN 2693-5015. doi: 10.21203/rs.3.rs-10574825/v1. Full text in Research Archive Show summary

  Abstract Occluded myocardial infarction (OMI) remains under-recognized in patients without ST-elevation, delaying revascularization despite a high risk of adverse outcomes. We fine-tuned and validated a foundation model for detecting OMI from standard 12-lead electrocardiograms (ECGs), recorded between 2016 and 2022. The study included 17 165 ECGs from 11 338 patients. Among these, 4 038 encounters proceeded to acute invasive coronary angiography, identified from the Norwegian Registry of Invasive Cardiology (NORIC), and 1 338 of these were diagnosed with OMI. OMI was defined as an acute culprit lesion with Thrombolysis In Myocardial Infarction (TIMI) flow grade 0–2 treated with percutaneous coronary intervention. A pretrained ECG foundation model was fine-tuned and evaluated on a held-out test set. The model achieved an area under the receiver operating characteristic (AUROC) curve of 0.93 and an area under the precision-recall curve (AUPRC) of 0.72 for detecting OMI cases. Performance was high for OMI with ST-elevation (AUROC 0.98) and moderate for OMI without ST-elevation (AUROC 0.84, AUPRC 0.20), reflecting the inherent difficulty of detecting non-ST-elevation occlusions. Among OMI cases with available door-to-procedure timestamps, the model identified 59 (53%) of those with delayed door-to-procedure time (>30 minutes), of which 32 (54%) were NSTEMIs. These findings highlight the potential of AI-enabled ECG interpretation to improve early recognition and timely management of high-risk OMIs.

• Madssen, Erik; Sverre, Elise Christine Bjørkholen; Nyen, Johanne E; Holmager, Therese L F; Kristensen, Anna M D & Bakken, Arnhild [Show all 13 contributors for this article] (2026). Beta-blocker therapy and physical activity after myocardial infarction: a preplanned sub-study of the BETAMI trial. European Journal of Preventive Cardiology (EJPC). ISSN 2047-4873. doi: 10.1093/eurjpc/zwag412. Full text in Research Archive Show summary

  Abstract Aims To investigate the effect of long-term beta-blocker therapy on physical activity (PA) level after myocardial infarction (MI) in patients without heart failure. Method The BETAMI trial, randomised patients hospitalised with a MI without heart failure (LVEF ≥40%) to beta-blocker or no beta-blocker. In this pre-planned sub-study PA level was assessed by guideline-recommended PA level (≥30 minutes moderate activity ≥5 days/week) or not and self-reported hours/week with light to moderate and vigorous PA. Between-group differences in PA from baseline before randomisation to 18-months were estimated by linear mixed models. Exploratory analysis assessed treatment effects on a composite of all-cause mortality and major adverse cardiovascular events using Cox proportional hazards model. Results Of the 2867 randomised patients, 2185 (76%) responded to the PA questions and were included in this analysis. Mean age was 62.5 (SD 10.1) years, 20.6% were women. No differences in guideline-recommended PA level or mean hours of light to moderate and vigorous PA were reported between the beta-blocker and non-beta-blocker group at baseline or during 18-months follow-up. At 12-month follow-up, 37.0% in the beta-blocker group and 36.7% in the no beta-blocker group reported guideline-recommended PA level (OR 0.97, 95% CI 0.69-1.37). Exploratory, hypothesis-generating analyses did not demonstrate a statistically significant interaction (p for interaction = 0.06) between treatment assignment and baseline PA level for recurrent clinical events. Conclusions Beta-blocker therapy did not result in a change in PA level in post-MI patients without heart failure during the 18 months follow-up.

• Holtrop, Joris; Gynnild, Mari Nordbø; Deo, Salil V; Lim, Carl-Emil; Logothetis, Stelios Boulitsakis & Läll, Kristi [Show all 37 contributors for this article] (2026). Predicting lifetime cardiovascular risk and benefits of preventive treatment in patients with established atherosclerotic cardiovascular disease: the SMART-REACH2 model. European Heart Journal. ISSN 0195-668X. doi: 10.1093/eurheartj/ehag400. Full text in Research Archive Show summary

  Abstract Background and Aims The 2021 ESC guidelines on cardiovascular (CV) disease prevention recommend the SMART-REACH lifetime risk model to guide treatment decisions in patients with established atherosclerotic CV disease. The aim was to develop the SMART-REACH2 model for estimating lifetime risk of recurrent CV events and treatment benefits in patients with established atherosclerotic CV disease, with systematic recalibration to the four European and other global risk regions. Methods SMART-REACH2 was derived in 8708 individuals aged 40–90 years with coronary, cerebrovascular, peripheral artery disease and/or abdominal aortic aneurysm from the UCC-SMART cohort. Sex-stratified, cause-specific Cox models for recurrent CV events and non-CV death were fitted using age as timescale and routinely available predictors. Recurrent CV events were defined as a composite of myocardial infarction, stroke, or CV death. Recalibration was based on representative cohorts per risk region. External validation was performed in 2 085 780 patients from 54 countries; model performance was assessed by calibration plots and Harrell's C-statistic. Results In the derivation cohort, 2057 recurrent CV events occurred over a median follow-up of 8.5 years (25th–75th: 4.3–13.0). In external validation, 307 706 events occurred. The pooled C-statistic was 0.68 (95% confidence interval 0.66–0.69) and ranged from 0.66 (0.64–0.69) for European low-risk region up to 0.72 (0.66–0.78) for Latin America, with adequate calibration across risk regions. Performance was consistent across sexes and CV disease subtypes. Using SMART-REACH2, estimated potential gains in CV disease-free life expectancy for a 50-year-old example patient receiving intensified preventive treatment (15 mmHg systolic blood pressure and 1.0 mmol/L low-density lipoprotein cholesterol reduction) ranged from 2 years in the low-risk region to 4.4 years in the very-high-risk region. Conclusions The updated SMART-REACH2 model accounts for geographical and sex-specific variations and allows estimation of short-term and lifetime risk of recurrent CV events and treatment benefits, facilitating shared decision-making as recommended by guidelines.

• Kristensen, Anna Meta Dyrvig; Jortveit, Jarle; Holmager, Therese; Atar, Dan; Olsen, Michael Hecht & Bakken, Arnhild [Show all 14 contributors for this article] (2026). Outcomes in the BETAMI-DANBLOCK trial compared with a Norwegian nationwide myocardial infarction population. European Heart Journal. ISSN 0195-668X. doi: 10.1093/eurheartj/ehag348. Full text in Research Archive Show summary

  Abstract Background and Aims In patients with myocardial infarction (MI), no heart failure, and left ventricular ejection fraction (LVEF) ≥ 40%, the combined BETAMI-DANBLOCK trial showed that beta-blockers reduced the risk of all-cause mortality or major adverse cardiovascular events. This study evaluated the representativeness of the trial. Methods Participants in BETAMI (n = 2867) and DANBLOCK (n = 2707) were compared with a cohort of revascularized MI patients with LVEF ≥40%, and no heart failure from the Norwegian Myocardial Infarction Registry (the NORMI cohort)(n = 20 804). Baseline characteristics were evaluated, and absolute risks of all-cause mortality and/or MI were estimated. A transportability analysis was conducted by weighting the BETAMI-DANBLOCK population according to the NORMI cohort. Results Median age was 66 years (interquartile range [IQR]: 57–74) in the NORMI cohort and 63 years (IQR: 55–70) in BETAMI and DANBLOCK. Patients in the NORMI cohort had a higher prevalence of diabetes, previous coronary artery disease, and LVEF 40–49%, compared with trial participants. At 3-year follow-up, the absolute risk of all-cause mortality or MI was 12.0% in the NORMI cohort, 7.7% in BETAMI, and 7.8% in DANBLOCK. Corresponding risks of MI were 6.3%, 5.6%, and 4.3%, respectively. The treatment effects of beta-blockers were similar when the trial population was weighted according to the characteristics of the NORMI cohort. Conclusions Compared with the NORMI cohort, participants in BETAMI and DANBLOCK were younger, had a lower proportion of certain comorbidities, and experienced a lower risk of all-cause mortality and MI. Despite these differences, the effect of beta-blockers remained consistent when the trial population was weighted according to the NORMI cohort.

• Braanaas, Karoline Svensen; Dammen, Toril; Fagerland, Morten; Husebye, Einar; Leinaas, Amund & Schirmer, Henrik [Show all 10 contributors for this article] (2026). Individually tailored monitoring at home after hospitalization for HEART failure (IT-HEART): design and baseline characteristics of a randomized clinical trial. Heart Failure Reviews. ISSN 1382-4147. 31(1). doi: 10.1007/s10741-026-10635-1. Full text in Research Archive Show summary

  Telemonitoring has emerged as a promising alternative to conventional heart failure (HF) management, but randomized trials show conflicting results, and data from high-risk populations with frailty, is scarce. The Individually Tailored monitoring at home after HEART failure (IT-HEART) trial evaluates whether a non-invasive multi-component telemonitoring program improves outcomes in HF patients after HF-hospitalization. The aim of this study is to describe flow of patients and baseline characteristics of the IT-HEART trial population. This multicenter, open-label, blinded-endpoint trial randomized HF patients to either written information and a standardized self-treatment plan (Control) or HF education, a personalized self-treatment plan, and three months of home telemonitoring (Intervention). The primary endpoint is the total number of HF hospitalizations or cardiovascular death. Of 1016 consecutively screened patients, 200 (19.7%) were randomized. At baseline, median age was 78 (IQR 70–83) years, and 29.5% were women. Participants were multimorbid (median 6 diagnoses) with a median Clinical Frailty Scale score 4 (IQR 4–5). Median score of the European Heart Failure Self-care Behaviour Scale was 53 (IQR 35–67), and 75.5% had inadequate self-care. Self-rated knowledge on HF management was 3 (IQR 0–7) on a 0–10 Likert scale. Only 35.5% (n = 71) weighed themselves weekly whereas 1% (n = 2) reported having a self-care plan. In conclusion, patients enrolled after a recurrent HF hospitalization were multimorbid and frail, and scored low on self‑care and health literacy. The IT-HEART intervention is targeted to these factors and has the potential to improve clinical and patient‑reported outcomes, and costs.

• Getz, Vilde; Pleym, Karin; Dammen, Toril; Husebye, Einar; Sverre, Elise Christine Bjørkholen & Papageorgiou, Constantinos [Show all 8 contributors for this article] (2026). Clinical and psychosocial factors predicting persistent smoking in hospitalized patients with atherosclerotic vascular disease: A prespecified analysis of two randomized controlled trials. Tobacco Prevention & Cessation. 12. doi: 10.18332/tpc/217328. Full text in Research Archive
• Nyen, Johanne E; Kristensen, Anna Meta D; Dammen, Toril; Zwisler, Ann-Dorthe; Olsen, Michael Hecht & Maeng, Michael [Show all 14 contributors for this article] (2026). Beta-blockers, depression, and anxiety after myocardial infarction: the BETAMI-DANBLOCK trial. European Heart Journal. ISSN 0195-668X. doi: 10.1093/eurheartj/ehag200. Full text in Research Archive
• Holmager, Therese Lucia Friis; Kristensen, Anna Meta Dyrvig; Fagerland, Morten; Atar, Dan; Olsen, Michael Hecht & Bakken, Arnhild [Show all 8 contributors for this article] (2026). Validating National Registry Data for Randomised Trials: Comparison of registry-derived cardiovascular events with and without adjudication in the BETAMI-DANBLOCK trial. European Heart Journal - Quality of Care and Clinical Outcomes. ISSN 2058-5225. doi: 10.1093/ehjqcco/qcag055. Full text in Research Archive Show summary

  Abstract Background Registry-based randomised clinical trials are increasingly applied in clinical research, providing advantages in feasibility and data capture. However, registry-based data may introduce bias through misclassification or missing information. Methods In the BETAMI-DANBLOCK trial, 5,574 patients with myocardial infarction (MI) and no heart failure were randomised to beta-blocker or no beta-blocker therapy. The primary endpoint events (all-cause mortality, MI, ischemic stroke, heart failure, unplanned coronary revascularisation, and malignant ventricular arrhythmias) were identified from the Danish/Norwegian national patient registries, self-reported questionnaires, and medical records. All registry-identified events, except all-cause mortality, underwent blinded adjudication. We compared non-adjudicated and adjudicated events by calculating incidence rates and hazard ratios (HRs) for beta-blocker therapy versus controls. Results National registries captured 99.7% of primary endpoint events registered by self-report and medical records. Of the primary endpoint events identified through the registries, 75% were confirmed by adjudication (incidence rate 6.23 versus 4.43/100 person-years). The confirmation rate was lower during the first six months and varied by event type (from 92% for ischemic stroke to 45% for unplanned coronary revascularisations and heart failure). Estimated treatment effects were consistent for the primary endpoint with non-adjudicated and adjudicated events (HR 0.88, 95% confidence interval (CI): 0.78-0.98 and HR 0.85, 95% CI: 0.75-0.98, respectively), with no apparent differences across event types except for heart failure and revascularisation. Conclusion Registry data provided effect estimates of beta-blockers comparable to adjudicated data. However, adjudication substantially reduced the number of cardiovascular endpoint events and event-specific misclassification appeared, particularly during the first months after the index-event.

• Getz, Vilde; Pleym, Karin; Dammen, Toril; Husebye, Einar; Sverre, Elise Christine Bjørkholen & Papageorgiou, Constantinos [Show all 8 contributors for this article] (2026). Clinical and psychosocial factors predicting persistent smoking in hospitalized patients with atherosclerotic vascular disease: A prespecified analysis of two randomized controlled trials. Tobacco Prevention & Cessation. 12(15). doi: https:/www.tobaccopreventioncessation.com/Clinical-and-psychosocial-factors-predicting-persistent-nsmoking-in-hospitalized,217328,0,2.html. Full text in Research Archive Show summary

  ABSTRACT Introduction: Smoking remains prevalent after hospitalization for atherosclerotic vascular disease, even with cessation programs. Understanding the clinical and psychosocial factors influencing long-term abstinence is essential for identifying patients who may benefit from tailored interventions. This study aimed to identify clinical and psychosocial factors associated with sustained smoking cessation in patients with atherosclerotic disease who were admitted to hospital for an elective or unplanned vascular event and enrolled in a cessation intervention study. Methods: This is a prespecified analysis of two randomized intervention trials that recruited participants from three secondary care hospitals in Norway between 2021 and 2023. Patients who smoked at least one cigarette daily before admission were randomized to: 1) motivational counselling and proactive referral to municipal cessation services (intervention); or 2) brief advice and contact information (control). Data were collected from medical records, a questionnaire, and telephone interviews. Logistic regression analyses were used to identify the prespecified factors associated with smoking status at 12 months. Results: In the total study population (n=262), 34% (n=88) reported 12-month sustained smoking abstinence. Anxiety diagnosis (adjusted odds ratio, AOR=4.2), shorter sleep duration per hour (AOR=1.3), living alone (AOR=2.2), somatic comorbidity per point on the Charlson score (AOR=1.5), and being in the precontemplation stage (AOR=2.9) were associated with persistent smoking. Increasing motivation per point on a 0–10 Likert scale (AOR=0.7), being in the preparation stage (AOR=0.4), and myocardial infarction or stroke as the index diagnosis (AOR=0.5) were associated with smoking abstinence. Results were generally consistent across intervention allocation groups. Conclusions: Motivation and readiness for smoking cessation were key predictors of abstinence. Living alone, anxiety disorders, and shorter sleep duration were associated with persistent smoking. These factors may help identify subgroups who could benefit from more targeted support.

• Jortveit, Jarle; Boskovic, Miroslav; Haraldsen, Marius Blørstad; Berge, Trygve; Grenne, Bjørnar L & Munkhaugen, John [Show all 7 contributors for this article] (2026). Cardiac-related symptoms in individuals ≥65 years without diagnosed cardiac disease: insights from the NORSCREEN-trial. European Heart Journal Open (EHJ Open). doi: 10.1093/ehjopen/oeag032. Full text in Research Archive Show summary

  Abstract Aims Population-based data on cardiac-related symptoms in individuals without diagnosed cardiac disease remain limited, despite important implications for early detection and management. We aimed to assess the prevalence of self-reported symptoms and the association with quality of life (QoL) among adults ≥65 years with ≥1 additional stroke risk factor, but without diagnosed cardiac disease. Methods Cross-sectional study of the NORSCREEN trial population at baseline. NORSCREEN is an ongoing, nationwide, randomised atrial fibrillation screening study in adults aged ≥65 years at increased risk of stroke (CHA2DS2-VA ≥2). All participants completed a baseline questionnaire capturing clinical information, symptoms, and QoL. Results Of 50,549 participants enrolled from 2023 to 2025, 39,281 (78%) reported no diagnosed cardiac disease. Among those, 17,069 (43%) reported cardiac-related symptoms compared to 7,551 (67%) of 11,268 individuals with known cardiac disease. Most common symptoms were fatigue, exertional dyspnoea and tachycardia. Female sex (adjusted odds ratio 1.66, [95% CI 1.58–1.75], physical inactivity (1.43 [1.32–1.55]), current smoking (1.24 [1.12–1.37]), age <75 years (1.14 [1.08-1.20]), living alone (1.13 [1.07–1.20]), and comorbidities including chronic obstructive pulmonary disease (6.51 [5.63-7.54]) and anxiety (3.99 [3.64-4.38]) were associated with cardiac-related symptoms. Symptomatic individuals reported significantly lower RAND-36 QoL scores across all domains compared to those without symptoms. Conclusion In this cohort of individuals ≥65 years at increased risk of stroke, but without diagnosed cardiac disease, nearly half reported cardiac-related symptoms, which were associated with substantially reduced QoL. These findings suggest there might be unmet needs in identifying and managing cardiovascular disease.

• Kristensen, Anna Meta Dyrvig; Rossello, Xavier; Atar, Dan; Yndigegn, Troels; Kimura, Takeshi & Latini, Roberto [Show all 30 contributors for this article] (2025). Beta-Blockers after Myocardial Infarction with Normal Ejection Fraction. New England Journal of Medicine. ISSN 0028-4793. 394(6), p. 540–550. doi: 10.1056/nejmoa2512686. Full text in Research Archive
• Pacheco, André Pekkola; Dammen, Toril; Munkhaugen, John; Papageorgiou, Constantinos; Kværner, Kari Jorunn & Støme, Linn Nathalie (2025). Potential benefits of group cognitive–behavioural therapy for insomnia in outpatients with coronary heart disease versus usual care: an early economic evaluation. BMJ Open. 15(12). doi: 10.1136/bmjopen-2024-092811. Full text in Research Archive Show summary

  Objective Insomnia afflicts about half of outpatients with coronary heart disease (CHD) and worsens prognosis. We aimed to simulate the potential socioeconomic savings of integrating group cognitive–behavioural therapy for insomnia (gCBT-I) into cardiac outpatient care for patients with CHD compared with usual care. Design Early health technology assessment using prospective and cross-sectional cohort data. Setting Secondary care for outpatients with CHD in Norway in a non-university hospital setting. Participants A hypothetical cohort of 100 outpatients with CHD and insomnia. Interventions Weekly sessions of gCBT-I over 5 weeks versus usual care. Primary and secondary outcome measures Potential savings related to possible effects on revascularisations and hospitalisations due to a recurrent CHD event, and reduced sick leave. Representative data on healthcare consumption and sick leave rates were collected from the NORwegian CORonary cohort study (n=528). Costs of productivity loss were drawn from public sources and calculated using a conservative human capital approach. Estimates of therapeutic effectiveness in conveying insomnia remission by gCBT-I were informed by results from randomised trials and meta-analyses. Results Rates of healthcare consumption and sick leave were higher in outpatients with CHD and insomnia compared with those without insomnia. Our model indicated that treating 100 patients with gCBT-I would cost €2406. If patients treated with gCBT-I show similar rates of revascularisations and hospitalisations as those without insomnia, there is a maximum potential saving of €117,221 per 100 patients tied to healthcare consumption. Similarly, the maximum potential savings related to reduced productivity loss from sick leave range from €53,244 to €692,172. Conclusion Treating insomnia among outpatients with CHD has the potential for substantial reduction of socioeconomic costs related to healthcare consumption and sick leave. Implementation into routine outpatient care seems relevant, but randomised controlled trials investigating the effects of gCBT-I in this population are warranted.

• Jortveit, Jarle; Munkhaugen, John; Kaldal, Anete & Halvorsen, Sigrun (2025). Sekundærforebygging hos hjerteinfarktpasienter med kjent koronarsykdom. Tidsskrift for Den norske legeforening (Tidsskriftet). ISSN 0029-2001. 145(15). doi: 10.4045/tidsskr.25.0186. Full text in Research Archive Show summary

  Bakgrunn Sekundærforebyggende behandling for pasienter med kjent koronarsykdom reduserer risikoen for nye kardiovaskulære hendelser. Vi har undersøkt i hvilken grad pasienter med kjent koronarsykdom, innlagt med akutt hjerteinfarkt, hadde oppnådd behandlingsmålene for sekundærforebygging. Materiale og metode Studien benyttet data fra Norsk hjerteinfarktregister og inkluderte pasienter yngre enn 85 år med kjent koronarsykdom, som ble innlagt med akutt type 1-hjerteinfarkt i norske sykehus i tidsrommet 1.1.2013–31.12.2022. Resultater Av 74 993 pasienter yngre enn 85 år som var innlagt med akutt type 1-hjerteinfarkt, hadde 22 825 (30,4 %) kjent koronarsykdom. Av disse var 24,4 % kvinner, og medianalderen var 72 år (interkvartilbredde 64–78). Andelen med kjent koronarsykdom var stabil i studieperioden. Andelen ikke-røykere økte fra 71 % til 75 % (+0,7 % per år), andelen normalvektige ble redusert fra 33 % til 29 % (−1,8 % per år), og andelen som brukte blodplatehemmer og/eller antikoagulasjon økte fra 88 % til 91 % (+0,3 % per år). Andelen som brukte lipidsenkende behandling (77,0 %) og andelen som hadde LDL-kolesterol < 1,8 mmol/L (21 %) var stabile. Andelen med blodtrykk < 140/90 mmHg ble redusert fra 43 % til 30 % (−4,6 % per år frem til 2020, og uendret etter det). Fortolkning Studien viser behov for tiltak for å bedre den sekundærforebyggende behandlingen hos pasienter med koronarsykdom i Norge.

• Pleym, Karin; Sverre, Elise Christine Bjørkholen; Weedon-Fekjær, Harald; kahlon, Mohpal Singh; Stugaard, Marie & Husebye, Einar [Show all 9 contributors for this article] (2025). Motivational smoking cessation counselling and community‐based follow‐up after hospitalisation for vascular disease: A randomised controlled trial. Addiction. ISSN 0965-2140. p. 1–13. doi: 10.1111/add.70249. Full text in Research Archive Show summary

  Background and aims Evidence for motivational interviewing for smoking cessation is weak, with limited data on long-term abstinence rates. This trial aimed to evaluate the effect of in-hospital motivational interviewing-based smoking cessation counselling combined with proactive referral to community-based follow-up on 6- and 12-month continuous smoking abstinence in patients with atherosclerotic vascular disease. Design Multicentre, randomised, open-label, blinded-end-point trial with 1:1 randomisation. Setting Three secondary care hospitals in Norway, with recruitment from November 2021 to October 2023. Participants Hospitalised patients with established atherosclerotic vascular disease who smoked ≥1 cigarette daily prior to unplanned or elective hospitalisation. A total of 221 were randomised (40% women, mean age 65.2 years), of whom 213 were included in the primary analysis due to 7 deaths and 1 withdrawal. Intervention and comparator In the intervention group (n = 109), a trained nurse conducted a single 30-minute motivational interviewing-based counselling session, provided a leaflet explaining the local community-based cessation programme, sent discharge information to the general practitioner and arranged for a personal telephone invitation from the centre staff to the follow-up programme. In the control group (n = 111), a physician gave brief cessation advice and the nurse provided a leaflet about the cessation programme and sent discharge information to the general practitioner. Measurements The primary outcome was self-reported continuous smoking abstinence at 6 months. Secondary outcomes included biochemically validated abstinence (measurement of exhaled carbon monoxide) at 6 months and self-reported abstinence at 12 months. Exploratory outcomes included recurrent vascular events over a median 18-month follow-up. Findings Smoking abstinence at 6 months was 49.5% (53/107) and 24.5% (26/106) in the intervention and control groups, respectively [odds ratio (OR) = 3.08, 95% confidence interval (CI) = 1.70–5.55, P < 0.001]. The number needed to treat to achieve one additional abstinence was 4 (95% CI = 3–9). Biochemically validated abstinence was 44.9% (48/107) and 20.8% (22/106) in the intervention and control groups, respectively (OR = 3.28, 95% CI = 1.76–6.12). At 12 months, smoking abstinence was 45.7% (48/105) and 27.5% (28/102) in the intervention and control groups, respectively (OR = 2.31, 95% CI = 1.27–4.20). After a median of 18-month follow-up, a prespecified vascular event occurred in 24.8% (27/109) and 34.2% (38/111) of intervention and control participants, respectively. Conclusions In-hospital motivational counselling combined with proactive referral to follow-up in a community-based cessation programme approximately doubled long-term smoking abstinence rates in patients with atherosclerotic vascular disease and reduced occurrence of a new vascular event.

• Rossello, Xavier; Prescott, Eva Irene Bossano; Kristensen, Anna Meta Dyrvig; Latini, Roberto; Fuster, Valentin & Fagerland, Morten [Show all 22 contributors for this article] (2025). β blockers after myocardial infarction with mildly reduced ejection fraction: an individual patient data meta-analysis of randomised controlled trials. The Lancet. ISSN 0140-6736. 406(10508), p. 1128–1137. doi: 10.1016/s0140-6736(25)01592-2. Full text in Research Archive Show summary

  Background The effects of β-blocker therapy on clinical outcomes in patients with myocardial infarction and mildly reduced (40–49%) left ventricular ejection fraction (LVEF) are largely unknown. Four recently conducted randomised trials tested the efficacy of β blockers after a recent myocardial infarction in patients without reduced LVEF (LVEF ≥40%). However, none were individually powered to assess these effects in the subgroup of patients with mildly reduced LVEF. We aimed to assess the efficacy of β blockers in patients with myocardial infarction and mildly reduced LVEF during the index hospitalisation. Methods We conducted an individual patient-level meta-analysis of patients with mildly reduced LVEF and no history or signs of heart failure from four recent clinical trials. These studies were included because they were randomised controlled trials testing long-term effects (median follow-up >1 year) of oral β-blocker therapy in patients who recently had a myocardial infarction (randomisation within 14 days) and had mildly reduced LVEF. No further studies were found in a systematic review (Jan 1, 2020 to June 26, 2025). A one-stage, fixed-effects, Cox proportional hazards regression model was used to assess the treatment effect of β blockers on the predefined primary composite endpoint of all-cause death, new myocardial infarction, or heart failure. All endpoints were independently adjudicated. This meta-analysis was registered with PROSPERO (CRD420251023480). Findings 1885 patients with myocardial infarction and mildly reduced LVEF were included in the meta-analysis: 979 from the REBOOT trial, 422 from the BETAMI trial, 430 from the DANBLOCK trial, and 54 from the CAPITAL-RCT trial. Overall, 991 patients were assigned to β blockers and 894 to control (no β blockers). The primary composite endpoint occurred in 106 patients (32·6 events per 1000 patient-years) in the β-blocker group and 129 patients (43·0 per 1000 patient-years) in the no β-blocker group (hazard ratio 0·75 [95% CI 0·58–0·97]; p=0·031). No heterogeneity between the trials (trial-by-treatment pinteraction=0·95) or between countries of enrolment was observed (pinteraction=0·98). Interpretation In patients with acute myocardial infarction with mildly reduced LVEF without history or clinical signs of heart failure, β-blocker therapy was associated with a reduction in the composite of all-cause death, new myocardial infarction, or heart failure. These results extend the known benefits of these agents in patients with myocardial infarction with reduced LVEF to the subgroup with mildly reduced LVEF.

