Henrik Schirmer

• Stenhede, Elias; Orstad, Eivind Bjørkan; Omland, Torbjørn; Schirmer, Henrik & Ranjbar, Arian (2026). Associations between echocardiographic traits and artificial intelligence-enabled electrocardiography predictions of heart failure. The European Heart Journal – Digital Health (EHJ-DH). 7(8). doi: 10.1093/ehjdh/ztag141. Full text in Research Archive
• Rösner, Assami; Kjønås, Didrik; Sandberg, Marie Leiros; Dalen, Håvard & Schirmer, Henrik (2026). Can Resting Segmental Strain Identify Obstructive Coronary Artery Disease in Chronic Coronary Syndrome Patients Referred to Coronary Artery Bypass Grafting? Cardiology. ISSN 0008-6312. p. 1–12. doi: 10.1159/000553322. Full text in Research Archive Show summary

  Introduction: Noninvasive identification of patients with chronic coronary syndrome (CCS) with obstructive coronary artery disease (CAD) remains a clinical challenge. Strain imaging enables detection of subtle myocardial dysfunction at rest and may serve as a sensitive marker of multivessel or left main CAD. This study aimed to assess whether segmental systolic strain at rest can identify patients with obstructive CAD referred for coronary artery bypass grafting (CABG) and to compare diagnostic performance of tissue Doppler imaging strain with two-dimensional speckle-tracking echocardiography in a retrospective analysis of a selected CABG-referred cohort. Methods: This retrospective study included 61 patients with CCS and obstructive CAD referred for CABG and 61 age- and sex-matched healthy controls from the population-based Nord-Trøndelag Health Study. All participants underwent echocardiography with both tissue Doppler and speckle-tracking strain analysis. The number of hypokinetic segments within one heart was counted, determined at different segmental peak longitudinal strain thresholds of −8% to −16%. The area under curve (AUC) using receiver operating characteristic analysis was used to evaluate diagnostic performance. Late gadolinium enhancement (LGE) cardiac magnetic resonance imaging (MRI) was used to assess myocardial scarring. Results: LGE MRI confirmed that 78% of patients had no visible myocardial scar and that overall scar burden was low (2.8%). At a hypokinetic strain threshold of −8%, tissue Doppler strain demonstrated excellent diagnostic accuracy for identifying myocardial dysfunction in CABG-referred patients (AUC 0.95, 95% confidence interval [CI]: 0.91–1.00), performing at least as well as speckle-tracking strain (AUC: 0.79, 95% CI: 0.70–0.87). Tissue Doppler strain identified obstructive CAD with 95% sensitivity and 86% specificity. Comparable AUCs were found in a subgroup of 20 patients without coronary occlusion or myocardial scarring, indicating that regional hypokinesia was equally detectable in patients with normal EF and no LGE-defined scars. Conclusion: Segmental strain imaging at rest – by both tissue Doppler and speckle tracking – can detect subclinical regional dysfunction in CABG-referred patients with obstructive CAD, even in patients with preserved global left ventricular function and no evidence of myocardial scarring. Tissue Doppler strain showed at least as high diagnostic accuracy as speckle-tracking strain. These findings underscore the clinical potential of resting segmental strain analysis as a sensitive, noninvasive tool for identifying obstructive CAD in this selected CABG-referred population.

• Stenhede, Elias; Ravn, Jesper; Schirmer, Henrik & Ranjbar, Arian (2026). Heart failure detection in electrocardiograms using Artificial Intelligence and pragmatic labelling. npj Digital Medicine. doi: 10.1038/s41746-026-02774-4. Full text in Research Archive Show summary

  The diagnosis of heart failure (HF) is resource-intensive, leading to severe underdiagnosis. This study proposes the use of a deep learning model to detect HF solely from electrocardiograms. HF has limited validity in diagnosis codes, lowering the viability of direct application of supervised learning. However, validating the codes with measured levels of circulating N-terminal proB-type natriuretic peptide (NT-proBNP) during training mitigates the impact of label noise. We developed and prospectively validated a neural network for HF detection, using a development cohort of 25,300 patients and an independent test cohort of 43,727 patients. The model achieved an AUC of 0.86 (95% CI 0.847–0.864) for hospital-diagnosed HF, which increased to 0.91 (95% CI 0.900–0.913) with age-adjusted NT-proBNP thresholds and 0.96 (95% CI 0.951–0.963) with stricter limits of 125 and 1000 ng/L. The model was externally validated using the MIMIC-IV cohort of 161,352 patients, yielding AUC values of 0.87 (95% CI 0.861–0.871), 0.90 (95% CI 0.895–0.908), and 0.96 (95% CI 0.950–0.964) with the same labelling strategies. Model predictions were further validated using echocardiographic assessments of diastolic function grade and the H2FPEF score, demonstrating that the model accurately captures both diastolic and systolic function. The model has been released as open source.

• 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.

• Azulay, Naomi; Singstad, Bjørn-Jostein; Schirmer, Henrik; Løchen, Maja-Lisa; Olsen, Roy Bjørkholt & Jenssen, Trond [Show all 10 contributors for this article] (2026). Exploring hemodynamic measurements from the Tromsø Study for prediction of cardiovascular disease using traditional statistical models and machine learning approaches. Scientific Reports. doi: 10.1038/s41598-026-57003-5. Full text in Research Archive Show summary

  Abstract In Norway, NORRISK2 is the government-recommended risk model for predicting an individual’s 10-year probability of getting cardiovascular disease (CVD). This study aims to investigate the potential for improvement of CVD prediction by using hemodynamic measurements from a non-invasive beat-to-beat blood pressure monitor, taken as part of pain sensitivity assessment with the cold-pressor test (CPT) during the Tromsø6 Study (2007–2008). Using 6694 recordings, ultra-short-term pulse rate variability (PRV) and baroreflex sensitivity (BRS) obtained during the CPT were added as additional variables into the existing NORRISK2 survival model (extended model). In addition, the time-series data was used in a machine learning (ML) model without the NORRISK2 background variables. Both models were compared to a recalibration of the original NORRISK2 model. The predictions from the recalibrated NORRISK2 model and the ML model were then combined with logistic regression. The statistical models performed similarly on the test set, with an area under the receiver operating characteristic (AUROC) of 0.8 (95% CI: 0.71–0.86), 0.79 (0.71–0.85) and 0.77 (0.69–0.84) (original, recalibrated and extended NORRISK2, respectively). The ML model using only hemodynamic measurements obtained a test set AUROC of 0.73 (0.67–0.80). Combining the NORRISK2 and ML model did not increase the AUROC. Adding ultra-short-term PRV and BRS derived from Tromsø6 did not improve the prediction of the NORRISK2 model either. Although with lower accuracy, the beat-to-beat time series of hemodynamic variables from a CPT had a significant (p < 0.01) ability to predict future CVD without any other person-specific data.

• Vijayakumar, Arya Panthalanickal; Wilsgaard, Tom; Schirmer, Henrik; Benavente, Ernest Diez; Es, René van & Leur, Rutger R. van de [Show all 11 contributors for this article] (2026). Electrocardiogram derived heart age models agreement, accuracy and predictive ability in the Tromsø study. npj Aging. 12(1). doi: 10.1038/s41514-026-00344-2. Full text in Research Archive
• Frigaard, Christine; Ofstad, Eirik Hugaas; Delor, Julia Menichetti; Schirmer, Henrik; Bjørnstad, Herman & Simonsen, Tone Breines [Show all 8 contributors for this article] (2026). Optimised heart failure medication in hospital-to-home transitions: An adherence burden for patients? Patient Education and Counseling. ISSN 0738-3991. 149. doi: 10.1016/j.pec.2026.109655. Full text in Research Archive Show summary

  Objectives When patients are hospitalised for heart failure (HF), doctors review and optimise their pharmacotherapy at subsequent care transitions. Studies show that patients, many of whom are old and frail, have adherence rates of only 40%-60%. Few communication studies have examined the burden of optimisation on patients as their regimens evolve. Focusing on prescription changes over multiple care transitions, we aimed to: (1) identify how many changes patients received, (2) characterise the support provided in discharge letters, and (3) assess patients’ implementation of changes at home. Methods We conducted an exploratory, observational cohort study with prospective longitudinal data collection. We recruited 23 older HF patients in Norway, collecting observational data (medical records, discharge letters, interviews, photographs) from their hospital visits (admission, discharge), general practitioner visit, and their homes. We inductively developed a systematic analytical procedure to identify prescription changes and to assess the quality of doctors’ written information about patients’ medication management at home. Results Doctors made a median of six prescription changes per patient (range 2–19) over a median timespan of 25 days, usually leading to more medications. Of the discharge letters patients received, 26% provided clear instructions about all changes and explanations of the benefit. While all patients reported adherence, home visits revealed 17% had discrepancies indicating non-adherence, and 61% dispensed medications from original pharmacy packaging with outdated dosing instructions. Conclusions To adhere to their optimised pharmacotherapy, HF patients needed to implement many incremental changes. Doctors' discharge letters were often unclear or lacked information about the changes. Practice implications To enhance patients’ ability to adhere to treatment, clinicians may consider: (i) improving the quality of discharge letters, including clarifying medication labels (ii) providing updated instructions for old medication packages, (iii) normalising and providing safety-net support for non-adherence to HF regimens. Further research is needed to test these actions.

• 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.

• Støyten, Martin; Knutsen, Tore; Thune, Inger; Stikbakke, Einar; Wilsgaard, Tom & Eggen, Anne Elise [Show all 10 contributors for this article] (2026). Cardiac Function and Prostate Cancer Risk and Prognosis: The PROCA-Life Study. Clinical Genitourinary Cancer. ISSN 1558-7673. 24(3). doi: 10.1016/j.clgc.2026.102508. Full text in Research Archive Show summary

  Background and Objective Prostate cancer (PCa) risk and the total cardiovascular disease (CVD) burden increases with age. The main objective was to evaluate the interplay between cardiac function and PCa risk and prognosis. Methods In the population-based cohort Prostate Cancer Study throughout life (PROCA-life), 2514 men participating in the Tromsø Study (1994-2016) had echocardiographic examinations. Overall, 235 were diagnosed with PCa during follow-up. Cox proportional hazard models were used to study associations between prediagnostic cardiac function and PCa risk and mortality. Results Mean time from echocardiography to PCa was 9.9 years for men with high risk/metastatic PCa, and the 10-year survival rate was 78.3 % among high risk/metastatic PCa. Men aged > 60.3 years at study entry with mitral peak E deceleration time (DT) < 140 ms or DT > 220 ms had a 1.66-3.37 times higher probability of high risk/metastatic PCa compared with men with normal DT (140-220 ms). Among men who developed PCa, low or high DT was associated with higher overall mortality compared to men with normal DT (HR 3.35, 95% CI, 1.35-8.33 and HR 2.00, 95% CI, 1.28-3.14, respectively). DT > 220 ms was associated with 2 times higher PCa-specific mortality (HR 2.09, 95% CI, 1.11-3.94). Conclusions and Clinical Implications Prediagnostic diastolic dysfunction may be associated with an increased risk of high risk/metastatic PCa, as well as higher overall mortality and PCa-specific mortality. These results support that cardiovascular follow-up among men with PCa is important.

• Rösner, Assami; Kornev, Mikhail; Hatice, Akay Caglayan; Malyutina, Sofia; Ryabikov, Andrew & Kudryavtsev, Alexander Valerievich [Show all 7 contributors for this article] (2025). Cardiac Systolic and Diastolic Function in Relation to Cardiovascular Risk Factors: Comparing Strain Imaging in Russian and Norwegian Populations: Heart-to-Heart—Norwegian-Russian Multilevel Educational Collaboration in Cardiovascular Disease Epidemiology. CJC Open. doi: 10.1016/j.cjco.2025.11.010. Full text in Research Archive Show summary

  Background Rates of cardiovascular morbidity and mortality are high in Russia. We compared conventional echocardiography and strain-based measures between Russian and Norwegian populations, and examined associations between hemodynamic and risk factors. Methods Echocardiography was performed in 1192 participants from Arkhangelsk or Novosibirsk (Russia), and 917 from Tromsø (Norway), aged 40–69 years. “Normal” was defined as the absence of hypertension or cardiovascular disease. Conventional parameters and 2-dimensional speckle-tracking longitudinal strain and strain rate (systolic, early and late diastolic) were analyzed. Participants were categorized into 4 groups: normal, controlled hypertension, hypertensive blood pressure, and cardiac disease. Between-population comparisons used linear regression adjusted for prespecified covariates: age, sex, height, body mass index, blood pressure, heart rate, atrial fibrillation, smoking, pulmonary hypertension, and serum biomarkers (lipids, triglycerides, creatinine, high-sensitivity C-reactive protein, and HbA1c). Results Russians showed a tendency toward lower longitudinal systolic functional indices, most evident in the normotensive group; however, these differences became nonsignificant after adjustment for hemodynamic and clinical covariates. Russians had lower stroke volume, higher heart rate, larger left atrial volume, and higher E/A ratio, indicating more impaired relaxation and elevated filling pressures. Groupwise comparisons (normal, controlled hypertension, hypertensive blood pressure, cardiac disease) showed that diastolic differences persisted after multivariable adjustment. Conclusions After accounting for factors that influence cardiac function, systolic longitudinal strain parameters did not differ between Norwegian and Russian populations. In contrast, diastolic abnormalities persisted after adjustment, suggesting residual confounding and/or unmeasured determinants of diastolic dysfunction in the Russian population.

• Lorem, Geir F; Lillevoll, Kjersti; Løchen, Maja-Lisa; Wilsgaard, Tom; Thimm, Jens & Wang, Catharina Elisabeth Arfwedson [Show all 7 contributors for this article] (2025). Investigating the association between stressful life events and the risk of myocardial infarction and mortality: the Tromsø study. BMC Cardiovascular Disorders. 25(1). doi: 10.1186/s12872-025-05269-4. Full text in Research Archive
• Davidsen, Anne Herefoss; Andersen, Stian; Halvorsen, Peder Andreas; Solis, Juan Carlos Aviles; Schirmer, Henrik & Melbye, Hasse (2025). Heart murmurs in the general population: diagnostic value and prevalence from the Tromsø Study. Heart. ISSN 1355-6037. 112(2), p. 103–110. doi: 10.1136/heartjnl-2024-325499. Full text in Research Archive Show summary

  Background Heart auscultation is a widely used and cost-effective clinical tool for detecting valvular heart disease (VHD), particularly in primary care. However, existing evidence on its diagnostic accuracy is limited by small sample sizes, specialist-led studies and high-prevalence settings. Robust population-based data are lacking. This study aimed to assess the prevalence and diagnostic accuracy of heart murmurs for identifying VHD in a general adult population, using echocardiography as the reference standard. Methods We conducted a diagnostic accuracy study within the Seventh Tromsø Study (2015–2016), involving 2082 participants aged ≥40 years (mean age 63 years). Heart sounds were recorded at four chest locations and independently classified by general practitioners (GPs) blinded to echocardiographic results. Murmurs were graded and categorised as systolic or diastolic. Clinically significant VHD was defined as ≥mild aortic stenosis (AS) or ≥moderate aortic regurgitation (AR) or mitral regurgitation (MR). We calculated sensitivity, specificity, predictive values and likelihood ratios for murmur detection. Results GPs detected heart murmurs in 487 participants (23%). Significant VHD was identified in 392 participants (19%), but only 139 of them (35.5%) had an audible murmur. Systolic murmurs detected all cases of AS (sensitivity 100%, specificity 78%). Sensitivity was lower for AR (43%) and MR (29%), while specificity of distinct murmurs exceeded 94% across all VHD types. Diastolic murmurs were rare (n=9) but highly specific (>99%). Among participants with murmurs, age ≥70 years (OR 2.0, 95% CI 1.2 to 3.4), male sex (OR 3.3, 95% CI 2.0 to 5.3) and previous myocardial infarction (OR 2.3, 95% CI 1.0 to 5.2) were independently associated with VHD. Conclusion In this general adult population, heart auscultation by GPs identified murmurs in nearly one in four individuals and showed high specificity but limited sensitivity for diagnosing VHD. Auscultation remains a valuable initial screening tool—especially for AS—but should be complemented by echocardiography in older or high-risk individuals.

• Bjørnstad, Herman; Frigaard, Christine; Gulbrandsen, Pål; Gerwing, Jennifer; Schirmer, Henrik & Menichetti, Julia (2025). How hospital doctors respond to contextual factors revealed by older patients with heart failure in hospital interactions: an interaction-based study. BMC Health Services Research. 25. doi: 10.1186/s12913-025-13505-y. Full text in Research Archive Show summary

  Background Patients with heart failure often face individual context-dependent challenges that affect their ability to follow a treatment plan. How hospital doctors recognize and respond to such contextual factors (CF) may influence health outcomes. This study aims to identify adherence related CF disclosed by older patients with heart failure during hospital interactions and to examine how doctors respond to them. Methods Audio-recordings from two key hospital interactions were collected from 42 older patients with heart failure. Occurrences of CF were identified based on a previously developed coding scheme and followed during the hospital interactions. We then analysed doctor’s responses to patient’s CF and categorized them as: (1) Solution-oriented, (2) Exploring (3) No follow-up. Results We identified 58 CF across 113 occurrences in 27 (64%) patients. Medication-related CF (47%) were the most frequently disclosed, followed by patient-specific (34%), condition-related (12%), and healthcare system-related factors (7%). Doctors’ responses varied: 26% (n = 15) of CF received no follow-up, 21% (n = 12) were only explored, 24% (n = 14) were explored and met with a solution-oriented action, and 29% (n = 17) were met with solution-oriented actions without any exploration from the doctor. Conclusions Older patients with heart failure often disclose important CF relevant to adherence during hospital interactions. Roughly half of these factors are not met with a solution-oriented response, with a substantial portion not being followed up by the doctors at all. Future research should explore how to better improve doctors’ ability to recognize and appropriately respond to CF disclosed by patients.

• 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

• Frigaard, Christine; Menichetti, Julia; Schirmer, Henrik; Wisløff, Torbjørn; Bjørnstad, Herman & Simonsen, Tone Breines [Show all 8 contributors for this article] (2025). How do doctors address heart failure patients’ disclosures of medication adherence problems during hospital and primary care consultations? An exploratory interaction-based observational cohort study. BMJ Open. 15(4). doi: 10.1136/bmjopen-2025-098826. Full text in Research Archive Show summary

  Objectives To investigate how doctors and self-managing older patients with heart failure (HF) discuss the patients’ potential or ongoing medication adherence problems, and how such discussions evolve as patients transition from hospital to home, with particular focus on: (1) doctors’ communicative actions aimed at addressing patient disclosures of adherence problems and (2) patients’ feedback indicating whether their doctor’s supportive actions were acceptable to them. Design Exploratory interaction-based observational cohort study. Inductive microanalysis of authentic patient–doctor consultations, audio recorded for each patient at: (1) first ward visit in hospital, (2) discharge visit from hospital and (3) follow-up visit with general practitioner (GP). Setting Hospital and primary care, Norway (2022–2023). Participants 25 patients with HF (+65 years) and their attending doctors (23 hospital doctors, 25 GPs). Results Analysis of 74 consultations revealed that 25 HF patients disclosed 23 practical adherence problems indicating risks of unintentional non-adherence (eg, limited resources to manage medications) and 39 perceptual problems indicating risks of intentional non-adherence (eg, worries, negative experience or stance). Doctors addressed 79% of patients’ disclosures by: (1) exploring the scope of the problem or (2) providing supportive actions to improve patients’ ability or motivation to adhere. We calculated nearly five times higher odds for doctors to address patients’ practical problems to their perceptual problems (OR 4.79, 95% CI 1.25 to 25.83). Unresolved problems included: (1) doctors addressed patients’ disclosures, but patients signalled the supportive actions were unsuitable (37%) and (2) doctors left disclosures unaddressed (21%). Conclusions In this explorative study, the doctors were more likely to address the patients’ adherence problems associated with unintentional non-adherence risks than those associated with intentional non-adherence risks. Even when doctors attempted to address HF patients’ medication adherence problems, half of the problems remained unresolved, usually because patients indicated that the doctor’s suggestion to improve their situation was against their preference.

• Bjørnstad, Herman; Frigaard, Christine; Gulbrandsen, Pål; Gerwing, Jennifer; Schirmer, Henrik & Menichetti, Julia (2025). Contextual Factors Affecting Adherence Revealed by Old Patients with Heart Failure in Hospital and Primary Care Interactions: A Descriptive Study. Patient Preference and Adherence. 19, p. 1075–1087. doi: 10.2147/ppa.s505297. Full text in Research Archive Show summary

  Introduction: Old patients with heart failure are a vulnerable patient group facing various challenges, specifically during the transition from hospital to home. Non-biomedical factors, or “contextual factors”, such as patient attitudes and social support, can influence treatment adherence. However, their role in clinical interactions is not well understood. This study aimed to identify and describe how and when these factors manifest during clinical interactions in the hospital-to-home transition. Methods: We audio-recorded 42 old patients with heart failure admitted to hospital interacting with their physicians at: 1. the first ward visit, 2. discharge visit, 3. first primary care visit after discharge. Based on an umbrella review, we developed a list of 48 factors known to affect adherence among cardiovascular patients. Patient utterances from the recordings containing information on one of these factors (contextual indicators (CI)) were extracted and categorized according to the type of factor, mentioned impact, and being a facilitator or barrier to adherence. Results: From the 105 audio recordings, 742 CI were identified, each interaction containing an average of 7 CI (SD = 4.2; median = 6). CI considered to have a potential impact on patient’s life or adherence were overall evenly split between facilitators (n = 82, 42%) and barriers (n = 115, 58%), and both types of CI appeared in most patient trajectories. The most salient barrier CI was related to patients’ concerns regarding medications side effects and regimen complexity, while CI facilitators were more commonly related to patients’ knowledge, motivation and social support. Discussion: The findings from this study provide insights for clinicians to the main types of non-biomedical factors revealed by old patients with heart failure in medical interactions, which affect their treatment adherence. Clinicians should particularly consider patient concerns regarding medications’ side effects and the regimen complexity as important aspects to discuss, leveraging on motivational and social resources if present.

• Iakunchykova, Olena; Schirmer, Henrik; Roe, James Michael; Sørensen, Øystein; Wilsgaard, Tom & Hopstock, Laila Arnesdatter [Show all 10 contributors for this article] (2025). Longitudinal and concurrent C-reactive protein and diet associations with cognitive function in the population-based Tromsø study. Journal of Alzheimer's Disease. ISSN 1387-2877. 104(2), p. 403–413. doi: 10.1177/13872877251317624. Full text in Research Archive
• Vijayakumar, Arya Panthalanickal; Wilsgaard, Tom; Schirmer, Henrik; Lindekleiv, Haakon; Attia, Zachi I & Lopez-Jimenez, Francisco [Show all 8 contributors for this article] (2025). Associations of educational level with ECG-derived cardiovascular ageing in a population-based cohort: a mediation analysis from the Tromsø Study. BMJ Open. 15(6). doi: 10.1136/bmjopen-2024-088671. Full text in Research Archive Show summary

  Objective To assess the association between educational level and cardiovascular age acceleration metric derived from ECG, and to determine whether this association is mediated by established cardiovascular disease (CVD) risk factors. Design Prospective population-based cohort study (the Tromsø Study). Setting General population of the Tromsø municipality, Norway. Participants The study sample consisted of 4367 participants of the Tromsø Study, who took part in both Tromsø6 (2007–2008) and Tromsø7 (2015–2016), had a 12-lead ECG obtained at Tromsø7 and did not report a history of heart attack, stroke or atrial fibrillation. Primary outcome measures δ-age, a biomarker of cardiovascular ageing, is defined as the difference (in years) between an individual’s ECG-predicted heart age and their chronological age. ECG-predicted heart age was estimated using a previously validated deep neural network. Results Our findings indicate an inverse association between education and δ-age, with a regression coefficient per increment increase in education of −0.24 (95% CI −0.41 to –0.07) in the overall sample, −0.38 (95% CI −0.59 to –0.16) for women and −0.04 (95% CI −0.31 to 0.23) for men. Participants with the highest level of education (university/college for 4 or more years) had the lowest estimated δ-age with a regression coefficient of −0.69 years (95% CI −1.23 to –0.16) compared with the group with primary education for the overall sample, −1.05 years (95% CI −1.73 to –0.37) for women and −0.15 years (95% CI −1.03 to 0.73) for men. CVD risk factors mediated up to 75% of the association between overall education and δ-age, and 80% of the association among those with the highest education level (university/college for 4 or more years). Among women, 50% of the effect of overall education on δ-age was mediated by CVD risk factors, rising to 53% in the category with the highest level of education. However, in the subsample of men, there was no significant association between education and δ-age, and the mediation analysis produced natural direct and indirect effects pointing in opposite directions. Conclusions Cardiovascular ageing is inversely associated with educational level, an effect that appears to be largely mediated through established risk factors.

• Ookeditse, Ookeditse; Ookeditse, Kebadiretse K.; Motswakadikgwa, Thusego R.; Masilo, Gosiame; Bogatsu, Yaone & Lekobe, Baleufi Calstro [Show all 9 contributors for this article] (2025). Age and sources of information variations and similarities on awareness of treatment and prevention of stroke among public and outpatients in Sub-Saharan Africa: a cross-sectional questionnaire study in Botswana. BMC Public Health. 25(1). doi: 10.1186/s12889-025-21900-7. Full text in Research Archive Show summary

  Objectives In this cross-sectional study from Botswana, we investigated awareness of acute stroke treatment and prevention among stroke-risk outpatients and the public based on age and sources of information, in addition to association of stroke risk factors with this awareness. Method Questionnaires on awareness of acute stroke treatment and prevention were administered by research assistants to a representative selection of outpatients and the public. Results The response rate was 93.0% for the public and 96.6% for outpatients. Public respondents had a mean age of 36.1 ± 14.5 years (age range 18–90 years) and 54.5% were females, while outpatients had a mean age of 37.4 ± 12.7 years (age range 18–80 years) and 58.1% were females. Awareness of medical therapy as acute stroke treatment was inadequate among outpatients (75.5% for public vs 43.4% for outpatients among all-age, p < 0.001), due to awareness differences among all ages. Awareness of stroke prevention was adequate (81.5% of outpatients vs 71.6% of public among all-age, p = 0.601%), and similar trend was observed also among individual age groups. For awareness of medical therapy as an acute stroke treatment among all ages, the public was more likely than outpatients to get stroke information (p < 0.001) from almost all sources of information, while for awareness of stroke prevention among all-age, outpatients were more likely than the public to get stroke information from family/ friends (83.9% vs 70.5%, p = 0.042). History of HIV/AIDS and having a healthy diet were associated with lower awareness of both acute stroke treatment and prevention (p < 0.05). Conclusion Results call for strategic educational stroke campaigns using best information relaying tool for each age and respondents’ group.

• Pettersen, Michelle Tuv; Schirmer, Henrik; Solis, Juan Carlos Aviles; Spigt, Marcus & Melbye, Hasse (2025). Detection of heart failure in a general population not aware of having the disease. Scandinavian Journal of Primary Health Care. ISSN 0281-3432. 43(4), p. 759–769. doi: 10.1080/02813432.2025.2503447. Full text in Research Archive
• Berge, Kristian; Schirmer, Henrik; Øvrebotten, Tarjei; Nahoui, Hamza; Gullestad, Lars & Ingul, Charlotte Ingeborg Björk [Show all 13 contributors for this article] (2025). Improvements in medical therapy and prognosis for patients with HFrEF following the 2021 ESC HF guidelines. ESC Heart Failure. 12(5), p. 3343–3352. doi: 10.1002/ehf2.15337. Full text in Research Archive Show summary

  Aims The guideline-directed medical therapy (GDMT) sequencing strategy for patients with heart failure (HF) and reduced ejection fraction (HFrEF) underwent a paradigm shift with the 2021 ESC HF guidelines, from stepwise escalation to rapid simultaneous initiation of quadruple therapy. We aimed to assess the temporal trends in the use of GDMT and prognosis for patients with HFrEF. Methods and results Through the Norwegian HF Registry, we obtained data on patients treated at HF outpatient clinics with left ventricular ejection fraction ≤40% from 2016 through 2023 (n = 13 992), including GDMT, HF hospitalisations and mortality. Since 2016, >90% of patients have been treated with beta-blockers and renin-angiotensin-system-inhibitors, with angiotensin receptor-neprilysin inhibitors (ARNI) utilisation increasing from 4% in 2016 to 54% in 2023. Mineralocorticoid-receptor-antagonists (MRA) utilisation was at 36% in 2016, increased by 3% per year to 54% in 2021, and thereafter increased by 12% per year to 78% in 2023. Sodium-glucose cotransporter-2-inhibitors (SGLT2i) utilisation increased rapidly from 3% in 2020 to 85% in 2023. The utilisation of ≥50% of target dose followed similar trends. From 2016 to 2021, the crude 6-month mortality rate remained at 2.7%, followed by a decline of approximately 0.5% per year to 1.8% in 2023. HF hospitalisations declined steadily from 12.9% in 2016 to 8.2% in 2021, with a further decline to 6.8% in 2023. Conclusions The utilisation of GDMT in Norwegian HF clinics has increased markedly since 2016, with a fourfold acceleration in MRA and a substantial increase in SGLT2i use following the 2021 ESC HF guidelines. HF hospitalisations have consistently declined, while mortality rates first declined after 2021.

• Tiwari, Sweta; Løvsletten, Ola; Jacobsen, Bjarne Koster; Wilsgaard, Tom; Mathiesen, Ellisiv Bøgeberg & Schirmer, Henrik [Show all 9 contributors for this article] (2025). Occasional smoking is a risk factor for myocardial infarction in the population-based Tromsø Study, 2001–21. European Journal of Preventive Cardiology (EJPC). ISSN 2047-4873. doi: 10.1093/eurjpc/zwaf182. Full text in Research Archive
• Wilsgaard, Tom; Rosamond, Wayne; Schirmer, Henrik; Lindekleiv, Haakon; Attia, Zachi I. & Lopez-Jimenez, Francisco [Show all 8 contributors for this article] (2025). A New Biomarker of Aging Derived From Electrocardiograms Improves Risk Prediction of Incident Cardiovascular Disease. JACC: Advances. 4(6, Part 1). doi: 10.1016/j.jacadv.2025.101764. Full text in Research Archive
• Koechlin, Luca; Boeddinghaus, Jasper; Lopez-Ayala, Pedro; Reber, Cornelia; Nestelberger, Thomas & Wildi, Karin [Show all 46 contributors for this article] (2024). Clinical and Analytical Performance of a Novel Point-of-Care High-Sensitivity Cardiac Troponin I Assay. Journal of the American College of Cardiology. ISSN 0735-1097. 84(8), p. 726–740. doi: 10.1016/j.jacc.2024.05.056. Full text in Research Archive
• Strand, Bjørn Heine; Håberg, Asta; Eyjólfsdóttir, Harpa Sif; Kok, Almar; Skirbekk, Vegard Fykse & Huxhold, Oliver [Show all 11 contributors for this article] (2024). Spousal bereavement and its effects on later life physical and cognitive capability: the Tromsø study. GeroScience. ISSN 2509-2715. 46(6), p. 6055–6069. doi: 10.1007/s11357-024-01150-y. Full text in Research Archive Show summary

  Spousal bereavement is associated with health declines and increased mortality risk, but its specific impact on physical and cognitive capabilities is less studied. A historical cohort study design was applied including married Tromsø study participants (N=5739) aged 50–70 years with baseline self-reported overall health and health-related factors and measured capability (grip strength, finger tapping, digit symbol coding, and short-term recall) at follow-up. Participants had data from Tromsø4 (1994–1995) and Tromsø5 (2001), or Tromsø6 (2007–2008) and Tromsø7 (2015–2016). Propensity score matching, adjusted for baseline confounders (and baseline capability in a subset), was used to investigate whether spousal bereavement was associated with poorer subsequent capability. Spousal bereavement occurred for 6.2% on average 3.7 years (SD 2.0) before the capability assessment. There were no significant bereavement effects on subsequent grip strength, immediate recall, or finger-tapping speed. Without adjustment for baseline digit symbol coding test performance, there was a negative significant effect on the digit symbol coding test (ATT −1.33; 95% confidence interval −2.57, −0.10), but when baseline digit symbol coding test performance was taken into account in a smaller subsample, using the same set of matching confounders, there was no longer any association (in the subsample ATT changed from −1.29 (95% CI −3.38, 0.80) to −0.04 (95% CI −1.83, 1.75). The results in our study suggest that spousal bereavement does not have long-term effects on the intrinsic capacity components physical or cognition capability to a notable degree.