• Munkhaugen, John; Kristensen, Anna Meta D.; Halvorsen, Sigrun; Holmager, Therese; Olsen, Michael Hecht & Bakken, Arnhild [Show all 64 contributors for this article] (2025). Beta-Blockers after Myocardial Infarction in Patients without Heart Failure. New England Journal of Medicine. ISSN 0028-4793. 393(19), p. 1901–1911. doi: 10.1056/nejmoa2505985. Full text in Research Archive Show summary

  Background: The evidence supporting beta-blocker therapy after myocardial infarction was established before the introduction of modern coronary reperfusion therapy and secondary prevention strategies. Methods: In an open-label, randomized trial with blinded end-point evaluation, conducted in Denmark and Norway, we assigned patients who had had a myocardial infarction and who had a left ventricular ejection fraction of at least 40%, in a 1:1 ratio, to receive long-term beta-blocker therapy within 14 days after the event or no beta-blocker therapy. The primary end point was a composite of death from any cause or major adverse cardiovascular events (new myocardial infarction, unplanned coronary revascularization, ischemic stroke, heart failure, or malignant ventricular arrhythmias). Results: A total of 5574 patients underwent randomization and were included in the main analyses - 2783 in the beta-blocker group and 2791 in the no-beta-blocker group. After a median follow-up of 3.5 years (interquartile range, 2.2 to 4.6), a primary end-point event had occurred in 394 patients (14.2%) in the beta-blocker group and in 454 patients (16.3%) in the no-beta-blocker group (hazard ratio, 0.85; 95% confidence interval [CI], 0.75 to 0.98; P = 0.03). Death from any cause occurred in 4.2% of the patients in the beta-blocker group and in 4.4% of those in the no-beta-blocker group; myocardial infarction occurred in 5.0% and 6.7%, respectively (hazard ratio, 0.73; 95% CI, 0.59 to 0.92), unplanned coronary revascularization in 3.9% and 3.9%, ischemic stroke in 1.6% and 1.3%, heart failure in 1.5% and 1.9%, and malignant ventricular arrhythmias in 0.5% and 0.6%. No apparent differences in safety outcomes were observed between the groups. Conclusions: Among patients with a myocardial infarction and a left ventricular ejection fraction of at least 40%, beta-blocker therapy led to a lower risk of death or major adverse cardiovascular events than no beta-blocker therapy

• Holtrop, Joris; Gynnild, Mari Nordbø; Dammen, Toril; Dalen, Håvard; Saltvedt, Ingvild Tina & Ellekjær, Hanne [Show all 11 contributors for this article] (2025). Psychological factors beyond the SMART2 model for predicting recurrent events in atherosclerotic cardiovascular disease patients. European Journal of Preventive Cardiology (EJPC). ISSN 2047-4873. doi: 10.1093/eurjpc/zwaf526. Full text in Research Archive Show summary

  Aims Guidelines recommend using cardiovascular (CV) risk prediction models to support treatment decisions. Psychological factors such as depression, anxiety, and insomnia may affect CV risk. The aim is to evaluate the added value of these psychological factors on top of the SMART2 model for estimating 10-year risk of recurrent CV events in patients with atherosclerotic CV disease. Methods and results Patients aged 40–80 with atherosclerotic CV disease were included from the UCC-SMART, HUNT3, HUNT4, NORCOR, and Nor-COAST cohorts. Potential added value of (self-reported) symptoms, diagnoses, and treatment for depression, anxiety, and insomnia on top of the SMART2 was investigated using Fine and Gray models, with SMART2 coefficients as an offset. Added value was assessed by change (Δ) in C-statistic and calibration. A total of 20 050 patients were eligible, with 2987 experiencing recurrent CV events. Psychological factors were present in 3–9%, 3–45%, and 10–14% of patients for diagnosis, self-reported symptoms, and prescribed treatment, respectively. No psychological factors were significantly associated with recurrent CV events on top of SMART2 and performance in patients with psychological factors was adequate (C-statistics 0.61–0.70). Added value of psychological factors was minimal, with the ΔC-statistic ranging from −0.0003 [95% confidence interval: −0.0005–0.0001] for symptoms of depression, to 0.0011 [0.0011–0.0011] for prescribed treatment with anxiolytics. There was no relevant difference in calibration. Conclusion SMART2 model reliably estimates recurrent CV event risk in patients with psychological factors. Psychological factors have no added value to CV risk prediction when integrated on top of the SMART2 risk score.

• Tunheim, Kristoffer Joe; Papageorgiou, Constantinos; Lie, Hanne Cathrine; Munkhaugen, John & Dammen, Toril (2025). Experiences of the attention training technique delivered in groups as treatment for anxiety and depression in patients with coronary heart disease: a qualitative study. BMC Psychiatry. 25. doi: 10.1186/s12888-025-07027-4. Full text in Research Archive Show summary

  Background Clinically significant anxiety and depression symptoms are common in patients with coronary heart disease (CHD) and associated with a range of negative outcomes. Preliminary evidence suggests that the attention training technique (ATT), a component of metacognitive therapy (MCT), delivered in a group format, is feasible and potentially effective in reducing symptoms of anxiety and depression in these patients. Patients’ experiences of treatment including facilitators and barriers are useful in order to further develop effective intervention. We are not aware of any previous qualitative studies conducted on ATT in patients with CHD. Our study aimed to assess the treatment experiences in these patients. Methods Patients (N = 10) with CHD and significant symptoms of anxiety and/or depression, who participated in a randomized controlled trial of the effectiveness of ATT delivered in a group format, were recruited to in-depth, individual interviews three months after treatment completion. The interviews were recorded, transcribed and analysed according to the principles of thematic analysis. Results Nine males and one female participated, with a mean age of 54.3 (range 45–63) years. Mean time since cardiac event was 54.2 months. We identified two main themes; non-specific ATT treatment factors and group ATT-specific treatment factors. Furthermore, non-specific ATT treatment factors included subthemes relating to individual and group factors. These subthemes encompassed the (relational aspects such as the) interaction between the group patients, interaction between the patients and the therapist, and the therapist’s delivery of the group ATT. Second, specific ATT treatment factors included subthemes concerning understanding and making sense of the technique and treatment, changes in relation to thoughts and thinking, and group format as a facilitator of ATT treatment. Conclusions Group ATT was perceived as helpful among outpatients with CHD in terms of symptom relief. Both general and ATT specific factors were regarded important, and the patients seemed to understand ATT in a way that is consistent with the rationale of ATT treatment. All patients emphasized the importance of the group format.

• Pivoriunas, Jonas; Engebretsen, Ingrid; Vethe, Nils Tore; Kristiansen, Oscar; Dammen, Toril & Husebye, Einar [Show all 9 contributors for this article] (2025). Statin adherence in coronary outpatients: The relationship between a novel blood test and pharmacy registry data. Atherosclerosis. ISSN 0021-9150. 403. doi: 10.1016/j.atherosclerosis.2025.119138. Full text in Research Archive
• Andersen, Silje Glenna; Sæterhagen, Henrik; Pacheco, André Pekkola; Pripp, Are Hugo; Hrubos-Strøm, Harald & Papageorgiou, Constantinos [Show all 8 contributors for this article] (2025). The effects of cognitive behavioral therapy for insomnia in patients with cardiovascular disease: a systematic review and meta-analysis. Journal of Clinical Sleep Medicine (JCSM). ISSN 1550-9389. 21(7), p. 1273–1284. doi: 10.5664/jcsm.11656. Full text in Research Archive
• Pivoriunas, Jonas; Vethe, Nils Tore; Kristiansen, Oscar; Bergan, Stein; Husebye, Einar & Munkhaugen, John [Show all 7 contributors for this article] (2025). Low-Density Lipoprotein Cholesterol Increases Significantly During Brief Discontinuation of Atorvastatin and Correlates With Metabolite Half-Lives. Pharmacology Research & Perspectives. 13(2). doi: 10.1002/prp2.70082. Full text in Research Archive Show summary

  Variability in low-densitylipoprotein cholesterol (LDL-C) has emerged as a potential independent cardiovascular risk factor, but the impact of short-term discontinuation of statins on LDL-C remains to be defined. Furthermore, the relationship between individual statin metabolites and changes in LDL-C has not yet been examined. The present study aimed to investigate changes in LDL-C concentrations during a four-day discontinuation of atorvastatin therapy and to examine correlations between the half-lives of atorvastatin metabolites and LDL-C concentrations. This pharmacokinetic intervention study included 60 adults with confirmed adherence to atorvastatin, using doses of 20 mg (N = 20), 40 mg (N = 20), or 80 mg (N = 20) at study start. Atorvastatin was then discontinued, and blood samples were collected from day zero to day four. We assessed daily concentrations of LDL-C and of atorvastatin with its metabolites by liquid chromatography–tandem mass spectrometry. The mean (SD) LDL-C at baseline was 1.84 (0.6) mmol/L. LDL-C increased on average by 0.50 mmol/L (27%) from day zero to day four. The increase in LDL-C was significant already 48 h after the last statin intake and was affected by individual variation in baseline concentrations and the slope of the daily increase. A moderate correlation was found between differences in LDL-C concentrations and the half-lives of hydroxylated atorvastatin metabolites. In conclusion, 4 days without atorvastatin resulted in an almost 30% increase in LDL-C concentrations, and the increase was significant already after the first omitted dose. The half-lives of hydroxylated atorvastatin metabolites showed a moderate correlation with the increase in LDL-C concentrations.

• Engebretsen, Ingrid; Ødegaard, Kristina Malene; Halvorsen, Sigrun; Bugge, Christoffer; Kristiansen, Ivar Sønbø & Støvring, Henrik [Show all 7 contributors for this article] (2024). Treatment with PCSK9 monoclonal antibodies is associated with discontinuation of oral lipid lowering therapy. European Heart Journal - Quality of Care and Clinical Outcomes. ISSN 2058-5225. doi: 10.1093/ehjqcco/qcae099. Full text in Research Archive Show summary

  Aims Proprotein convertase subtilisin/kexin type 9 monoclonal antibodies (PCSK9 mAbs) are recommended for high-risk patients if the low-density lipoprotein cholesterol targets are not achieved with statins and ezetimibe. We studied persistence and adherence to (i) PCSK9 mAbs and (ii) statins and ezetimibe in a nationwide cohort of incident PCSK9 mAb users. Methods and results Information on all PCSK9 mAb users ≤80 years from 2015 through 2023 were extracted from the Norwegian Drug Registry. Discontinuation was defined as a gap in treatment ≥180 days and ≥90 days. Adherence was measured as the proportion of days covered during the initial year of PCSK9 mAb therapy. We analysed adherence of statins and ezetimibe before and after PCSK9 mAb initiation. Of 4784 patients initiating PCSK9 mAbs, the median age was 63 years, 41% were female, 61% had atherosclerotic disease, and 34% had familial hypercholesterolaemia. Within 3 years after initiation, 17% experienced a PCSK9 mAb treatment gap exceeding 180 days. In the 12-month period preceding PCSK9 mAb initiation, 74% dispensed statins whereas 67% dispensed ezetimibe. These numbers were reduced to 35% for statins and 42% for ezetimibe during the 12-month period after PCSK9 mAb initiation. Atherosclerotic disease, using ≥3 statins previously, and older age were significantly associated with discontinuation of statins and ezetimibe. Conclusion In this high-risk cohort of incident PCSK9 mAb users, more than 1 out of 2 stopped taking statin treatment whereas 40% discontinued ezetimibe. There is a major potential for improving adherence to oral LLD treatment following initiation of PCSK9 mAb.

• Pivoriunas, Jonas; Vethe, Nils Tore; Husebye, Einar; Fagerland, Morten; Bergan, Stein & Kristiansen, Oscar [Show all 8 contributors for this article] (2024). Validation of a novel direct method to determine reduced adherence to atorvastatin therapy. European Heart Journal (EHJ) - Cardiovascular Pharmacotherapy. ISSN 2055-6837. 10(4), p. 307–315. doi: 10.1093/ehjcvp/pvae001. Full text in Research Archive Show summary

  Aims Objective methods to determine statin adherence are requested to improve lipid management. We have recently established a method to detect reduced adherence to atorvastatin therapy with cut‐off values based on the sum of atorvastatin and its major metabolites in blood. We aimed to validate this method in patients with and without cardiovascular disease, and optimize previous cut-off values. Methods and results The pharmacokinetic study included 60 participants treated with atorvastatin 20 mg (N=20), 40 mg (N=20), and 80 mg (N=20). Atorvastatin was then stopped and blood samples collected from day zero to day four. Quantification of the parent drug and its metabolites in blood plasma was performed with a liquid chromatography-tandem mass spectrometry assay. The cut-off values for reduced adherence were validated and optimized by calculating diagnostic sensitivity and specificity. Our candidate cut-off value of dose-normalized six-component sum of atorvastatin plus metabolites <0.10 nM/mg provided a sensitivity of 97% and a specificity of 93% for detecting ≥2 omitted doses. An optimized cut-off <0.062 nM/mg provided a sensitivity of 90% and a specificity of 100%. An alternative simplified two-component metabolite sum with cut-off value <0.05 nM/mg provided a sensitivity of 98% and a specificity of 76%. An optimized cut-off <0.02 nM/mg provided a sensitivity of 97% and a specificity of 98%. Conclusion This validation study confirms that our direct method discriminates reduced adherence from adherence to atorvastatin therapy with high diagnostic accuracy. The method may improve lipid management in clinical practice and serve as a useful tool in future studies.

• Lauritzen, Trine; Munkhaugen, John; Bergan, Stein; Peersen, Kari; Svarstad, Anja Camilla & Andersen, Anders Mikal [Show all 9 contributors for this article] (2024). The atorvastatin metabolite pattern in muscle tissue and blood plasma is associated with statin muscle side effects in patients with coronary heart disease; An exploratory case-control study. Atherosclerosis Plus. ISSN 2667-0909. 55, p. 31–38. doi: 10.1016/j.athplu.2024.01.001. Full text in Research Archive Show summary

  Background and aims Statin-associated muscle symptoms (SAMS) is a prevalent cause of statin discontinuation. It is challenging and time-consuming for clinicians to assess whether symptoms are caused by the statin or not, and diagnostic biomarkers are requested. Atorvastatin metabolites have been associated with SAMS. We aimed to compare atorvastatin pharmacokinetics between coronary heart disease (CHD) patients with and without clinically statin intolerance and statin-dependent histopathological alterations in muscle tissue. Secondarily we aimed to assess genetic variants relevant for the observed pharmacokinetic variables. Methods Twenty-eight patients with CHD and subjective SAMS were included in the exploratory MUSE biomarker study in 2020. Participants received atorvastatin 40 mg/day for seven weeks followed by no statins for eight weeks. Muscle biopsies and blood were collected at the end of each period. Four patients were categorized as clinically intolerant to ≥3 statins prior to study start whereas four patients had signs of muscle cell damage during treatment. Results We found significantly lower levels of atorvastatin acids, and higher lactone/acid ratios in the statin intolerant, both in muscle and plasma. With optimal cut-off, the combination of 2-OH-atorvastatin acid and the 2-OH-atorvastatin lactone/acid ratio provided sensitivity, specificity, and predictive values of 100 %. Patients with variants in UGT1A1 and UGT1A3 had higher lactone metabolite levels than those with wild type, both in muscle and plasma. Conclusion Atorvastatin metabolites appear promising as biomarkers for the identification of clinical statin intolerance in patients with self-perceive

• Otterstad, Jan Erik; Munkhaugen, John; Ruddox, Vidar; Edvardsen, Thor & Hjelmesæth, Jøran Sture (2024). Association of normal body mass index and weight loss with long-term major cardiovascular events after PCI for myocardial infarction. Scandinavian Cardiovascular Journal. ISSN 1401-7431. 58(1). doi: 10.1080/14017431.2024.2386984. Full text in Research Archive Show summary

  Objectives: To investigate whether normal body mass index (BMI) shortly after percutaneous coronary intervention (PCI) for myocardial infarction is associated with increased risk of long-term major cardiovascular events (MACE), and to explore potential clinical determinants of long-term weight loss (WL) after PCI. Methods: Single-center cohort study with 5-year follow-up of patients treated with PCI for myocardial infarction between 2016 and 2018. Categorical WL was defined as > 0 kg body weight reduction from baseline to end of follow-up. Results: Of 236 patients (24% women), mean age was 64.9 ± 10.2 years and mean BMI within 4 days after PCI was 27.1 ± 4.3 kg/m2. Seventy-five patients (32%) had at least one MACE, equally distributed between those with normal weight (31%), overweight (32%), and obesity (31%). Patients with overweight or obesity had a lower crude mortality rate than their normal weight counterparts (7.4% vs 16.4%, p = 0.049), but the relative hazard of death did not differ from those with normal weight, HR 0.50, 95% CI 0.22-1.15. Patients with either a long-term WL (n = 112) or no WL (n = 95) had a comparable incidence of non-fatal MACE (27% vs 22%, p = 0.518). The proportion of patients reporting unintentional weight loss was significantly higher in the normal weight group (82%) compared with those with overweight (41%) or obesity (28%), p < 0.001. Conclusion: Our results did not confirm any association between normal BMI after PCI and long-term MACE. However, patients with normal BMI at baseline had a higher incidence of unintentional WL than those with elevated BMI. Trial registration: Current research information system in Norway (CRISTIN): ID 542528

• Lauritzen, Trine; Munkhaugen, John; Bergan, Stein; Sverre, Elise Christine Bjørkholen; Peersen, Kari & Lindahl, Sofia [Show all 8 contributors for this article] (2024). Mevalonate in blood and muscle: Response to atorvastatin treatment and the relationship to statin intolerance in patients with coronary heart disease. Clinical and Translational Science (CTS). ISSN 1752-8054. 17:e70025(10), p. 1–9. doi: 10.1111/cts.70025. Full text in Research Archive Show summary

  Statin-associated muscle symptoms are frequently reported and often lead to discontinuation of statin therapy with an increased risk of cardiovascular events. In vitro studies suggest that statin-mediated inhibition of the mevalonate pathway leads to muscle cell toxicity. We aimed to determine the relationship between mevalonate, LDL-cholesterol, and atorvastatin metabolites in patients with coronary heart disease and self-perceived muscle side effects. Furthermore, we assessed the correlation between mevalonate in blood and muscle and the relationship to statin intolerance due to muscle symptoms. We used blood plasma from a randomized crossover trial (n = 70) and muscle biopsies and plasma from a subgroup in a subsequent open intervention study (n = 26). Both studies tested atorvastatin 40 mg/day. Seven patients did not tolerate ≥3 statins throughout the follow-up and were classified as statin-intolerant. Mevalonate in blood plasma decreased during atorvastatin treatment (median difference −38%, range −77% to 43%, p < 0.001), whereas mevalonate in muscle tissue was not lowered (0.05%, range −47% to 145%). Mevalonate correlated poorly with LDL-cholesterol and atorvastatin metabolites (Spearman's rho −0.28 to 0.10). The statin-intolerant patients had a smaller reduction in circulating mevalonate compared with the tolerant patients; median difference −8.1 (−22 to 3.5) nmol/L versus −25 (−93 to 12) nmol/L, p = 0.028. A similar observation was made for LDL-cholesterol. Cutoffs based on these biomarkers classified >50% correctly as tolerant. Inhibition of the mevalonate pathway does not appear to be the mechanism underlying statin intolerance in the present study. Further studies of mevalonate as a biomarker for statin tolerance are needed to clarify the potential.

• Engebretsen, Ingrid; Bugge, Christoffer; Støvring, Henrik; Husebye, Einar; Sverre, Elise Christine Bjørkholen & Dammen, Toril [Show all 8 contributors for this article] (2024). Treatment patterns and adherence to lipid-lowering drugs during eight-year follow-up after a coronary heart disease event. Atherosclerosis. ISSN 0021-9150. 393. doi: 10.1016/j.atherosclerosis.2024.117550. Full text in Research Archive Show summary

  Background and aims Proper prescription and high adherence to intensive lipid lowering drugs (LLD) in patients with coronary heart disease (CHD) is crucial and strongly recommended. The aim of this study is to investigate long-term treatment patterns and adherence to LLD following hospitalization for a CHD event. Methods Patients admitted to two Norwegian hospitals with a CHD event from 2011-2014 (N=1094) attended clinical examination and completed a questionnaire, median 16 months later. Clinical data were linked to pharmacy dispensing data from 2010-2020. The proportions using high-intensity statin therapy (atorvastatin 40/80 mg or rosuvastatin 20/40 mg) and non-statin LLD after the CHD event were assessed. Adherence was evaluated by proportion of days covered (PDC) and gaps in treatment. Results Median age at hospitalization was 63 (IQR 12) years, 21% were female. Altogether, 1054 patients (96%) were discharged with a statin prescription, while treatment was dispensed in 85% within the following 90 days. During median 8 (SD 2.5) years follow-up, the proportion using high-intensity statin therapy ranged 62-68%, whereas the use of ezetimibe increased from 4-26 %. PDC <0.8 was found in 22% of statin users and 26% of ezetimibe users. The proportions with a treatment gap exceeding 180 days were 22% for statins and 28% for ezetimibe. Smoking at hospitalization and negative affectivity were significantly associated with reduced statin adherence, regardless of adherence measure. Conclusions In this long-term follow-up of patients with CHD, less than 70% used high-intensity statin therapy with only small changes over time, and only 25% used additional treatment with ezetimibe. We identified factors associated with reduced statin adherence that may be target for interventions.

• Pleym, Karin; Dammen, Toril; Weedon-Fekjær, Harald; Husebye, Einar; Sverre, Elise Christine Bjørkholen & Tonstad, Serena [Show all 7 contributors for this article] (2024). A multi-component intervention increased access to smoking cessation treatment after hospitalization for atherosclerotic cardiovascular disease: A randomized trial. European Heart Journal Open (EHJ Open). 4(2). doi: 10.1093/ehjopen/oeae028. Full text in Research Archive Show summary

  Aims To evaluate the effects of a multi-component intervention for smokers hospitalized for atherosclerotic cardiovascular disease (ASCVD) on the participation rate in community-based cessation programmes and the use of cessation drugs. Additionally, to explore the impact on the cessation rates at 6 months. Methods and results A randomized parallel-group study was conducted at a Norwegian secondary care hospital in 2021. The intervention group was: (i) counselled using motivational interviewing techniques during hospitalization; (ii) given an information leaflet, detailing the cessation programme; and (iii) referred to the community-based smoking cessation treatment including a post-discharge pro-active telephone invitation. The control group received usual care and the same information leaflet containing clear contact details for initiating participation. Data were collected at baseline, 1, 3, and 6 months. Among 99 smokers hospitalized with ASCVD, 40 were excluded. Of 59 randomized patients, 4 were lost to follow-up and 55 completed the study. The mean age was 65.1 (standard deviation 9.3) years, 35% were female, and 88% had smoked >20 years. Co-morbidity was prevalent (mean Charlson score 4.8). The intervention group was more likely to participate in the smoking cessation treatment {48 vs. 7%, difference: 41% [95% confidence interval (CI): 14%, 63%]} and used cessation drugs more frequently [59 vs. 21%, difference: 38% (95% CI: 17%, 59%)]. At the 6 months point prevalence, we observed notable between-group differences in self-reported cessation rate (48 vs. 25%). Conclusion The intervention significantly increased the participation rate at community-based smoking cessation programmes and the use of cessation drugs among multi-morbid smokers hospitalized for ASCVD.

• Ihle-Hansen, Hege Beate; Ihle-Hansen, Håkon; Rostoft, Siri; Munkhaugen, John; Westbye, Siri Færden & Romøren, Maria [Show all 13 contributors for this article] (2024). Forhåndssamtaler om siste livsfase. Tidsskrift for Den norske legeforening (Tidsskriftet). ISSN 0029-2001. 144(13). doi: 10.4045/tidsskr.24.0105. Full text in Research Archive Show summary

  Bakgrunn: Det foreligger nye nasjonale faglige råd om forhåndssamtaler om siste livsfase. Trygghet i kommunikasjon er viktig for implementering. Formålet med denne studien var å kartlegge helsepersonells selvopplevde trygghet i kommunikasjon om fremtidig helsehjelp og pasientens ønsker i livets sluttfase. Materiale og metode: Helsepersonell ved tolv geriatriske enheter i Helse Sør-Øst besvarte en nettbasert spørreundersøkelse høsten 2022. De fire svaralternativene for selvrapportert trygghet – «lite trygg», «nokså trygg», «meget trygg» og «svært trygg» – er slått sammen til to kategorier: «begrenset trygghet» («lite trygg» og «nokså trygg») og «høy trygghet» («meget trygg» og «svært trygg»). Resultater: Vi fikk svar fra 289 av 470 (61,5 %) av de inviterte, med en gjennomsnittsalder på 37,8 ± 11,3 år, hvorav 217 av 289 (75 %) hadde mer enn fem års yrkeserfaring. Blant legene rapporterte 15 av 67 (22 %) begrenset trygghet i kommunikasjon om «fremtidig forverring av pasientens helsetilstand», 20 av 67 (30 %) om «livsforlengende behandling» og 13 av 67 (19 %) om «ønsker for livets sluttfase». For annet helsepersonell var tilsvarende responser 119 av 222 (54 %), 140 av 222 (63 %) og 109 av 222 (49 %). Fortolkning: Egenvurdert trygghet i kommunikasjon om fremtidig forverring, fremtidig helsehjelp og pasientens egne ønsker i livets sluttfase varierer, og er begrenset blant mye helsepersonell i geriatriske enheter. Det synes nødvendig med tiltak for å øke tryggheten i kommunikasjon og implementering av forhåndssamtaler i helsetjenesten. Hovedfunn: Blant leger oppga 20 av 67 (30 %) begrenset trygghet i kommunikasjon om «fremtidig helsehjelp», mens av annet helsepersonell svarte 140 av 222 (63 %) det samme. For kommunikasjon om «ønsker for livets siste fase» fant vi at 13 av 67 (19 %) av legene og 109 av 222 (49 %) av annet helsepersonell oppga begrenset trygghet.

• Getz, Vilde; Munkhaugen, John; Lie, Hanne Cathrine & Dammen, Toril (2023). Barriers and facilitators for smoking cessation in chronic smokers with atherosclerotic cardiovascular disease enrolled in a randomized intervention trial: A qualitative study. Frontiers in Psychology. 14. doi: 10.3389/fpsyg.2023.1060701. Full text in Research Archive Show summary

  Objectives: Smoking is common in patients with cardiovascular disease. Despite strong recommendations for cessation and the existence of efficacious pharmacological and behavioral interventions, cessation rates remain low. Therefore, in this study, we explore perceived facilitators and barriers to smoking cessation in patients with atherosclerotic cardiovascular disease who have participated in a cessation intervention study. Methods: Participants (N = 10) from the intervention arm of a randomized controlled study with access to free cessation support and pharmacological aids completed a semi-structured, in-depth telephone interview after a 6-monthfollow-up between October 2021 and July 2022. The interviews were audio recorded, transcribed, and analyzed according to principles of thematic analysis. Results: The mean age was 65.7 (range: 55–79) years, and three of the 10 participants were women. Among the participants, five had quit smoking, three had relapsed, and two were persistent smokers. The themes identified encompassed barriers and facilitators to cessation, both including individual and contextual factors. Barriers included the upsides of smoking, difficult life situations, addiction to smoking, smoking in social circles, perceived lack of support and understanding from health professionals. Facilitators included intrinsic motivation, concerns about the health condition, financial implications, specific behavioral strategies, positive influence from the social environment, and helpful components of the cessation intervention. Conclusion: Smokers with cardiovascular disease who have attended a cessation intervention study report several facilitators weighted against barriers, interacting with the intention to cease smoking. The most important potentially modifiable factors of significance for cessation identified may be addressed through motivational interviews and focus groups with other smokers.