• Folkvord, Frans; Würth, Ana Roca-Umbert; Houten, Karlijn van; Liefveld, Aad R.; Carlson, Jim Ingebretsen & Bol, Nadine [Show all 26 contributors for this article] (2024). A systematic review on experimental studies about patient adherence to treatment. Pharmacology Research & Perspectives. 12(1). doi: 10.1002/prp2.1166. Full text in Research Archive Show summary

  A better understanding of patients' adherence to treatment is a prerequisite to maximize the benefit of healthcare provision for patients, reduce treatment costs, and is a key factor in a variety of subsequent health outcomes. We aim to understand the state of the art of scientific evidence about which factors influence patients' adherence to treatment. A systematic literature review was conducted using PRISMA guidelines in five separate electronic databases of scientific publications: PubMed, PsycINFO (ProQuest), Cochrane library (Ovid), Google Scholar, and Web of Science. The search focused on literature reporting the significance of factors in adherence to treatment between 2011 and 2021, including only experimental studies (e.g., randomized controlled trials [RCT], clinical trials, etc.). We included 47 experimental studies. The results of the systematic review (SR) are grouped according to predetermined categories of the World Health Organization (WHO): socioeconomic, treatment, condition, personal, and healthcare-related factors. This review gives an actual overview of evidence-based studies on adherence and analyzed the significance of factors defined by the WHO classification. By showing the strength of certain factors in several independent studies and concomitantly uncovering gaps in research, these insights could serve as a basis for the design of future adherence studies and models.

• Rösner, Assami; Kornev, Mikhail; Hatice, Akay Caglayan; Queiros, Sandro; Malyutina, Sofia & Ryabikov, Andrew [Show all 8 contributors for this article] (2024). Atrial Strain and Strain Rate in a General Population: Do These Measures Improve the Assessment of Elevated NT-proBNP Levels? Cardiology Research and Practice. ISSN 2090-8016. 2024(1). doi: 10.1155/2024/1546629. Full text in Research Archive Show summary

  Background - Noninvasive assessment of elevated filling pressure in the left ventricle (LV) remains an unresolved problem. Of the many echocardiographic parameters used to evaluate diastolic pressure, the left atrial strain and strain rate (LA S/SR) have shown promise in clinical settings. However, only a few previous studies have evaluated LA S/SR in larger populations. <p> <p>Methods - A total of 2033 participants from Norwegian (Tromsø 7) and Russian (Know Your Heart) population studies, equally distributed by age and sex, underwent echocardiography, including atrial and ventricular S/SR and NT-proBNP measurements. Of these, 1069 were identified as healthy (without hypertension (HT), atrial fibrillation (AF), or structural cardiac disease) and were used to define the age- and sex-adjusted normal ranges of LA S/SR. Furthermore, the total study population was divided into groups according to ejection fraction (EF) ≥50%, EF <50%, and AF. In each group, uni- and multiple regression and receiver operating characteristic curve analyses were performed to test LA and LV functional parameters as potential indicators of NT-proBNP levels above 250 ng/ml. <p> <p>Results - The mean LA S/SR values in this study were higher than those in previous large studies, whereas the lower references were comparable. In normal hearts, atrial total strain (ATS) and mitral valve E deceleration time (MV DT) were independent factors indicating elevated NT-proBNP levels, whereas in hearts with reduced EFs, the independent indicators were peak atrial contraction strain (PACS) and LV stroke volume. The areas under the curve for these significant indicators to discriminate elevated NT-proBNP levels were 0.639 (95% confidence interval (CI): 0.577–0.701) for normal EF and 0.805 (CI: 0.675–0.935) for reduced EF. <p> <p>Conclusion - The results confirm good intrastudy reproducibility, with mean values in the upper range of previous meta-analyses. In the future, automated border-detection algorithms may be able to generate highly reproducible normal values. Furthermore, the study showed atrial S/SR as an additional indicator of elevated NT-proBNP levels in the general population, demonstrating the incremental value of both ATS and PACS in addition to conventional and ventricular strain echocardiography. Thus, the LA S/SR may be regarded as an important addition to the multiparametric approach used for evaluating LV filling.

• Ookeditse, Ookeditse; Ookeditse, Kebadiretse K.; Motswakadikgwa, Thusego R.; Masilo, Gosiame; Bogatsu, Yaone & Lekobe, Baleufi Calstro [Show all 9 contributors for this article] (2024). Age and healthy lifestyle behavior’s disparities and similarities on knowledge of myocardial infarction symptoms and risk factors among public and outpatients in a resource-limited setting, cross-sectional study in greater Gaborone, Botswana. BMC Cardiovascular Disorders. 24(1). doi: 10.1186/s12872-024-03792-4. Full text in Research Archive Show summary

  Objectives In this cross-sectional study from Botswana, we investigated knowledge of myocardial infarction (MI) symptoms and risk factors among the general public and outpatients with MI risk factors based on age and lifestyle behaviors, in addition to assessing associations with sociodemographic and MI risk factors.<p> <p>Method Open-ended questionnaires about 8 MI symptoms and 10 risk factors, were administered by research assistants to a representative selection of outpatients (n=525) and the public (n=2248). Weight and height were measured in all participants and BMI was calculated. Knowledge scores were compared between the two groups. We examined whether sociodemographic and MI risk factors had impact on the scores. Analyses were further adjusted for lifestyle behavior (smoking status, dietary status and physical activities). <p>Results The valid response rate was 97.9% comprising 97.8% for the public (n=2199) and 98.1% for outpatients (n=515). Public respondents (35.2±12.3 years) were younger than outpatients (38.5±12.6 years). The public comprised 56.9% females while outpatients 54.6%. In general, outpatients had higher knowledge of MI symptoms than the public, with mean scores±SD of 3.49±2.84 vs 2.80±2.54. Outpatients also had higher knowledge score of MI risk factors than the public, with mean scores, 5.33±3.22 vs 3.82±3.07. For MI symptoms, outpatients were more aware than the public for chest pains among all ages, for arm pain/ numbness, neck/ jaw pain radiating to/ from chest, and feeling sick or looking pallor on the skin among those aged 35–49 years. Among both the public and outpatients, lower knowledge of both MI symptoms and risk factors was associated with primary education, not residing/working together, history of hypertension, no history of heart disease/stroke, and obesity. There were similarities and disparities on MI knowledge among respondents with various numbers of healthy lifestyle behaviours. <p>Conclusion Results call for urgent educational campaigns on awareness and knowledge of MI and using strategies based on age and lifestyle behavior.

• Frigaard, Christine; Delor, Julia Menichetti; Schirmer, Henrik; Bjørnstad, Herman; Simonsen, Tone Breines & Wisløff, Torbjørn [Show all 8 contributors for this article] (2024). What do patients with heart failure disclose about medication adherence at home to their hospital and primary care doctors? Exploratory interaction-based observational cohort study. BMJ Open. 14(8). doi: 10.1136/bmjopen-2024-086440. Full text in Research Archive Show summary

  Abstract Objectives: The main objective of this study was twofold: to investigate what kind of information patients with heart failure (HF) tell their doctors about their medication adherence at home, and how often such information is provided in consultations where medication reconciliation is recommended. To meet these objectives, we developed an analysis to recognise, define, and count (1) patient utterances including medication adherence disclosures in clinical interactions (MADICI), (2) MADICI including red-flags for non-adherence, and (3) MADICI initiated by patients without prompts from their doctor. Design: Exploratory interaction-based observational cohort study. Inductive microanalysis of authentic patient–doctor consultations, audio-recorded at three time-points for each patient: (1) first ward visit in hospital, (2) discharge visit from hospital, and (3) follow-up visit with general practitioner (GP). Setting: Norway (2022–2023). Participants: 25 patients with HF (+65 years) and their attending doctors (23 hospital doctors, 25 GPs). Results: We recognised MADICI by two criteria: (1) they are about medication prescribed for use at home, AND (2) they involve patients’ action, experience, or stance regarding medications. Using these criteria, we identified 427 MADICIs in 25 patient trajectories: 143 (34%) at first ward visit (min–max=0–35, median=3), 57 (13%) at discharge visit (min–max=0–8, median=2), 227 (53%) at GP-visit (min–max=2–24, median=7). Of 427 MADICIs, 235 (55%) included red-flags for non-adherence. Bumetanide and atorvastatin were most frequently mentioned as problematic. Patients initiated 146 (34%) of 427 MADICIs. Of 235 ‘red-flag MADICIs’, 101 (43%) were initiated by patients. Conclusions: Self-managing older patients with HF disclosed information about their use of medications at home, often including red-flags for non-adherence. Patients who disclosed information that signals adherence problems tended to do so unprompted. Such disclosures generate opportunities for doctors to assess and support patients’ medication adherence at home.

• Melum, Tonje Anita; Steingrímsdóttir, Ólöf A.; Jacobsen, Henrik B.; Johnsen, Bente; Stubhaug, Audun & Schirmer, Henrik [Show all 8 contributors for this article] (2024). Associations between cognitive test scores and pain tolerance: The Tromsø study. Scandinavian Journal of Pain. ISSN 1877-8860. 24(1), p. 1–10. doi: 10.1515/sjpain-2023-0082. Full text in Research Archive Show summary

  The aim of this study is to assess this relationship in a large population-based sample.<p> <p>Methods ‒ We included 5,753 participants (aged 40–84 years) from the seventh wave of the population-based Tromsø Study who had been examined with cognitive tests and experimental pain assessments, and for whom informa tion on covariates were available. Cox regression models were fitted using standardized scores on cognitive tests (12- word immediate recall test, digit symbol coding test, and Mini-Mental State Examination [MMS-E]) as the independent variable and cold pressor or cuff pressure pain tolerance as the dependent variables. Statistical adjustment was made for putative confounders, namely, age, sex, education, smoking, exercise, systolic blood pressure, body mass index, symptoms indicating anxiety or depression, analgesic use, and chronic pain. <p>Results ‒ In multivariate analysis, cold pressor tolerance time was significantly associated with test scores on the 12- word immediate recall test (hazard ratio [HR] 0.93, 95% confidence interval [CI] 0.90–0.97, p < 0.001), the digit symbol coding test (HR 0.94, 95% CI 0.89–0.98, p = 0.004), and the MMS-E (HR 0.93, 95% CI 0.90–0.96 p < 0.001). Tolerance to cuff pressure algometry was significantly associated with 12-word immediate recall (HR 0.94–0.97, p < 0.001) and Digit Symbol Coding test scores (HR 0.93, 95% CI 0.89–0.96, p < 0.001) while there was no significant association with Mini Mental State Examination test score (HR 0.98, 95% CI 0.95–1.00, p = 0.082). <p>Conclusion ‒ Lower pain tolerance was associated with poorer performance on cognitive tests.

• Tiwari, Sweta; Cerin, Ester; Wilsgaard, Tom; Løvsletten, Ola; Grimsgaard, Anne Sameline & Hopstock, Laila Arnesdatter [Show all 10 contributors for this article] (2023). Lifestyle factors as mediators of area-level socioeconomic differentials in mental health and cognitive function: The Tromsø Study. Journal of Epidemiology and Community Health. ISSN 0143-005X. 78(2), p. 88–97. doi: 10.1136/jech-2023-220928. Full text in Research Archive Show summary

  Introduction Low socioeconomic status (SES) is associated with poor mental health and cognitive function. Individual-level SES and area-level SES (ASES) may affect mental health and cognitive function through lifestyle. We aimed to quantify the associations of ASES with mental health and cognitive function and examine the mediating role of lifestyle behaviours independent of individual-level SES in a Norwegian population. Methods In this cross-sectional study, we included 7211 participants (54% women) from the seventh survey of the Tromsø Study (2015–2016) (Tromsø7). The exposure variable ASES was created by aggregating individual-level SES variables (education, income, housing ownership) from Statistics Norway at the geographical subdivision level. Tromsø7 data were used as mediators (smoking, snuff, alcohol, physical activity, diet) and outcomes (cognitive function, anxiety, depression, insomnia). Mediation and mediated moderation analysis were performed with age as a moderator, stratified by sex. Results Higher ASES was associated with better cognitive function and fewer depression and insomnia symptoms, independent of individual-level SES. These associations were mediated by smoking and physical activity. Alcohol was a mediator for depression and cognitive function in women. Age was a significant moderator of the association between ASES and global cognitive function in women. The largest total indirect effect of ASES was found for depression, with the joint effect of the mediators accounting for 36% of the total effect. Conclusions People living in areas with lower ASES are at higher risk of poor mental health, such as depression and insomnia, and have lower cognitive function possibly due to unhealthy lifestyle (smoking, alcohol and physical inactivity).

• Iakunchykova, Olena; Schirmer, Henrik; Vangberg, Torgil Riise; Wang, Yunpeng; Benavente, Ernest D. & Es, René van [Show all 12 contributors for this article] (2023). Machine-learning-derived heart and brain age are independently associated with cognition. European Journal of Neurology. ISSN 1351-5101. 30(9), p. 2611–2619. doi: 10.1111/ene.15902. Full text in Research Archive Show summary

  Background and purpose - A heart age biomarker has been developed using deep neural networks applied to electrocardiograms. Whether this biomarker is associated with cognitive function was investigated.<p> <p>Methods - Using 12-lead electrocardiograms, heart age was estimated for a population-based sample (N = 7779, age 40–85 years, 45.3% men). Associations between heart delta age (HDA) and cognitive test scores were studied adjusted for cardiovascular risk factors. In addition, the relationship between HDA, brain delta age (BDA) and cognitive test scores was investigated in mediation analysis.<p> <p>Results - Significant associations between HDA and the Word test, Digit Symbol Coding Test and tapping test scores were found. HDA was correlated with BDA (Pearson's r = 0.12, p = 0.0001). Moreover, 13% (95% confidence interval 3–36) of the HDA effect on the tapping test score was mediated through BDA.<p> <p>Discussion - Heart delta age, representing the cumulative effects of life-long exposures, was associated with brain age. HDA was associated with cognitive function that was minimally explained through BDA.

• Waaler, Per Niklas Benzler; Melbye, Hasse; Schirmer, Henrik; Johnsen, Markus Kreutzer; Dønnem, Tom & Ravn, Johan Fredrik [Show all 11 contributors for this article] (2023). Algorithm for predicting valvular heart disease from heart sounds in an unselected cohort. Frontiers in Cardiovascular Medicine. 10. doi: 10.3389/fcvm.2023.1170804. Full text in Research Archive Show summary

  Objective: This study aims to assess the ability of state-of-the-art machine learning algorithms to detect valvular heart disease (VHD) from digital heart sound recordings in a general population that includes asymptomatic cases and intermediate stages of disease progression.<p> <p>Methods: We trained a recurrent neural network to predict murmurs from heart sound audio using annotated recordings collected with digital stethoscopes from four auscultation positions in 2,124 participants from the Tromsø7 study. The predicted murmurs were used to predict VHD as determined by echocardiography.<p> <p>Results: The presence of aortic stenosis (AS) was detected with a sensitivity of 90.9%, a specificity of 94.5%, and an area under the curve (AUC) of 0.979 (CI: 0.963–0.995). At least moderate AS was detected with an AUC of 0.993 (CI: 0.989–0.997). Moderate or greater aortic and mitral regurgitation (AR and MR) were predicted with AUC values of 0.634 (CI: 0.565–703) and 0.549 (CI: 0.506–0.593), respectively, which increased to 0.766 and 0.677 when clinical variables were added as predictors. The AUC for predicting symptomatic cases was higher for AR and MR, 0.756 and 0.711, respectively. Screening jointly for symptomatic regurgitation or presence of stenosis resulted in an AUC of 0.86, with 97.7% of AS cases (n = 44) and all 12 MS cases detected.<p> <p>Conclusions: The algorithm demonstrated excellent performance in detecting AS in a general cohort, surpassing observations from similar studies on selected cohorts. The detection of AR and MR based on HS audio was poor, but accuracy was considerably higher for symptomatic cases, and the inclusion of clinical variables improved the performance of the model significantly.

• Johnsen, Bente; Martinaityte, Ieva; Wilsgaard, Tom & Schirmer, Henrik (2023). Incidence of dementia over a period of 20 years in a Norwegian population. Alzheimer's and Dementia: Diagnosis, Assessment and Disease Monitoring. 15(4). doi: 10.1002/dad2.12479. Full text in Research Archive Show summary

  INTRODUCTION: In Norway, the prevalence of dementia is higher than in demographically comparable, high income countries, but reliable incidence studies are lacking. This study calculated the incidence of age-specific dementia from 2000 to 2019.<p> <p>METHODS: Participants from The Tromsø Study (n = 44,214) were included. Participants with a dementia diagnosis (n = 2049 cases) were identified. Poisson regression was used to calculate age-specific yearly and 5-year incidence rates from 2000 to 2019. <p>RESULTS: The incidence of dementia has decreased from 2000 to 2019. The trend was highly significant for ages of 60–99 years, and was similar for both sexes. <p>DISCUSSION: The incidence of dementia in North Norway has decreased over the past two decades similar to that in Western countries, indicating that the total prevalence is increasing due to an aging population. This decrease of incidence could introduce a reduction in future estimation of dementia prevalence.

• Heide, Frank C. T. van der; Khawaja, Anthony; Berendschot, Tos T. J. M.; Littlejohns, Thomas J.; Kuźma, Elżbieta & Luben, Robert [Show all 17 contributors for this article] (2023). Associations of inner retinal layers with risk of incident dementia: An individual participant data analysis of four prospective cohort studies. Alzheimer's & Dementia. ISSN 1552-5260. doi: 10.1002/alz.13167. Full text in Research Archive Show summary

  INTRODUCTION - Our main objective was to investigate whether retinal neurodegeneration, estimated from lower thickness of inner retinal layers, was associated with incident all-cause dementia and Alzheimer's disease (AD).<p> <p>METHODS - We performed an individual participant data meta-analysis using unpublished data from four prospective cohort studies with a total of 69,955 participants (n = 1087 cases of incident all-cause dementia; n = 520 cases incident AD; follow-up time median [interquartile range] 11.3 [8.8–11.5] years).<p> <p>RESULTS - General baseline characteristics of the study population were mean (standard deviation) age, 58.1 (8.8) years; 47% women. After adjustment, lower baseline macular retinal nerve fiber layer thickness was significantly associated with a 10% and 11% higher incidence of all-cause dementia and AD, respectively. Lower baseline macular ganglion cell-inner plexiform layer thickness was not significantly associated with these outcomes.<p> <p>DISCUSSION - These findings suggest that retinal neurodegeneration precedes the onset of clinical dementia. Retinal imaging tools may be informative biomarkers for the study of the early pathophysiology of dementia.

• Lorem, Geir Fagerjord; Næss, Eva Therese; Løchen, Maja-Lisa; Lillevoll, Kjersti Rønningen; Molund, Else-Marie & Rösner, Assami [Show all 8 contributors for this article] (2023). Post-traumatic stress disorder among heart disease patients: a clinical follow-up of individuals with myocardial infarction in the Tromsø Study. BMC Psychiatry. 23(1). doi: 10.1186/s12888-023-05431-2. Full text in Research Archive Show summary

  Background Myocardial infarction is likely to be experienced as a life-threatening and potentially traumatic event. Approximately one-third of patients with myocardial infarction experience clinically significant symptoms of anxiety/ depression. However, it is unclear how many of these patients experience these symptoms because of post-traumatic stress disorder (PTSD). We conducted a clinical screening of individuals with a confirmed myocardial infarction diagnosis. Our goal was to examine the prevalence of PTSD in myocardial infarction patients and study how PTSD symptoms were associated with exposure to potentially traumatic events.<p> <p>Method This is epidemiological research with a cross-sectional design following up participants from the Tromsø Study with a confirmed diagnosis of myocardial infarction. We sent invitations to participants in the Tromsø Study with clinically significant self-reported anxiety or depression symptoms following myocardial infarction. A cross-sectional sample of N=79 participants (61 men and 18 women) was collected. During an interview, participants completed the Stressful Life Events Screening Questionnaire and the PTSD checklist PCL-5. <p>Results We found nine participants (11.6%) with probable PTSD. This was significantly higher than the postulated population prevalence in Norway (p<0.015). We found no direct association between myocardial infarction as illness trauma and symptom levels (p=0.123). However, we found a significant linear trend (p=0.002), indicating that symptom severity increased proportionately as the number of post-traumatic events increased. <p>Conclusion PTSD prevalence in myocardial infarction patients was related to lifetime exposure to traumatic events, not the myocardial infarction event alone. More research is required to examine the interaction between myocardial infarction and PTSD. Clinicians should be aware that anxiety or depression symptoms after MI could be secondary symptoms of PTSD.

• Kornev, Mikhail; Hatice, Akay Caglayan; Kudryavtsev, Alexander V; Malyutina, Sofia; Ryabikov, Andrew & Schirmer, Henrik [Show all 7 contributors for this article] (2023). Influence of hypertension on systolic and diastolic left ventricular function including segmental strain and strain rate. Echocardiography. ISSN 0742-2822. 40(7), p. 623–633. doi: 10.1111/echo.15625. Full text in Research Archive Show summary

  Background - Left ventricular (LV) systolic and diastolic functions are important cardiovascular risk predictors in patients with hypertension. However, data on segmental, layer-specific strain, and diastolic strain rates in these patients are limited. The aim of this study was to investigate segmental two-dimensional strain rate imaging (SRI)-derived parameters to characterize LV systolic and diastolic function in hypertensive individuals compared with that in normotensive individuals.<p> <p>Methods - The study sample comprised 1194 participants from the population-based Know Your Heart study in Arkhangelsk and Novosibirsk, Russia, and 1013 individuals from the Seventh Tromsø Study in Norway. The study population was divided into four subgroups: (A) healthy individuals with normal blood pressure (BP), (B) individuals on antihypertensive medication with normal BP, (C) individuals with systolic BP 140–159 mmHg and/or diastolic BP > 90 mm HG, and (D) individuals with systolic BP ≥160 mmHg. In addition to conventional echocardiographic parameters, global and segmental layer-specific strains and strain rates in early diastole and atrial contraction (SR E, SR A) were extracted. The strain and SR (S/SR) analysis included only segments without strain curve artifacts.<p> <p>Results - With increasing BP, the systolic and diastolic global and segmental S/SR gradually decreased. SR E, a marker of impaired relaxation, showed the most distinctive differences between the groups. In normotensive controls and the three hypertension groups, all segmental parameters displayed apico-basal gradients, with the lowest S/SR in the basal septal and highest in apical segments. Only SR A did not differ between the segmental groups but increased gradually with increasing BP. End-systolic strain showed incremental epi-towards endocardial gradients, irrespective of the study group.<p> <p>Conclusion - Arterial hypertension reduces global and segmental systolic and diastolic left ventricular S/SR parameters. Impaired relaxation determined by SR E is the dominant factor of diastolic dysfunction, whereas end-diastolic compliance (by SR A) does not seem to be influenced by different degrees of hypertension. Segmental strain, SR E and SR A provide new insights into the LV cardio mechanics in hypertensive hearts.

• Davidsen, Anne Herefoss; Andersen, Stian; Halvorsen, Peder Andreas; Schirmer, Henrik; Reierth, Eirik & Melbye, Hasse (2023). Diagnostic accuracy of heart auscultation for detecting valve disease: a systematic review. BMJ Open. 13(3), p. 1–14. doi: 10.1136/bmjopen-2022-068121. Full text in Research Archive Show summary

  Objective The objective of this study was to determine the diagnostic accuracy in detecting valvular heart disease (VHD) by heart auscultation, performed by medical doctors.<p> <p>Design/methods A systematic literature search for diagnostic studies comparing heart auscultation to echocardiography or angiography, to evaluate VHD in adults, was performed in MEDLINE (1947–November 2021) and EMBASE (1947–November 2021). Two reviewers screened all references by title and abstract, to select studies to be included. Disagreements were resolved by consensus meetings. Reference lists of included studies were also screened. The results are presented as a narrative synthesis, and risk of bias was assessed using Quality Assessment of Diagnostic Accuracy Studies-2. <p>Main outcome measures Sensitivity, specificity and likelihood ratios (LRs). <p>Results We found 23 articles meeting the inclusion criteria. Auscultation was compared with full echocardiography in 15 of the articles; pulsed Doppler was used as reference standard in 2 articles, while aortography and ventriculography was used in 5 articles. One article used point-of-care ultrasound. The articles were published from year 1967 to 2021. Sensitivity of auscultation ranged from 30% to 100%, and specificity ranged from 28% to 100%. LRs ranged from 1.35 to 26. Most of the included studies used cardiologists or internal medicine residents or specialists as auscultators, whereas two used general practitioners and two studied several different auscultators. <p>Conclusion Sensitivity, specificity and LRs of auscultation varied considerably across the different studies. There is a sparsity of data from general practice, where auscultation of the heart is usually one of the main methods for detecting VHD. Based on this review, the diagnostic utility of auscultation is unclear and medical doctors should not rely too much on auscultation alone. More research is needed on how auscultation, together with other clinical findings and history, can be used to distinguish patients with VHD.

• Heitmann, Kim Arne; Løchen, Maja-Lisa; Stylidis, Michael; Hopstock, Laila Arnesdatter; Schirmer, Henrik & Morseth, Bente (2022). Associations between physical activity, left atrial size and incident atrial fibrillation: the Tromsø Study 1994–2016. Open heart. 9(1), p. 1–10. doi: 10.1136/openhrt-2021-001823. Full text in Research Archive Show summary

  Aims Left atrial (LA) enlargement is an independent risk factor for atrial fibrillation (AF). Interestingly, some athletes have increased risk of AF, which may be linked to LA enlargement; however, little is known about the relationship between LA enlargement and AF risk at moderate-level physical activity (PA). We aimed to explore the associations between PA, LA size and risk of incident AF, and if PA can attenuate the risk of AF with LA enlargement. Methods This prospective study followed 2479 participants (52.4% female), free from known cardiac pathology, for median 20.2 years. Participants were followed up for hospital-diagnosed AF, confirmed by electrocardiography, from 1994-95 through 2016. At baseline, LA size was evaluated by anteroposterior LA diameter, and PA was self-reported by questionnaire. Results We observed a U-shaped relationship between PA and AF, and moderately active had 32% lower AF risk than inactive (HRadjusted 0.68, 95% CI 0.50 to 0.93). Participants with LA enlargement had 38% higher AF risk compared with participants with normal LA size (HRadjusted 1.38, 95% CI 1.12 to 1.69). However, the increased AF risk with LA enlargement was attenuated by PA; compared with inactive participants with LA enlargement, the AF risk was 45% lower among active with LA enlargement (HRadjusted 0.55, 95% CI 0.39 to 0.79). AF risk in active participants with LA enlargement did not differ from active with normal LA size. These patterns were observed in both men and women, and in participants over/under 65 years. Conclusion Moderate PA was associated with reduced AF risk, and PA attenuated the increased risk of AF with LA enlargement in both men and women and all age groups.

• Ookeditse, Ookeditse; Ookeditse, Kebadiretse K.; Motswakadikgwa, Thusego R.; Masilo, Gosiame; Bogatsu, Yaone & Lekobe, Baleufi Calstro [Show all 9 contributors for this article] (2022). Public and outpatients’ awareness of calling emergency medical services immediately by acute stroke in an upper middle-income country: a cross-sectional questionnaire study in greater Gaborone, Botswana. BMC Neurology. 22. doi: 10.1186/s12883-022-02859-z. Full text in Research Archive Show summary

  Objectives In this cross-sectional study from Botswana, we investigated awareness of calling emergency medical services (EMS) and seeking immediate medical assistance by acute stroke among stroke risk outpatients and public. Method Closed-ended questionnaires on awareness of calling EMS and seeking immediate medical assistance by acute stroke, were administered by research assistants to a representative selection of outpatients and public. Results The response rate was 96.0% (93.0% for public (2013) and 96.6% for outpatients (795)). Public respondents had mean age of 36.1 ± 14.5 years (age range 18–90 years) and 54.5% were females, while outpatients had mean age of 37.4 ± 12.7 years (age range 18–80 years) and 58.1% were females. Awareness of calling EMS (78.3%), and of seeking immediate medical assistance (93.1%) by stroke attack was adequate. For calling EMS by acute stroke, outpatients had higher awareness than the public (p < 0.05) among those with unhealthy diet (90.9% vs 71.1%), family history of both stroke and heart diseases (90.7% vs 61.2%), no history of psychiatric diseases (93.2% vs 76.0%) and sedentary lifestyle (87.5% vs 74.8%). Predictors of low awareness of both calling EMS and seeking immediate medical assistance were no medical insurance, residing/working together, history of psychiatric diseases, and normal weight. Male gender, ≥50 years age, primary education, family history of both stroke and heart diseases, current smoking, no history of HIV/AIDS, and light physical activity were predictors of low awareness of need for calling EMS. Conclusion Results call for educational campaigns on awareness of calling EMS and seeking immediate medical assistance among those with high risk factor levels. Highlights • This is the first study comparing awareness of calling EMS among outpatients and public in sub-Saharan Africa • Awareness of calling EMS or seeking immediate medical services by acute stroke was adequate among both outpatients and public • Predictors of low awareness of both calling EMS and seeking immediate medical assistance were no medical insurance, residing/working together, history of psychiatric diseases, and normal weight • Results call for educational campaigns on awareness of calling EMS/ seeking immediate medical assistance by stroke.

• Johnsen, Bente; Strand, Bjørn Heine; Martinaityte, Ieva; Lorem, Geir F & Schirmer, Henrik (2022). Leisure Time Physical Activities’ Association With Cognition and Dementia: A 19 Years’ Life Course Study. Frontiers in Aging Neuroscience. 14. doi: 10.3389/fnagi.2022.906678. Full text in Research Archive Show summary

  Introduction: Cognitive impairment is one of the main disabilities in dementia. Physical activity (PA) has been suggested as protective for dementia. However, the findings are disparate in studies, and the question of whether this is because of reverse causality is still open. We aimed to explore the association of PA with cognition in people who later developed dementia compared to those who did not.<p> <p>Method: Since 2001, 11,512 (55% women) participants over the age of 50 years had taken at least one cognitive test in the Tromsø Study. Of these, 1,123 (58% women) later developed dementia. The cases were extracted from hospital journals and entered into an endpoint registry. Leisure time PA (LTPA) was self-reported. Multilevel mixed-effects linear regression was used to address whether LTPA was associated with cognition, stratified by those later developing dementia, and dementia-free in a separate analysis. <p>Results: Leisure time PA was associated with scores in cognitive tests that were 55% (z-score 0.14) higher in those who did not develop dementia. For those in a preclinical phase of dementia, there was no association with LTPA on global cognitive scores. However, in a multifactorial test on processing speed and memory, women had a positive association with processing speed and memory. <p>Conclusion: Leisure time PA had a positive association with global cognition function only for those who did not develop dementia. In women who were developing dementia, LTPA had a positive association with processing speed and memory, while in men, there were no such associations.