• Lauritzen, Trine; Munkhaugen, John; Peersen, Kari; Kristiansen, Oscar; Sverre, Elise Christine Bjørkholen & Nebauer, Shane Desmond [Show all 13 contributors for this article] (2023). Atorvastatin Metabolite Pattern in Skeletal Muscle and Blood from Patients with Coronary Heart Disease and Statin-Associated Muscle Symptoms. Clinical Pharmacology and Therapeutics. ISSN 0009-9236. 113(4), p. 887–895. doi: 10.1002/cpt.2844. Full text in Research Archive Show summary

  Self-perceived statin-associated muscle symptoms (SAMS) are prevalent, but only a minority is drug-dependent. Diagnostic biomarkers are not yet identified. The local statin exposure in skeletal muscle tissue may correlate to the adverse effects. We aimed to determine whether atorvastatin metabolites in blood reflect the corresponding metabolite levels in skeletal muscle, and whether genetic variants of statin transporters modulate this relationship. We also addressed atorvastatin metabolites as potential objective biomarkers of SAMS. Muscle symptoms were examined in patients with coronary disease and self-perceived SAMS during 7 weeks of double-blinded treatment with atorvastatin 40 mg/day and placebo in randomized order. A subset of 12 patients individually identified with more muscle symptoms on atorvastatin than placebo (confirmed SAMS) and 15 patients with no difference in muscle symptom intensity (non-SAMS) attended the present follow-up study. All received 7 weeks of treatment with atorvastatin 40 mg/day followed by 8 weeks without statins. Biopsies from the quadriceps muscle and blood plasma were collected after each treatment period. Strong correlations (rho > 0.7) between muscle and blood plasma concentrations were found for most atorvastatin metabolites. The impact of the SLCO1B1 c.521T>C (rs4149056) gene variant on atorvastatin's systemic pharmacokinetics was translated into muscle tissue. The SLCO2B1 c.395G>A (rs12422149) variant did not modulate the accumulation of atorvastatin metabolites in muscle tissue. Atorvastatin pharmacokinetics in patients with confirmed SAMS were not different from patients with non-SAMS. In conclusion, atorvastatin metabolite levels in skeletal muscle and plasma are strongly correlated, implying that plasma measurements are suitable proxies of atorvastatin exposure in muscle tissue. The relationship between atorvastatin metabolites in plasma and SAMS deserves further investigation.

• Torgersen, Kristin Stensland; Sverre, Elise Christine Bjørkholen; Weedon-Fekjær, Harald; Andreassen, Ole; Munkhaugen, John & Dammen, Toril (2023). Risk of recurrent cardiovascular events in coronary artery disease patients with Type D personality. Frontiers in Psychology. 14. doi: 10.3389/fpsyg.2023.1119146. Full text in Research Archive Show summary

  Introduction Data on the association between Type D personality, its traits negative affectivity (NA) and social inhibition (SI), and risk of major adverse cardiac events (MACE) in coronary outpatients is sparse. Furthermore, the associations between Type D subgroups and cardiovascular risk factors are largely unknown. Methods We investigated i) Type D personality, NA and SI and risk of recurrent MACE, and ii) the relationship between Type D subgroups and risk factors in a coronary population. This prospective cohort study included 1083 patients` median 16 months after a myocardial infarction and/or a revascularization procedure who were followed-up for 4.2 (SD 0.4) years. Type D personality was assessed by DS14. Anxiety and depression, statin adherence, and risk factors were assessed by patients’ self-report and a clinical examination with blood samples. MACE, defined as cardiovascular death, myocardial infarction, revascularization, stroke or heart failure, were obtained from hospital records from index event to end of study lasting 5.7 years. Data were analyzed by Cox proportional hazard regression. Results In all, 352 MACE occurred in 230 patients after average 4.2 years follow-up. Higher NA score was associated with MACE after adjustment for age, risk factors and comorbidity (HR 1.02 per unit increase, 95% CI 1.00-1.05), whereas we found a weaker, not statistically significant estimated effect of higher SI score. After additional adjustment for symptoms of anxiety and depression, we found a weaker, not statistically significant association between NA and MACE (HR 1.01 per unit increase, 95% CI 0.98-1.05). Low statin adherence and smoking were more prevalent in the Type D and high NA group. Discussion Our results indicate that the NA trait is related to worse prognosis in outpatients with coronary artery disease.

• Dammen, Toril; Munkhaugen, John; Sverre, Elise Christine Bjørkholen; Moum, Torbjørn & Papageorgiou, Constantinos (2023). Psychiatric disorders, rumination, and metacognitions in patients with type D personality and coronary heart disease. Nordic Journal of Psychiatry. ISSN 0803-9488. 77(6), p. 540–546. doi: 10.1080/08039488.2023.2182358. Full text in Research Archive Show summary

  Background: Little is known regarding the prevalence of psychiatric disorders in patients with both coronary heart disease (CHD) and type D personality, and whether these patients may benefit from psychotherapy that modifies metacognitive beliefs implicated in disorder maintenance. This study explored prevalence rates among these patients and associations between type D characteristics, rumination and metacognitions. Methods: Forty-seven consecutive patients with CHD who scored positive for type D personality were included in this pre-planned study. Participants underwent structured clinical interviews for mental and personality disorders and completed questionnaires assessing rumination and metacognitions. Results: Mean age was 53.8 (SD 8.1) years and 21.3% were female. At least one mood disorder or anxiety disorder was found in 70.2% and 61.7% of the patients. The most common disorders were major depressive disorder (59.6%), social phobia (40.4%), and generalized anxiety disorder (29.8%). At least one personality disorder was detected in 42.6%. Only 21% reported ongoing treatment with psychotropic medication whereas none had psychotherapy. Metacognitions and rumination were significantly associated with negative affectivity but not social inhibition. Conclusion: Mood and anxiety disorders were highly prevalent and relatively untreated among these patients. Future studies should test the metacognitive model for type D personality.

• Sverre, Elise Christine Bjørkholen; Munkhaugen, John; Kristiansen, Oscar; Weedon-Fekjær, Harald; Peersen, Kari & Gjertsen, Erik [Show all 10 contributors for this article] (2023). Plasma concentration of atorvastatin metabolites correlates with low-density lipoprotein cholesterol reduction in patients with coronary heart disease. Pharmacology Research & Perspectives. 11(3). doi: 10.1002/prp2.1089. Full text in Research Archive Show summary

  In this exploratory study from a randomized double-blinded crossover trial including 70 patients with coronary heart disease and self-perceived muscular side effects of statins, we aimed to determine the relationship between low-density lipoprotein cholesterol (LDL-C) reduction and atorvastatin metabolite plasma concentrations. All patients underwent a 7 weeks treatment period with atorvastatin 40 mg/day and a 7 weeks placebo period in random order. Nonlinear regression with a three-parameter equation explored the relationship between percentage LDL-C reduction (statin vs. placebo) and the pharmacokinetic variables. Mean LDL-C reduction was 49% (range 12% to 71%). The sum of 4-OH-atorvastatin acid and lactone correlated moderately with the LDL-C response (Spearman ρ 0.27, 95% confidence interval [CI]: 0.03 to 0.48). Accordingly, nonlinear regression showed R2 of 0.14 (95% CI: 0.03 to 0.37, R2 adjusted equaled 0.11). Even a perfect underlying correlation of 1.0 showed R2 = 0.32 by simulation, using historical intra-individual LDL-C variation (8.5%). The 90% inhibitory concentration was 2.1 nmol/L, and the 4-OH-metabolite sum exceeded this threshold in 34% of the patients. In conclusion, trough plasma concentrations of 4-OH-atorvastatin metabolites correlated moderately to the LDL-C reduction. A plateau LDL-C response was observed above a pharmacokinetic threshold, below which the response was highly variable. The usefulness of monitoring concentrations of atorvastatin metabolites to optimize the individual dosage have limitations, but its supportive potential may be pursued in relevant patient subsets to achieve adequate efficacy at the lowest possible dose. The results add knowledge to the overall understanding of the variable LDL-C response mediated by atorvastatin.

• Aastebøl, Lars Frøjd; Munkhaugen, John; Papageorgiou, Constantinos; Sverre, Elise Christine Bjørkholen; Moum, Torbjørn & Dammen, Toril (2023). Predictors of health-related quality of life in outpatients with coronary heart disease. Frontiers in Psychology. 14. doi: 10.3389/fpsyg.2023.1119093. Full text in Research Archive Show summary

  Health-related quality of life (HRQoL) is an important treatment target in patients with coronary heart disease (CHD) and is associated with poor outcomes. Therefore, it is of clinical importance to identify the key determinants of HRQoL among these patients. There is, however, limited knowledge of how a comprehensive set of psychosocial factors influence HRQoL. We aimed to determine the relative associations of clinical and psychosocial factors with mental and physical components of HRQoL in a sample of CHD outpatients. This cross-sectional study included 1042 patients 2-36 (mean 16) months after a CHD event recruited from two general Norwegian hospitals with a combined catchment area making up 7% of the Norwegian population, representative with regards to demographic and clinical factors. We collected data on HRQoL, demographics, comorbidities, coronary risk factors, and psychosocial factors. HRQoL was assessed using the Short Form 12 (SF12), which comprises a Mental Component Scale (MCS) and the Physical Component Scale (PCS). Crude and multi-adjusted linear regression analyses were used to investigate the association between covariates and MCS and PCS. Mean age was 61 (standard deviation [SD] 10) years, 20 % were females, 18% had type D personality, 20% significant depression symptoms, 14% significant symptoms of anxiety whereas 45% reported insomnia. The presence of type D personality (β:-.19), significant symptoms of depression (β:-.15), and the presence of insomnia (β:-.13) were negatively associated with MCS, but not PCS in multi-adjusted analyses. The presence of chronic kidney disease (β:-.11) was associated with reduced MCS, whereas the presence of chronic obstructive pulmonary disease (β:-.08) and low physical activity (β:-.14) were negatively associated with PCS. Younger age was associated with lower MCS, whereas older age was associated with lower PCS. We conclude that Type D personality, depressive symptoms, insomnia, and chronic kidney disease were the strongest determinants of the mental component of HRQoL. Assessing and managing these psychological factors among CHD outpatients may improve their mental HRQoL

• Kristensen, Anna Meta Dyrvig; Munkhaugen, John; Halvorsen, Sigrun; Olsen, Michael Hecht; Bakken, Arnhild & Sehested, Thomas Steen Gyldenstierne [Show all 12 contributors for this article] (2023). The Danish-Norwegian randomized trial on beta-blocker therapy after myocardial infarction: Design, rationale, and baseline characteristics. European Heart Journal (EHJ) - Cardiovascular Pharmacotherapy. ISSN 2055-6837. 10(3), p. 175–183. doi: 10.1093/ehjcvp/pvad093. Full text in Research Archive
• Norekvål, Tone Merete; Bale, Marte; Hole, Torstein; Bedane, Haji Kedir; Hole, Torstein Laurits & Ingul, Charlotte Ingeborg Björk [Show all 7 contributors for this article] (2023). Cardiac rehabilitation participation within 6 months of discharge in 37 136 myocardial infarction survivors: a nationwide registry study. European Journal of Preventive Cardiology (EJPC). ISSN 2047-4873. 31(16), p. 1977–1980. doi: 10.1093/eurjpc/zwad350. Full text in Research Archive
• Frøjd, Lars Aastebøl; Munkhaugen, John; Papageorgiou, Constantinos; Sverre, Elise Christine Bjørkholen; Moum, Torbjørn & Dammen, Toril (2023). Health-related quality of life in outpatients with coronary heart disease: impact of type D personality, depression, anxiety and insomnia. European Journal of Preventive Cardiology (EJPC). ISSN 2047-4873. 30. doi: 10.1093/eurjpc/zwad125.285. Full text in Research Archive
• Munkhaugen, John; Sverre, Elise Christine Bjørkholen; Dammen, Toril; Husebye, Einar; Gjertsen, Erik & Kristiansen, Oscar [Show all 7 contributors for this article] (2023). Skrøpelighet, helsekompetanse og egenomsorg hos pasienter som innlegges med akutt hjertesvikt. Tidsskrift for Den norske legeforening (Tidsskriftet). ISSN 0029-2001. 143(17). doi: 10.4045/tidsskr.23.0297. Full text in Research Archive Show summary

  BAKGRUNN Det er lite kunnskap fra Norge om kliniske karakteristika, egenomsorg og helsekompetanse hos sykehusinnlagte pasienter med akutt hjertesvikt. Formålet var å kartlegge disse faktorene i denne gruppen. MATERIALE OG METODE Vi inkluderte fortløpende innlagte pasienter med akutt hjertesvikt over seks måneder (2022/2023) ved Drammen sykehus og Sykehuset i Vestfold. Kardiologiske sykepleiere innhentet opplysninger fra pasientene, inkludert egenvurdert kunnskap på en ordinal skala fra 0 (lite) til 10 (mye). Klinisk skrøpelighetsskala ble beregnet, og data ble registrert fra sykehusjournalen. RESULTATER Av 136 pasienter med akutt hjertesvikt ble 81 inkludert. Median alder var 79 (spredning 35–95) år, 35 (43 %) var kvinner. 35 (43 %) hadde vært innlagt med hjertesviktforverring det siste året. Pasientene hadde median 5 (1–10) diagnoser, og median skår på klinisk skrøpelighetsskala var 4 (1–7), som tilsvarer «sårbar». 63 (78 %) var diagnostisert med hjertesvikt før den aktuelle innleggelsen. Blant disse var 13 (21 %) ikke klar over diagnosen, og egenvurdert kunnskap var median 3 (25- og 75-prosentiler, 0–5) for håndtering av hjertesvikt, 2 (25- og 75-prosentiler, 0–5) for livsstilstiltak og 0 (25- og 75-prosentiler, 0–2) for hjertemedisiner. 42 av 63 (67 %) veide seg ≥ 1 gang/uke, 13 (21 %) målte blodtrykk, mens 3 (5 %) hadde egenbehandlingsplan. Av 50 pasienter med venstre ventrikkel- ejeksjonsfraksjon ≤ 40 % ble 32 (64 %) utskrevet med betablokker og angiotensin II-hemmer eller kombinasjonspreparat med neprilysinhemmer, mens 11 (22 %) også fikk SGLT2-hemmer og mineralreseptorantagonist. FORTOLKNING De inkluderte pasientene var multimorbide og hadde lav grad av egenomsorg og helsekompetanse. Det foreligger et potensial for å optimalisere veldokumentert medikamentell behandling.

• Dammen, Toril; Tunheim, Kristoffer; Munkhaugen, John; Klungsøyr, Ole & Papageorgiou, Constantinos (2023). Attention training technique delivered in groups as treatment for anxiety and depression in patients with coronary heart disease: study protocol for a waiting-list randomized controlled trial. Frontiers in Psychology. 14. doi: 10.3389/fpsyg.2023.1226539. Full text in Research Archive
• Engebretsen, Ingrid; Munkhaugen, John; Bugge, Christoffer; Halvorsen, Sigrun; Ødegaard, Kristina Malene & Støvring, Henrik [Show all 7 contributors for this article] (2022). Gaps and discontinuation of statin treatment in Norway: potential for optimizing management of lipid lowering drugs. European Heart Journal Open (EHJ Open). 2(6). doi: 10.1093/ehjopen/oeac070. Full text in Research Archive Show summary

  Abstract Aims In clinical practice many patients do not reach the recommended treatment targets for LDL-cholesterol levels. We aimed to examine treatment patterns and adherence for patients on lipid lowering drugs in Norway to inform future strategies to improve therapies. Methods and results We obtained information on all dispensed statins, ezetimibe and PCSK9 inhibitors 2010-2019 from the Norwegian Prescription Database. Treatment gaps were assessed assuming patients take one tablet per day and was defined to occur if a patient did not refill a prescription when the previous one should have been depleted. Treatment was defined as discontinued when the preceding prescription would have been used and no new subsequent prescription was filled. The mean proportion of days covered (PDC) was calculated by aggregating the total number of tablets dispensed during each calendar year and dividing by 365. Patients >80 years were excluded. A considerable proportion of statin users in Norway had long treatment gaps or discontinuation in treatment. 19.6% of the patients had treatment gaps of 180 days or more, and 10.8% had gaps or greater than 365 days. Similar results were found for patients on antidiabetics and hypertensives. PDC ranged from 84.9% for simvastatin to 72.2% for ezetimibe (2019). The most common lipid lowering drugs in 2019 were atorvastatin, simvastatin and ezetimibe. Conclusion There is a great potential for improving drug adherence and optimizing lipid lowering therapy by switching to more effective statins in greater doses, and more Powered by Editorial Manager® and ProduXion Manager® from Aries Systems Corporation often add ezetimibe and PCSK9 inhibitors to treatment.

• Dammen, Toril; Tunheim, Kristoffer Joe; Munkhaugen, John & Papageorgiou, Constantinos (2022). The Attention Training Technique Reduces Anxiety and Depression in Patients With Coronary Heart Disease: A Pilot Feasibility Study. Frontiers in Psychology. 13. doi: 10.3389/fpsyg.2022.948081. Full text in Research Archive Show summary

  Background and Objectives: Depression and anxiety symptoms are highly prevalent in coronary heart disease (CHD) patients and associated with poor outcome. Most psychological treatments have shown limited effectiveness on anxiety and depression in these patients. This study evaluates the feasibility of the attention training technique (ATT) in CHD patients with symptoms of anxiety and/or depression. Methods: Five consecutive CHD patients with significant depression and anxiety symptoms with Hospital Anxiety and Depression rating scale (HADS) -anxiety or -depression subscale score > 8 received 6 weekly group-sessions of ATT in an open trial. Outcomes included feasibility and symptoms measured by HADS, at baseline, post-treatment and at 6 months follow-up. We also assessed psychiatric diagnoses, type D personality, insomnia, worry, and rumination. Results: The sample comprised five men with a mean age of 59.9 (SD 4.4) years. Four of the patients attended all six sessions, and one patient attended all but one session. Mean HADS-A scores at baseline, post-treatment, and follow-up were 9.4 (SD 3.0), 4.2 (SD 3.0), and 4.0 (SD 2.5), and for HADS-D 8.6 (SD 3.3), 3.0 (SD 3.7), and 1.6 (SD 1.5), respectively. The results showed clinically significant changes in anxiety, depression, psychiatric disorders, insomnia, worry, and rumination. Statistically significant changes were found from pre- to post-treatment scores for HADS-A and worry, which were maintained at follow-up, and HADS-D scores significantly decreased from pre-treatment to 6-months follow-up. Conclusions: ATT in a group format appears to be a feasible stand-alone metacognitive treatment for CHD patients. An adequately powered randomized controlled trial is warranted.

• Frøyd, Lars; Dammen, Toril; Munkhaugen, John; Weedon-Fekjær, Harald; Nordhus, Inger Hilde & Papageorgiou, Constantinos [Show all 7 contributors for this article] (2022). Insomnia as a predictor of recurrent cardiovascular events in patients with coronary heart disease. SLEEP Advances. 3(1). doi: 10.1093/sleepadvances/zpac007. Full text in Research Archive Show summary

  Abstract Study Objectives Insomnia is highly prevalent in patients with coronary heart disease (CHD). However, the potential effect of insomnia on the risk of recurrent major adverse cardiovascular events (MACE) remains uncertain. Methods This prospective cohort study included 1082 consecutive patients 2–36 (mean 16) months after myocardial infarction and/or coronary revascularization. Data on clinical insomnia, coronary risk factors, and comorbidity were collected at baseline. Clinical insomnia was assessed using the Bergen Insomnia Scale (BIS). The primary composite endpoint of MACE (cardiovascular death, hospitalization due to myocardial infarction, revascularization, stroke, or heart failure) was assessed with an average follow-up of 4.2 (SD 0.3) years after baseline. Data were analyzed using Cox proportional hazard regression models stratified by prior coronary events before the index event. Results At baseline, mean age was 62 years, 21% were females, and 45% reported clinical insomnia. A total of 346 MACE occurred in 225 patients during the follow-up period. For clinical insomnia, the relative risk of recurrent MACE was 1.62 (95% confidence interval [CI]: 1.24–2.11, p

• Tunheim, Kristoffer Joe; Dammen, Toril; Bårdstu, Silje Kvam; Moum, Torbjørn Åge; Munkhaugen, John & Papageorgiou, Constantinos (2022). Relationships between depression, anxiety, type D personality, and worry and rumination in patients with coronary heart disease. Frontiers in Psychology. 13. doi: 10.3389/fpsyg.2022.929410. Full text in Research Archive Show summary

  Psychological distress, including depression and anxiety, and Type-D personality are prevalent in patients with coronary heart disease (CHD) and associated with poor cardiovascular outcomes. Worry and rumination may be among the core features responsible for driving psychological distress in these patients. However, the nature of associations between these constructs remains to be delineated, yet they may have implications for the assessment and treatment of CHD patients. This study aimed to (1) explore the factorial structure and po-tential overlap between measures of depression, anxiety and the Type-D personality factors known as nega-tive affectivity and social inhibition, and (2) examine how these constructs relate to worry and rumination in a sample of 1042 CHD outpatients who participated in the in the cross-sectional NORwegian CORonary Pre-vention study. We conducted confirmatory factor analyses (n=1042) and regression analyses (n=904) within a structural equation modelling framework. Results showed all constructs to have acceptable factor structure and indicated an overlap between the constructs of depression and negative affectivity. Worry was most strongly associated with anxiety, whereas rumination was most strongly associated with depression and neg-ative affectivity. The results suggest conceptual similarities across the measures of depression and negative affectivity. They further suggest that intervention efforts could benefit from targeting worry and/or rumina-tion in the treatment of CHD outpatients presenting with symptoms of psychological distress Keywords: Anxiety, Depression, Type D personality, worry, rumination, metacognition, Metacognitive Therapy, coronary heart disease Received: 26 Apr 2022; Accepted: 24 Aug 2022.

• Vethe, Nils Tore; Husebye, Einar; Andersen, Anders Mikal; Bergan, Stein; Kristiansen, Oskar & Fagerland, Morten [Show all 7 contributors for this article] (2022). Monitoring Simvastatin Adherence in Patients With Coronary Heart Disease: A Proof-of-Concept Study Based on Pharmacokinetic Measurements in Blood Plasma. Therapeutic Drug Monitoring. ISSN 0163-4356. 44(4), p. 558–567. doi: 10.1097/FTD.0000000000000992. Full text in Research Archive Show summary

  Background:  Poor statin adherence remains a public health concern associated with adverse outcomes. We evaluated the use of pharmacokinetic measurements to monitor adherence to simvastatin in patients with coronary heart disease (CHD). Methods:  Eighteen patients with CHD taking an evening dose of simvastatin 20 mg (n = 7), 40 mg (n = 5), or 80 mg (n = 6) were examined at steady-state pharmacokinetics. Ten patients were instructed to interrupt simvastatin dosing and return for blood sampling for the subsequent 3 days. Dose-normalized plasma concentrations of simvastatin lactone and simvastatin acid and the sum of the 2 were evaluated to discriminate between adherent dosing and dose omission. Bioanalytical quantification was performed using liquid chromatography–tandem mass spectrometry. Results:  A simvastatin acid cutoff of 1.0 × 10−2 nmol−1·L−1·mg−1 identified 100% of those omitting 2 doses and 60% of those omitting a single dose. Simvastatin acid showed superior ability to discriminate dose omission, as well as the best agreement between samples handled at ambient and cool temperatures (median deviation 3.5%; interquartile range −2.5% to 13%). The cutoff for a morning dose schedule, with a similar ability to discriminate, was estimated at 2.0 × 10−3 nmol−1·L−1·mg−1. Conclusions:  The present method discriminated between adherence and reduced adherence to simvastatin therapy in patients with CHD. Sample handling is feasible for routine practice, and the assessment of adherence can be performed by direct measurement of simvastatin acid in a blood sample, according to defined cutoff values. Further studies validating the cutoff value and utility for clinical application are encouraged.

• Pleym, Karin; Sverre, Elise Christine Bjørkholen; Weedon-Fekjær, Harald; kahlon, Mohpal Singh; Husebye, Einar & Tonstad, Serena [Show all 8 contributors for this article] (2022). Effect of in-hospital nurse-led smoking cessation intervention for patients with atherosclerotic cardiovascular disease: a randomised pilot study. European Heart Journal. ISSN 0195-668X. 43. doi: 10.1093/eurheartj/ehac544.2329. Full text in Research Archive
• Sverre, Elise Christine Bjørkholen; Peersen, Kari; Kristiansen, Oscar; Fagerland, Morten; Perk, Joep & Husebye, Einar [Show all 9 contributors for this article] (2022). Tailored clinical management after blinded statin challenge improved the lipid control in coronary patients with self-perceived muscle side effects. Journal of Internal Medicine. ISSN 0954-6820. 291(6), p. 891–893. doi: 10.1111/joim.13454. Full text in Research Archive
• Johannessen, Tonje Rambøll; Halvorsen, Sigrun; Atar, Dan; Munkhaugen, John; Nore, Anne Kathrine & Wisløff, Torbjørn [Show all 7 contributors for this article] (2022). Cost-effectiveness of a rule-out algorithm of acute myocardial infarction in low-risk patients: emergency primary care versus hospital setting. BMC Health Services Research. 22(1). doi: 10.1186/s12913-022-08697-6. Full text in Research Archive Show summary

  Aims: Hospital admissions of patients with chest pain considered as low risk for acute coronary syndrome contribute to increased costs and crowding in the emergency departments. This study aims to estimate the cost-effectiveness of assessing these patients in a primary care emergency setting, using the European Society of Cardiology (ESC) 0/1-h algorithm for high-sensitivity cardiac troponin T, compared to routine hospital management. Methods: A cost-effectiveness analysis was conducted. For the primary care estimates, costs and health care expenditure from the observational OUT-ACS (One-hoUr Troponin in a low-prevalence population of Acute Coronary Syndrome) study were compared with anonymous extracted administrative data on low-risk patients at a large general hospital in Norway. Patients discharged home after the hs-cTnT assessment were defined as low risk in the primary care cohort. In the hospital setting, the low-risk group comprised patients discharged with a non-specific chest pain diagnosis (ICD-10 codes R07.4 and Z03.5). Loss of health related to a potential increase in acute myocardial infarctions the following 30-days was estimated. The primary outcome measure was the costs per quality-adjusted life year (QALY) of applying the ESC 0/1-h algorithm in primary care. The secondary outcomes were health care costs and length of stay in the two settings. Results: Differences in costs comprise personnel and laboratory costs of applying the algorithm at primary care level (€192) and expenses related to ambulance transports and complete hospital costs for low-risk patients admitted to hospital (€1986). Additional diagnostic procedures were performed in 31.9% (181/567) of the low-risk hospital cohort. The estimated reduction in health care cost when using the 0/1-h algorithm outside of hospital was €1794 per low-risk patient, with a mean decrease in length of stay of 18.9 h. These numbers result in an average per-person QALY gain of 0.0005. Increased QALY and decreased costs indicate that the primary care approach is clearly cost-effective. Conclusion: Using the ESC 0/1-h algorithm in low-risk patients in emergency primary care appears to be cost-effective compared to standard hospital management, with an extensive reduction in costs and length of stay per patient.

• Torgersen, Kristin Stensland; Rahman, Zillur; Bahrami, Shahram; Hindley, Guy Frederick Lanyon; Parker, Nadine & Frei, Oleksandr [Show all 14 contributors for this article] (2022). Shared genetic loci between depression and cardiometabolic traits. PLoS Genetics. ISSN 1553-7390. 18(5). doi: 10.1371/journal.pgen.1010161. Full text in Research Archive Show summary

  Epidemiological and clinical studies have found associations between depression and cardiovascular disease risk factors, and coronary artery disease patients with depression have worse prognosis. The genetic relationship between depression and these cardiovascular phenotypes is not known. We here investigated overlap at the genome-wide level and in individual loci between depression, coronary artery disease and cardiovascular risk factors. We used the bivariate causal mixture model (MiXeR) to quantify genome-wide polygenic overlap and the conditional/conjunctional false discovery rate (pleioFDR) method to identify shared loci, based on genome-wide association study summary statistics on depression (n = 450,619), coronary artery disease (n = 502,713) and nine cardiovascular risk factors (n = 204,402–776,078). Genetic loci were functionally annotated using FUnctional Mapping and Annotation (FUMA). Of 13.9K variants influencing depression, 9.5K (SD 1.0K) were shared with body-mass index. Of 4.4K variants influencing systolic blood pressure, 2K were shared with depression. ConjFDR identified 79 unique loci associated with depression and coronary artery disease or cardiovascular risk factors. Six genomic loci were associated jointly with depression and coronary artery disease, 69 with blood pressure, 49 with lipids, 9 with type 2 diabetes and 8 with c-reactive protein at conjFDR < 0.05. Loci associated with increased risk for depression were also associated with increased risk of coronary artery disease and higher total cholesterol, low-density lipoprotein and c-reactive protein levels, while there was a mixed pattern of effect direction for the other risk factors. Functional analyses of the shared loci implicated metabolism of alpha-linolenic acid pathway for type 2 diabetes. Our results showed polygenic overlap between depression, coronary artery disease and several cardiovascular risk factors and suggest molecular mechanisms underlying the association between depression and increased cardiovascular disease risk.

• Torgersen, Kristin Stensland; Bahrami, Shahram; Frei, Oleksandr; Shadrin, Alexey; O'Connell, Kevin Sean & Smeland, Olav Bjerkehagen [Show all 10 contributors for this article] (2021). Shared genetic architecture between neuroticism, coronary artery disease and cardiovascular risk factors. Translational Psychiatry. 11(1), p. 1–13. doi: 10.1038/s41398-021-01466-9. Full text in Research Archive Show summary

  Neuroticism is associated with poor health, cardiovascular disease (CVD) risk factors and coronary artery disease (CAD). The conditional/conjunctional false discovery rate method (cond/conjFDR) was applied to genome wide association study (GWAS) summary statistics on neuroticism (n = 432,109), CAD (n = 184,305) and 12 CVD risk factors (n = 188,577–339,224) to investigate genetic overlap between neuroticism and CAD and CVD risk factors. CondFDR analyses identified 729 genomic loci associated with neuroticism after conditioning on CAD and CVD risk factors. The conjFDR analyses revealed 345 loci jointly associated with neuroticism and CAD (n = 30), body mass index (BMI) (n = 96) or another CVD risk factor (n = 1–60). Several loci were jointly associated with neuroticism and multiple CVD risk factors. Seventeen of the shared loci with CAD and 61 of the shared loci with BMI are novel for neuroticism. 21 of 30 (70%) neuroticism risk alleles were associated with higher CAD risk. Functional analyses of the genes mapped to the shared loci implicated cell division, nuclear receptor, elastic fiber formation as well as starch and sucrose metabolism pathways. Our results indicate polygenic overlap between neuroticism and CAD and CVD risk factors, suggesting that genetic factors may partly cause the comorbidity. This gives new insight into the shared molecular genetic basis of these conditions.

• Peersen, Kari; Munkhaugen, John; Sverre, Elise Christine Bjørkholen; Kristiansen, Oskar; Fagerland, Morten & Vethe, Nils Tore [Show all 9 contributors for this article] (2021). Clinical and psychological factors in coronary heart disease patients with statin associated muscle side-effects. BMC Cardiovascular Disorders. 21, p. 1–9. doi: 10.1186/s12872-021-02422-7. Full text in Research Archive Show summary

  Background: To compare clinical and psychological factors among patients with self-perceived statin-associated muscle symptoms (SAMS), confirmed SAMS, and refuted SAMS in coronary heart disease patients (CHD). Methods: Data were obtained from a cross-sectional study of 1100 CHD outpatients and a study of 71 CHD outpatients attending a randomized, double-blinded, placebo-controlled, crossover study to test effects of atorvastatin 40 mg/day on muscle symptom intensity. Clinical and psychosocial factors were compared between patients with and without SAMS in the cross-sectional study, and between patients with confirmed SAMS and refuted SAMS in the randomized study. Results: Bilateral, symmetric muscle symptoms in the lower extremities during statin treatment were more prevalent in patients with confirmed SAMS compared to patients with refuted SAMS (75% vs. 41%, p = 0.01) in the randomized study. No significant differences in psychological factors (anxiety, depression, worry, insomnia, type D personality characteristics) were detected between patients with and without self-perceived SAMS in the cross-sectional study, or between patients with confirmed SAMS and refuted SAMS, in the randomized study. Conclusions: Patients with confirmed SAMS more often present with bilateral lower muscle symptoms compared to those with refuted SAMS. Psychological factors were not associated with self-perceived SAMS or confirmed SAMS. A careful pain history and a search for alternative causes of muscle symptoms are likely to promote communication in patients with SAMS, and may reduce the risk for statin discontinuation.

• Peersen, Kari; Munkhaugen, John; Olsen, Siv Jorunn Storli; Otterstad, Jan Erik & Sverre, Elise Christine Bjørkholen (2021). Rehabilitering og sekundærforebygging etter hjerteinfarkt ved sykehus. Tidsskrift for Den norske legeforening (Tidsskriftet). ISSN 0029-2001. doi: 10.4045/tidsskr.21.0349. Full text in Research Archive Show summary

  BAKGRUNN I norske studier er det dokumentert dårlig kardiovaskulær risikofaktorkontroll og høy forekomst av nye hjerte- og karhendelser hos hjerteinfarktpasienter. Det foreligger lite kunnskap om omfang av sekundærforebyggende behandling og hjerterehabilitering ved norske sykehus. Vi ønsket derfor å gjennomføre en kartlegging av rutiner ved utskrivning og poliklinisk oppfølging etter hjerteinfarkt. MATERIALE OG METODE I oktober 2018 ble avdelingsoverleger på hjerteavdelinger og avdelingssykepleier/fysioterapeut på hjertepoliklinikker ved alle norske sykehus (N = 51) kontaktet med forespørsel om å delta i et telefonintervju. RESULTATER Til sammen 40 (78 %) leger og 51 (100 %) sykepleiere/fysioterapeuter gjennomførte telefonintervjuet. Elleve sykehus brukte standardiserte epikrisemaler med behandlingsmål og forventet oppfølging. Ti sykehus tilbød rutinemessig poliklinisk kontroll. 47 sykehus (92 %) tilbød tverrfaglig hjerterehabilitering, hjerteskole eller hjertetrening, og av disse tilbød ni (18 %) tverrfaglig, sammensatt hjerterehabilitering i henhold til internasjonale anbefalinger. FORTOLKNING Kartleggingen avdekket betydelige forskjeller i rapporterte rutiner ved utskrivning og tilbud om hjerterehabilitering og poliklinisk oppfølging ved norske sykehus. HOVEDFUNN Vi fant betydelig variasjon i rapporterte rutiner for utskrivning og omfang av hjerterehabilitering for pasienter etter akutt koronarsykdom. Under 20 % av norske sykehus tilbød tverrfaglig, sammensatt hjerterehabilitering.

• Otterstad, Jan Erik; Norum, Ingvild Billehaug; Ruddox, Vidar; Le, An Chau Maria; Bendz, Bjørn & Munkhaugen, John [Show all 8 contributors for this article] (2021). Prognostic impact of non-improvement of global longitudinal strain in patients with revascularized acute myocardial infarction. The International Journal of Cardiovascular Imaging. ISSN 1569-5794. 37, p. 3477–3487. doi: 10.1007/s10554-021-02349-2. Full text in Research Archive Show summary

  Global longitudinal strain (GLS) is a more sensitive prognostic factor than left ventricular ejection fraction (LVEF) in various cardiac diseases. Little is known about the clinical impact of GLS changes after acute myocardial infarction (AMI). The present study aimed to explore if non-improvement of GLS after 3 months was associated with higher risk of subsequent composite cardiovascular events (CCVE). Patients with AMI were consecutively included at a secondary care center in Norway between April 2016 and July 2018 within 4 days following percutaneous coronary intervention. Echocardiography was performed at baseline and after 3 months. Patients were categorized with non-improvement (0 to − 100%) or improvement (0 to 100%) in GLS relative to the baseline value. Among 214 patients with mean age 65 (± 10) years and mean LVEF 50% (± 8) at baseline, 50 (23%) had non-improvement (GLS: − 16.0% (± 3.7) to − 14.2% (± 3.6)) and 164 (77%) had improvement (GLS: − 14.0% (± 3.0) to − 16.9% (± 3.0%)). During a mean follow-up of 3.3 years (95% CI 3.2 to 3.4) 77 CCVE occurred in 52 patients. In adjusted Cox regression analyses, baseline GLS was associated with all recurrent CCVE (HR 1.1, 95% CI 1.0 to 1.2, p < 0.001) whereas non-improvement versus improvement over 3 months follow-up was not. Baseline GLS was significantly associated with the number of CCVE in revascularized AMI patients whereas non-improvement of GLS after 3 months was not. Further large-scale studies are needed before repeated GLS measurements may be recommended in clinical practice.

• Frøjd, Lars Aastebø; Papageorgiou, Constantinos; Munkhaugen, John; Moum, Torbjørn Åge; Sverre, Elise Christine Bjørkholen & Nordhus, Inger Hilde [Show all 7 contributors for this article] (2021). Worry and rumination predict insomnia in patients with coronary heart disease: a cross-sectional study with long-term follow-up. Journal of Clinical Sleep Medicine (JCSM). ISSN 1550-9389. doi: 10.5664/jcsm.9712. Full text in Research Archive
• Frøyd, Lars; Munkhaugen, John; Moum, Torbjørn Åge; Sverre, Elise Christine Bjørkholen; Nordhus, Inger Hilde & Papageorgiou, Constantinos [Show all 7 contributors for this article] (2021). Insomnia in patients with coronary heart disease: Prevalence and correlates. Journal of Clinical Sleep Medicine (JCSM). ISSN 1550-9389. 17(5). doi: 10.5664/jcsm.9082. Full text in Research Archive Show summary

  Study Objectives: The aim of this study was to determine the prevalence of insomnia and its association with clinical and psychosocial factors in a large sample of outpatients with coronary heart disease. Methods: The sample comprised 1,082 patients, mean age 62 years (21% female), who participated in the cross-sectional NORwegian CORonary Prevention Study. Patients who were hospitalized with myocardial infarction and/or a coronary revascularization procedure in 2011–2014 responded to a self-report questionnaire and participated in a clinical examination with blood samples 2–36 (mean, 16) months later. Insomnia was assessed using the Bergen Insomnia Scale, a questionnaire based on the criteria for the clinical diagnosis of insomnia as described in the Diagnostic and Statistical Manual of Mental Disorders, fourth version. We performed bivariate logistic regressions for crude analysis and backward stepwise logistic regressions for multiadjusted odds ratios (OR). Results: In total, 488 patients (45%) reported insomnia, and 24% of these patients had used sleep medication in the previous week. Anxiety symptoms (OR: 5.61) were the strongest determinants of insomnia, followed by female sex (OR: 1.88), diabetes (OR: 1.83), eating fish fewer than three times a week (OR: 1.69), type D personality (OR: 1.69), and C-reactive protein ≥ 2 mg/L (OR:1.58), in multiadjusted analyses. Conclusions: Insomnia was highly prevalent in coronary heart disease outpatients. Psychological factors, lifestyle factors, and subclinical inflammation were associated with insomnia. Our results emphasize the need to identify patients with insomnia and provide appropriate management of insomnia in outpatients with coronary heart disease.

• Kristiansen, Oskar; Sverre, Elise Christine Bjørkholen; Peersen, Kari; Fagerland, Morten; Gjertsen, Erik & Gullestad, Lars [Show all 11 contributors for this article] (2021). The relationship between directly measured statin adherence, self-reported adherence measures and cholesterol levels in patients with coronary heart disease. Atherosclerosis. ISSN 0021-9150. 336, p. 23–29. doi: 10.1016/j.atherosclerosis.2021.09.020. Full text in Research Archive Show summary

  Background and aims: We aimed to determine the relationship between statin adherence measured directly, and by self-report measures and serum cholesterol levels. Methods: Patients prescribed atorvastatin (N = 373) participated in a cross-sectional study 2–36 months after a coronary event. Self-reported adherence included statin adherence the past week, the 8-item Morisky medication adherence scale (MMAS-8), and the Gehi et al. adherence question. Atorvastatin was measured directly in spot blood plasma by a novel liquid chromatography tandem mass-spectrometry method discriminating adherence (0–1 doses omitted) and reduced adherence (≥2 doses omitted). Participants were unaware of the atorvastatin analyses at study participation. Results: Mean age was 63 (SD 9) years and 8% had reduced atorvastatin adherence according to the direct method. In patients classified with reduced adherence by the direct method, 40% reported reduced statin adherence, 32% reported reduced adherence with the MMAS-8 and 22% with the Gehi question. In those adherent by the direct method, 96% also reported high statin adherence, 95% reported high adherence on the MMAS-8 whereas 94% reported high adherence on the Gehi question. Cohen’s kappa agreement score with the direct method was 0.4 for self-reported statin adherence, 0.3 for the Gehi question and 0.2 for the MMAS-8. Adherence determined by the direct method, self-reported statin adherence last week, and the Gehi question was inversely related to LDL-cholesterol levels with a p-value of <0.001, 0.001 and 0.004, respectively. Conclusions: Plasma-statin measurements reveal reduced adherence with higher sensitivity than self-report measures, relate to cholesterol levels, and may prove to be a useful tool to improve lipid management.

• Munkhaugen, John; Sverre, Elise Christine Bjørkholen; Peersen, Kari; Kristiansen, Oscar; Gjertsen, Erik & Gullestad, Lars [Show all 7 contributors for this article] (2020). Is the novel LDL-cholesterol goal <1.4 mmol/L achievable without a PCSK9 inhibitor in a chronic coronary population from clinical practice?. European Journal of Preventive Cardiology (EJPC). ISSN 2047-4873. 28(8), p. E10–E11. doi: 10.1177/2047487320923187. Full text in Research Archive
• Sverre, Elise; Peersen, Kari; Weedon-Fekjær, Harald; Perk, J.; Gjertsen, Erik & Husebye, Einar [Show all 10 contributors for this article] (2020). Preventable clinical and psychosocial factors predicted two out of three recurrent cardiovascular events in a coronary population. BMC Cardiovascular Disorders. 20. doi: 10.1186/s12872-020-01368-6. Full text in Research Archive Show summary

  Background The relative importance of lifestyle, medical and psychosocial factors on the risk of recurrent major cardiovascular (CV) events (MACE) in coronary patients’ needs to be identified. The main objective of this study is to estimate the association between potentially preventable factors on MACE in an outpatient coronary population from routine clinical practice. Methods This prospective follow-up study of recurrent MACE, determine the predictive impact of risk factors and a wide range of relevant co-factors recorded at baseline. The baseline study included 1127 consecutive patients 2–36 months after myocardial infarction (MI) and/or revascularization procedure. The primary composite endpoint of recurrent MACE defined as CV death, hospitalization due to MI, revascularization, stroke/transitory ischemic attacks or heart failure was obtained from hospital records. Data were analysed using cox proportional hazard regression, stratified by prior coronary events before the index event. Results During a mean follow-up of 4.2 years from study inclusion (mean time from index event to end of study 5.7 years), 364 MACE occurred in 240 patients (21, 95% confidence interval: 19 to 24%), of which 39 were CV deaths. In multi-adjusted analyses, the strongest predictor of MACE was not taking statins (Relative risk [RR] 2.13), succeeded by physical inactivity (RR 1.73), peripheral artery disease (RR 1.73), chronic kidney failure (RR 1.52), former smoking (RR 1.46) and higher Hospital Anxiety and Depression Scale-Depression subscale score (RR 1.04 per unit increase). Preventable and potentially modifiable factors addressed accounted for 66% (95% confidence interval: 49 to 77%) of the risk for recurrent events. The major contributions were smoking, low physical activity, not taking statins, not participating in cardiac rehabilitation and diabetes. Conclusions Coronary patients were at high risk of recurrent MACE. Potentially preventable clinical and psychosocial factors predicted two out of three MACE, which is why these factors should be targeted in coronary populations. Trial registration Registered at ClinicalTrials.gov: NCT02309255. Registered at December 5th, 2014, registered retrospectively.

• Kristiansen, Oskar; Vethe, Nils Tore; Peersen, Kari; Fagerland, Morten; Sverre, Elise Christine Bjørkholen & Jensen, Elena Prunès [Show all 15 contributors for this article] (2020). Effect of Atorvastatin on Muscle Symptoms in Coronary Heart Disease Patients With Self-Perceived Statin Muscle Side-Effects: A Randomized, Double Blinded Crossover Trial. European Heart Journal (EHJ) - Cardiovascular Pharmacotherapy. ISSN 2055-6837. 7(6), p. 507–516. doi: 10.1093/ehjcvp/pvaa076. Full text in Research Archive Show summary

  Aims: To estimate the effect of atorvastatin on muscle symptom intensity in coronary heart disease (CHD) patients with self-perceived statin-associated muscle symptoms (SAMS) and to determine the relationship to blood levels of atorvastatin and/or metabolites. Methods and results: A randomized multi-center trial consecutively identified 982 patients with previous or ongoing atorvastatin treatment after a CHD event. Of these, 97 (9.9%) reported SAMS and 77 were randomized to 7-weeks double-blinded treatment with atorvastatin 40 mg/day and placebo in a crossover design. The primary outcome was the individual mean difference in muscle symptom intensity between the treatment periods, measured by visual-analogue scale (VAS) scores. Atorvastatin did not affect the intensity of muscle symptoms among 71 patients who completed the trial. Mean VAS difference [statin-placebo] was 0.31 (95% CI -0.24-0.86). The proportion with more muscle symptoms during placebo than atorvastatin was 17% (n = 12), 55% (n = 39) had the same muscle symptom intensity during both treatment periods whereas 28% (n = 20) had more symptoms during atorvastatin than placebo (confirmed SAMS). There were no differences in clinical or pharmacogenetic characteristics between these groups. The levels of atorvastatin and/or metabolites did not correlate to muscle symptom intensity among patients with confirmed SAMS (Spearmans rho ≤0.40, for all variables). Conclusion: Re-challenge with high-intensity atorvastatin did not affect the intensity of muscle symptoms in CHD patients with self-perceived SAMS during previous atorvastatin therapy. There was no relationship between muscle symptoms and the systemic exposure to atorvastatin and/or its metabolites. The findings encourage an informed discussion to elucidate other causes of muscle complaints and continued statin use.

• Peersen, Kari; Otterstad, Jan Erik; Sverre, Elise; Perk, Joep; Gullestad, Lars & Moum, Torbjørn Åge [Show all 8 contributors for this article] (2020). Medical and Psychosocial Factors Associated With Low Physical Activity and Increasing Exercise Level After a Coronary Event. Journal of Cardiopulmanory Rehabilitation and Prevention (JCRP). ISSN 1932-7501. 40(1), p. 35–40. doi: 10.1097/HCR.0000000000000399. Full text in Research Archive Show summary

  PURPOSE: The reasons why many coronary patients are inactive or have a low level of physical activity (PA) are not completely understood. We identified medical and psychosocial factors associated with PA status and increasing exercise level after a coronary event. METHODS: A cross-sectional study investigated the factors associated with PA in 1101 patients hospitalized with myocardial infarction (MI) and/or a revascularization procedure. Data were collected from hospital records, a self-report questionnaire, and a clinical examination. PA was categorized as inactivity, low activity, and adequate activity (≥ moderate intensity of 30 min ≥2-3 times/wk), an overall summary PA-index was measured as a continuous variable, and self-reported PA increase since the index event was measured on a 0- to 10-point Likert Scale. RESULTS: In all, 18% reported inactivity, 42% low, and 40% adequate activity at follow-up after median 16 mo. In multiadjusted linear regression analyses, low PA-index was significantly associated with smoking, obesity, unhealthy diet, depression, female, low education, MI as index diagnosis, and ≥1 previous coronary event. Motivation, risk and illness perceptions, and low reported need of help to increase PA were significantly associated with self-reported increasing PA level in adjusted continuous analyses. CONCLUSIONS: Daily smoking, obesity, unhealthy diet, and depression were the major potentially modifiable factors associated with insufficient PA, whereas high motivation and risk and illness perceptions were associated with increasing PA level. Further research on the effect of interventions tailored to the reported significant factors of failure is needed to improve PA level in CHD patients.

• Sverre, Elise Christine Bjørkholen; Peersen, Kari; Perk, Joep; Husebye, Einar; Gullestad, Lars & Dammen, Toril [Show all 8 contributors for this article] (2020). Challenges in coronary heart disease prevention - experiences from a long-term follow-up study in Norway. Scandinavian Cardiovascular Journal. ISSN 1401-7431. 55(2), p. 73–81. doi: 10.1080/14017431.2020.1852308. Full text in Research Archive Show summary

  Objective. To determine longitudinal changes in lifestyle behaviour and lipid management in a chronic coronary heart disease (CHD) population. Design. A multi-centre cohort study consecutively included 1127 patients at baseline in 2014–2015, on average 16 months after a CHD event. Data were collected from hospital records, a questionnaire and clinical examination. Seven hundred and seven of 1021 eligible patients participated in a questionnaire-based follow-up in 2019. Data were analysed with univariate statistics. Results. After a mean follow-up of 4.7 years (SD 0.4) from baseline, the percentage of current smokers (15% versus 16%), obesity (23% versus 25%) and clinically significant symptoms of anxiety (21% versus 17%) and depression (13% versus 14%) remained unchanged, whereas the proportion with low physical activity increased from 53% to 58% (p < .001). The proportions with reduced physical activity level were similar in patients over and under 70 years of age. Most patients were still taking statins (94% versus 92%) and more patients used high-intensity statin (49% versus 54%, p < .001) and ezetimibe (5% versus 15%, p < .001) at follow-up. 73% reported ≥1 primary-care consultation(s) for CHD during the last year while 27% reported no such follow-up. There were more smokers among participants not attending primary-care consultations compared to those attending (19% versus 14%, p = .026). No differences were found for other risk factors. Conclusions. We found persistent suboptimal risk factor control in coronary outpatients during long-term follow-up. Closer follow-up and intensified risk management including lifestyle and psychological health are needed to improved secondary prevention and outcome of CHD.

• Årvik, Magnus Dahl; Sandven, Irene; Dondo, Tatendashe B; Gale, Chris P; Ruddox, Vidar & Munkhaugen, John [Show all 8 contributors for this article] (2019). Effect of Oral β-blocker Treatment on Mortality in Contemporary Post-myocardial Infarction Patients: a systematic review and meta-analysis. European Heart Journal (EHJ) - Cardiovascular Pharmacotherapy. ISSN 2055-6837. 5(1), p. 12–20. doi: 10.1093/ehjcvp/pvy034. Full text in Research Archive Show summary

  Aims: Guidelines concerning β-blocker treatment following acute myocardial infarction (AMI) are based on studies undertaken before the implementation of reperfusion and secondary prevention therapies. We aimed to estimate the effect of oral β-blockers on mortality in contemporary post-AMI patients with low prevalence of heart failure and/or reduced left ventricular ejection fraction. Methods and results: A random effects model was used to synthetize results of 16 observational studies published between 1 January 2000 and 30 October 2017. Publication bias was evaluated, and heterogeneity between studies examined by subgroup and random effects meta-regression analyses considering patient-related and study-level variables. The pooled estimate showed that β-blocker treatment [among 164 408 (86.8%) patients, with median follow-up time of 2.7 years] was associated with a 26% reduction in all-cause mortality [rate ratio (RR) 0.74, 95% confidence interval (CI) 0.64–0.85] with moderate heterogeneity (I2 = 67.4%). The patient-level variable mean age of the cohort explained 31.5% of between study heterogeneity. There was presence of publication bias, or small study effect, and when controlling for bias by the trim and fill simulation method, the effect disappeared (adjusted RR 0.90, 95% CI 0.77–1.04). Also, small study effect was demonstrated by a cumulative meta-analysis starting with the largest study showing no effect, with increasing effect as the smaller studies were accumulated. Conclusion: Evidence from this study suggests that there is no association between β-blockers and all-cause mortality. A possible beneficial effect in AMI survivors needs to be tested by large randomized clinical trials.

• Munkhaugen, John; Vethe, Nils Tore; Fagerland, Morten; Dammen, Toril; Perk, Joep & Gjertsen, Erik [Show all 10 contributors for this article] (2019). Statin-associated muscle symptoms in coronary patients: design of a randomized study. Scandinavian Cardiovascular Journal. ISSN 1401-7431. 53(3), p. 162–168. doi: 10.1080/14017431.2019.1612085. Full text in Research Archive Show summary

  Objectives. Estimate the effect of atorvastatin on muscular symptom intensity in coronary patients with subjective statin-associated muscle symptoms (SAMS) and to determine the association with blood levels of atorvastatin and its metabolites, to obtain an objective marker for true SAMS. Design. A randomized, double-blinded, cross-over study will include 80 coronary patients with subjectively reported SAMS during ongoing atorvastatin therapy or previous muscle symptoms that led to discontinuation of atorvastatin. Patients will be randomized to 7-weeks treatment with atorvastatin 40 mg/day in the first period and matched placebo in the second 7-weeks period, or placebo in the first period and atorvastatin in the second period. Each period is preceded by 1-week wash-out. A control group (n = 40) without muscle symptoms will have 7 weeks open treatment with atorvastatin 40 mg/day. Blood samples will be collected at baseline and at the end of each treatment period, and muscular symptoms will be rated by the patients weekly using a Visual Analogue Scale (VAS). The primary outcome is the difference in aggregated mean VAS scores between the last three weeks of atorvastatin treatment and of placebo treatment. The main purpose is to develop an objective marker for true SAMS, by comparing SAMS associated with blinded atorvastatin treatment with blood concentrations of atorvastatin and its metabolites. Diagnostic and discrimination performance will be determined. Conclusions. The study provides new knowledge on SAMS in coronary patients and may contribute to more personalized statin treatment and monitoring, fewer side-effects and consequently improved adherence and lipid management in future practice.

• Kristiansen, Oscar; Vethe, Nils Tore; Fagerland, Morten; Bergan, Stein; Munkhaugen, John & Husebye, Einar (2019). A novel direct method to determine adherence to atorvastatin therapy in patients with coronary heart disease. British Journal of Clinical Pharmacology. ISSN 0306-5251. p. 1–8. doi: 10.1111/bcp.14122. Full text in Research Archive Show summary

  Aims Objective methods to monitor statin adherence are needed. We have established a liquid chromatography–tandem mass spectrometry assay for quantification of atorvastatin and its metabolites in blood. This study aimed to develop an objective drug exposure variable with cut‐off values to discriminate among adherence, partial adherence and nonadherence to atorvastatin therapy in patients with coronary heart disease. Methods Twenty‐five patients treated with atorvastatin 10 mg (n = 5), 20 mg (n = 6), 40 mg (n = 7) and 80 mg (n = 7) participated in a directly observed atorvastatin therapy study to confirm baseline adherence. After the directly observed therapy, half of the patients (test group ) were instructed to stop taking atorvastatin and return for blood sample collection the subsequent 3 days. Levels of atorvastatin and metabolites were compared between the test group and the adherent control group. Results The sum of parent drug and all measured primary metabolites correlated well with the atorvastatin dose administered (Spearman's rho = 0.71, 95% CI 0.44–0.87). The dose‐normalized atorvastatin plus metabolites concentrations completely separated the partially adherent test group from the controls at 0.18 nM/mg after 3 days without atorvastatin. To reduce the risk of misinterpreting adherent patients as partially adherent, a corresponding cut‐off at 0.10 nM/mg is proposed. A metabolite level of 2‐OH atorvastatin acid <0.014 nmol/L provided the optimal cut‐off for nonadherence. Conclusion A direct method to discriminate among adherence, partial adherence and nonadherence to atorvastatin therapy in patients with coronary heart disease has been developed. This tool may be important for novel studies on adherence and potentially useful in clinical practice.