• Andreassen, Runa Marie; Kronborg, Jens; Schirmer, Henrik; Mathiesen, Ellisiv B.; Melsom, Toralf & Eriksen, Bjørn Odvar [Show all 8 contributors for this article] (2022). Urinary orosomucoid is associated with diastolic dysfunction and carotid arteriopathy in the general population. Cross-sectional data from the Tromsø study. Scandinavian Cardiovascular Journal. ISSN 1401-7431. 56(1), p. 148–156. doi: 10.1080/14017431.2022.2079714. Full text in Research Archive Show summary

  Objectives. Urinary albumin excretion is a risk marker for cardiovascular disease (CVD). Studies suggest that urinary orosomucoid may be a more sensitive marker of general endothelial dysfunction than albuminuria. The aim of this population-based cross-sectional study was to examine the associations between urinary orosomucoid to creatinine ratio (UOCR), urinary albumin to creatinine ratio (UACR) and subclinical CVD. Design. From the Tromsø Study (2007/2008), we included all men and women who had measurements of urinary orosomucoid (n = 7181). Among these, 6963 were examined with ultrasound of the right carotid artery and 2245 with echocardiography. We assessed the associations between urinary markers and subclinical CVD measured as intima media thickness of the carotid artery, presence and area of carotid plaque and diastolic dysfunction (DD). UOCR and UACR were dichotomized as upper quartile versus the three lowest. Results. High UOCR, adjusted for UACR, age, cardiovascular risk factors and kidney function, was associated with presence of DD in men (OR: 3.18, 95% CI [1.27, 7.95], p = .013), and presence of plaque (OR: 1.20, 95% CI [1.01, 1.44], p = .038) and intima media thickness in women (OR: 1.34, 95% CI [1.09, 1.65], p = .005). Analyses showed no significant interaction between sex and UOCR for any endpoints. UACR was not significantly associated with DD, but the associations with intima media thickness and plaque were of magnitudes comparable to those observed for UOCR. Conclusions. UOCR was positively associated with subclinical CVD. We need prospective studies to confirm whether UOCR is a clinically useful biomarker and to study possible sex differences. 2022 The Author(s). Published by Informa UK Limited, trading as Taylor & Francis Group. This is an Open Access article distributed under the terms of the Creative Commons Attribution-NonCommercial License (http://creativecommons.org/licenses/by-nc/4.0/), which permitsunrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited. SCANDINAVIAN CARDIOVASCULAR JOURNAL2022, VOL. 56, NO. 1, 148-156 https://doi.org/10.1080/14017431.2022.2079714

• Gravningen, Kirsten Midttun; Henriksen, Stian; Hungnes, Olav; Svendsen, Kristian; Macdonald, Emily Ann & Schirmer, Henrik [Show all 12 contributors for this article] (2022). Risk factors, immune response and whole‐genome sequencing of SARS‐CoV‐2 in a cruise ship outbreak in Norway. International Journal of Infectious Diseases. ISSN 1201-9712. 118, p. 10–20. doi: 10.1016/j.ijid.2022.02.025. Full text in Research Archive Show summary

  Objective: To improve understanding of SARS-CoV-2-transmission and prevention measures on cruise ships, we investigated a Norwegian cruise ship outbreak from July to August 2020 using a multidisciplinary approach after a rapid outbreak response launched by local and national health authorities. Methods: We conducted a cross-sectional study among crew members using epidemiologic data and results from SARS-CoV-2 polymerase chain reaction (PCR) of nasopharynx-oropharynx samples, antibody analyses of blood samples, and whole-genome sequencing. Results: We included 114 multinational crew members (71% participation), median age 36 years, and 69% male. The attack rate was 33%; 32 of 37 outbreak cases were seropositive 5-10 days after PCR. One PCRnegative participant was seropositive, suggesting a previous infection. Network-analysis showed clusters based on common exposures, including embarkation date, nationality, sharing a cabin with an infected cabin-mate (adjusted odds ratio [AOR] 3.27; 95% confidence interval [CI] 0.97-11.07, p = 0.057), and specific workplaces (mechanical operations: 9.17 [1.82-45.78], catering: 6.11 [1.83-20.38]). Breaches in testing, quarantine, and isolation practices before/during expeditions were reported. Whole-genome sequencing revealed lineage B.1.36, previously identified in Asia. Despite extensive sequencing, the continued transmission of B.1.36 in Norway was not detected. Conclusions: Our findings confirm the high risk of SARS-CoV-2-transmission on cruise ships related to workplace and cabin type and show that continued community transmission after the outbreak could be stopped by implementing immediate infection control measures at the final destination.

• Kornev, Mikhail; Hatice, Akay Caglayan; Kudryavtsev, Alexander V; Malyutina, Sofia; Ryabikov, Andrew & Stylidis, Michael [Show all 8 contributors for this article] (2022). Novel approach to artefact detection and the definition of normal ranges of segmental strain and strain-rate values. Open heart. 9(2), p. 1–10. doi: 10.1136/openhrt-2022-002136. Full text in Research Archive Show summary

  Aims - Strain artefacts are known to hamper the correct interpretation of segmental strain and strain-rate (S/SR). Defining the normal ranges of myocardial segmental deformation is important in clinical studies and routine echocardiographic practice. In order to define artefact-free normal ranges for segmental longitudinal S/SR parameters, we investigated the extent to which different types of artefacts and their segmental localisation in the three different myocardial layers created a bias in the results of echocardiographic strain measurements.<p> <p>Methods - The study included echocardiograms from men and women aged 40–69 years from two population-based studies, namely the Know Your Heart study (Russia) and the Tromsø Study (Norway). Of the 2207 individuals from these studies, 840 had normal results, defined as the absence of hypertension or indicators of any cardiovascular disease. Two-dimensional (2D) global and segmental S/SR of the three myocardial layers were analysed using speckle tracking echocardiography. Artefacts were assessed with two different methods: visual identification of image-artefacts and a novel conceptual approach of ‘curve-artefacts’ or unphysiological strain-curve formation.<p> <p>Results - Segmental strain values were found to have significantly reduced in the presence of strain-curve artefacts (14.9%±5.8% towards −20.7%±4.9%), and increased with the foreshortening of the 2D image. However, the individual global strain values were not substantially altered by discarding segmental artefacts. Reduction due to artefacts was observed in all segments, layers, systolic and diastolic strain, and SR. Thus, we presented normal ranges for basal-septal, basal, medial and apical segment groups after excluding artefacts.<p> <p>Conclusion - Strain-curve artefacts introduce systematic errors, resulting in reduced segmental S/SR values. In terms of artefact-robust global longitudinal strain, the detection of curve-artefacts is crucial for the correct interpretation of segmental S/SR patterns. Intersegmental S/SR gradients and artefacts need to be considered for the correct definition of normalcy and pathology.

• Voors, Adriaan A.; Angermann, Christiane E.; Teerlink, John R.; Collins, Sean P.; Kosiborod, Mikhail & Biegus, Jan [Show all 30 contributors for this article] (2022). The SGLT2 inhibitor empagliflozin in patients hospitalized for acute heart failure: a multinational randomized trial. Nature Medicine. ISSN 1078-8956. 28(3), p. 568–574. doi: 10.1038/s41591-021-01659-1. Full text in Research Archive
• Pedersen, Elisabeth; Primicerio, Raul; Halvorsen, Kjell H.; Eggen, Anne Elise; Garcia, Beate Hennie & Schirmer, Henrik [Show all 7 contributors for this article] (2022). Medication adherence among persons with coronary heart disease and associations with blood pressure and low-density-lipoprotein-cholesterol. European Journal of Clinical Pharmacology. ISSN 0031-6970. 78(5), p. 857–867. doi: 10.1007/s00228-022-03276-4. Full text in Research Archive Show summary

  Purpose - To describe medication adherence to lipid-lowering drugs (LLDs), antihypertensive drugs, and acetylsalicylic acid (ASA) among persons with coronary heart disease (CHD) and explore its association with low-density-lipoprotein (LDL)-cholesterol, and systolic and diastolic blood pressure.<p> <p>Methods - Based on record linkage between the seventh wave of the Tromsø Study and the Norwegian Prescription Database, medication adherence was calculated as the proportion of days covered (PDC) for persistent prevalent users in the period of 365 days before the attendance date. Multivariable linear regression models were used to assess the association between systolic and diastolic blood pressure and medication nonadherence to antihypertensive drugs, age, sex, lifestyle, body mass index (BMI), current and previous diabetes, and between LDL-cholesterol and medication nonadherence to LLDs, age, sex, lifestyle, BMI, and current and previous diabetes.<p> <p>Results - Mean PDC was 0.94 for LLDs and antihypertensive drugs and 0.97 for ASA. Among persons with PDC ≥ 0.80 for LLDs, 12.0% had an LDL-cholesterol < 1.8 mmol/L. Blood pressure < 140/90 mmHg (< 140/80 mmHg if diabetes patient) was reached by 55.1% of those with a PDC ≥ 0.80 for antihypertensive drugs. Adherence to LLDs was associated with lower LDL-cholesterol, while neither systolic nor diastolic blood pressure was associated with adherence to antihypertensive drugs.<p> <p>Conclusion - Adherence to antihypertensive drugs, LLDs, and ASA among persons with CHD were high despite low achievement of treatment goals for blood pressure and LDL-cholesterol. There was a statistically significant association between adherence to LLDs and LDL-cholesterol, but not between adherence to antihypertensive drugs and blood pressure.

• Fladseth, Kristina; Wilsgaard, Tom; Lindekleiv, Haakon; Kristensen, Andreas; Mannsverk, Jan Torbjørn & Løchen, Maja-Lisa [Show all 12 contributors for this article] (2022). Outcomes after coronary angiography for unstable angina compared to stable angina, myocardial infarction and an asymptomatic general population. International journal of cardiology: Heart and Vasculature (IJCHA). 42. doi: 10.1016/j.ijcha.2022.101099. Full text in Research Archive Show summary

  Background: The outcomes of real-world unstable angina (UA) in the high-sensitivity troponin era are unclear. We aimed to investigate the outcomes of UA referred to coronary angiography compared to stable angina (SA), nonST-segment elevation myocardial infarction (NSTEMI), STEMI and a general population.<p> <p>Methods: We included the 9,694 patients with no prior coronary artery disease (CAD) referred to invasive or CT coronary angiography from 2013 to 2018 in Northern Norway (51% SA, 12% UA, 23% NSTEMI and 14% STEMI), and 11,959 asymptomatic individuals recruited from the Tromsø Study. We used Cox models to estimate the hazard ratios (HR) for all-cause mortality and major adverse cardiovascular events (MACE), defined as cardiovascular death, MI or obstructive CAD. <p>Results: The median follow-up time was 2.8 years. The incidence rate of death was 8.5 per 1000 person-years (95 % confidence interval [CI] 8.0–9.0) in the general population, 9.7 (95 % CI 8.3–11.5) in SA, 14.9 (95 % CI 11.4–19.6) in UA, 29.7 (95 % CI 25.6–34.3) in NSTEMI and 36.5 (95 % CI 30.9–43.2) in STEMI. In multivariable adjusted analyses, compared with UA, SA had a 38 % lower risk of death and a non-significant lower risk of MACE (HR 0.62, 95 % CI 0.44–0.89; HR 0.86, 95 % CI 0.66–1.11). NSTEMI had a 2.4-fold higher risk of death (HR 2.39, 95 % CI 1.38–4.14) and a 1.6-fold higher risk of MACE (HR 1.62, 95 % CI 1.11–2.38) compared tox UA during the first year after coronary angiography, but a similar risk thereafter. There was no difference in the risk of death for UA with non-obstructive CAD and obstructive CAD (HR 0.78, 95 % CI 0.39–1.57). <p>Conclusion: UA had a higher risk of death but a similar risk of MACE compared to SA and a lower 1-year risk of death and MACE compared to NSTEMI.

• Tiwari, Sweta; Cerin, Ester; Wilsgaard, Tom; Løvsletten, Ola; Njølstad, Inger & Grimsgaard, Sameline [Show all 11 contributors for this article] (2022). Lifestyle factors as mediators of area-level socio-economic differentials in cardiovascular disease risk factors. The Tromsø Study. SSM - Population Health. ISSN 2352-8273. 19. doi: 10.1016/j.ssmph.2022.101241. Full text in Research Archive Show summary

  Introduction: Cardiovascular disease (CVD) is a leading cause of death and disability and living in areas with low socio-economic status (SES) is associated with increased risk of CVD. Lifestyle factors such as smoking, physical inactivity, an unhealthy diet and harmful alcohol use are main risk factors that contribute to other modifiable risk factors, such as hypertension, raised blood cholesterol, obesity, and diabetes. The potential impact of arealevel socio-economic status (ASES) on metabolic CVD risk factors via lifestyle behaviors independent of individual SES has not been investigated previously.<p> <p>Aims: To estimate associations of ASES with CVD risk factors and the mediating role of lifestyle behaviors independent of individual-level SES. <p>Methods: In this cross-sectional study, we included 19,415 participants (52% women) from the seventh survey of the Tromsø Study (2015–2016) (Tromsø7). The exposure variable ASES was created by aggregating individuallevel SES variables (education, income, housing ownership) at the geographical subdivision level. Individuallevel SES data and geographical subdivision of Tromsø municipality (36 areas) were obtained from Statistics Norway. Variables from questionnaires and clinical examinations obtained from Tromsø7 were used as mediators (smoking, snuff, alcohol, and physical activity), while the outcome variables were body mass index (BMI), total/ high-density lipoprotein (HDL) cholesterol ratio, waist circumference, hypertension, diabetes. Mediation and mediated moderation analysis were performed with age as a moderator, stratified by sex. <p>Results: ASES was significantly associated with all outcome variables. CVD risk factor level declined with an increase in ASES. These associations were mediated by differences in smoking habits, alcohol use and physical activity. The associations of ASES with total/HDL cholesterol ratio and waist circumference (women) were moderated by age, and the moderating effects were mediated by smoking and physical activity in both sexes. The largest mediated effects were seen in the associations of ASES with total/HDL cholesterol ratio, with the mediators accounting for 43% of the observed effects. <p>Conclusions: Living in lower SES areas is associated with increased CVD risk due to unhealthy lifestyle behaviors, such as smoking, alcohol use and physical inactivity. These associations were stronger in women and among older participants.

• Stavem, Knut; Schirmer, Henrik & Gulsvik, Amund (2022). Respiratory symptoms and cardiovascular causes of deaths: A population-based study with 45 years of follow-up. PLOS ONE. 17(10). doi: 10.1371/journal.pone.0276560. Full text in Research Archive Show summary

  This study determined the association between respiratory symptoms and death from cardiovascular (CV) diseases during 45 years in a pooled sample of four cohorts of random samples of the Norwegian population with 95,704 participants. Respiratory symptoms were assessed using a modification of the MRC questionnaire on chronic bronchitis. We analyzed the association between respiratory symptoms and specific cardiovascular deaths by using Cox regression analysis with age as the time variable, accounting for cluster-specific random effects using shared frailty for study cohort. Hazard ratios (HR) for death were adjusted for sex, highest attained education, smoking habits, occupational air pollution, and birth cohort. Overall, 12,491 (13%) of participants died from CV diseases: 4,123 (33%) acute myocardial infarction, 2,326 (18%) other ischemic heart disease, 2,246 (18%) other heart diseases, 2,553 (20%) cerebrovascular diseases, and 1,120 (9%) other vascular diseases. The adjusted HR (95% confidence interval) for CV deaths was 1.9 (1.7–2.1) in men and 1.5 (1.2–1.9) in women for “yes” to the question “Are you breathless when you walk on level ground at an ordinary pace?”. The same item response showed an adjusted HR for death from acute myocardial infarction of 1.8 (1.5–2.1), other ischemic heart disease 2.2 (1.8–2.7), other heart diseases 1.5 (1.1–1.9), cerebrovascular disease 1.8 (1.5–2.3), and other circulatory diseases 1.7 (1.2–2.4). The adjusted HR for CV death was 1.3 (1.2–1.4) when answering positive to the question” Are you more breathless than people of your own age when walking uphill?”. However, positive answers to questions on cough, phlegm, wheezing and attacks of breathlessness were after adjustments not associated with early CV deaths. The associations between CV deaths and breathlessness were also present in never smokers. Self-reported breathlessness was associated with CV deaths and could be an early marker of CV deaths.