• Munkhaugen, John; Ruddox, Vidar; Halvorsen, Sigrun; Dammen, Toril; Fagerland, Morten & Hernæs, Kjersti Helene [Show all 23 contributors for this article] (2019). BEtablocker Treatment After acute Myocardial Infarction in revascularized patients without reduced left ventricular ejection fraction (BETAMI): Rationale and design of a prospective, randomized, open, blinded end-point study. American Heart Journal. ISSN 0002-8703. 208, p. 37–46. doi: 10.1016/j.ahj.2018.10.005. Full text in Research Archive Show summary

  Background - Current guidelines on the use of β-blockers in post–acute myocardial infarction (MI) patients without reduced left ventricular ejection fraction (LVEF) are based on studies before the implementation of modern reperfusion and secondary prevention therapies. It remains unknown whether β-blockers will reduce mortality and recurrent MI in contemporary revascularized post-MI patients without reduced LVEF. Design - BETAMI is a prospective, randomized, open, blinded end point multicenter study in 10,000 MI patients designed to test the superiority of oral β-blocker therapy compared to no β-blocker therapy. Patients with LVEF ≥40% following treatment with percutaneous coronary intervention or thrombolysis and/or no clinical signs of heart failure are eligible to participate. The primary end point is a composite of all-cause mortality or recurrent MI obtained from national registries over a mean follow-up period of 3 years. Safety end points include rates of nonfatal MI, all-cause mortality, ventricular arrhythmias, and hospitalizations for heart failure obtained from hospital medical records 30 days after randomization, and from national registries after 6 and 18 months. Key secondary end points include recurrent MI, heart failure, cardiovascular and all-cause mortality, and clinical outcomes linked to β-blocker therapy including drug adherence, adverse effects, cardiovascular risk factors, psychosocial factors, and health economy. Statistical analyses will be conducted according to the intention-to-treat principle. A prespecified per-protocol analysis (patients truly on β-blockers or not) will also be conducted. Conclusions - The results from the BETAMI trial may have the potential of changing current clinical practice for treatment with β-blockers following MI in patients without reduced LVEF. EudraCT number 2018-000590-75.

• Vethe, Nils Tore; Munkhaugen, John; Andersen, Anders Mikal; Husebye, Einar & Bergan, Stein (2019). A Method for Direct Monitoring of Atorvastatin Adherence in Cardiovascular Disease Prevention: Quantification of the Total Exposure to Parent Drug and Major Metabolites Using 2-Channel Chromatography and Tandem Mass Spectrometry. Therapeutic Drug Monitoring. ISSN 0163-4356. 41(1), p. 19–28. doi: 10.1097/FTD.0000000000000578. Full text in Research Archive Show summary

  Background: Low adherence to statin therapy remains a public health concern associated with poor prognosis in cardiovascular disease patients. A feasible method for statin adherence monitoring in clinical practice has yet to be developed. In this article, we describe a novel method designed for the direct monitoring of atorvastatin adherence based on the sum of parent drug and major metabolites in blood samples. Methods: Acid and lactone forms of atorvastatin, 2-OH-atorvastatin, and 4-OH-atorvastatin were assayed. Plasma proteins were precipitated with an acidified mixture of methanol, acetonitrile, and aqueous zinc sulfate, and the supernatant was analyzed with 2-channel reversed-phase chromatography coupled to tandem mass spectrometry. Assay validation was performed according to the guidelines provided by the European Medicines Agency and the US Food and Drug Administration. Results: The effective run time was 1 minute and 45 seconds per sample. Mean accuracy ranged from 92% to 110%, and coefficients of variation were ≤8.1% over the measurement ranges for individual compounds. The sum of acids and corresponding lactones was stable in clinical plasma samples kept at ambient temperature for up to 6 days after blood sampling (mean sum within 96.6%–101% of baseline). Conclusions: A fast and reliable assay for the quantification of atorvastatin and its 5 major metabolites in clinical blood samples is reported. Limitations of preanalytical stability were solved using the sum of the acid and lactone forms. The assay is feasible for implementation in clinical practice, and the sum of parent drug and metabolites may be used for direct monitoring of atorvastatin adherence.

• Munkhaugen, John; Hjelmesæth, Jøran; Otterstad, Jan Erik; Helseth, Ragnhild; Sollid, Stina Therese & Gjertsen, Erik [Show all 11 contributors for this article] (2018). Managing patients with prediabetes and type 2 diabetes after coronary events: individual tailoring needed - a cross-sectional study. BMC Cardiovascular Disorders. 18(1). doi: 10.1186/s12872-018-0896-z. Full text in Research Archive Show summary

  Background Understanding the determinants associated with prediabetes and type 2 diabetes in coronary patients may help to individualize treatment and modelling interventions. We sought to identify sociodemographic, medical and psychosocial factors associated with normal blood glucose (HbA1c < 5.7%), prediabetes (HbA1c 5.7–6.4%), and type 2 diabetes. Methods A cross-sectional explorative study applied regression analyses to investigate the factors associated with glycaemic status and control (HbA1c level) in 1083 patients with myocardial infarction and/or a coronary revascularization procedure. Data were collected from hospital records at the index event and from a self-report questionnaire and clinical examination with blood samples at 2–36 months follow-up. Results In all, 23% had type 2 diabetes, 44% had prediabetes, and 33% had normal blood glucose at follow-up. In adjusted analyses, type 2 diabetes was associated with larger waist circumference (Odds Ratio 1.03 per 1.0 cm, p = 0.001), hypertension (Odds Ratio 2.7, p < 0.001), lower high-density lipoprotein cholesterol (Odds Ratio 0.3 per1.0 mmol/L, p = 0.002) and insomnia (Odds Ratio 2.0, p = 0.002). In adjusted analyses, prediabetes was associated with smoking (Odds Ratio 3.3, p = 0.001), hypertension (Odds Ratio 1.5, p = 0.03), and non-participation in cardiac rehabilitation (Odds Ratio 1.7, p = 0.003). In patients with type 2 diabetes, a higher HbA1c level was associated with ethnic minority background (standardized beta [β] 0.19, p = 0.005) and low drug adherence (β 0.17, p = 0.01). In patients with prediabetes or normal blood glucose, a higher HbA1c was associated with larger waist circumference (β 0.13, p < 0.001), smoking (β 0.18, p < 0.001), hypertension (β 0.08, p = 0.04), older age (β 0.16, p < 0.001), and non-participation in cardiac rehabilitation (β 0.11, p = 0.005). Conclusions Along with obesity and hypertension, insomnia and low drug adherence were the major modifiable factors associated with type 2 diabetes, whereas smoking and non-participation in cardiac rehabilitation were the factors associated with prediabetes. Further research on the effect of individual tailoring, addressing the reported significant predictors of failure, is needed to improve glycaemic control. Trial registration Retrospectively registered at ClinicalTrials.gov: NCT02309255, December 5th 2014.

• Munkhaugen, John; Otterstad, Jan Erik; Dammen, Toril; Gjertsen, Erik; Moum, Torbjørn Åge & Husebye, Einar [Show all 7 contributors for this article] (2018). The prevalence and predictors of elevated C-reactive protein after a coronary heart disease event. European Journal of Preventive Cardiology (EJPC). ISSN 2047-4873. 25(9), p. 923–931. doi: 10.1177/2047487318768940. Full text in Research Archive
• Peersen, Kari; Munkhaugen, John; Gullestad, Lars; Dammen, Toril; Moum, Torbjørn Åge & Otterstad, Jan Erik (2017). Reproducibility of an extensive self-report questionnaire used in secondary coronary prevention. Scandinavian Journal of Public Health. ISSN 1403-4948. 45(3), p. 269–276. doi: 10.1177/1403494816688375. Full text in Research Archive
• Sverre, Elise; Otterstad, Jan Erik; Gjertsen, Erik; Gullestad, Lars; Husebye, Einar & Dammen, Toril [Show all 8 contributors for this article] (2017). Medical and sociodemographic factors predict persistent smoking after coronary events. BMC Cardiovascular Disorders. 17(1). doi: 10.1186/s12872-017-0676-1. Full text in Research Archive
• Ruddox, Vidar; Sandven, Irene; Munkhaugen, John; Skattebu, Julie; Edvardsen, Thor & Otterstad, Jan Erik (2017). Atrial fibrillation and the risk for myocardial infarction, all-cause mortality and heart failure: A systematic review and meta-analysis. European Journal of Preventive Cardiology (EJPC). ISSN 2047-4873. 24(14), p. 1555–1566. doi: 10.1177/2047487317715769. Full text in Research Archive
• Sverre, Elise; Peersen, Kari; Husebye, Einar; Gjertsen, Erik; Gullestad, Lars & Moum, Torbjørn Åge [Show all 9 contributors for this article] (2017). Unfavourable risk factor control after coronary events in routine clinical practice. BMC Cardiovascular Disorders. 17(1). doi: 10.1186/s12872-016-0387-z. Full text in Research Archive Show summary

  Background Risk factor control after a coronary event in a recent European multi-centre study was inadequate. Patient selection from academic centres and low participation rate, however, may underscore failing risk factor control in routine clinical practice. Improved understanding of the patient factors that influence risk factor control is needed to improve secondary preventive strategies. The objective of the present paper was to determine control of the major risk factors in a coronary population from routine clinical practice, and how risk factor control was influenced by the study factors age, gender, number of coronary events, and time since the index event. Methods A cross-sectional study determined risk factor control and its association with study factors in 1127 patients (83% participated) aged 18-80 years with acute myocardial infarction and/or revascularization identified from medical records. Study data were collected from a self-report questionnaire, clinical examination, and blood samples after 2-36 months (median 16) follow-up. Results Twenty-one percent were current smokers at follow-up. Of those smoking at the index event 56% continued smoking. Obesity was found in 34%, and 60% were physically inactive. Although 93% were taking blood-pressure lowering agents and statins, 46% were still hypertensive and 57% had LDL cholesterol >1.8 mmol/L at follow-up. Suboptimal control of diabetes was found in 59%. The patients failed on average to control three of the six major risk factors, and patients with >1 coronary events (p < 0.001) showed the poorest overall control. A linear increase in smoking (p < 0.01) and obesity (p < 0.05) with increasing time since the event was observed. Conclusions The majority of coronary patients in a representative Norwegian population did not achieve risk factor control, and the poorest overall control was found in patients with several coronary events. New strategies for secondary prevention are clearly needed to improve risk factor control. Even modest advances will provide major health benefits. Trial registration Registered at ClinicalTrials.gov (ID NCT02309255).

• Sverre, Elise; Peersen, Kari; Otterstad, Jan Erik; Gullestad, Lars; Perk, Joep & Gjertsen, Erik [Show all 10 contributors for this article] (2017). Optimal blood pressure control after coronary events: the challenge remains. Journal of the American Society of Hypertension : JASH. ISSN 1933-1711. 11(12), p. 823–830. doi: 10.1016/j.jash.2017.10.007. Full text in Research Archive
• Munkhaugen, John; Sverre, Elise; Otterstad, Jan Erik; Peersen, Kari; Gjertsen, Erik & Perk, Joep [Show all 10 contributors for this article] (2017). Medical and psychosocial factors and unfavourable low-density lipoprotein cholesterol control in coronary patients. European Journal of Preventive Cardiology (EJPC). ISSN 2047-4873. 24(9), p. 981–989. doi: 10.1177/2047487317693134. Full text in Research Archive
• Peersen, Kari; Munkhaugen, John; Gullestad, Lars; Liodden, Toril; Moum, Torbjørn Åge & Dammen, Toril [Show all 8 contributors for this article] (2017). The role of cardiac rehabilitation in secondary prevention after coronary events. European Journal of Preventive Cardiology (EJPC). ISSN 2047-4873. 24(13), p. 1360–1368. doi: 10.1177/2047487317719355. Full text in Research Archive
• Munkhaugen, John; Sverre, Elise; Peersen, Kari; Gjertsen, Erik; Gullestad, Lars & Moum, Torbjørn Åge [Show all 10 contributors for this article] (2016). The role of medical and psychosocial factors for unfavourable coronary risk factor control. Scandinavian Cardiovascular Journal. ISSN 1401-7431. 50(1), p. 1–8. doi: 10.3109/14017431.2015.1111408. Full text in Research Archive
• Munkhaugen, John; Sverre, Elise; Peersen, Kari; Egge, Oystein; Gjertsen, Caroline Eikeseth & Gjertsen, Erik [Show all 10 contributors for this article] (2016). Patient characteristics and risk factors of participants and non-participants in the NOR-COR Study. Scandinavian Cardiovascular Journal. ISSN 1401-7431. 50(5-6), p. 317–322. doi: 10.1080/14017431.2016.1202445. Full text in Research Archive
• Munkhaugen, John; Lydersen, Stian; Widerøe, Tor-Erik & Hallan, Stein (2009). Prehypertension, Obesity, and Risk of Kidney Disease: 20-Year Follow-up of the HUNT I Study in Norway. American Journal of Kidney Diseases. ISSN 0272-6386. 54(4), p. 638–646. doi: 10.1053/j.ajkd.2009.03.023. Full text in Research Archive
• Munkhaugen, John; Lydersen, Stian; Romundstad, Pål Richard; Widerøe, Tor Erik; Vikse, Bjørn Egil & Hallan, Stein (2009). Kidney function and future risk for adverse pregnancy outcomes: a population-based study from HUNT II, Norway. Nephrology, Dialysis and Transplantation. ISSN 0931-0509. 24(12), p. 3744–3750. doi: 10.1093/ndt/gfp320. Full text in Research Archive
• Munkhaugen, John; Lydersen, Stian; Widerøe, Tor-Erik & Hallan, Stein (2008). Blood pressure reference values in adolescents: methodological aspects and suggestions for Northern Europe tables based on the Nord-Trøndelag Health Study II. Journal of Hypertension. ISSN 0263-6352. 26(10), p. 1912–1918. Full text in Research Archive

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• Singstad, Bjørn-Jostein; Turan, B; Hov, K R; Ravn, Jesper; Sovershaev, Timofey & Aksnes, Tonje Amb [Show all 12 contributors for this article] (2026). Artificial intelligence for detecting acute occluded myocardial infarction: fine-tuning and evaluation of an ECG foundation model. European Heart Journal. ISSN 0195-668X. 47(Supplement_1). doi: 10.1093/eurheartj/ehag785.4264. Full text in Research Archive Show summary

  Abstract Background ST-elevation myocardial infarction (STEMI) patients are usually revascularized within 120 minutes, whereas fewer than one-third of non-ST-elevation myocardial infarction (NSTEMI) occlusions are treated this quickly [1], potentially contributing to worse long-term outcomes [2]. Purpose We aimed to fine-tune and validate a foundation model to detect occluded myocardial infarction (OMI) from 12-lead ECGs. Methods This study included digital ECGs recorded at a tertiary PCI center and affiliated ambulances between 2016 and 2022. ECGs were linked to data from the catheterization laboratory as well as troponin (TnT) measurements. The primary outcome was OMI, defined as an acute culprit lesion, qualitatively determined to be &lt;3 months old, with TIMI flow 0–2 and treated with PCI. To be eligible, ECGs had to be recorded &lt;72 hours prior to the acute invasive procedure. A foundation model was fine-tuned on our dataset using asymmetric focal loss and Muon optimizer. The data were split at the patient level and stratified by outcome into 80% development and 20% test sets, with performance evaluated on the held-out test set. Results We included 16 346 ECGs from 10 880 patients. In the test set, 254 (12%) cases were classified as OMI, of which 93 (37%) were NSTEMIs. As shown in the Figure, the fine-tuned OMI model achieved an area under the Receiver Operating Characteristic curve (AUROC) of 0.91 (95% CI, 0.88-0.93) and an Area Under the Precision–Recall Curve (AUPRC) of 0.73 (95% CI, 0.66-0.79) for detecting all OMI cases. For ST-elevation OMI, performance improved to an AUROC 0.98 (95% CI, 0.96-0.99) and an AUPRC 0.87 (95% CI, 0.77-0.94), whereas for OMI without visible ST-elevations the AUROC was 0.85 (95% CI, 0.81-0.89) and the AUPRC 0.34 (95% CI, 0.25-0.47). A prediction threshold of 0.181 was selected to obtain a positive predictive value (PPV) of =0.5 for NSTEMIs. The model's sensitivity, specificity, PPV, and negative predictive value (NPV) for all OMI cases, STEMIs and NSTEMIs are presented in the Table. Of the OMI cases with door-to-balloon time &gt;120 minutes (n=120), the model flagged 56 cases (47%), of whom 88% had NSTEMI, and a median TnT of 1213 (IQR, 104-12373) ng/L. In contrast, the remaining 64 OMI cases (53%) with door-to-balloon time &gt;120 minutes that were not flagged by the model (98 % NSTEMIs), TnT levels were significantly lower (400 ng/L; IQR, 42–4 123; p = 0.05). This difference may partly be explained by a higher prevalence of collateral circulation in the unflagged group (p &lt; 0.05). Conclusion The fine-tuned foundation model shows performance within the range of state-of-the-art in detecting OMI from ECGs [3], including NSTEMIs with occlusions. Notably, the model identified almost half of OMIs currently receiving PCI later than 120 minutes upon hospital arrival, underscoring the model’s potential to enhance early diagnosis and timely management of under-recognized, but high-risk OMIs.Figure.ROC & PRC for OMI detectionTable.Model performance at threshold=0.181

• Nyen, J; Kristensen, A M D; Fagerland, Morten; Dammen, Toril; Zwisler, A D & Olsen, M H [Show all 13 contributors for this article] (2026). Beta-blocker therapy and sexual dysfunction after myocardial infarction: a sub-study of the BETAMI-DANBLOCK trial. European Heart Journal. ISSN 0195-668X. 47(Supplement_1). doi: 10.1093/eurheartj/ehag785.4110. Full text in Research Archive Show summary

  Abstract Background Sexual dysfunction is common after myocardial infarction (MI), but the role of beta-blockers on these disturbances remains unclear. Purpose To evaluate the presence of beta-blocker induced sexual dysfunction in post-MI patients without a reduced left ventricular ejection fraction (LVEF ≥40%) enrolled in the BETAMI-DANBLOCK trial. Methods A prespecified analysis of data from BETAMI-DANBLOCK which randomly assigned patients with a recent MI and an LVEF ≥40% to open-label beta-blocker therapy (median treatment dose metoprolol 50mg/day) or no beta-blocker therapy. For patients reporting sexual activity within the past 12 months, sexual function during the past 4 weeks was assessed at baseline and follow-up (3, 12, and 21 months) with the 5-item International Index of Erectile Function (IIEF, men) and the 6-item Female Sexual Function Index (FSFI, women). Sum scores for IIEF (range 5–25) and FSFI (6–30) provides measures of sexual function increasing with higher sexual function; thresholds for dysfunction were IIEF ≤21 and FSFI ≤19. Beta-blocker effects on IIEF and FSFI scores were analysed as between-group differences in change using linear mixed models (negative estimates indicating worse sexual function with beta-blockers). Odds ratios (ORs) for sexual dysfunction were estimated with multivariable logistic regression adjusting for randomisation stratification variables LVEF and study site. Results Among 5574 patients in BETAMI-DANBLOCK, 2850 stated sexual activity within past year at baseline. Of these, 2332/2850 (82%) responded to IIEF or FSFI at least once during the trial period. Among men, baseline median IIEF score was 23 (IQR: 19-24) in the beta-blocker group and 23 (IQR: 19-25) in the no beta-blocker group, with 39% reporting scores indicating erectile dysfunction and 12% in DANBLOCK dispensing sildenafil. We found no statistically significant effect of beta-blockers on the total IIEF score during follow-up (Table). However, the odds of erectile dysfunction was slightly higher in the beta-blocker group at the first follow-up (3 months OR: 1.58, 95% CI: 1.02, 2.42), but not on the subsequent timepoints. The proportion of filled sildenafil prescriptions was similar in the beta-blocker and no beta-blocker group (18% vs 17%) during follow-up in DANBLOCK. Among women, median FSFI score at baseline was 24 (IQR: 20-27) and 24 (IQR: 18-27), with 24% and 31% of patients having a score indicating sexual dysfunction for the beta-blocker group and the no beta-blocker group, respectively. We found no effect of beta-blocker therapy on FSFI scores during follow-up, but effect estimates were uncertain. Conclusions In the BETAMI-DANBLOCK trial, beta-blocker therapy after MI was associated with a small transient increase in erectile dysfunction among men, but no long-term effects were observed.

• Caglar, H; Holmager, T H; Kristensen, A M D; Fagerland, Morten; Halvorsen, Sigrid Groven & Atar, Dan [Show all 8 contributors for this article] (2026). Effect of beta-blockers on cardiovascular hospitalisation after myocardial infarction: A substudy of the BETAMI-DANBLOCK trial. European Heart Journal. ISSN 0195-668X. 47(Supplement_1). doi: 10.1093/eurheartj/ehag785.4116. Full text in Research Archive Show summary

  Abstract Background The role of long-term beta-blocker therapy after myocardial infarction (MI) in patients with LVEF ≥40% remains debated. In the ABYSS trial, patients with a prior MI (≥6 months before enrolment) were randomised to interruption or continuation of long-term beta-blocker therapy. Interruption was associated with an increased risk of a composite of death, MI, stroke, or cardiovascular hospitalisation, primarily driven by cardiovascular hospitalisations. We therefore examined whether our findings in BETAMI-DANBLOCK align with these results. Purpose To assess whether continued beta-blocker therapy beyond 6 months after MI is associated with a lower risk of the composite of death, MI, stroke, or cardiovascular hospitalisation. Methods This is a post hoc analysis of the open-label, randomised BETAMI-DANBLOCK trial which randomized patients with LVEF ≥40%. to beta-blocker therapy or no beta-blocker therapy within 14 days after MI. To reflect a clinically stable population comparable to that enrolled in ABYSS, only patients who were alive and free from heart failure and recurrent MI at 6 months were included in the analysis. Outcomes were assessed from this 6-month landmark until the end of follow-up. The primary outcome was aligned with ABYSS and defined as a composite of death, nonfatal MI, nonfatal stroke, or hospitalisation for cardiovascular reasons. Cardiovascular hospitalisations were identified through national registries using International Statistical Classification of Diseases and Related Health Problems, 10th Revision (ICD-10) I-diagnosis codes (diseases of the circulatory system). Hazard ratios were estimated using Cox proportional hazards models adjusted for the randomisation stratification variables (site and LVEF &lt;50%). Risk differences with 95% confidence intervals (CI) were calculated. Patients were censored at emigration Results At 6 months after randomisation, the study population comprised 5,431 patients. A primary composite-outcome event occurred in 639 of 2,720 patients (23.5%) assigned to beta-blocker therapy and in 698 of 2,711 patients (25,7%) assigned to no beta-blocker therapy (risk difference, 2.3 percentage points; 95% CI, 0.0 to 4.5) corresponding to a hazard ratio of 1.13 (95% CI, 1.01 to 1.25) (Figure 1),. The individual components of the composite outcome are shown in Figure 2. Conclusions In BETAMI-DANBLOCK, long-term beta-blocker therapy among patients with MI and LVEF ≥40% was associated with a lower risk of cardiovascular events, including hospitalisation for cardiovascular reasons, beyond 6 months after randomisation. These findings are consistent with the ABYSS trial and provide additional evidence supporting continued beta-blocker therapy in clinically stable post-MI patients.Cumulative incidence of composite outcomeComposite outcome and its components

• Berge, Kristian; Stenseth, P R; Ovrebotten, T; Nahoui, Hamza; Schirmer, Henrik & Gullestad, Lars [Show all 11 contributors for this article] (2026). Beta-blocker dose titration, functional capacity, and all-cause mortality in patients with heart failure and reduced ejection fraction. European Heart Journal. ISSN 0195-668X. 47(Supplement_1). doi: 10.1093/eurheartj/ehag785.1307. Full text in Research Archive Show summary

  Abstract Background Physical activity is recommended as part of comprehensive heart failure (HF) management alongside pharmacotherapy to improve outcomes. Treatment with beta-blockers (BB) reduces mortality and improves HF symptoms but may also impair exercise capacity due to BB-induced chronotropic incompetence. Purpose To explore the association between change in BB dose during GDMT titration, physical activity, and mortality in patients with chronic HF with reduced left ventricular ejection fraction (LVEF). Methods We analysed all HF patients with an LVEF ≤40% registered in the Norwegian Heart Failure Registry from 2013–2025 who had self-reported physical activity and 6-minute walking test (6MWT) data available at the first and last visit during guideline-directed medical therapy (GDMT) titration follow-up. Patients were stratified according to change in BB dose during follow-up, and associations with changes in physical activity and 6MWT were analysed using linear and logistic regression. Cox regression was used to determine associations with all-cause mortality. All models were adjusted for age, sex, body mass index, smoking status, HF aetiology, LVEF, blood pressure, heart rate, NYHA functional class, comorbidities, NT-proBNP, eGFR, and haemoglobin, and use of ACEi/ARBs/ARNIs, MRA, and SGLT2i. Results In total, 16,441 patients (mean age 68.4±11.8 years; 24.6% females) were included. After a median (IQR) up-titration period of 143 (81–239) days, 40% had escalated BB therapy, 48% had no change, and 12% had reduced the BB dose. In adjusted analyses, BB dose reduction was associated with a small increase in absolute 6MWT distance (6.32 meters [95% CI 1.58 – 11.07]) but with a 25% higher likelihood of decreasing light physical activity (RRR 1.25 [1.02–1.53]). BB dose escalation was associated with a decrease in absolute 6MWT distance (-6.53 meters [-9.67 – -3.38)) but with a 23% higher likelihood of increasing light physical activity (RRR 1.23 [1.07–1.42]) and 13% higher likelihood of increasing vigorous physical activity (RRR 1.13 [1.02–1.25]). Changes in BB dose during the titration visits were not associated with all-cause mortality during one year of follow-up after the last titration visit. Increased 6WMT and vigorous physical activity during follow-up were associated with reduced all-cause mortality risk (HR 0.53 [0.42–0.67] and HR 0.45 [0.35–0.60], respectively), whereas increased light physical activity was not associated with all-cause mortality. Conclusion During GDMT titration in HFrEF, BB dose adjustments were associated with small, divergent changes in 6MWT distance and self-reported physical activity, but not with one-year all-cause mortality. Improvements in 6MWT distance and increases in vigorous physical activity were associated with lower 1-year mortality. This underscores the complexity of optimizing BB therapy in HFrEF and supports an individualized approach to BB dosing.

• Johannessen, Tonje Rambøll; Atar, Dan; Halvorsen, Sigrid Groven; Munkhaugen, John; Vallersnes, Odd Martin & Bakken, Arnhild [Show all 7 contributors for this article] (2026). Point-of-care high-sensitivity troponin testing for rapid chest pain triage in emergency primary care: preliminary efficacy findings from the OUT-POC Study. European Heart Journal. ISSN 0195-668X. 47(Supplement_1). doi: 10.1093/eurheartj/ehag785.1892. Full text in Research Archive Show summary

  Abstract Background High-sensitivity troponin testing at the point-of-care (POC) level may enable faster and more accurate assessment of chest pain in low-resource, out-of-hospital settings. The ongoing prospective OUT-POC study (One-hoUr Troponin using a high-sensitivity Point-Of-Care assay in emergency primary care), initiated in June 2025, aims to enrol 2,500 patients across six emergency primary care clinics in Norway. Purpose This interim analysis evaluates the triage efficacy of the study`s POC assay (TRIAGETRUE High Sensitivity Troponin I (hs-cTnI) Test) using the ESC 0/1-hour algorithm, comparing it to the standard-of-care central laboratory assay (Elecsys 5th-generation hs-cTnT) to identify discrepancies and assess potential safety concerns for patients classified as rule-out by the POC assay. Methods A prespecified interim analysis was performed on the first 300 participants enrolled at the largest study site. EDTA whole blood was collected for the POC assay, and lithium heparin samples were sent to the central laboratory via pneumatic tube for hs-cTnT analysis. The hs-cTnT results were blinded to the treating physicians. Major discrepancies were defined as cases in which the POC assay triaged a patient for direct rule-out, while the central laboratory assay classified the same patient as rule-in. Results During the first three months of inclusion, data were analysed from 308 patients with a median age of 55 years (IQR 42–69) and 47.4% (N=146) female. The POC assay triaged 65.6% (n=202) to 0-hour rule-out (&lt;4 ng/L and ≥3 hours since symptom onset), compared with 45.5% (n=140) triaged by the hs-cTnT assay (&lt;5 ng/L and ≥3 hours since symptom onset). The 0-hour rule-in rates were 4.2% for the POC assay (≥60 ng/L) and 2.6% for the hs-cTnT assay (≥52 ng/L). The POC assay also triaged 90 patients (29.2%) to the indeterminate observation group, requiring a repeat 1-hour sample. In comparison, the hs-cTnT assay would have required repeat sampling in 160 patients (51.9%), though 70 of these were not obtained due to blinded results. After the repeat sample, the POC 0/1-hour algorithm triaged 74.0% of the patients as rule-out, suggesting potential eligibility for discharge. No major discrepancies between the two assays were identified after a single sample. Technical error codes occurred in 3 of 308 patients (1.0%) during POC testing. Conclusions Compared with the standard-of-care central laboratory hs-cTnT assay, the TRIAGETRUE hs-cTnI POC assay provides a higher single-sample rule-out rate and a shorter turnaround time. Together, these features enable faster identification of rule-out patients and may improve patient flow and chest pain management in busy clinics. No safety concerns have been identified for the point-of-care assay, supporting continuation of the larger implementation study.Triage Efficacy after a single blood sample

• Pettersen, Trond Røed; Norekval, T M; Hagen, M; Helland, Arne; Munkhaugen, John & Vethe, Nils Tore [Show all 7 contributors for this article] (2026). Long term adherence to prescribed cardiovascular medications in patients after percutaneous coronary intervention. European Heart Journal. ISSN 0195-668X. 47(Supplement_1). doi: 10.1093/eurheartj/ehag785.4229. Full text in Research Archive Show summary

  Abstract Background Optimal long-term medication adherence is a crucial part of secondary prevention in patients after percutaneous coronary intervention (PCI) to achieve guideline-based treatment goals. Therapeutic drug monitoring (TDM) provides an objective method of assessing adherence to prescribed medications. Although patients generally respond positively to TDM when it is delivered within a supportive and autonomy-respecting clinician–patient relationship, the extent of non-adherence that persists is underexplored. Purpose To quantify adherence to prescribed cardiovascular medications using TDM 12 months after PCI. Methods A sub-sample of 500 patients from the prospective multicentre cohort CONCARDPCI were invited to undergo TDM of a range of cardiovascular medications 12 months after hospital discharge. The panel comprised 21 antihypertensive agents or metabolites, 3 direct oral anticoagulants (DOACs), and 2 statins. Serum samples were analysed utilizing ultra-high performance liquid chromatography coupled with tandem mass spectrometry. Sampling was done at the time of inclusion, permitting spontaneous sampling irrespective of timing of drug intake. Medication adherence was dichotomized as either full or suboptimal adherence. Results from the TDM analyses were compared to self-reported medication adherence utilizing the Medication Adherence Report Scale (MARS-5). To assess representativeness of the sample, it was compared with the full CONCARDPCI data (n=1970) on selected background variables (e.g. age, sex, polypharmacy, number of comorbidities, and education). Results In all, 167 patients consented to TDM and provided spontaneous blood samples and an updated medication list. The TDM sample was similar to the CONCARDPCI cohort except for age (median age 65.5 vs 67.2 for CONCARDPCI and TDM sample respectively, p=0.043). The number of concomitant measurable medications ranged from 1 to 5 (median 2). Non-adherence to one or more prescribed medications was identified in 19 patients (12%). Of these, 13 had MARS-5 scores of ≥24, indicating high medication adherence. In 15 patients (9%), cardiovascular medications not documented in the patients’ medication lists were detected. Adherence to DOACs, calcium channel blockers, and doxazosin was 100%. For beta-blockers, angiotensin-converting enzyme inhibitors, angiotensin II receptor blockers, and diuretics, adherence ranged from 90% to 100%. Non-adherence to atorvastatin however was 12%. Conclusions Long-term adherence to prescribed cardiovascular medications, especially statins, was suboptimal. Non-adherence and the presence of undocumented medications persisted even among patients who consented to TDM, indicating that TDM is superior to self-reported medication adherence. This supports the clinical value of TDM in identifying discrepancies in medication use and supporting patient-centred adherence-improvement strategies.

• Lunde, Ida Gjervold; Dahle, L; Chuhan, A N; Bratseth, Vibeke; Palmero, Sheryl & Almli, Gunhild Bakken [Show all 12 contributors for this article] (2026). Effects of beta-blocker treatment on circulating biomarkers of fibrosis in patients with myocardial infarction without heart failure: A substudy of the BETAMI-DANBLOCK trial. European Heart Journal. ISSN 0195-668X. 47(Supplement_1). doi: 10.1093/eurheartj/ehag785.1321. Full text in Research Archive Show summary

  Abstract Background Myocardial infarction (MI) is caused by ischemia, leading to irreversible myocardial injury, chronic inflammation and collagenous scarring, i.e., fibrosis. Beta-blockers (BB) reduce the risk of heart failure progression in MI patients with reduced ejection fraction (EF), however their use and effects in patients with preserved (pEF) or mildly reduced (mrEF) EF is debated. Purpose To evaluate circulating levels of fibrillar collagen peptides in MI patients without heart failure, randomized to prolonged use of BB or not. Methods The BETAMI-DANBLOCK trial (beta blockers after myocardial infarction in patients without heart failure) randomized patients with MI and EF≥ 40% to BBs or not. Patients (n= 5574) were followed for 3.5 years for clinical endpoints. The biobank consisted of n=490 participants (median age 61, 19% women) recruited at four sites in Norway within 7 days of the index event, where n=65 had a primary endpoint. Procollagen has peptides at amino and carboxy termini that are cleaved off by proteases prior to fibril incorporation. They can reach the circulation, e.g. type I collagen C-terminal propeptide (PICP), which provides a stoichiometric representation of collagen type I synthesis. PICP was measured by ELISA (Microvue) in serum at baseline (n=436) and after six months (n=343). Cox proportional hazards regression was used to analyze time to primary composite endpoint, i.e., all-cause death and recurrent cardiovascular event. Results Median (IQR) of PICP was 76 (62, 100) ng/mL at baseline and increased to 97 (77, 126) ng/mL after six months (p&lt;0.001). Baseline PICP was higher in those with age&gt;median vs. those &lt;median (80 vs. 73 ng/ml, p=0.03), but not different in those with pEF (n=393; 76 (62, 99) ng/ml) vs. mrEF (n=44; 80 (61, 107) ng/ml), p=0.533. Baseline PICP was lower in those experiencing a primary endpoint vs. those without (median 70 vs. 77 ng/mL, p=0.043). ΔPICP was increased in both groups; BB users: n=116 up/30 down, and no users: n=122 up/28 down (both p&lt;0.001), with no difference in ΔPICP between BB users (+20 (+2, +41) ng/mL) vs. no users (+24 (+5, +40) ng/mL), p=0.371 (Table). In multivariable analysis, PICP was not associated with the primary composite endpoint (hazard ratio 0.842=[95% confidence interval, 0.074, 9.530]), p=0.889. The treatment effect of BB on clinical endpoints was not modified by baseline PICP concentrations (p-for-interaction=0.404). Conclusion Circulating levels of PICP were lower 7 days and 6 months post-MI, in EF≥ 40% patients with a primary endpoint, suggestive of an impaired fibrotic response. PICP levels were unaffected by 6 months of BB treatment. A recent meta-analysis incorporating BETAMI-DANBLOCK reported neutral effects of prolonged BB therapy in MI patients with preserved EF, and our data provide a mechanistic correlate to this conclusion.Table

• Almli, Gunhild Bakken; Nyen, J; Fagerland, Morten; Jensen, J K; Kristensen, A M D & Prescott, E [Show all 14 contributors for this article] (2026). Long-term adherence to secondary preventive medications after myocardial infarction: a post-hoc analysis of the BETAMI trial. European Heart Journal. ISSN 0195-668X. 47(Supplement_1). doi: 10.1093/eurheartj/ehag785.1680. Full text in Research Archive Show summary

  Abstract Introduction The combined BETAMI-DANBLOCK trial demonstrated that long-term beta-blocker therapy after myocardial infarction (MI) reduced the risk of recurrent cardiovascular events. Detailed knowledge of long-term adherence to allocated treatment and other secondary preventive therapies is important for appropriate interpretation of the trial results. Purpose To describe the long-term adherence to the assigned treatment strategy and other secondary preventive drug use patterns in post-MI patients in a contemporary pragmatic trial setting. Methods In BETAMI-DANBLOCK patients hospitalised with MI without heart failure and a left ventricular ejection fraction (LVEF) ≥40% were randomised to beta-blocker therapy or no beta-blocker (PROBE design). For this sub-study of the BETAMI cohort, data on dispensed secondary preventive drugs were obtained from the Norwegian Prescribed Drug Registry from 6 months prior to inclusion until 3 years post-inclusion or end of follow-up (April 1, 2025), whichever occurred first. Patients were classified as “on treatment” if previously dispensed tablets, when taken according to standard treatment practice (1 or 2 tablets/day), would still have been available at the assessment date. Otherwise, they were classified as “off treatment”. Results All patients included in this substudy were revascularized for their index MI. Among the 2,867 included patients, only a minority had been treated with cardiovascular drugs during the six months period prior to their index-MI (Table). Within seven days after inclusion, 1300/1431 (91%) of patients randomised to beta-blocker therapy had dispensed a beta-blocker, compared to 71/1436 (5%) randomised to no beta-blockers (Table). Metoprolol was prescribed in 98% of patients dispensing beta-blocker in the beta-blocker arm, at a median dose of 50 mg/day (IQR: 25-50). In addition, most patients in both groups were discharged with acetylsalicylic acid (ASA, 86%) at a median dose of 75 mg/day (IQR: 75-75), statins (88%) with a median atorvastatin dose of 80 mg/day (IQR: 40-80), and P2Y12 inhibitors (85%). During follow-up, the median doses remained unchanged, and adherence to other cardiovascular drugs was high in both treatment arms (Figure). For patients randomised to beta-blocker therapy, the proportion on beta-blockers was 88% at 6 months, 82% at 12 months, decreasing to 71% at 3 years. In the no beta-blocker arm, 10% were on a beta-blocker at 6 months, 11% at 12 months, and 14% at three years follow-up. Conclusions In the BETAMI trial, long-term adherence to the allocated beta-blocker strategy was high, although a gradual decline in beta-blocker use was observed over time in the active treatment arm. In this pragmatic clinical trial, an even higher adherence to beta-blockers would be expected to yield an even stronger favourable effect on MACE. Adherence to other guideline-recommended secondary preventive therapies after AMI was consistently high in both groups.ESC_Adherence_TableESC_Adherence_Figure

• Johannessen, Tonje Rambøll; Atar, Dan; Halvorsen, Sigrun; Munkhaugen, John; Vallersnes, Odd Martin & Bakken, Arnhild [Show all 7 contributors for this article] (2026). Point-of-Care High-Sensitivity Troponin Testing for Rapid Chest Pain Triage in Emergency Primary Care: Preliminary Single-Sample Efficacy Findings from the OUT-POC Study. Full text in Research Archive
• Otterstad, Jan Erik; Atar, Dan & Munkhaugen, John (2026). Betablokkerbehandling etter hjerteinfarkt? Oppdatert kunnskapsgrunnlag etter nyere studier. Indremedisineren. ISSN 1891-1617. p. 32–35. Full text in Research Archive
• Rolland, J; Ovrebotten, T; Berge, Kristian; Nahoui, Hamza; Bjorkelund, O A & Broch, Kaspar [Show all 15 contributors for this article] (2026). Contemporary post-discharge management in heart failure at home (STRONG@HOME). European Journal of Heart Failure. ISSN 1388-9842. 28(Supplement_2). doi: 10.1093/ejhf/xuag193.1424. Full text in Research Archive Show summary

  Abstract Background The post-discharge period after heart failure (HF) hospitalisation is associated with high-risk, and the uptake of guideline-directed medical therapy (GDMT) remains suboptimal. In the STRONG-HF trial, an intensive strategy of rapid GDMT up-titration and close follow-up after an acute HF admission reduced the risk of all-cause mortality and HF readmissions compared to usual care. Based on the STRONG-HF results, this strategy received a Class IB recommendation in the 2023 Focused Update of the ESC HF Guidelines, but requires substantial resources and may offer logistical challenges. Whether follow-up visits can safely be performed virtually at home and still achieve the same degree of GDMT without excess adverse events remains unknown. Objectives This abstract describes the design and methodological framework of STRONG@HOME. This trial evaluates whether patients discharged after hospitalisation for acute HF can safely achieve the same level of GDMT via digital follow-up at home as compared to hospital visits, according to the STRONG-HF strategy. Methods STRONG@HOME is a randomised, multicentre, open-label, parallel group trial. In total, 462 patients hospitalised for acute HF will be randomised in a 1:1 ratio to receive digital (experimental arm) or in-person (control arm) follow-up at 1-, 2-, 3- and 6-weeks post-discharge (See Figure). Patients in the control arm are followed at outpatient HF clinics, while patients in the experimental arm are followed up via video consultations and telemonitoring. The dual primary outcomes (Bonferroni corrected with 0.025 as significance level) are assessed for non-inferiority after 90 days at the final follow-up visit. Efficacy is measured by the GDMT-score (0-9), based on four drug classes. Safety is assessed as treatment-emergent adverse events, including eGFR &lt;30 mL/min/1.73 m², systolic BP &lt;95 mm Hg, heart rate &lt;50 bpm, and serum potassium &gt;5.5 mmol/L. The expected median GDMT-score in the control arm is 7 (SD 2.5). With a 10% non-inferiority margin, a sample size of 404 is needed for 80% power and a significance level of 0.025. For safety, a 51% expected adverse events rate requires a sample size of 416. At an expected 10% dropout rate, the final overall target sample size is 462. Per January 1, 2026, 83 patients have been enrolled, and all sites are activated. Conclusion STRONG@HOME is the first study to assess if patients with acute HF can safely achieve the same level of GDMT through digital home follow-up as through hospital visits, using the STRONG-HF strategy. This approach could enable broader implementation of guideline-recommended post-discharge management at reduced cost, improve accessibility for patients in rural or underserved areas, and alleviate capacity constraints at specialised HF clinics. Digital follow-up may also enhance patient convenience and adherence while maintaining clinical outcomes, potentially transforming post-discharge HF care delivery at scale.Strong@Home flow chartFor image description, please refer to the figure legend and surrounding text.

• Kristensen, A M D; Holmager, T L F; Halvorsen, Sigrun; Olsen, M H; Bakken, Arnhild & Atar, Dan [Show all 8 contributors for this article] (2026). Beta-blocker therapy and angina pectoris after myocardial infarction: a BETAMI-DANBLOCK substudy. European Journal of Preventive Cardiology (EJPC). ISSN 2047-4873. 33(Supplement_2). doi: 10.1093/eurjpc/zwag249.435. Full text in Research Archive Show summary

  Abstract Background Angina pectoris after myocardial infarction (MI) remains prevalent despite contemporary treatment strategies and affects quality of life and healthcare use. The evidence for the effects of beta-blocker therapy on angina pectoris in MI patients treated according to contemporary standards is limited. Purpose We aimed to evaluate the effects of beta-blockers on diagnostic procedures and hospitalizations for angina pectoris, as well as redeemed anti-anginal prescriptions and self-reported symptoms of angina among MI patients with LVEF ≥40% enrolled in the BETAMI-DANBLOCK trial. Methods Participants in the BETAMI-DANBLOCK trial were randomized to open-label long-term beta-blocker therapy or no such therapy within 14 days from MI. In this pre-specified substudy, we analyzed the effect of beta-blocker therapy on time to first diagnostic procedure (coronary angiogram, coronary CT angiography, PET-CT, myocardial perfusion scintigraphy, or stress echocardiography), hospitalization for angina, and ≥2 redeemed prescriptions for anti-anginal medications (calcium-antagonists, short-/long-acting nitrates) using Fine-Gray subdistribution hazards models with death as a competing risk. Self-reported angina symptoms were measured using the Canadian Cardiovascular Society angina grading and the New York Heart Association functional classification. Differences in self-reported symptoms (symptoms vs. no symptoms) at 1 year were compared between treatment groups using the chi-square test. Results In the DANBLOCK trial, 1352 patients were randomized to beta-blockers and 1355 to no beta-blockers. After a median follow-up of 3.5 years, 329 patients (24.3%) in the beta-blocker group and 395 patients (29.2%) in the no beta-blocker group underwent at least one diagnostic procedure for angina pectoris (subdistribution hazard ratio [sHR] 0.85; 95% confidence interval [CI] 0.74-0.99) (Table 1). Hospitalization for angina pectoris occurred in 59 patients (4.4%) in the beta-blocker group and 60 patients (4.4%) in the no beta-blocker group (sHR 0.99; 95% CI 0.69-1.42). A higher proportion of patients in the no-beta-blocker group redeemed ≥2 prescriptions for calcium-antagonists, whereas no difference was seen for nitrates (Table 1). Self-reported angina symptoms at 1 year did not differ significantly between treatment groups (Table 2). If accepted for presentation at the ESC Preventive Cardiology 2026 the results from BETAMI will also be included. Conclusion Among MI patients with LVEF ≥40%, beta-blocker therapy was associated with a lower risk of undergoing a diagnostic procedure for angina pectoris, and of redeeming ≥2 prescriptions for calcium antagonists, but not with a lower risk of hospitalization for angina pectoris. Self-reported angina symptoms appeared similar between treatment groups.For image description, please refer to the figure legend and surrounding text.  For image description, please refer to the figure legend and surrounding text.

• Getz, Vilde; Pleym, Karin; Dammen, Toril; Husebye, Einar; Sverre, Elise Christine Bjørkholen & Peersen, Kari [Show all 9 contributors for this article] (2026). Patient- and healthcare system predictors of participation in a municipal smoking cessation programme after hospitalisation for atherosclerotic cardiovascular disease. European Journal of Preventive Cardiology (EJPC). ISSN 2047-4873. 33(Supplement_2). doi: 10.1093/eurjpc/zwag249.268. Full text in Research Archive Show summary

  Abstract Introduction Few patients with atherosclerotic vascular disease attend hospital-based cardiac rehabilitation, and alternative models have been called for (1). Municipal Healthy Life Centres (HLCs) in Norway provide evidence-based lifestyle support, including smoking cessation programmes. We have recently demonstrated that a single in-hospital motivational counselling session with proactive referral to a HLC programme resulted in a higher programme uptake and doubled long-term cessation rates (25% to 50%) (2,3). Purpose To identify patient- and healthcare system factors associated with participation in a municipal cessation programme among patients hospitalised with atherosclerotic vascular disease included in a smoking cessation trial. Methods A pre-specified analysis of two smoking cessation intervention trials conducted from 2021 to 2024. Patients who smoked daily at hospital admission for an atherosclerotic vascular event were randomised 1:1 to in-hospital motivational counselling session combined with proactive referral to the HLC cessation programme (intervention) or to brief advice and written information about the HLC programme (control). Study data were collected from medical records at hospitals and HLCs and from self-report questionnaires. Associations between patient- and healthcare system factors and programme participation were estimated with logistic regression. Results Among 280 randomised patients, mean age was 65 years (SD 10), and 39% were women. Myocardial infarction was the most prevalent cause of hospitalisation (36%) followed by peripheral artery disease (18%) and cerebrovascular disease (14%). At six months 268 patients were available for analysis, excluding two who withdrew consent and ten who had died. Participation in the municipal smoking cessation programme was 42% (56/134) in the intervention group versus 9% (12/134) in the control group. In adjusted analyses of the total population, living with a smoking partner was positively associated with participation at the HLC (odds ratio 2.6) (Table 1). Factors inversely associated with HLC participation were older age (OR 0.7 per 10 years), living alone (OR 0.3), and low education (OR 0.4). Readiness for cessation and psychological distress were not significantly associated with participation. No healthcare system factor reached statistical significance, although inclusion during the summer holiday period appeared to reduce participation. Analysis of the intervention group (N=134) showed comparable results (Table 2). Conclusions Participation in a municipal smoking cessation programme among hospitalised patients with atherosclerotic vascular disease included in the trial was suboptimal, despite proactive referral. Older patients, those living alone, and those with lower education were less likely to participate, highlighting groups that need targeted referral strategies and tailored support to improve the participation rate.For image description, please refer to the figure legend and surrounding text.  For image description, please refer to the figure legend and surrounding text.

• Sverre, Elise Christine Bjørkholen; Madssen, Erik; Kristensen, A M D; Nyen, J E; Bakken, Arnhild & Holmager, T [Show all 12 contributors for this article] (2026). Effect of long-term beta-blocker therapy on physical activity after myocardial infarction: a post hoc analysis of the BETAMI trial. European Journal of Preventive Cardiology (EJPC). ISSN 2047-4873. 33(Supplement_2). doi: 10.1093/eurjpc/zwag249.065. Full text in Research Archive Show summary

  Abstract Introduction The BETAMI-DANBLOCK trial recently found that beta-blockers reduced the risk of all-cause death or major adverse cardiovascular events in patients with a recent myocardial infarction (MI) without heart failure symptoms and left ventricular ejection fraction ≥40%. Some observational data and small intervention studies indicate a possible negative relationship between beta-blocker therapy and physical activity (PA) levels. However, it is still unclear how beta-blocker treatment influences PA after an acute MI. Purpose To investigate the effect of long-term beta-blocker therapy on PA level after MI in patients without heart failure. Method In this post-hoc analysis of the multicentre, randomized, open-label BETAMI trial with blinded endpoint evaluation, patients hospitalized with a MI and without heart failure were assigned to beta-blocker therapy within seven days after the event or no beta-blocker therapy. PA levels were assessed prior to randomization and at 1-, 6-, 12- and 18-months follow-up by self-reported questionnaires. The main endpoints were between-group changes in hours/week of light- (e.g., walking, dancing, cycling) and vigorous PA (e.g., brisk uphill walking, running) from baseline to 18 months, estimated by linear mixed models. Additionally, we assessed between-group differences in the proportion with guideline-recommended PA level (≥30 minutes of moderate activity on ≥5 days/week) and the participation rates in cardiac rehabilitation or organized PA programs. Results Of the 2867 patients, 2148 (75%) responded to the questions regarding PA in the follow-up period. Median age was 62 (IQR 55-70) years, and 19.6% were women. The median beta-blocker dose in the intervention arm was equivalent to metoprolol depot 50 mg/day. No differences in mean hours of light and vigorous physical activity were reported between the beta-blocker and non-beta-blocker groups at baseline, and these remained comparable throughout the 18 months follow-up (Figure 1). At baseline 31.2% met the guideline-recommended level of PA. This proportion increased to 39.2% at 6 months, with no significant differences between treatment arms at any time point (Figure 2). We found no effect of beta-blocker dose on the PA level. Participation in cardiac rehabilitation or organized PA at 12 months follow-up was 43.6% in the beta-blocker group and 42.3% in the non-beta-blocker group. Conclusions Beta-blocker therapy did not affect the PA level in post-MI patients without heart failure during 18 months follow-up.For image description, please refer to the figure legend and surrounding text.  For image description, please refer to the figure legend and surrounding text.

• Braanaas, Karoline Svensen; Dammen, Toril; Fagerland, Morten; Husebye, Einar; Leinaas, A & Schirmer, Henrik [Show all 10 contributors for this article] (2026). Individually Tailored monitoring at home after hospitalization for HEART failure (IT-HEART): Design and baseline characteristics of a randomized clinical trial. European Journal of Preventive Cardiology (EJPC). ISSN 2047-4873. 33(2). doi: 10.1093/eurjpc/zwag249.461. Full text in Research Archive Show summary

  Abstract Background Telemonitoring has emerged as a promising alternative to conventional heart failure (HF) management. Despite its potential, evidence from randomized controlled trials remains inconclusive, and data from high-risk populations with frailty, is scarce. The Individually Tailored remote monitoring at home after HEART failure (IT-HEART) trial evaluates whether a non-invasive telemonitoring program improves clinical, patient reported, and health economic outcomes in HF patients after a recurrent hospitalization. Purpose To describe flow of patients and baseline characteristics of the IT-HEART study population. Methods This multicentre, open-label, blinded-endpoint trial randomized HF patients to either written information and a self-management plan (Control) or HF education, a personalized self-management plan, and three months of home telemonitoring (Intervention). The primary endpoint is the total number of HF hospitalizations or cardiovascular death. Secondary endpoints include hospitalizations and outpatient visits, adherence the intervention, patient reported outcomes, and health economic measures. End of follow-up will be in October 2026. Results Of 1027 consecutively screened patients, 200 (19.5%) were randomized. Median age was 78 (IQR (70-83) years, and 29.5% were women. At baseline, participants had substantial multimorbidity with median Clinical Frailty Scale score 4, median Charlson Comorbidity Index score 6, and symptom burden was high (Table). Median self-rated HF management knowledge was 3 (IQR 0-7) on a 0-10 Likert scale. Only 35.5% weighed themselves weekly whereas 1 % (n=2) reported having a formal self-care plan at baseline. In the intervention arm (N=100), 64 participants used a digital telemonitoring platform and 36 received telephone-based monitoring. Conclusion Patients enrolled after a recurrent HF hospitalization were older, multimorbid, and frail, with high symptom burden, and low self-care and health literacy. The IT-HEART telemonitoring intervention is targeted to these modifiable deficits and has the potential to improve clinical and patient-reported outcomes.For image description, please refer to the figure legend and surrounding text.

• Caglar, H; Holmager, T; Kristensen, A; Atar, Dan; Munkhaugen, John & Prescott, E (2026). Risk stratified effect of beta-blockers after myocardial infarction in patients without heart failure: A substudy of the BETAMI-DANBLOCK trial. European Journal of Preventive Cardiology (EJPC). ISSN 2047-4873. 33(Supplement_2). doi: 10.1093/eurjpc/zwag249.076. Full text in Research Archive Show summary

  Abstract Background Recent meta-analyses show that beta-blockers benefit patients with mildly reduced left ventricular ejection fraction (LVEF) after myocardial infarction (MI), but not those with preserved LVEF. Whether simple clinical risk factors can identify patients who derive greater absolute benefit remains unknown. Purpose To assess whether the clinical effect of long-term beta-blocker therapy after MI differs across baseline risk strata defined by a modified Thrombolysis in Myocardial Infarction Risk Score for Secondary Prevention (TRS-2P) Methods This was a substudy of the BETAMI-DANBLOCK trial, which randomized patients with recent MI and LVEF &gt;40% to long-term beta-blocker or no beta-blocker therapy. A modified TRS-2P score (0–8 points) was constructed by excluding current smoking and incorporating mildly reduced LVEF (41–49%). Patients were categorized as low- (0 points), intermediate- (1–2 points), or high-risk (≥3 points). The primary endpoint was a composite of all-cause mortality, MI, unplanned coronary revascularization, ischemic stroke, heart failure, or malignant ventricular arrhythmia. The secondary endpoint was recurrent MI. Within each TRS-2P strata the effect of beta-blocker was estimated using Cox proportional hazard model and Fine-Gray subdistribution hazard model. Three-year absolute risk reduction (ARR) and number needed to treat (NNT) were estimated for each TRS-2P stratum using the total trial hazard ratio (HR) applied to stratum-specific cumulative incidences derived from Kaplan–Meier estimates Results Among the 5,558 patients included in the analysis, 38.4% were low-, 52.8% intermediate-, and 8.8% high-risk. Event rates increased stepwise across risk strata (2.96, 4.58, and 11.05 per 100 person-years, respectively). Relative treatment effects were consistent in low-risk (HR 0.88, 95% CI 0.67-1.13), intermediate-risk (HR 0.81, 95% CI 0.67-0.97), and high-risk patients (HR 0.88, 95% CI 0.63-1.20). Absolute benefit increased with risk strata: 3-year ARR was 1.4% (NNT 72) in low-risk-, 2.1% (NNT 47) in intermediate-risk-, and 3.6% (NNT 28) in high-risk patients. Recurrent MI demonstrated the same pattern, with greater absolute benefit in the higher-risk strata. Conclusions The modified TRS-2P score showed clear prognostic ability, and the absolute benefit of beta-blockers increased with baseline risk despite similar relative effects. These findings support the use of simple clinical risk stratification to guide long-term beta-blocker therapy after MI.Treatment effect of beta-blockersFor image description, please refer to the figure legend and surrounding text.  Cumulative incidence of primary endpointFor image description, please refer to the figure legend and surrounding text.