• Azulay, Naomi; Olsen, Roy Bjørkholt; Nielsen, Christopher Sivert; Stubhaug, Audun; Jenssen, Trond Geir & Schirmer, Henrik [Show all 9 contributors for this article] (2022). Reduced heart rate variability is related to the number of metabolic syndrome components and manifest diabetes in the sixth Tromsø study 2007–2008. Scientific Reports. 12(1). doi: 10.1038/s41598-022-15824-0. Full text in Research Archive Show summary

  Both diabetes mellitus (DM) and the metabolic syndrome (MetS) are associated with autonomic neuropathy, which predisposes to cardiac events and death. Measures of heart rate variability (HRV) can be used to monitor the activity of the autonomic nervous system (ANS), and there are strong indications that HRV can be used to study the progression of ANS-related diabetes complications. This study aims to investigate diferences in HRV in healthy, MetS and diabetic populations. Based on 7880 participants from the sixth health survey in Tromsø (Tromsø 6, 2007–2008), we found a signifcant negative association between the number of MetS components and HRV as estimated from short-term pulse wave signals (PRV). This decrease in PRV did not appear to be linear, instead it leveled of after the third component, with no signifcant diference in PRV between the MetS and DM populations. There was a signifcant negative association between HbA1c and PRV, showing a decrease in PRV occurring already within the normal HbA1c range. The MetS and DM populations are diferent from healthy controls with respect to PRV, indicating impaired ANS in both conditions. In the future, a study with assessment of PRV measurements in relation to prospective cardiovascular events seems justifed.

• Andersen, Stian; Davidsen, Anne Herefoss; Schirmer, Henrik; Melbye, Hasse; Spigt, Marcus & Solis, Juan Carlos Aviles (2022). Interrater and intrarater agreement on heart murmurs. Scandinavian Journal of Primary Health Care. ISSN 0281-3432. 40(4), p. 491–497. doi: 10.1080/02813432.2022.2159204. Full text in Research Archive Show summary

  Objective: To investigate interrater and intrarater agreement between physicians and medical students on heart sound classification from audio recordings, and factors predicting agreement with a reference classification.<p> <p>Design: Intra- and interrater agreement study. <p>Subjects: Seventeen GPs and eight cardiologists from Norway and the Netherlands, eight medical students from Norway. <p>Main outcome measures: Proportion of agreement and kappa coefficients for intrarater agreement and agreement with a reference classification. <p>Results: The proportion of intrarater agreement on the presence of any murmur was 83% on average, with a median kappa of 0.64 (range k ¼ 0.09–0.86) for all raters, and 0.65, 0.69, and 0.61 for GPs, cardiologist, and medical students, respectively. <p>Results: The proportion of agreement with the reference on any murmur was 81% on average, with a median kappa of 0.67 (range 0.29–0.90) for all raters, and 0.65, 0.69, and 0.51 for GPs, cardiologists, and medical students, respectively. Results: Distinct murmur, more than five years of clinical practice, and cardiology specialty were most strongly associated with the agreement, with ORs of 2.41 (95% CI 1.63–3.58), 2.19 (1.58–3.04), and 2.53 (1.46–4.41), respectively. <p>Conclusion: We observed fair but variable agreement with a reference on heart murmurs, and physician experience and specialty, as well as murmur intensity, were the factors most strongly associated with agreement.

• Heitmann, Kim Arne; Welde, Boye; Løchen, Maja-Lisa; Stylidis, Michael; Schirmer, Henrik & Morseth, Bente (2022). Longitudinal Associations Between Cumulative Physical Activity and Change in Structure and Function of the Left Side of the Heart: The Tromsø Study 2007–2016. Frontiers in Cardiovascular Medicine. 9, p. 1–12. doi: 10.3389/fcvm.2022.882077. Full text in Research Archive Show summary

  Background: Current knowledge about the relationship between physical activity (PA) and cardiac remodeling is mainly derived from cross-sectional studies of athletes, and there is a knowledge gap of this association in the general adult and elderly population. Therefore, we aimed to explore the longitudinal association between cumulative PA and change in cardiac structure and function in a general adult and elderly population.<p> <p>Methods: This longitudinal study includes 594 participants from the sixth (Tromsø6, 2007–08) and seventh (Tromsø7, 2015–16) survey of the Tromsø Study. Cardiac structure and function were assessed by echocardiography at two time points, and PA was self-reported by questionnaire at both time points. PA volume was expressed as cumulative PA (Low, Moderate, and Hard) and the association with left atrial (LA) and left ventricular (LV) structure and function was assessed using ANCOVA. <p>Results: Overall, LA diameter index (LADi) increased significantly more in Hard compared to Moderate PA (+0.08 cm/m² , 95% CI 0.01–0.15, p = 0.020) from Tromsø6 to Tromsø7. When stratified by sex or age, higher levels of cumulative PA were associated with increased LADi in males and in participants <65 years only. Indexed LV mass (LVMi) increased significantly more in Moderate than in Low PA (+3.9 g/m^2.7, 95% CI 0.23– 7.57, p = 0.037). When stratified by sex or age, these changes in LVMi and indexed LV diameter (LVDi) were only significant in females. No significant associations were observed between cumulative PA and change in relative wall thickness, E/e’ ratio, e’ velocity, LV ejection fraction, and LADi/LVDi ratio. <p>Conclusion: Higher levels of cumulative PA were associated with increased LADi in males and participants <65 years, and with increased LVMi and LVDi in females. Despite cardiac chamber enlargement, the pump function of the heart did not change with higher levels of PA, and the atrioventricular ratio was unchanged. Our results indicate that cardiac chamber enlargement is a physiological response to PA.

• Lorem, Geir F; Opdal, Ida Marie; Wilsgaard, Tom; Schirmer, Henrik; Løchen, Maja-Lisa & Olsen, Ingrid Petrikke [Show all 8 contributors for this article] (2022). Assessment of mental health trajectories before and after myocardial infarction, atrial fibrillation or stroke: analysis of a cohort study in Tromsø, Norway (Tromsø Study, 1994-2016). BMJ Open. 12(4). doi: 10.1136/bmjopen-2021-052948. Full text in Research Archive Show summary

  Objectives - The increased survival rate of cardiovascular disease (CVD) implies a higher proportion of individuals who live with CVD. Using data from the Tromsø Study, we aimed to investigate mental health symptom trajectories before and after myocardial infarction, atrial fibrillation or stroke in a general population and to explore factors that contribute to the association.<p> <p>Design - Cohort study.<p> <p>Setting - Sample drawn from inhabitants of the municipality of Tromsø, Norway, who participated in the Tromsø Study (1994–2016).<p> <p>Participants - A total of 18 719 participants (52.3% women) were included, and of these 2098 (32.9% women) were diagnosed with myocardial infarction, 1896 (41.9% women) with atrial fibrillation and 1263 (42.9% women) with stroke.<p> <p>Primary outcome measures - Mental health symptoms were assessed using the Hopkins Symptom Checklist-10 and the Conor Mental Health Index.<p> <p>Results - The participants who were diagnosed with either myocardial infarction or stroke had a significant monotonous increase in mental health symptoms before myocardial infarction (p=0.029) and stroke (p=0.029) that intensified at the time of diagnosis. After the event, the study found a higher prevalence of mental health symptoms with a decline in symptom levels over time for myocardial infarction (p<0.001) and stroke (p=0.004), but not for atrial fibrillation (before: p=0.180, after: p=0.410). The risk of elevated mental health symptoms with myocardial infarction, atrial fibrillation and stroke was associated with sex (p<0.001), age (p<0.01), physical activity (p<0.001), diabetes (p<0.05) and other comorbidities (p<0.001).<p> <p>Conclusion - The study indicates that mental health problems among individuals with myocardial infarction, atrial fibrillation and stroke may have started to develop several years before the cardiovascular event and suggests that successful CVD rehabilitation may need to consider previous life factors. Future research is recommended to examine whether health promotion measures in a general population also create mental health resilience after a CVD event.

• Tveit, Sjur Hansen; Myhre, Peder Langeland; Hanssen, Tove Aminda; Forsdahl, Signe Helene; Iqbal, Amjid & Omland, Torbjørn [Show all 7 contributors for this article] (2022). Cardiac troponin I and T for ruling out coronary artery disease in suspected chronic coronary syndrome. Scientific Reports. 12. doi: 10.1038/s41598-022-04850-7. Full text in Research Archive Show summary

  To compare the performance of high-sensitivity cardiac troponin I and T (hs-cTnI; hs-cTnT) in diagnosing obstructive coronary artery disease (CAD₅₀) in patients with suspected chronic coronary syndrome (CCS). A total of 706 patients with suspected CCS, referred for Coronary Computed Tomography Angiography, were included. cTn concentrations were measured using the Singulex hs-cTnI (limit of detection [LoD] 0.08 ng/L) and Roche hs-cTnT (LoD 3 ng/L) assays. Obstructive coronary artery disease (CAD₅₀) was defned as ≥ 50% coronary stenosis. Cardiovascular risk was determined by the NORRISK2-score. Median age of the patients was 65 (range 28–87) years, 35% were women. All patients had hs-cTnI concentrations above the LoD (median 1.9 [Q1-3 1.2–3.6] ng/L), 72% had hs-cTnT above the LoD (median 5 [Q1-3 2–11] ng/L). There was a graded relationship between hs-cTn concentrations and coronary artery calcium. Only hs-cTnI remained associated with CAD₅₀ in adjusted analyses (OR 1.20 95% Confdence Interval [1.05–1.38]), p = 0.009). The C-statistics for hs-cTnI and hs-cTnT were 0.65 (95% CI [0.60–0.69]) and 0.60 (0.56–0.64). The highest specifcity and negative predictive values for CAD₅₀ were in the lowest NORRISK2-tertile. hs-cTn concentrations provide diagnostic information in patients with suspected CCS, with superior performance of hs-cTnI compared to hs-cTnT in regard to CAD₅₀. The diagnostic performance appeared best in those with low cardiovascular risk.

• Halvorsen, Sigrun; Mehilli, Julinda; Cassese, Salvatore; Hall, Trygve Sørdahl; Schirmer, Henrik & Atar, Dan [Show all 7 contributors for this article] (2022). 2022 ESC Guidelines on cardiovascular assessment and management of patients undergoing non-cardiac surgery. European Heart Journal. ISSN 0195-668X. doi: 10.1093/eurheartj/ehac270. Full text in Research Archive
• Gencer, Baris; Gale, Chris P; Aktaa, Suleman; Halvorsen, Sigrun; Beska, Ben & Abdelhamid, Magdy [Show all 16 contributors for this article] (2022). European Society of Cardiology quality indicators for the cardiovascular pre-operative assessment and management of patients considered for non-cardiac surgery. Developed in collaboration with the European Society of Anaesthesiology and Intensive Care. European Heart Journal - Quality of Care and Clinical Outcomes. ISSN 2058-5225. 9(4), p. 331–341. doi: 10.1093/ehjqcco/qcac057. Full text in Research Archive
• Sharashova, Ekaterina; Gerdts, Eva; Ball, Jocasta; Espnes, Hilde; Jacobsen, Bjarne K. & Kildal, Simon [Show all 12 contributors for this article] (2022). Sex-specific time trends in incident atrial fibrillation and the contribution of risk factors: the Tromsø Study 1994-2016. European Journal of Preventive Cardiology (EJPC). ISSN 2047-4873. 30(1), p. 72–81. doi: 10.1093/eurjpc/zwac234. Full text in Research Archive Show summary

  Aims To explore sex-specific time trends in atrial fibrillation (AF) incidence and to estimate the impact of changes in risk factor levels using individual participant-level data from the population-based Tromsø Study 1994–2016. Methods and results A total of 14 818 women and 13 225 men aged 25 years or older without AF were enrolled in the Tromsø Study between 1994 and 2008 and followed up for incident AF throughout 2016. Poisson regression was used for statistical analyses. During follow-up, age-adjusted AF incidence rates in women decreased from 1.19 to 0.71 per 1000 person-years. In men, AF incidence increased from 1.18 to 2.82 per 1000 person-years in 2004, and then declined to 1.94 per 1000 person-years in 2016. Changes in systolic blood pressure (SBP) and diastolic blood pressure (DBP), body mass index (BMI), physical activity, smoking and alcohol consumption together accounted for 10.9% [95% confidence interval (CI): −2.4 to 28.6] of the AF incidence decline in women and for 44.7% (95% CI: 19.2; 100.0) of the AF incidence increase in men. Reduction in SBP and DBP had the largest contribution to the decrease in AF incidence in women. Increase in BMI had the largest contribution to the increase in AF incidence in men. Conclusion In the population-based Tromsø Study 1994–2016, AF incidence decreased in women and increased following a reverse U-shape in men. Individual changes in SBP and DBP in women and individual changes in BMI in men were the most important risk factors contributing to the AF incidence trends.

• Averina, Maria; Stylidis, Michael; Brox, Jan & Schirmer, Henrik (2022). NT-ProBNP and high-sensitivity troponin T as screening tests for subclinical chronic heart failure in a general population. ESC Heart Failure. 9(3), p. 1954–1962. doi: 10.1002/ehf2.13906. Full text in Research Archive Show summary

  Aims The aim of this study was to establish age-specific and sex-specific cut-off values for N-terminal pro-brain natriuretic peptide (NT-proBNP) and high-sensitivity troponin T (hs-troponin T) in healthy subjects and assess cardiac biomarkers as screening tools for subclinical heart failure (HF) in a general population.<p> <p>Methods and results Altogether, 1936 participants were randomly selected from the general population Tromsø 7 study in Northern Norway. Diagnostic accuracy (sensitivity, specificity, and negative and positive predictive value) of cardiac markers for echocardiographically defined subclinical HF was evaluated. The receiver-operating characteristic analysis showed that areas under the curve were relatively low (under 0.75) for both NT-proBNP and hs-troponin T, suggesting that the diagnostic accuracy of these biomarkers for subclinical HF was not excellent, especially for mild forms of HF and younger age group 40–49 years. Sex-specific and age-specific cut-offs for hs-troponin T (99th percentiles) and NT-proBNP (97.5th percentiles) were established in healthy subjects from the same general population. The sex-specific and age-specific cut-offs for NT-proBNP had higher specificity for subclinical HF compared with the previously established single cut-off 125 pg/mL. Age-specific cut-off for hs-troponin T (18 ng/L) for men ≥60 years had also higher specificity than the single cut-off 14 ng/L. These cut-offs had high specificity, but low sensitivity, that makes hs-troponin T and NT-proBNP good biomarkers to rule in HF in case of a positive test, but not good enough to rule out all unrecognized HF due to false negative results.<p> <p>Conclusions N-terminal pro-brain natriuretic peptide and hs-troponin T are suboptimal screening tools for subclinical HF in a general population due to low sensitivity.

• Benavente, Ernest Diez; Jimenez-Lopez, Francisco; Attia, Zachi I.; Malyutina, Sofia; Kudryavtsev, Alexander & Ryabikov, Andrew [Show all 14 contributors for this article] (2021). Studying accelerated cardiovascular ageing in Russian adults through a novel deep-learning ECG biomarker. Wellcome Open Research. 6, p. 1–12. doi: 10.12688/wellcomeopenres.16499.1. Full text in Research Archive Show summary

  Background: A non-invasive, easy-to-access marker of accelerated cardiac ageing would provide novel insights into the mechanisms and aetiology of cardiovascular disease (CVD) as well as contribute to risk stratification of those who have not had a heart or circulatory event. Our hypothesis is that differences between an ECG-predicted and chronologic age of participants (δage) would reflect accelerated or decelerated cardiovascular ageing Methods: A convolutional neural network model trained on over 700,000 ECGs from the Mayo Clinic in the U.S.A was used to predict the age of 4,542 participants in the Know Your Heart study conducted in two cities in Russia (2015-2018). Thereafter, δage was used in linear regression models to assess associations with known CVD risk factors and markers of cardiac abnormalities. Results: The biomarker δage (mean: +5.32 years) was strongly and positively associated with established risk factors for CVD: blood pressure, body mass index (BMI), total cholesterol and smoking. Additionally, δage had strong independent positive associations with markers of structural cardiac abnormalities: N-terminal pro b-type natriuretic peptide (NT-proBNP), high sensitivity cardiac troponin T (hs-cTnT) and pulse wave velocity, a valid marker of vascular ageing. Conclusion: The difference between the ECG-age obtained from a convolutional neural network and chronologic age (δage) contains information about the level of exposure of an individual to established CVD risk factors and to markers of cardiac damage in a way that is consistent with it being a biomarker of accelerated cardiovascular (vascular) ageing. Further research is needed to explore whether these associations are seen in populations with different risks of CVD events, and to better understand the underlying mechanisms involved.

• Pedersen, Elisabeth; Garcia, Beate Hennie; Halvorsen, Kjell H.; Eggen, Anne Elise; Schirmer, Henrik & Waaseth, Marit (2021). Adherence to prescription guidelines and achievement of treatment goals among persons with coronary heart disease in Tromsø 7. BMC Cardiovascular Disorders. 21(1), p. 1–11. doi: 10.1186/s12872-021-01866-1. Full text in Research Archive Show summary

  Background - Adherence to clinical practice guidelines for coronary heart disease (CHD) reduces morbidity, mortality and treatment costs. We aimed to describe and compare adherence to prescription guidelines for persons with CHD, and explore its association with treatment goal achievement.<p> <p>Method - We included all participants reporting myocardial infarction, angina, percutaneous coronary intervention and/or coronary artery bypass surgery in the seventh wave of the Tromsø Study (2015–2016, n = 1483). Medication use and treatment goal measures (blood pressure, low-density lipoprotein (LDL)-cholesterol and HbA1c) were compared to clinical practice guidelines on secondary CHD prevention. Propensity score matched logistic regression was used to assess the association between the use of antihypertensive drugs and achievement of treatment goal for blood pressure, and the use of lipid-lowering drugs (LLDs) and achievement of treatment goal for LDL-cholesterol.<p> <p>Results - The prevalence of pharmacological CHD treatment was 76% for LLDs, 72% for antihypertensive drugs and 66% for acetylsalicylic acid. The blood pressure goal (< 140/90 mmHg, < 140/80 mmHg if diabetic) was achieved by 58% and the LDL-cholesterol goal (< 1.8 mmol/l or < 70 mg/dL) by 9%. There was a strong association between using LLDs and achieving the treatment goal for LDL-cholesterol (OR 14.0, 95% CI 3.6–54.7), but not between using antihypertensive drugs and blood pressure goal achievement (OR 1.4, 95% CI 0.7–2.7).<p> <p>Conclusion - Treatment goal achievement of LDL-cholesterol and blood pressure was low, despite the relatively high use of LLDs and antihypertensive drugs. Further research is needed to find the proper actions to increase achievement of the treatment goals.

• Fladseth, Kristina; Lindekleiv, Haakon; Nielsen, Christopher Sivert; Øhrn, Andrea; Kristensen, Andreas & Mannsverk, Jan Torbjørn [Show all 15 contributors for this article] (2021). Low pain tolerance is associated with coronary angiography, coronary artery disease, and mortality: The Tromsø study. Journal of the American Heart Association (JAHA). 10(22). doi: 10.1161/JAHA.121.021291. Full text in Research Archive Show summary

  BACKGROUND: The initial presentation to coronary angiography and extent of coronary artery disease (CAD) vary greatly among patients, from ischemia with no obstructive CAD to myocardial infarction with 3-vessel disease. Pain tolerance has been suggested as a potential mechanism for the variation in presentation of CAD. We aimed to investigate the association between pain tolerance, coronary angiography, CAD, and death.<p> <p>METHODS AND RESULTS: We identified 9576 participants in the Tromsø Study (2007–2008) who completed the cold-pressor pain test, and had no prior history of CAD. The median follow-up time was 10.4 years. We applied Cox-regression models with age as time-scale to calculate hazard ratios (HR). More women than men aborted the cold pressor test (39% versus 23%). Participants with low pain tolerance had 19% increased risk of coronary angiography (HR, 1.19 [95% CI, 1.03–1.38]) and 22% increased risk of obstructive CAD (HR, 1.22 [95% CI, 1.01–1.47]) adjusted by age as time-scale and sex. Among women who underwent coronary angiography, low pain tolerance was associated with 54% increased risk of obstructive CAD (HR, 1.54 [95% CI, 1.09–2.18]) compared with high pain tolerance. There was no association between pain tolerance and nonobstructive CAD or clinical presentation to coronary angiography (ie, stable angina, unstable angina, and myocardial infarction). Participants with low pain tolerance had increased risk of mortality after adjustment for CAD and cardiovascular risk factors (HR, 1.40 [95% CI, 1.19–1.64]).<p> <p>CONCLUSIONS: Low cold pressor pain tolerance is associated with a higher risk of coronary angiography and death.

• Kjønås, Didrik; Dahle, Gry; Schirmer, Henrik; Malm, Siri; Eidet, Jo & Aaberge, Lars [Show all 10 contributors for this article] (2021). Risk scores for prediction of 30-day mortality after transcatheter aortic valve implantation: Results from a two-center study in Norway. Health Science Reports. 4(2). doi: 10.1002/hsr2.283. Full text in Research Archive Show summary

  Objectives Transcatheter aortic valve implantation (TAVI)-specific risk scores have been developed based on large registry studies. Our aim was to evaluate how both surgical and novel TAVI risk scores performed in predicting all cause 30-day mortality. In addition, we wanted to explore the validity of our own previously developed model in a separate and more recent cohort. Methods The derivation cohort included patients not eligible for open surgery treated with TAVI at the University Hospital of North Norway (UNN) and Oslo University Hospital (OUS) from February 2010 through June 2013. From this cohort, a logistic prediction model (UNN/OUS) for all cause 30-day mortality was developed. The validation cohort consisted of patients not included in the derivation cohort and treated with TAVI at UNN between June 2010 and April 2017. EuroSCORE, Logistic EuroSCORE, EurosSCORE 2, STS score, German AV score, OBSERVANT score, IRRMA score, and FRANCE-2 score were calculated for both cohorts. The discriminative accuracy of each score, including our model, was evaluated by receiver operating characteristic (ROC) analysis and compared using DeLong test where P< .05 was considered statistically significant. Results The derivation cohort consisted of 218 and the validation cohort of 241 patients. Our model showed statistically significant better accuracy than all other scores in the derivation cohort. In the validation cohort, the FRANCE-2 had a significantly higher predictive accuracy compared to all scores except the IRRMA and STS score. Our model showed similar results. Conclusion Existing risk scores have shown limited accuracy in predicting early mortality after TAVI. Our results indicate that TAVI-specific risk scores might be useful when evaluating patients for TAVI.

• Iakunchykova, Olena; Schirmer, Henrik; Leong, Darryl; Malyutina, Sofia; Ryabikov, Andrew & Averina, Maria [Show all 12 contributors for this article] (2021). Heavy alcohol drinking and subclinical echocardiographic abnormalities of structure and function. Open heart. 8(1). doi: 10.1136/openhrt-2020-001457. Full text in Research Archive Show summary

  Objective - The aim of the study is to assess changes in heart structure and function associated with heavy alcohol use by comparing echocardiographic indices in a population-based sample to those in patients admitted to an inpatient facility with severe alcohol problems.<p> <p>Methods and results - We used data from the Know Your Heart study (2015–2017) which is a cross-sectional study that recruited 2479 participants aged 35–69 years from the general population of the city of Arkhangelsk in Northwest Russia and 278 patients from the Arkhangelsk Regional Psychiatric Hospital with a primary diagnosis related to chronic alcohol use (narcology clinic subsample). The drinking patterns of the population-based sample were characterised in detail. We used regression models controlling for age, sex, smoking, education and waist to hip ratio to evaluate the differences in echocardiographic indices in participants with different drinking patterns. The means of left ventricular end-diastolic diameter and indexed left atrial systolic diameter were increased among heavy drinkers (narcology clinic subsample), while mean left ventricular ejection fraction was decreased in this group compared with the population-based sample. In contrast, the harmful and hazardous drinkers in the population-based sample did not differ from non-problem drinkers with respect to echocardiographic indices of systolic and diastolic function.<p> <p>Conclusions - Extremely heavy drinking is associated with a specific set of structural and functional abnormalities of the heart that may be regarded as precursors of alcohol-related dilated cardiomyopathy.

• Attia, Itzhak Zachi; Tseng, Andrew S.; Benavente, Ernest Diez; Medina-Inojosa, Jose R.; Clark, Taane & Malyutina, Sofia [Show all 16 contributors for this article] (2021). External validation of a deep learning electrocardiogram algorithm to detect ventricular dysfunction. International Journal of Cardiology. ISSN 0167-5273. 329, p. 130–135. doi: 10.1016/j.ijcard.2020.12.065. Full text in Research Archive Show summary

  Objective - To validate a novel artificial-intelligence electrocardiogram algorithm (AI-ECG) to detect left ventricular systolic dysfunction (LVSD) in an external population.<p> <p>Background - LVSD, even when asymptomatic, confers increased morbidity and mortality. We recently derived AI-ECG to detect LVSD using ECGs based on a large sample of patients treated at the Mayo Clinic.<p> <p>Methods - We performed an external validation study with subjects from the Know Your Heart Study, a cross-sectional study of adults aged 35–69 years residing in two cities in Russia, who had undergone both ECG and transthoracic echocardiography. LVSD was defined as left ventricular ejection fraction ≤ 35%. We assessed the performance of the AI-ECG to identify LVSD in this distinct patient population.<p> <p>Results - Among 4277 subjects in this external population-based validation study, 0.6% had LVSD (compared to 7.8% of the original clinical derivation study). The overall performance of the AI-ECG to detect LVSD was robust with an area under the receiver operating curve of 0.82. When using the LVSD probability cut-off of 0.256 from the original derivation study, the sensitivity, specificity, and accuracy in this population were 26.9%, 97.4%, 97.0%, respectively. Other probability cut-offs were analysed for different sensitivity values.<p> <p>Conclusions - The AI-ECG detected LVSD with robust test performance in a population that was very different from that used to develop the algorithm. Population-specific cut-offs may be necessary for clinical implementation. Differences in population characteristics, ECG and echocardiographic data quality may affect test performance.

• Kjønås, Didrik; Schirmer, Henrik; Aakhus, Svend; Eidet, Jo; Malm, Siri & Aaberge, Lars [Show all 8 contributors for this article] (2021). Clinical and Echocardiographic Parameters Predicting 1- and 2-Year Mortality After Transcatheter Aortic Valve Implantation. Frontiers in Cardiovascular Medicine. 8. doi: 10.3389/fcvm.2021.739710. Full text in Research Archive Show summary

  Background: Transcatheter aortic valve implantation (TAVI) has become a standard treatment option for patients with symptomatic aortic stenosis. Elderly high-risk patients treated with TAVI have a high residual mortality due to preexisting comorbidities. Knowledge of factors predicting futility after TAVI is sparse and clinical tools to aid the preoperative evaluation are lacking. The aim of this study was to evaluate if echocardiographic measures, including speckle-tracking analysis, in addition to clinical parameters, could aid in the prediction of mortality beyond 30 days after TAVI. Methods: This prospective observational cohort study included 227 patients treated with TAVI at the University Hospital of North Norway, Tromsø and Oslo University Hospital, Rikshospitalet from February 2010 to June 2013. All the patients underwent preoperative echocardiographic evaluation with retrospective speckle-tracking analysis. Primary endpoints were 1- and 2-year mortality beyond 30 days after TAVI. Results: All-cause 1- and 2-year mortality beyond 30 days after TAVI was 12.1 and 19.5%, respectively. Predictors of 1-year mortality beyond 30 days were body mass index [hazard ratio (HR): 0.88, 95% CI: 0.80–0.98, p = 0.018], previous myocardial infarction (HR: 2.69, 95% CI: 1.14–6.32, p = 0.023), and systolic pulmonary artery pressure ≥ 60 mm Hg (HR: 5.93, 95% CI: 1.67–21.1, p = 0.006). Moderate-to-severe mitral regurgitation (HR: 2.93, 95% CI: 1.53–5.63, p = 0.001), estimated glomerular filtration rate (HR: 0.98, 95% CI: 0.96–0.99, p = 0.002), and chronic obstructive pulmonary disease (HR: 1.9, 95% CI: 1.01–3.58, p = 0.046) were predictors of 2-year mortality. Conclusion: Both the clinical and echocardiographic parameters should be considered when evaluating high-risk patients for TAVI, as both are predictive of 1-and 2-year mortality. Our results support the importance of individual risk assessment using a multidisciplinary, multimodal, and individual approach.

• Berge, Kristian; Lyngbakken, Magnus Nakrem; Omland, Torbjørn; Juliebø, Vibeke; Schirmer, Henrik & Røsjø, Helge Rørvik (2021). Ytterligere læringsmomenter fra et kardiologisk perspektiv. Tidsskrift for Den norske legeforening (Tidsskriftet). ISSN 0029-2001. 141(1). doi: 10.4045/tidsskr.20.1025. Full text in Research Archive
• Stikbakke, Einar; Schirmer, Henrik; Knutsen, Tore; Støyten, Martin; Wilsgaard, Tom & Giovannucci, Edward L. [Show all 11 contributors for this article] (2021). Systolic and diastolic blood pressure, prostate cancer risk, treatment, and survival. The PROCA-life study. Cancer Medicine. doi: 10.1002/cam4.4523. Full text in Research Archive Show summary

  Background: Inflammation has been linked to prostate cancer and hypertension, but it remains equivocal whether elevated blood pressure (BP) influence prostate cancer risk and survival.<p> <p>Method: Using Cox regression models, we examined the association between prediagnostic BP and prostate cancer risk among 12,271 men participating in the Prostate Cancer throughout life (PROCA-life) study. Systolic and diastolic BP were measured. A total of 811 men developed prostate cancer, and followed for additional 7.1 years, and we studied the association between prediagnostic BP and overall mortality among patients with prostate cancer.<p> <p>Results: Men (>45 years) with a systolic BP >150 mmHg had a 35% increased risk of prostate cancer compared with men with a normal systolic BP (<130 mmHg) (HR 1.35, 95% CI 1.08–1.69). Among patients with prostate cancer, men with systolic BP >150 mmHg had a 49% increased overall mortality compared with men with a normal systolic BP (HR 1.49, 1.06–2.01). Among patients with prostate cancer treated with curative intent, those with a high diastolic BP (>90 mmHg) had a threefold increase in overall mortality risk (HR 3.01, 95% CI 1.40–6.46) compared with patients with a normal diastolic BP (<80 mmHg).<p> <p>Conclusion: Our results support that systolic and diastolic BP are important factors when balancing disease management in patients with prostate cancer.

• Ookeditse, Ookeditse; Motswakadikgwa, Thusego R.; Ookeditse, Kebadiretse K.; Masilo, Gosiame; Bogatsu, Yaone & Lekobe, Baleufi Calstro [Show all 9 contributors for this article] (2021). Healthcare professionals' knowledge of modifiable stroke risk factors: A cross-sectional questionnaire survey in greater Gaborone, Botswana. eNeurologicalSci. 25, p. 1–6. doi: 10.1016/j.ensci.2021.100365. Full text in Research Archive Show summary

  Background Stroke remains the second leading cause of deaths and disability globally, with highest mortality in Africa (low- and middle-income countries). It is crucial for healthcare professionals to have sufficient stroke risk factors' knowledge in order to reduce the stroke burden. Aims We investigated healthcare professionals' knowledge of modifiable stroke risk factors, and identified demographic factors influencing this knowledge. Methods In this cross-sectional survey study from Botswana (upper middle-income country), structured questionnaires reflecting recent stroke guidelines were administered to a representative selection of healthcare workers in greater Gaborone. The response rate was 61.4%, comprising 84 doctors, 227 nurses and 33 paramedics. Categorical data were described using percentages and Chi-square tests. Associations between stroke risk factors' knowledge and demographic factors were analyzed with one-way ANOVA using SPSS 25 statistical software. Results Awareness rate of individual stroke risk factors was highest for hypertension (96.5%), followed by obesity (93.3%), smoking (91.9%), elevated total cholesterol (91.0%), physical inactivity (83.4%), elevated low-density lipoprotein (LDL) cholesterol (81.1%), excessive alcohol drinking (77.0%), and lowest for diabetes (73.3%). For all-8 risk factors, doctors had the highest knowledge, followed by nurses and paramedics lowest (7.11 vs 6.85 vs 6.06, P < 0.05). Conclusion In Botswana, specific healthcare professionals' subgroups need to be targeted for continuing education on stroke risk factors for improving stroke prevention and reducing stroke-related disability and mortality.