• Nyen, J; Kristensen, A M D; Fagerland, Morten; Dammen, Toril; Zwisler, A D & Olsen, M H [Show all 14 contributors for this article] (2026). Beta-blocker therapy and sleep disturbances after myocardial infarction: a prespecified sub-study of the BETAMI-DANBLOCK trial. European Journal of Preventive Cardiology (EJPC). ISSN 2047-4873. 33(Issue Supplement_2). doi: 10.1093/eurjpc/zwag249.074. Full text in Research Archive Show summary

  Abstract Introduction Sleep disturbances have been proposed as a side effect of beta-blocker therapy, but evidence from large, randomised controlled trials are lacking. Purpose To evaluate the effects of beta-blockers on insomnia and nightmare frequency in patients with myocardial infarction (MI) and preserved or mildly reduced left ventricular ejection fraction (LVEF≥40%) enrolled in the BETAMI-DANBLOCK trial. Methods BETAMI-DANBLOCK was an open-label trial in Norway and Denmark in which MI-patients were randomised to receive long-term beta-blocker therapy or no such therapy. For this prespecified analysis, patients completed the Bergen Insomnia Scale (BIS) (all patients) and the Nightmare Frequency Questionnaire (NFQ) (Norwegian patients only) at baseline, 1-6, 12 and 18-24-months follow-up. BIS provides a continuous score (0-42) increasing with symptoms severity. BIS can also be used as a diagnostic tool (insomnia vs. no insomnia) based on self-reported diagnostic criteria scores. NFQ measures the number of nights with nightmares per week/month/year. The main endpoint was the incidence of insomnia during the first 12 months of follow-up in the two groups, estimated with logistic regression. Additional endpoints included between-group changes in BIS scores and nightmare frequency from baseline to 12 months, estimated by linear mixed models. Results Of 5574 randomised patients, 4728 (85% of all patients) completed BIS and 2031 (71% of the Norwegian patients) completed NFQ during the trial period. Median age was 62 (IQR: 55-70) years, 21% were women, and median metoprolol dose was 50 mg/day. At baseline, median self-reported sleep duration was 7 hours/night (IQR: 6-7.5) in both groups, median BIS score was 10 (IQR: 4-19) in both groups, and 40% fulfilled diagnostic criteria for insomnia. Beta-blocker therapy was associated with a negligible increase of 0.63 (95% CI: 0.03 to 1.24) in continuous BIS score. We found no statistically significant effect of beta-blockers on the incidence of insomnia during follow-up (Table 1). At baseline, the proportion of patients reporting nightmares at least monthly was 16% in the beta-blocker group and 15% in the no-beta-blocker group. A higher proportion of patients on beta-blockers reported at least monthly nightmares at 6 (25% vs 18%) and 12 (23% vs. 18%) months follow-up (6 months OR 2.12, 95% CI 1.02 to 4.40; 12 months OR 1.08, 95% CI 0.51 to 2.25). No significant change in the number of monthly nightmares was observed at 12 months (0.21, 95% CI: -0.15 to 0.57). Conclusions We found no clear and substantial effects of beta-blocker therapy on the incidence of insomnia or nightmare frequency among post-MI patients with LVEF ≥40%; however, a small effect cannot be ruled out.For image description, please refer to the figure legend and surrounding text.

• Holmager, T; Kristensen, A; Fagerland, Morten; Atar, Dan; Olsen, M & Bakken, Arnhild [Show all 8 contributors for this article] (2026). Validating national registry data for randomised trials: comparison of adjudicated and registry-derived cardiovascular outcomes in the BETAMI-DANBLOCK trial. European Journal of Preventive Cardiology (EJPC). ISSN 2047-4873. 33(Supplement_2). doi: 10.1093/eurjpc/zwag249.475. Full text in Research Archive Show summary

  Abstract Background Registry-based randomised clinical trials are increasingly dependent on registry-derived outcomes, providing advantages in feasibility and data capture. However, registry data may introduce bias through misclassification or incomplete information. In the BETAMI-DANBLOCK trial, we compared registry-based cardiovascular events with and without adjudication, using information from national registries, electronic health records, and patient reports. Purpose To investigate whether registry-based endpoints can substitute adjudicated endpoints without materially altering trial results. Methods BETAMI-DANBLOCK enrolled 5,574 patients with myocardial infarction (MI) and a left ventricular ejection fraction ≥40% from 2018 through 2024. Patients were randomised to beta-blocker therapy or no beta-blocker therapy. The primary endpoint events (death, MI, ischemic stroke, heart failure, unplanned coronary revascularisation, and ventricular arrhythmias) were identified from the Danish and Norwegian national patient registries, self-reported questionnaires, and medical records. All registry-identified events, except death, underwent blinded adjudication. We compared events with and without adjudication by calculating incidence rates and hazard ratios (HRs) for beta-blocker treatment versus controls. Results National registries had almost complete capture of events when compared to site-reporting. In total, 75% of the primary endpoint events identified through the registries were confirmed by adjudication. The confirmation rate was lower during the first six months and varied by event type (from 92% for ischemic stroke to 45% for unplanned coronary revascularisations). The incidence rate of the primary endpoint was 6.23 per 100 person-years using registry data without adjudication and 4.43 with adjudication. Estimated treatment effects were consistent for the primary endpoint (0.88, 95% confidence interval (CI): 0.78-0.98 without adjudication and 0.85, 95% CI: 0.75-0.98 with adjudication), with no apparent differences across event types. Conclusion Registry data provide treatment effect estimates comparable to those obtained from adjudicated data in BETAMI-DANBLOCK. However, adjudication substantially reduced the total number of endpoint events and event-specific misclassification was a limitation, particularly during the first months after the index event.Cumulative incidence of primary endpointFor image description, please refer to the figure legend and surrounding text.  Forest plot of hazard ratiosFor image description, please refer to the figure legend and surrounding text.

• Pleym, Karin; Engebretsen, Ingrid; Sverre, Elise Christine Bjørkholen; Dammen, Toril; Husebye, Einar & kahlon, Mohpal Singh [Show all 10 contributors for this article] (2026). Cost-effectiveness of in-hospital motivational smoking cessation counselling and proactive referral to community-based follow-up. European Journal of Preventive Cardiology (EJPC). ISSN 2047-4873. 33(Supplement_2). doi: 10.1093/eurjpc/zwag249.265. Full text in Research Archive Show summary

  Abstract Background Hospital-based smoking cessation interventions are generally cost-effective, but most economic evaluations among inpatients with atherosclerotic cardiovascular disease (ASCVD) rely on modelled data only rather than patient-level data (1). Moreover, cost-effectiveness evidence for motivational interviewing in smoking cessation is limited and is primarily derived from non-hospitalised populations (2,3). Purpose To evaluate the cost-effectiveness of an in-hospital smoking cessation intervention with proactive referral to community-based follow-up among patients with ASCVD. Methods We performed an economic evaluation alongside a randomised controlled trial using a hospital perspective. The analysis included the cost of training, materials, and personnel. We recorded survival over sixteen months. Hospital costs during this period were monetised using Diagnosis Related Group cost weights. Survival beyond follow-up was projected using national mortality data adjusted for age, sex, and ASCVD. Remaining lifetime costs were estimated from mean costs in the final six months of follow-up. Costs and life-years were discounted at four percent. Uncertainty was assessed with 2000 bootstrap replicates. The primary outcome was net monetary benefit using a willingness-to-pay threshold of €38,346 per life-year. Results Mean baseline age was 65.2 years. During the sixteen-month follow-up, five participants in the intervention group and nine in the control group died. The intervention group had lower per-patient hospital costs during follow-up (€9,114 versus €13,973; difference: €4,859; 95% confidence interval [CI]: –€1,514 to €11,232). Lifetime costs were higher in the intervention group due to longer projected survival (€114,170 versus €110,522; difference: €3,648; uncertainty estimates [UE]: -€19,816 to €27,718). Undiscounted remaining life expectancy was 20.5 years in the intervention group and 18.7 years in the control group, (difference: 1.7 years, 95% UE: –1.9 to 6.1). The estimated net monetary benefit was €37,475 (95% CI: -15,868 to 107,797) and the probability that the intervention was cost-effective at the €38,346 per life-year threshold was 90.5% (Figure). Conclusion An in-hospital, motivational smoking cessation intervention with proactive referral to community-based support is likely to be cost-effective from a hospital perspective for patients with atherosclerotic vascular disease.FigureFor image description, please refer to the figure legend and surrounding text.

• Uduma, Amara Synøve Øgaard; Sverre, Elise Christine Bjørkholen; Munkhaugen, John; Svarstad, Anja Camilla; Tuv, Silja Skogstad & Vethe, Nils Tore (2026). Effect of the ugt1a3*2 haplotype on pharmacokinetics and pharmacodynamics of atorvastatin in patients with coronary heart disease. European Journal of Preventive Cardiology (EJPC). ISSN 2047-4873. 33(Supplement_2). doi: 10.1093/eurjpc/zwag249.436. Full text in Research Archive Show summary

  Abstract Background Atorvastatin reduces the risk of atherosclerotic cardiovascular disease but exhibits wide interindividual variability in efficacy and adverse effects, possibly due to genetic predispositions. The SLCO1B1*5 variant causes higher systemic exposure to atorvastatin, and has been associated with increased risk of muscular side effects. The UGT1A3*2 haplotype potentially relate to poorer cholesterol response and increased risk of muscle toxicity by skewing the metabolism towards increased lactonization of atorvastatin metabolites. Purpose To explore the relationship between the UGT1A3*2 haplotype and the pharmacokinetics and pharmacodynamics of atorvastatin in patients with coronary heart disease. Methods We used data from the MUSE study, a double-blinded crossover trial in patients with coronary heart disease. The intervention group with statin-associated muscle symptoms (SAMS, n=70) underwent two 7-week periods with atorvastatin 40 mg and placebo. The control group with no history of SAMS (n=39) received atorvastatin 40 mg during an open-label 7-week period. Blood samples were collected 24h after atorvastatin administration, at the end of each period. We determined pharmacogenetic variants with a multiplex-PCR MALDI-TOF assay. Atorvastatin, its main metabolites, and mevalonate, were quantified with liquid chromatography mass spectrometry. Results Mean age was 64 years and 32% were females. UGT1A3*2 was present in 54% of patients, and the SLCO1B1*5, CYP3A4*22 and CYP3A7*1C variants were present in 29%, 8.3% and 13% (Table 1). In the SAMS group, atorvastatin versus placebo produced mean changes in mevalonate -34 ± 24%, LDL-C -47 ± 19%, and CK +10 ± 33%. In adjusted analysis, SLCO1B1*5 was consistently associated with higher concentrations of atorvastatin and in both acid and lactone form (Table 2). The UGT1A3*2 haplotype was associated with higher levels of hydroxylated atorvastatin and its metabolites. The effects of CYP3A4*22 and CYP3A7*1C were selective towards the non-hydroxylated atorvastatin lactone and 4-hydroxylated atorvastatin lactone, respectively. Regression analysis indicated a more pronounced reduction in mevalonate, a response marker of HMG-CoA reductase inhibition among carriers of UGT1A3*2 whereas none of the examined variants predicted LDL-C response. Unexpectedly, SLCO1B1*5 and CYP3A7*1C were associated with an atorvastatin-related decrease in CK. Conclusions UGT1A3*2 was observed in approximately half of the patients with coronary heart disease and is associated with higher concentrations of hydroxylated atorvastatin metabolites. This haplotype should be considered together with SLCO1B1*5 when predicting effects related to systemic exposure. The results indicate that UGT1A3*2 may have indirect impact on the pharmacodynamics of atorvastatin while further studies are needed to clarify clinical implications for LDL-C lowering and muscle safety.For image description, please refer to the figure legend and surrounding text.  For image description, please refer to the figure legend and surrounding text.

• Getz, Vilde; Pleym, Karin; Dammen, Toril; Husebye, Einar; Sverre, Elise Christine Bjørkholen & Peersen, Kari [Show all 9 contributors for this article] (2026). Patient- and healthcare system predictors of participation in a municipal smoking cessation programme after hospitalisation for atherosclerotic cardiovascular disease. doi: https:/esc365.escardio.org/preventive-cardiology/sessions/18511-prognostic-factors-in-populations. Full text in Research Archive
• Pleym, Karin; Engebretsen, Ingrid; Sverre, Elise Christine Bjørkholen; Dammen, Toril; Husebye, Einar & kahlon, Mohpal Singh [Show all 10 contributors for this article] (2026). Cost-effectiveness of in-hospital motivational smoking cessation counselling and proactive referral to community-based follow-up. doi: https:/esc365.escardio.org/preventive-cardiology/sessions/18493-feasibility-and-outcomes-of-lifestyle-and-behavioural-interventions. Full text in Research Archive
• Uduma, Amara Synnøve; Sverre, Elise Christine Bjørkholen; Munkhaugen, John; Svarstad, Anja Camilla; Tuv, Silja Skogstad & Vethe, Nils Tore (2026). Effect of the ugt1a3*2 haplotype on pharmacokinetics and pharmacodynamics of atorvastatin in patients with coronary heart disease. doi: https:/esc365.escardio.org/preventive-cardiology/sessions/18479-heterogeneity-of-vascular-and-atherosclerotic-risk-phenotypes. Full text in Research Archive
• Sverre, Elise Christine Bjørkholen; Madssen, Erik; Nyen, Johanne; Bakken, Arnhild; Holmager, Therese & Jortveit, Jarle [Show all 11 contributors for this article] (2026). Effect of long-term beta-blocker therapy on physical activity after myocardial infarction: a post hoc analysis of the BETAMI trial. doi: https:/esc365.escardio.org/preventive-cardiology/sessions/18492-behaviour-and-awareness-in-risk-development-and-successful-risk-management. Full text in Research Archive
• Nyen, Johanne; Kristensen, Anna Meta; Fagerland, Morten; Dammen, Toril; Zwisler, Ann-Dorthe & Olsen, Michael Hecht [Show all 14 contributors for this article] (2026). Beta-blocker therapy and sleep disturbances after myocardial infarction: a prespecified sub-study of the BETAMI-DANBLOCK trial. doi: https:/esc365.escardio.org/preventive-cardiology/sessions/18499-risk-management-in-acute-coronary-syndrome. Full text in Research Archive
• Munkhaugen, John (2026). Skal vi fortsatt gi betablokker etter hjerteinfarkt? Hjerteforum. ISSN 0802-1465. 39(1), p. 86–88. Full text in Research Archive
• Kristensen, Anna Meta Dyrvik; Rosello, Xavier; Atar, Dan; Yndigegn, Troels; Kimura, Takeshi & Latini, Roberto [Show all 25 contributors for this article] (2026). Bata-Blocker therapy after myocardial infraction in patients with preserved left ventricular ejection fraction: An individual patient data meta-analysis of randomized controlled trials. Hjerteforum. ISSN 0802-1465. 39(1), p. 120–121. Full text in Research Archive
• Munkhaugen, John; Atar, Dan & Prescott, Eva (2026). Beta-Blockers after Myocardial Infarction. Reply. New England Journal of Medicine. ISSN 0028-4793. 394(8), p. 825–825. doi: 10.1056/nejmc2518019. Full text in Research Archive
• Munkhaugen, John; Bakken, Arnhild; Kristiansen, Anna Meta Dyrvig; Edvardsen, Thor; Wiseth, Rune & Steigen, Terje [Show all 12 contributors for this article] (2026). Sekundærforebygging med betablokkere etter hjerteinfarkt. 146. doi: 10.4045/tidsskr.25.0735. Full text in Research Archive
• Munkhaugen, John (2025). Skal vi fortsatt gi betablokker etter hjerteinfarkt? Hjerteforum. ISSN 0802-1465. 38(4), p. 57–59. doi: https:/indd.adobe.com/view/98ace418-b1fc-430f-a093-651296c8f47e. Full text in Research Archive
• Sverre, Elise Christine Bjørkholen & Munkhaugen, John (2025). Hvordan kan vi hjelpe hjertepasienten med livsstilsendringer i 2024? Hjerteforum. ISSN 0802-1465. 38(1), p. 108–112. Full text in Research Archive Show summary

  Introduksjon «Sagt blir ikke hørt, hørt blir ikke forstått, forstått er ikke avtalt, avtalt blir ikke anvendt, anvendt blir overhodet ikke opprettholdt», skrev den østeriske atferdsbiologen Konrad Lorenz (1903-1969). Livsstil er knyttet til mer eller mindre bevisste personlige preferanser og valg, men påvirkes også i høy grad av omgivelsene. Dette er av grunnene til at pårørende bør delta i forebyggende konsultasjoner. Nevrobiologiske endringer i hjernen som inntrer når bl.a. røyking og fedme har vedvart over tid, medfører at flere livsstilsfaktorer også defineres som en avhengigheter. Til tross for stort kunnskapsgrunnlag og klasse 1 anbefalinger for å identifisere og endre livsstils-risikofaktorer (tobakk, fysisk aktivitet, kosthold og fedme), så er det mindre klart hvordan man skal å gjennomføre disse endringene hos hjertepasientene vi møter i klinisk praksis. Foredraget gir en oversikt over utvalgte livsstilsintervensjoner med dokumenterte vedvarende effekter på livsstilsfaktorer og/eller kardiovaskulære endepunkter, som kan være gjennomførbare i klinisk praksis i Norge i 2024. Kort nevnes også lovende intervensjoner som trolig vil kunne få en sentral plass i årene som kommer. https://www.legeforeningen.no/contentassets/74b22fdc557a487cb0518a33a35265f2/10-norsk-cardiologisk-hostmote-hf-1-2025.pdf

• Pacheco, André Pekkola; Dammen, Toril; Munkhaugen, John; Papageorgiou, Constantinos; Kvaerner, Kari Jorunn & Støme, Linn Nathalie (2025). Potential benefits of group cognitive-behavioural therapy for insomnia in patients with coronary heart disease versus usual care: an early economic evaluation. Full text in Research Archive Show summary

  Purpose To simulate the potential socioeconomic savings of integrating group cognitive-behavioural therapy for insomnia (gCBT-I) into cardiac outpatient care for patients with CHD compared with usual care, focusing on potential savings related to possible effects on (1) revascularizations and hospitalizations due to a recurrent CHD event; and (2) effects on sick leave. Methods Representative data on healthcare consumption and sick leave rates collected from the NORwegian CORonary (NORCOR) cohort study (n=1127). Costs of productivity loss were drawn from public sources and calculated using a conservative human capital approach. Estimates of therapeutic effectiveness in conveying insomnia remission by CBT-I were informed by results from randomized trials and meta-analyses. The comparator conditions in this early health technology assessment were weekly sessions of group cognitive-behavioural therapy for insomnia over five weeks versus usual care in 100 hypothetical outpatients with coronary heart disease and insomnia. Results Rates of healthcare consumption and sick leave were higher in outpatients with CHD and insomnia compared to those without insomnia. Our model indicated that treating 100 patients with gCBT-I would cost €2,406. If patients treated with gCBT-I show similar rates of recurrent revascularizations and hospitalizations as those without insomnia, there is a maximum potential saving of €117,221 per 100 patients tied to healthcare consumption. Similarly, the maximum potential savings related to reduced productivity loss from sick leave range from €53,244 to €692,172. Conclusions Treating insomnia among outpatients with CHD has the potential for substantial reduction of socioeconomic costs related to healthcare consumption and sick leave. Implementation into routine outpatient care seems relevant but randomized controlled trials investigating the effects of gCBT-I in this population are warranted.

• Pleym, Karin; Sverre, Elise Christine Bjørkholen; Weedon-Fekjaer, Harald; kahlon, Mohpal Singh; Stugaard, Marie & Husebye, Einar [Show all 9 contributors for this article] (2025). Motivational smoking cessation counselling with proactive referral to community-based follow-up after hospitalisation for vascular disease: a pragmatic, randomised trial. Full text in Research Archive Show summary

  Purpose: To evaluate the effect of an intervention consisting of one session of in-hospital motivational interviewing smoking cessation counselling combined with proactive referral to follow-up in a community-based cessation program on continuous smoking abstinence rates at six and twelve months. Methods: We conducted a multi-centre pragmatic, randomised, open, blinded endpoint (PROBE) intervention trial at three secondary care hospitals. We included patients with established atherosclerotic vascular disease smoking ≥ 1 cigarette daily prior to unplanned or elective hospitalisation. Participants were randomised 1:1 to (i) brief advice, a leaflet with contact information for a community-based cessation program, and discharge information to their general practitioner (control), or (ii) identical interventions as (i), plus a single in-hospital motivational counselling session that included referral to the cessation program, and a proactive telephone invitation from the community-based centre staff within two weeks post-discharge (intervention). Results: Among 332 screened patients, 110 were excluded, and 221 (67%) were randomised. The mean age was 65 years (SD 10, range of 37 to 85 years), with 40% being women. In intention-to-treat analyses (excluding 7 deaths and one consent withdrawal), 50% (53/107) in the intervention group and 25% (26/106) in the control group reported smoking abstinence at six months (adjusted odds ratio [OR] 3.1, 95% confidence interval [CI] 1.7-5.6, p<0.001), biochemically confirmed in 89% (70/79) with carbon monoxide measurements. The number needed to treat to achieve abstinence in one additional patient who smoke was 4 (95% CI 3 to 8). The intervention increased participation in the cessation programme (41% vs. 11%) and increased the number of participants that obtained coupons for free cessation medications (36% vs. 11%). At 12 months, abstinence was reported by 46% of the intervention group and 28% of the control group (Figure 1). After a median follow-up of 18 months (range 12–24), recurrent vascular events occurred in 26% (28/109) of the intervention group and 34% (38/111) of the control group. Conclusions: One session of in-hospital motivational counselling combined with proactive referral to follow-up in a community-based cessation program nearly doubled long-term smoking abstinence rates in patients with atherosclerotic vascular disease. Moreover, early data suggests that the intervention might translate into a numeric reduction in recurrent cardiovascular events and death during a follow-up period of 1-2 years.

• Getz, Vilde; Pleym, Karin; Dammen, Toril; Tonstad, Serena; Husebye, Einar & Sverre, Elise Christine Bjørkholen [Show all 9 contributors for this article] (2025). Clinical and psychosocial predictors of long-term smoking cessation in patients with atherosclerotic vascular disease: a pre-specified analysis of two randomised trials. Full text in Research Archive Show summary

  Purpose: To identify clinical and psychosocial factors associated with long-term smoking cessation in patients admitted for cardiovascular disease enrolled in a smoking cessation intervention study. Methods: A pre-specified analysis of two randomised intervention trials conducted at three secondary care hospitals. Patients with atherosclerotic vascular disease who smoked ≥1 cigarette daily before admission for an elective or unplanned event were randomised 1:1 to i.) motivational counselling and proactive referral to a municipal cessation program (intervention) or ii.) brief advice and a leaflet with contact information to the cessation program (control). Data were collected from hospital medical records, a questionnaire, and telephone interviews. Logistic regression analyses were applied to explore associations between clinical and psychosocial factors at the time of randomisation and smoking status at the 12 months follow-up. Results: Among 280 randomised participants, two withdrew consent, 16 died, and 262 completed the 12-month follow-up. Mean age was 65 (SD 10) years, 39% were women, 78% had low education, 37% were hospitalised due to coronary artery disease, 17% due to peripheral artery disease, and 14% due to cerebrovascular disease. At 12 months, 88 out of 262 participants reported sustained smoking cessation. In analyses adjusted for age and site, increasing motivation (OR 1.35/1 point on a 0 to 10 Likert scale) and being in the preparation stage (OR 2.46) were significantly associated with a higher likelihood of sustained smoking cessation. Comorbidity (odds ratio (OR) 0.64/1.0 point on the Charlson score), living alone (OR 0.48) and shorter sleep duration (OR 0.76/hour) were significantly inversely associated with smoking cessation (Table, model 1). Further adjustment for group allocation (intervention vs. control) had only minor impact on the effect estimates (Table, model 2). Conclusions: Higher motivation and readiness for smoking cessation increased the likelihood of abstinence in patients with atherosclerotic vascular disease who attended a cessation intervention, whereas living alone, comorbidity and shorter sleep duration were inversely associated with smoking cessation. These factors may be targets for future interventions tailored to vulnerable subgroups of patients in need of a more tailored approach.

• Uduma, Amara Synøve; Sverre, Elise Christine Bjørkholen; Munkhaugen, John; Retterstøl, Kjetil; Bogsrud, Martin Prøven & Holven, Kirsten Bjørklund [Show all 7 contributors for this article] (2025). More musculoskeletal disorders and poor pain management in patients with familial hypercholesterolemia and self-perceived side effects to cholesterol-lowering treatment. Full text in Research Archive Show summary

  Purpose: To compare clinical and psychosocial characteristics of patients with FH, with and without self-perceived side effects to cholesterol-lowering treatment. Methods: A group of 929 adult outpatients with confirmed genetic FH from a regional treatment register in Norway were invited to an observational study. The participants completed a digital questionnaire covering self-perceived side effects (any symptoms), use of cholesterol-lowering medications, musculoskeletal disorders or rheumatic diseases, and muscular symptoms and pain treatment. We collected data on FH diagnosis, comorbidities, and biomarkers in blood from the last consultation listed in the treatment register. Results: Mean age was 52 (SD 15) years, and 57% were women. Thirty-eight (15%) out of 255 participants reported self-perceived side effects to cholesterol-lowering treatment. Patients with self-perceived side effects were more frequently living alone (26% vs. 12%, p=0.025) and had slightly higher LDL-C than those without side effects, whereas no differences in creatine kinase or alanine transaminase were observed. Patients with self-perceived side effects had a higher frequency of musculoskeletal disorders or rheumatic diseases (58% vs. 37%, p<0.001) than those with no side effects (Table 1). They also reported more muscle symptoms the last month in general, and specifically from the hips, thighs, calves, shoulders, and neck. Median pain intensity the last 24-hours was significantly higher (3 vs. 1 on a 0 [no] to 10 [worst imaginable] numeric rating scale, p<0.001) in patients with side effects, and 58% currently used no pain medication (Table 2). Conclusions: Patients with FH and self-perceived side effects frequently have musculoskeletal disorders or rheumatic diseases and clinically significant pain without treatment. Our study suggests that a considerable proportion of patients misattribute muscle symptoms and pain to their cholesterol-lowering medications. Future work should focus on musculoskeletal- and rheumatic conditions as an alternative explanation for self-perceived side effects to cholesterol-lowering medication.

• Holtrop, Joris; Gynnild, Mari Nordbø; Dammen, Toril; Dalen, Håvard; Hageman, Steven HJ & Visseren, Frank [Show all 9 contributors for this article] (2025). Integration of psychological risk modifiers on-top the SMART2-risk score for estimation of recurrent cardiovascular events in patients with atherosclerotic cardiovascular disease. European Journal of Preventive Cardiology (EJPC). ISSN 2047-4873. doi: 10.1093/eurjpc/zwaf236.210. Full text in Research Archive
• Holtrop, Joris; Gynnild, Mari Nordbø; Dalen, Håvard; Dammen, Toril; McEvoy, John William & Hageman, Steven H. J. [Show all 9 contributors for this article] (2025). Integration of guideline-recommended psychosocial risk modifiers on-top the SMART2-risk score for estimation of recurrent cardiovascular events in patients with established cardiovascular disease. Full text in Research Archive
• Engebretsen, Ingrid; Ødegaard, Kristina Malene; Halvorsen, Sigrun; Bugge, Christoffer; Kristiansen, Ivar Sønbø & Støvring, Henrik [Show all 7 contributors for this article] (2024). High discontinuation rate of statins among PCSK9i users: a nationwide study from 2015-2023. European Heart Journal, Supplement. ISSN 1520-765X. 45. doi: 10.1093/eurheartj/ehae666.2863. Full text in Research Archive
• Engebretsen, Ingrid; Ødegaard, Kristina Malene; Halvorsen, Sigrun; Bugge, Christoffer; Kristiansen, Ivar Sønbø & Støvring, Henrik [Show all 7 contributors for this article] (2024). High discontinuation rate of statins among PCSK9i users:A nationwide study from 2015-2023. Full text in Research Archive
• Atar, Dan; Munkhaugen, John & Sverre, Elise Christine Bjørkholen (2024). Statin discontinuation: How can we improve on the multiple pathways that contribute to suboptimal statin adherence? Kardiologia Polska. ISSN 0022-9032. 82(9), p. 828–830. doi: 10.33963/v.phj.102335. Full text in Research Archive
• Pacheco, André Pekkola; Munkhaugen, John; Hrubos-Strøm, Harald; Klungsøyr, Ole; Kværner, Kari Jorunn & Støme, Linn Nathalie [Show all 8 contributors for this article] (2024). Cognitive behavioural therapy for insomnia (CBT-I) in patients with coronary heart disease: a protocol for a randomized controlled trial with six months follow-up. European Journal of Preventive Cardiology (EJPC). ISSN 2047-4873. 31(Supplement_1). doi: 10.1093/eurjpc/zwae175.434. Full text in Research Archive
• Pivoriunas, Jonas; Engebretsen, Ingrid; Vethe, Nils Tore; Kristiansen, Oscar; Dammen, Toril & Fagerland, Morten Wang [Show all 9 contributors for this article] (2024). Statin adherence in coronary outpatients: a novel direct method compared with pharmacy registry data. European Journal of Preventive Cardiology (EJPC). ISSN 2047-4873. 31(Supplement_1). doi: 10.1093/eurjpc/zwae175.063. Full text in Research Archive
• Pivoriunas, Jonas; Engebretsen, Ingrid; Vethe, Nils Tore; Kristiansen, Oscar; Dammen, Toril & Husebye, Einar [Show all 9 contributors for this article] (2024). Statin adherence in coronary outpatients: the relationship between a novel direct method and pharmacy registry data. Full text in Research Archive Show summary

  Introduction An optimal method to assess adherence to statin therapy is needed. We developed a novel blood test to determine adherence to atorvastatin and simvastatin therapy. The relationship between statin adherence measured in blood and long-term adherence is yet to be defined. Purpose To compare statin adherence measured by single blood test with pharmacy registry data: i. the three months period prior to the blood test, and ii. from six months before until six months after the blood test. Methods In a cross-sectional study including 451 patients using either atorvastatin or simvastatin, a spot blood sample was collected median 18 months after a coronary heart disease event. Participants were unaware of the forthcoming statin analyses. Adherence (0 or 1 omitted dose) and reduced adherence, defined as ≥2 consecutively omitted doses of atorvastatin and simvastatin was determined by drug concentration measurements using liquid chromatography - tandem mass spectrometry. Study data was linked to the pharmacy registry. Indirect reduced adherence was defined as statin treatment gap exceeding 90 days. Results Thirty-nine (9%) out of 412 patients had reduced adherence to statins, determined by the novel blood test. Among patients classified as adherent by the blood test, only three (0.7%) had a treatment gap exceeding 90 days during the preceding three months. Correspondingly, of 39 patients with reduced adherence by the blood test, 11 (28%) had treatment gaps exceeding 90 days. The positive agreement between the methods was 96% and the negative agreement 42%. Among patients classified as adherent by the blood test, 21 (5%) had treatment gaps exceeding 90 days from six months before until six months after the blood test. Correspondingly, of 39 patients with reduced adherence by the blood test, 15 (39%) had at least one treatment gap exceeding 90 days. The positive agreement between measurements was 95% and the negative agreement 40%. Conclusions Among coronary patients classified as adherent by the statin blood test, registry data only identified three patients (0.7%) with a treatment gap exceeding 90 days in the three months prior to the blood test. The novel blood test emerges as a promising tool to identify patients adherent to statins, and thus may improve lipid management in clinical practice.

• Holtrop, Joris; Gynnild, Mari Nordbø; Munkhaugen, John; Dalen, Håvard; Lim, Carl-Emil & Ueda, Peter [Show all 14 contributors for this article] (2024). Estimation of individual lifetime cardiovascular disease risk and treatment benefit in patients with established atherosclerotic cardiovascular disease: the updated SMART-REACH2 model. European Heart Journal, Supplement. ISSN 1520-765X. 45(1). doi: 10.1093/eurheartj/ehae666.2695. Full text in Research Archive
• Lauritzen, Trine; Munkhaugen, John; Lindahl, Sofia Helena; Bergan, Stein; Peersen, Kari & Husebye, Einar [Show all 7 contributors for this article] (2024). The effect of atorvastatin on mevalonate levels in blood plasma in patients with coronary heart disease and muscle side effects. European Journal of Preventive Cardiology (EJPC). ISSN 2047-4873. 31(Supplement_1). doi: 10.1093/eurjpc/zwae175.357. Full text in Research Archive
• Lia-Engene, Anja; Pleym, Karin & Munkhaugen, John (2024). Kardiologisk forskning i Vestre Viken – sykepleieren er viktig. Hjerteposten : fagtidsskrift for NSFs landsgruppe av kardiologiske sykepleiere. ISSN 1891-2532. 3, p. 18–22. Full text in Research Archive Show summary

  INNLEDNING Sykepleierens profesjon har i løpet av 170 år utviklet seg fra klosterlivets religiøse kall til en vitenskapelig, evidensbasert utdannelse, men det er først de siste 50 årene at sykepleierens rolle innen forskning virkelig har tatt form. Florence Nightingale revolusjonerte sykepleien og dens status på 1850 tallet ved å anvende systematiske observasjoner og analyse av data for å identifisere sykdommer og gi riktig behandling (1). Dette pionerarbeidet la grunnlaget for moderne sykepleie, og Nightingale videreførte sin nye innsikt i etableringen av en sykepleierutdanning som vektla kritisk tenkning og metodisk analyse. Sykepleieryrket har siden den gangen utviklet seg fra en tradisjonsbundet praksis til en akademisk og vitenskapelig disiplin, hvor sykepleieforskningen er i stor fremdrift. Det er utvilsomt fortsatt utfordringer knyttet til integrasjonen av forskningsarbeid i pasientbehandling, samtidig er klinikknær forskning i positiv vekst, og her er sykepleieren vesentlig. DISKUSJON – HVA ER FORDELENE MED Å BRUKE SYKEPLEIERE? I NORCOR gruppen er sykepleiere sentrale i alle faser av studiene. Denne tverrfagligheten i hele prosessen sikrer involvering fra den faggruppen som senere skal implementere og bruke intervensjonen. I utviklingsfasen har vi sett flere fordeler med dette knyttet opp mot valg av design og utforming av innhold. I den omtalte digitale løsningen til aterosklerosepasientene var det av stor betydning å bruke sykepleiere med god kjennskap til forhold som lav helsekommunikasjonsforståelse, søvnvansker, angst og depresjon. Sett med sykepleierøyne kan man identifisere utfordringer på bakgrunn av en klinisk ekspertise man har tilegnet seg ved utstrakt tidsbruk hos pasienten, og dette gir sykepleieren en potent kombinasjon av teoretisk kompetanse og inngående kjennskap til en pasientpopulasjon. Forutsatt solid praktisk erfaring har sykepleiere ofte de beste forutsetninger for å si noe om hva som er realistisk å få til med aktuell pasientgruppe og hvordan en intervensjon kan tilpasses for bruk av sykepleiere i drift. I gjennomføringsfasen av kliniske studier har sykepleiere noe lengre tradisjon for å være aktører. Sykepleiere har et godt grunnlag for å danne relasjonelle forbindelser som gir fortrinn i forbindelse med for eksempel inklusjon av pasienter og retensjon i studier. Sykepleierkompetansen har vært helt nødvendig for gjennomførbarheten og kvaliteten i IT-heart studien hvor inklusjon og oppfølging av sårbare og skrøpelige hjertesviktspasienter er sentralt. Like lang fartstid har ikke doktorgradsstipendiatene, men andelen sykepleiere som tar PhD-utdannelse er økende. Ved å involvere sykepleieren som det primære analyseinstrumentet tilrettelegger man for at profesjonens perspektiver og erfaringer beriker analyseprosessen. Sykepleierens innsikt i pasientsituasjoner og kliniske mønstre gir en kontekstualisering som kan løfte frem viktige nyanser og gi dybde og mening til dataene. Utdanning av sykepleiere i doktorgradsprogram bidrar til at sykepleieren erverver seg vitenskapelig kompetanse og kan se på egen virksomhet med forskningsbriller. Her er det mye upløyd mark, og store muligheter for utvikling. Forskning er den grundigste evalueringen av klinisk praksis, og hovedandelen av helsearbeidere er sykepleiere. Hva er da mer naturlig enn at sykepleiere tar del i forskning? Nedfelt i yrkesetiske retningslinjer for sykepleiere er ikke bare ansvaret for kontinuerlig faglig utvikling og bruk av evidensbasert praksis, men også ansvar for å fremme og delta i forskning. Det er en målsetting at forskning skal være en integrert del av den kliniske behandlingen som pasientene våre mottar. Kardiologisk forskning er en viktig arena for sykepleiere å delta på, og deres bidrag inn i dette arbeidet er av stor betydning for kvaliteten og resultatet.

• Frøjd, Lars Aastebøl; Munkhaugen, John; Papageorgiou, Constantinos; Torbjørn, Moum; Dammen, Toril & Sverre, Elise Christine Bjørkholen (2023). Insomnia was associated with increased risk of recurrent cardiovascular events in coronary heart disease patients. Full text in Research Archive
• Atar, Dan; Bakken, Arnhild & Munkhaugen, John (2023). Achieving the unachievable: How to optimize lipid-lowering therapy in survivors of acute myocardial infarction. Kardiologia Polska. ISSN 0022-9032. 81(4), p. 327–329. doi: 10.33963/KP.a2023.0087. Full text in Research Archive
• Munkhaugen, John (2023). Individualisert risikoreduksjon. 2021 Guidelines in CVD prevention. Hjerteforum. ISSN 0802-1465. 1(36), p. 90–93. Full text in Research Archive
• Munkhaugen, John (2023). Validation of a novel direct method to determine reduced adherence to atorvastatin therapy. Full text in Research Archive
• Lauritzen, Trine; Munkhaugen, John; Peersen, Kari; Kristiansen, Oscar; Sverre, Elise Christine Bjørkholen & Andersen, Anders Mikal [Show all 10 contributors for this article] (2023). Atorvastatin lactone/acid ratios are promising biomarkers for statin dependent muscular side effects in patients with coronary heart disease. Full text in Research Archive
• Munkhaugen, John (2023). Emerging tools in statin treatment for improved cardiovascular disease prevention. Full text in Research Archive
• Engebretsen, Ingrid; Bugge, Christoffer; Husebye, Einar; Stovring, Henrik; Halvorsen, Sigrun & Sverre, Elise Christine Bjørkholen [Show all 7 contributors for this article] (2023). Treatment patterns and adherence to lipid-lowering drugs during 8 years of follow-up after a cardiovascular event. European Heart Journal. ISSN 0195-668X. 44. doi: 10.1093/eurheartj/ehad655.2524. Full text in Research Archive
• Lauritzen, Trine; Munkhaugen, John; Peersen, Kari; Andersen, Anders Mikal; Bergan, Stein & Husebye, Einar [Show all 7 contributors for this article] (2023). Atorvastatin lactonization is associated with statin-dependent muscular side effects in patient with coronary heart disease. Full text in Research Archive
• Sverre, Elise Christine Bjørkholen; Halvorsen, Sigrun; Løchen, Maja-Lisa & Munkhaugen, John (2023). E. Sverre og medarbeidere svarer. Tidsskrift for Den norske legeforening (Tidsskriftet). ISSN 0029-2001. 143(3). doi: 10.4045/tidsskr.23.0062. Full text in Research Archive
• Semb, Anne Grete; Vesterbekk, Elisabeth Kleivhaug; Retterstøl, Kjetil; Atar, Dan; Solberg, Erik E. & Schirmer, Henrik [Show all 11 contributors for this article] (2023). PCSK9-hemmere på blå resept for hvem? Tidsskrift for Den norske legeforening (Tidsskriftet). ISSN 0029-2001. 143(8). doi: 10.4045/tidsskr.23.0191. Full text in Research Archive
• Munkhaugen, John; Kristiansen, Oscar; Pivoriunas, Jonas; Fagerland, Morten; Bergan, Stein & Sverre, Elise Christine Bjørkholen [Show all 8 contributors for this article] (2023). Validation of a novel direct method to determine reduced adherence to atorvastatin therapy. European Journal of Preventive Cardiology (EJPC). ISSN 2047-4873. 30. doi: 10.1093/eurjpc/zwad125.339. Full text in Research Archive
• Lauritzen, Trine; Munkhaugen, John; Peersen, Kari; Kristiansen, Oscar; Sverre, Elise Christine Bjørkholen & Andersen, Anders Mikal [Show all 10 contributors for this article] (2023). Atorvastatin lactone/acid ratios are promising biomarkers for statin dependent muscular side effects in patients with coronary heart disease. European Journal of Preventive Cardiology (EJPC). ISSN 2047-4873. 30. doi: 10.1093/eurjpc/zwad125.340. Full text in Research Archive
• Pivoriunas, Jonas & Munkhaugen, John (2023). Utvalgte høydepunkter innen forebyggende kardiologi. Hjerteforum. ISSN 0802-1465. 36(4), p. 109–110. Full text in Research Archive Show summary

  https://www.legeforeningen.no/contentassets/67f43cb919b141d7bc9d6d6465cd176a/hjerteforum-4-2023.pdf

• Bakken, Arnhild; Atar, Dan; Ruddox, Vidar; Halvorsen, Sigrun & Munkhaugen, John (2023). BETABLOKKERE ETTER HJERTEINFARKT– SKAL DEN FORTSATT GIS? Hjerteposten : fagtidsskrift for NSFs landsgruppe av kardiologiske sykepleiere. ISSN 1891-2532. p. 28–32. Full text in Research Archive Show summary

  Betablokkere har vært standard sekundærforebyggende behandling etter akutt hjerteinfarkt siden 1980-tallet. Siden den gang har diagnostikken og behandlingen av hjerteinfarkt forandret seg betydelig. Om betablokkere fortsatt er nyttig, skal BETAMI-studien gi svar på. Studien startet opp i oktober 2018 og er en av de største ikke-industrisponsede hjertestudiene som er gjennomført i Norge.

• Munkhaugen, John; Papageorgiou, Constantinos; Hagen, Roger; Johnson, Sverre Urnes; Einvik, Gunnar & Dammen, Toril (2023). Editorial: Progress in understanding and treating distress, sleep, and personality in heart and lung disease. Frontiers in Psychology. 14. doi: 10.3389/fpsyg.2023.1323677. Full text in Research Archive
• Engebretsen, Ingrid; Christoffer, Bugge; Husebye, Einar; Støvring, Henrik; Halvorsen, Sigrun & Sverre, Elise Christine Bjørkholen [Show all 7 contributors for this article] (2023). Treatment patterns and adherence to lipid-lowering drugs during 8 years of follow-up after a cardiovascular event. Full text in Research Archive
• Sverre, Elise Christine Bjørkholen; Halvorsen, Sigrun; Løchen, Maja-Lisa & Munkhaugen, John (2022). Persontilpasset hjerte- og karforebygging i nye retningslinjer. 142(17), p. 1–6. doi: 10.4045/tidsskr.22.0508. Full text in Research Archive Show summary

  I de nye europeiske retningslinjene for forebygging av hjerte- og karsykdommer introduseres en trinnvis tiltaksmodell. Livsstilstiltak er basis. Bruk av medikamenter anbefales basert på en risikovurdering der man tar hensyn til pasientens skrøpelighet, komorbiditet og egne preferanser.

• Lauritzen, Trine; Munkhaugen, John; Peersen, Kari; Sverre, Elise Christine Bjørkholen; Kristiansen, Oscar & Jensen, Elena Prunès [Show all 9 contributors for this article] (2022). Clinical and pharmacological characteristics in plasma and mononuclear blood cells in patients with coronary heart disease and low statin tolerance. European Journal of Preventive Cardiology (EJPC). ISSN 2047-4873. 29. doi: 10.1093/eurjpc/zwac056.177. Full text in Research Archive Show summary

  Background Statin-associated muscle symptoms (SAMS) cover a broader range of clinical presentations, with normal or mildly elevated creatine kinase (CK) in blood, and is a prevalent challenge in clinical practice. Our understanding of the pathophysiology of SAMS remains largely unknown. Purpose To gain new knowledge on the molecular effects of atorvastatin in plasma and blood cells in patients with coronary heart disease (CHD) and SAMS, and to identify potential diagnostic biomarkers for statin-dependent SAMS. Methods In 2019, 71 consecutively recruited CHD patients with self-perceived SAMS were randomised to 7-weeks double-blinded treatment with atorvastatin 40 mg/day and placebo in a crossover design. The primary outcome was individual mean difference in muscle symptom intensity between treatment periods, measured weekly with a Visual Analogue Scale (VAS) (0= no to 10=maximal symptoms). Twenty patients were categorised as having statin-dependent SAMS and the remaining as non-SAMS. During trial and post-trial follow-up period, a subgroup of statin-dependent SAMS, who did not tolerate statins (N=7) or only rosuvastatin 5mg/day (N=2) was identified. Atorvastatin metabolites in plasma and peripheral blood mononuclear cells (PBMC) were measured with liquid chromatography tandem mass spectrometry in blood drawn two hours after tablet intake at the last day of the atorvastatin treatment period. Statistical analyses were performed with SPSS. Results Clinical and pharmacological characteristics in patients with low statin-tolerance (N=9) and those without (N=62) are summarised in Figure 1. The reduction in LDL cholesterol (LDL-C) from the placebo period to the atorvastatin period was significantly lower in the group with low statin tolerance, despite confirmed adherence to allocated treatment. The ratio between the sum of all atorvastatin- lactones and acids (SumLactones/SumAcids) was significantly higher in the group with low statin tolerance both in plasma and PBMC analyses compared to those who tolerated statins. The atorvastatin lactone and acid ratio (AL/AA) was borderline significant in both plasma and PBMC. ROC-analyses of these four variables are displayed in Figure 2. Areas under the curves (AUCs) are 0.71 for the sumLactones/sumAcids both in plasma and PBMC, and 0.69 for the AL/AS in plasma and PBMC. There were no significant differences between the groups regarding age, gender or known pharmacogenetic variants (CYP3A and SLCO1B1) or in the differences in creatine kinase (CK) level between the atorvastatin and placebo treatment periods. Conclusions The ratio between atorvastatin lactones and acids in plasma and in mononuclear blood cells is associated with low statin tolerance in patients with CHD. Excess lactone relative to acid metabolites may be involved in the pathophysiology of SAMS. Future studies in muscle tissue may further elucidate the relationship between SAMS and atorvastatin metabolites and other biomarkers in these patients.

• Munkhaugen, John; Kristiansen, Oscar; Sverre, Elise Christine Bjørkholen; Retterstøl, Kjetil & Tonstad, Serena (2022). Statiner gir sjelden bivirkninger. 2. doi: 10.4045/tidsskr.21.0885. Full text in Research Archive
• Munkhaugen, John & Løchen, Maja-Lisa (2022). 2021 ESC Guidelines on Cardiovaskular Disease Prevention in Clinical Practice. Hjerteforum. ISSN 0802-1465. 35(2), p. 28–31. Full text in Research Archive
• Munkhaugen, John (2022). Preventiv behandling. Hjerteforum. ISSN 0802-1465. 35(4), p. 70–72. Full text in Research Archive
• Pleym, Karin; Sverre, Elise Bjerkholen; Weedon-Fekjaer, H; Kahlon, Mohpal Singh; Husebye, Einar & Tonstad, Serena [Show all 8 contributors for this article] (2022). Effect of in-hospital nurse-led smoking cessation intervention for patients with atherosclerotic cardiovascular disease: a randomised pilot study. Full text in Research Archive
• Munkhaugen, John; Kristiansen, Oskar; Sverre, Elise Christine Bjørkholen; Retterstøl, Kjetil & Tonstad, Serena (2022). Statiner gir sjelden bivirkninger. 142(2). doi: 10.4045/tidsskr.21.0885. Full text in Research Archive
• Retterstøl, Kjetil; Munkhaugen, John; Ingul, Charlotte Björk; Grimsmo, Jostein; Kask, Anne & Schirmer, Henrik [Show all 8 contributors for this article] (2021). Lavere behandlingsmål for LDLkolesterol bør innføres. 141(2), p. 1–6. doi: 10.4045/tidsskr.20.0761. Full text in Research Archive
• Johannessen, Tonje Rambøll; Halvorsen, Sigrun; Atar, Dan; Munkhaugen, John; Nore, Anne Kathrine & Wisløff, Torbjørn [Show all 7 contributors for this article] (2021). Cost-minimization analysis of acute myocardial infarction rule-out in low-risk patients: emergency primary care versus hospital. Full text in Research Archive
• Johannessen, Tonje Rambøll; Halvorsen, Sigrun; Atar, Dan; Munkhaugen, John; Nore, Anne Kathrine & Wisløff, Torbjørn [Show all 7 contributors for this article] (2021). Cost-minimisation analysis of acute myocardial infarction rule-out in low-risk patients: primary care emergency setting versus hospital setting. Full text in Research Archive
• Peersen, Kari; Sverre, Elise Christine Bjørkholen; Kristiansen, Oscar; Fagerland, Morten; Gullestad, Lars & Otterstad, Jan Erik [Show all 8 contributors for this article] (2020). Clinical factors, psychological factors and beliefs about statin use in patients with coronary heart disease and self-perceived muscle side-effects. European Heart Journal. ISSN 0195-668X. 41(Supplement_2). doi: 10.1093/ehjci/ehaa946.3337. Full text in Research Archive Show summary

  Abstract Background Statin associated muscle symptoms (SAMS) are commonly reported and constitute the principal reason for statin non-adherence and/or discontinuation. Understanding the determinants of SAMS may enhance the clinical management and form the basis of interventions. The association between psychological distress and the beliefs about statin treatment and SAMS have previously not been investigated under randomized, controlled conditions. Purpose To compare clinical and psychological factors among coronary patients with confirmed SAMS and non-SAMS. Methods This pre-planned exploratory study included 71 consecutively recruited patients with self-perceived SAMS enrolled in the MUscle Side-Effect of atorvastatin in coronary patients (MUSE) randomized double-blinded crossover trial. Muscle symptom (pain, weakness, tenderness, stiffness and/or cramps) intensity was registered weekly in a patient diary using a 0 (no symptoms) to 10 (worst imaginable) cm visual-analogue scale (VAS). Confirmed SAMS was predefined as a 25% higher individual mean VAS-scores during 7-weeks treatment with atorvastatin 40 mg/day versus 7-weeks treatment with placebo, and ≥1cm absolute difference. Clinical factors (10 variables), psychological factors (5 variables) and beliefs about medicine (3 variables) were obtained from a questionnaire and a clinical examination at study start. Results Mean age was 63 (SD 9.5) years, 32% were women, and each participant had tried average 1.3 (SD 0.6, range 1 to 3) statins prior to study start. In all, 28% (n=20) had confirmed SAMS and 72% (n=51) had non-SAMS. There were no differences in mean VAS score at study start between the groups (mean VAS score 4.5 vs. 4.7, p=0.20). More patients with confirmed SAMS than non-SAMS (25% vs. 6%, p&lt;0.001) did not use statin treatment at study start, and mean LDL-cholesterol level was borderline higher (2.8 vs. 2.3 mmol/L, p=0.06). Patients with confirmed SAMS had a weaker belief in their statin use compared to patients with non-SAMS (3.1 vs. 3.6, p&lt;0.001) using a 5-category scale from 1 (weak belief) to 5 (strongest belief). There were no differences in the sociodemographic, clinical (pre-existing muscle skeletal disorders, somatic comorbidity, cardiovascular risk factors) or psychological (symptoms of anxiety or depression, type D personality, worry, insomnia) factors explored between patients with confirmed SAMS or with non-SAMS. There were no associations between these factors and increasing VAS scores in continuous analyses among patients with confirmed SAMS and non-SAMS. Conclusions Patients with statin dependent muscle side-effects reported a weaker belief on the necessity to take statins than patients with muscle complaints not caused by the statin. Otherwise, we found no differences in clinical or psychological factors between these populations. The results indicate that these factors do not distinguish patients with and without associated muscle symptoms in clinical practice. Funding Acknowledgement Type of funding source: Public hospital(s). Main funding source(s): Vestfold Hospital Trust, research grant

• Munkhaugen, John; Sverre, Elise Christine Bjørkholen; Kristiansen, Oscar; Fagerland, Morten; Peersen, Kari & Bergan, Stein [Show all 9 contributors for this article] (2020). Drug related metabolites and genetic polymorphisms predict low low-density lipoprotein cholesterol response to atorvastatin treatment in patients with coronary heart disease. European Heart Journal. ISSN 0195-668X. 41(Supplement_2). doi: 10.1093/ehjci/ehaa946.2985. Full text in Research Archive Show summary

  Abstract Background There is considerable individual variation in the low-density lipoprotein cholesterol (LDL-C) reduction at all classes and doses of statins. Knowledge of the determinants of individual variation LDL-C response upon statin treatment may pave the way for personalized and optimized statin treatment. Purpose We aimed to determine clinical and drug related predictors of variability of LDL-C response to atorvastatin 40 mg in patients with coronary heart disease. Methods This is an explorative study among 70 patients enrolled in the MUscle Side-Effects of atorvastatin in coronary patients (MUSE) randomized double blinded cross-over trial. Absolute and relative changes in LDL-C after 7 weeks treatment with atorvastatin 40 mg/day and 7 weeks treatment with placebo, were calculated for each patient. Linear regression analyses were applied to investigate the association between clinical (10 variables) and drug related (atorvastatin and/or metabolites, 18 variables) predictors and changes in LDL-C. Results Adherence to allocated treatment was high as confirmed by atorvastatin levels in blood and a mean proportion of days covered of 99% (range 91–100%). Mean reduction in LDL-C on atorvastatin treatment (LDL-C atorvastatin – LDL-C placebo) was 2.1 (SD 0.7, range 0.3 to 3.4) mmol/L. Mean percentage reduction in LDL-C was 51.1 (SD 11.2, range 29 to 60)%, and 37 patients (52.9%) had &lt;50% LDL-C reduction. Genetic polymorphisms in SLCO1B1 or CYP3A (B 0.06, 95% CI 0.01 to 0.12, p=0.026), increasing number of coronary events (B 0.06, 95% CI 0.002 to 0.10, p=0.005), increasing trough concentration of 4-OH atorvastatin lactone (B 0.05, 95% CI 0.01 to 0.08, p=0.005) and increasing trough concentration of 4-OH atorvastatin acid (B 0.05, 95% CI 0.01 to 0.08, p=0.006) were the significant determinants of lower relative change (%) in LDL-C, in adjusted analyses. Age, gender, somatic comorbidity, cardiovascular risk factors, statin dependent muscle side-effects and other clinical and drug related determinants were not associated with changes in LDL-C. Conclusions There is considerable inter-individual variation in the LDL-C response upon treatment with atorvastatin despite confirmed high statin adherence. This is the first study reporting that genetic polymorphisms involved in the metabolism of statins and atorvastatin metabolites predict lower LDL-C response. Funding Acknowledgement Type of funding source: Public Institution(s). Main funding source(s): National Association of Health, Grant/Award

• Munkhaugen, John; Peersen, Kari; Sverre, Elise; Gjertsen, Erik; Gullestad, Lars & Dammen, Toril [Show all 8 contributors for this article] (2018). Oppfølging etter hjerteinfarkt - er den god nok? 138(5), p. 434–437. doi: 10.4045/tidsskr.17.1050. Full text in Research Archive
• Otterstad, Jan Erik; Munkhaugen, John; Ruddox, Vidar; Haffner, Johan F W; Thelle, Dag Steinar & Thelle, Dag S (2016). Utdatert kunnskapsgrunnlag for betablokkere etter hjerteinfarkt? 136(7), p. 624–627. doi: 10.4045/tidsskr.15.0884. Full text in Research Archive
• Munkhaugen, John & Vikse, BE (2009). New aspects of pre-eclampsia: lessons for the nephrologist. Nephrology, Dialysis and Transplantation. ISSN 0931-0509. 24(10), p. 2964–2967. doi: 10.1093/ndt/gfp341. Full text in Research Archive
• Munkhaugen, John (2007). Blood pressure in normal weight adolescents; reference values from The Young-HUNT 1 study in Norway. Full text in Research Archive

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