• Heitmann, Kim Arne; Løchen, Maja-Lisa; Hopstock, Laila Arnesdatter; Stylidis, Michael; Welde, Boye & Schirmer, Henrik [Show all 7 contributors for this article] (2021). Cross-sectional associations between accelerometry-measured physical activity, left atrial size, and indices of left ventricular diastolic dysfunction: The Tromsø Study. Preventive Medicine Reports. 21, p. 1–8. doi: 10.1016/j.pmedr.2020.101290. Full text in Research Archive Show summary

  Whereas left atrial (LA) enlargement is an independent predictor for adverse cardiovascular events and all-cause mortality, this is regarded a physiological adaption of exercise. Paradoxically, LA size in athletes may overlap the enlargement observed in patients with cardiac pathology. Current knowledge is mainly derived from studies of athletes, and little is known about cardiac adaptations to physical activity (PA) in the general population. We explored the association between objectively measured PA and LA volume index (LAVi), and between LAVi enlargement and indices of diastolic dysfunction stratified by PA-level. Our study included 1573 participants from the population-based Tromsø Study (2015–16). PA was assessed with an ActiGraph wGT3X-BT accelerometer. Echocardiography was performed according to current guidelines. The associations between PA and LAVi, and between LAVi enlargement and indices of diastolic dysfunction were estimated by univariable and multivariable linear regression analyses, adjusted for sex, age, and cardiovascular risk factors. Our multiple adjusted analyses showed significant linear associations between PA and LAVi in ages

• Johnsen, Bente; Strand, Bjørn Heine; Martinaityte, Ieva; Mathiesen, Ellisiv Bøgeberg & Schirmer, Henrik (2021). Improved Cognitive Function in the Tromsø Study in Norway From 2001 to 2016. Neurology: Clinical Practice. ISSN 2163-0402. 11(6), p. e856–e866. doi: 10.1212/CPJ.0000000000001115. Full text in Research Archive

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• Vinje-Jakobsen, Victoria; Gynnild, Mari Nordbø; Mecinaj, Albulena; Wisløff, Torbjørn; Holte, Espen & Wethal, Torgeir [Show all 13 contributors for this article] (2026). The effect of sacubitril/valsartan on functional disability and skeletal muscle injury during breast cancer therapy: insights from the PRADA II trial. Full text in Research Archive Show summary

  Background: Anthracycline therapy induces dose-dependent cardiotoxicity and systemic adverse effects, including functional disability. While sacubitril/valsartan attenuates early subclinical myocardial injury during breast cancer therapy, its impact on functional capacity and skeletal muscle injury remains unknown. Purpose: To evaluate whether sacubitril/valsartan attenuates anthracycline-induced decline in functional capacity and skeletal muscle injury compared to placebo. Methods: PRADA II was a randomised, double-blind, placebo-controlled multicentre trial including 138 women with early breast cancer receiving (neo)adjuvant anthracycline therapy±trastuzumab. Participants were randomised prior to anthracycline initiation to sacubitril/valsartan or placebo for 18 months. The predefined primary outcome of this substudy was change in maximal handgrip strength from baseline to 18 months. Secondary outcomes included changes in 6-minute walk distance and circulating creatine kinase (CK) and myoglobin concentrations. Assessments were performed at baseline, post-anthracycline (Visit 2), and at 18 months (Visit 3). Changes were analysed using generalised linear mixed models, and a two-sided alpha level of 0.05 was applied to the primary outcome of this predefined substudy. Results: Maximal handgrip strength declined in both groups from baseline to Visit 2, with partial recovery at Visit 3 in the sacubitril/valsartan group and continued decline in the placebo group. No significant between-group difference was observed in handgrip strength (between-group change from baseline to Visit 3: -0.3 kg, 95% CI -1.5 to 0.8, p=0.57). However, a greater decline from baseline to Visit 2 was observed with sacubitril/valsartan than placebo, corresponding to a between-group difference of -1.8 kg, 95% CI -3.0 to -0.6. 6-minute walk distance increased from baseline to both follow-up timepoints in the sacubitril/valsartan group, and a transient reduction was observed in the placebo group from baseline to Visit 2. Between-group changes did not differ at Visit 2 (8.8 m, 95% CI -19.3 to 36.9) or Visit 3 (13.6 m, 95% CI -13.3 to 40.5). CK and myoglobin were numerically higher in the placebo group from baseline to Visit 3, however, the confidence intervals for between-group differences included the null value (CK geometric mean ratio 1.17, 95% CI 0.94 to 1.45; myoglobin 1.10, 95% CI 0.98 to 1.23). Temporal changes by randomisation group are shown in Figure 1. Conclusions: Sacubitril/valsartan did not significantly attenuate anthracycline-related decline in functional capacity assessed by maximal handgrip strength and 6-minute walk distance or changes in biomarkers of skeletal muscle injury. These findings suggest a neutral effect of sacubitril/valsartan on functional capacity, without challenging its potential cardioprotective role during anthracycline therapy.

• Vinje-Jakobsen, Victoria; Orstad, Eivind Bjørkan; Gulati, Geeta; Nerdrum, Tone; Iqbal, Naveed & Schirmer, Henrik [Show all 9 contributors for this article] (2026). Incidence and severity of cancer-therapy-related cardiac dysfunction during contemporary breast cancer therapy in a real-world cohort. Full text in Research Archive Show summary

  Background: Cancer therapy-related cardiac dysfunction (CTRCD) is a well-known complication in breast cancer patients exposed to anthracyclines and Human Epidermal Growth Factor Receptor 2 (HER2) targeted therapy. However, the incidence of CTRCD in unselected contemporary breast cancer populations treated according to current standard-of-care regimens remains incompletely investigated. Purpose: To determine the incidence of CTRCD in women receiving (neo-)adjuvant breast cancer therapy in a real-world setting. Methods: In this prospective observational study, women scheduled for (neo-)adjuvant breast cancer therapy were included. Participants were categorized into three treatment regimen groups: 1) anthracycline therapy only, 2) HER2-targeted therapy only, and 3) sequential treatment with anthracycline therapy followed by HER2-targeted therapy. The primary endpoint was the incidence of CTRCD, defined according to the echocardiographic criteria included in the 2022 ESC Cardio-Oncology Guidelines (Figure 1), from baseline to 12 months after completion of scheduled therapy. Echocardiography was assessed at baseline, after completion of scheduled therapy, and 12 months thereafter. In addition, echocardiography was performed every 3 months during HER2-targeted therapy and when clinically indicated. Results: In total, 515 women were included (median age: 53 years (IQR 45,64)). During follow-up, 123 (24%) developed CTRCD. Of these, 78% were classified as mild, 19% moderate, and 2% severe. The highest incidence of CTRCD was observed among participants receiving sequential anthracycline therapy (EC90 x 4) and HER2-targeted therapy (Table 1). This regimen also had the highest incidence of moderate and severe CTRCD (13%), compared with 4% in the anthracycline-only group and 1% in the HER2-only group. Overall, severe CTRCD was observed in 0.6% of all study participants. The cumulative incidence of the worst observed severity of CTRCD during follow-up, overall and by treatment regimen, is summarized in Table 1. Conclusion: In this real-world breast cancer cohort, nearly one in four women developed CTRCD during follow-up; however, most cases were categorised as mild. Moderate and severe cardiac dysfunction were primarily observed in patients receiving sequential anthracycline and HER2-targeted therapy. Severe CTRCD was rare in the overall study population.

• Vinje-Jakobsen, Victoria; Orstad, Eivind Bjørkan; Gulati, Geeta; Caliskan, Gulser; Nerdrum, Tone & Iqbal, Naveed [Show all 10 contributors for this article] (2026). Rationale, design and baseline characteristics of the cardio-oncology registry (CARE) study: a prospective, observational study of cardiotoxic effects during breast cancer therapy. European Heart Journal, Supplement. ISSN 1520-765X. 28(Supplement_8). doi: 10.1093/eurheartjsupp/suag097.103. Full text in Research Archive Show summary

  Background: Anthracycline and Human Epidermal Growth Factor Receptor 2 (HER2) targeted therapy may induce cancer therapy-related cardiac dysfunction (CTRCD). Current guidelines recommend risk stratification using the Heart Failure Association–International Cardio-Oncology Society (HFA-ICOS) risk assessment tool. However, data on the incidence of CTRCD in contemporary breast cancer populations treated according to current standard-of-care regimens remain limited. Moreover, the actual cardiovascular risk associated with the HFA-ICOS risk categories in breast cancer treatment remains uncertain. Real-world evaluation of whether this consensus-based stratification appropriately separates patients according to subsequent CTRCD risk has been highlighted as a key research priority. Purpose: Overall, the study aims to determine the incidence of CTRCD and to evaluate cardiovascular risk stratification using the HFA-ICOS tool and its association with subsequent CTRCD. Methods: CARE is a prospective observational study including women scheduled for (neo)adjuvant anthracycline therapy and/or HER2-targeted therapy. Echocardiography, using standard and novel echocardiographic parameters, and circulating cardiac biomarkers were assessed at baseline (visit 1), after completion of scheduled therapy (visit 2), and 12 months after completion of scheduled therapy (visit 3). Participants were categorized into three treatment regimen groups: 1) Anthracycline therapy only, 2) HER2-targeted therapy only, and 3) HER2-targeted therapy sequentially to anthracyclines (Figure 1). The primary outcome is incidence of CTRCD. Secondary outcomes include HFA-ICOS risk stratification in relation to subsequent CTRCD. Results: In total, 515 women (median age (Q1,Q3): 53 (45,64) years) were included. Overall, 335 (63%) participants received anthracycline therapy only, 100 (15%) received HER2-targeted therapy only, and 80 (19%) received anthracycline therapy followed by HER2-targeted therapy. Baseline cardiovascular risk factors included hypertension in 20%, current smoking in 13%, diabetes in 7%, and a history of heart disease in 7.6%, while 3.5% had received previous anti-cancer treatment (Table 1). Conclusion: The CARE study is a large prospective observational cardio-oncology study evaluating the incidence of CTRCD after contemporary breast cancer therapy regimens. With systematic echocardiographic and biomarker assessment, the study will provide important insights into the incidence of CTRCD, the performance of the HFA-ICOS risk stratification tool and follow-up strategies in routine cardio-oncology care.Table 1Baseline Characteristics CARE  Figure 1Consort Diagram

• 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.

• 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.

• 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
• Moen, Oda Klavestad; Johannessen, Øyvind; Myhre, Peder Langeland; Heck, Siri Lagethon; Corbett, Rebecca Aure & Windstad, Vilde Malo [Show all 10 contributors for this article] (2025). Pre-test probability (PTP) for coronary artery disease (CAD) is enhanced by incorporating risk factors and coronary artery calcium (CAC) score. European Society of Cardiology. Full text in Research Archive
• Johansson, Elias Stenhede; Ravn, Jesper; Schirmer, Henrik & Ranjbar, Arian (2025). Detection of hospital-admitted heart failure regardless of ejection fraction using artificial intelligence-enhanced electrocardiograms. European Heart Journal. ISSN 0195-668X. 46. doi: https:/academic.oup.com/eurheartj/article/46/Supplement_1/ehaf784.1167/8310259. Full text in Research Archive Show summary

  Heart failure (HF) presents with diverse and often non-specific symptoms, frequently overlapping with those of other conditions, making it challenging to diagnose accurately. Developing a more affordable and widely available diagnostic method that provides immediate feedback could improve the care and management of patients with HF. Previous work on AI-enabled ECG for detecting HF has largely been based on echocardiographic labelling for model training, and often focused on particular phenotypes of HF like HF with reduced or preserved ejection fraction (EF). Our aim was to develop an AI model identifying HF across the EF spectrum and to show that explicit echocardiographic labelling is in fact not necessary, and that a cheaper data labelling strategy results in AI models with desirable diagnostic properties. ECGs from a network of four tertiary hospitals in the period 2016-2024 were used, with data from 2016-2022 for development (40,000 patients, 161,000 ECGs) and 2023-2024 (43,000 new patients) for prospective testing. Using our proposed labelling strategy based on ICD-10 codes and NT-proBNP levels in the development set, 20,000 ECGs were labelled as HF and 58,000 as non-HF, while 83,000 ECGs were excluded due to uncertain status i.e. NT-proBNP between 125 and 1000 ng/L. An ensemble of cross-validated AI models was evaluated on the first ECG of each of the 43,000 patients (3,500 with HF diagnosis), including 5,000 who had an echocardiogram within 14 days. The model achieved high diagnostic accuracy for hospital-diagnosed heart failure (HF) with an AUC of 0.84 (95% CI 0.831-0.848), regardless of EF and NT-proBNP levels. For the population with measured NT-proBNP levels, the model outperformed NT-proBNP in diagnostic accuracy (p = 7.5e-7). In the test set with echocardiography, the model detected HF with reduced EF with an AUC of 0.91 (95% CI 0.894-0.931) and HF with preserved EF with an AUC of 0.68-0.89, depending on definition. Comparison with the H2FPEF risk score showed that model-predicted risk increased with the score and further stratified risk within each category. To highlight the impact of underdiagnosis in evaluating the model, we conducted a small-scale retrospective clinical evaluation of 60 patients with EF >50%, no HF diagnosis, and normal NT-proBNP levels (<125 ng/L). Out of the 60 patients, 30 had a low model-predicted risk while 30 had a high risk; 24 of the 30 highest-risk patients met HFpEF criteria, while 27 of the 30 lowest-risk patients did not. Our study shows that using a dataset of patients with clinical HF or no HF validated via NT-proBNP in the development phase, a neural network can be trained to detect of HF independent of EF, including HFpEF with low NT-proBNP. The model could serve as an accessible diagnostic marker for HF in primary care, as a screening tool to identify patients who may benefit from further evaluation by e.g. echocardiography.

• Schirmer, Henrik (2025). Livet etter hjerteinfarkt. Tidsskrift for Den norske legeforening (Tidsskriftet). ISSN 0029-2001. 145(5). doi: 10.4045/tidsskr.25.0168. Full text in Research Archive
• Fladseth, Kristina; Mannsverk, Jan Torbjørn & Schirmer, Henrik (2024). Kronisk koronarsyndrom. Hjerteforum. ISSN 0802-1465. 37(1), p. 44–53. Full text in Research Archive
• Ranjbar, Arian; Singstad, Bjørn-Jostein; Ravn, Jesper & Schirmer, Henrik (2023). Towards Invariant Soft Biometrics from Electrocardiograms. Computing in cardiology. ISSN 2325-8861. 50. doi: 10.22489/CinC.2023.156. 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
• Iakunchykova, Olena; Schirmer, Henrik; Vangberg, Torgil Riise; Wang, Yunpeng; Benavente, Ernest Diez & Es, Rene Van [Show all 11 contributors for this article] (2023). Machine-learning derived measures of vascular and brain age are independently associated with cognitive function. European Journal of Preventive Cardiology (EJPC). ISSN 2047-4873. Full text in Research Archive
• Vijayakumar, Arya Panthalanickal; Wilsgaard, Tom; Schirmer, Henrik; Lindekleiv, Haakon; Attia, Zachi I & Lopez-Jimenez, Francisco [Show all 8 contributors for this article] (2023). Associations of educational level with cardiovascular aging described with a novel machine learning derived biomarker based on electrocardiograms. Full text in Research Archive
• Heitmann, Kim Arne; Løchen, Maja-Lisa; Hopstock, Laila Arnesdatter; Stylidis, Michael; Welde, Boye & Schirmer, Henrik [Show all 7 contributors for this article] (2022). Associations between accelerometer-measured physical activity and left atrial size in a general population: The Tromsø Study 2015-16. Full text in Research Archive
• Hämäläinen, Soile; Salamonsen, Anita; Musial, Frauke; Graff, Ola; Schirmer, Henrik & Olsen, Torjer Andreas [Show all 7 contributors for this article] (2022). Kan joik være bra for helsa? Full text in Research Archive
• Heitmann, Kim Arne; Løchen, Maja-Lisa; Hopstock, Laila Arnesdatter; Stylidis, Michael; Welde, Boye & Schirmer, Henrik [Show all 7 contributors for this article] (2022). Associations between accelerometer-measured physical activity and left atrial size in a general population: The Tromsø Study 2015-16. Full text in Research Archive
• Morseth, Bente; Løchen, Maja-Lisa; Hopstock, Laila Arnesdatter; Stylidis, Michael; Welde, Boye & Schirmer, Henrik [Show all 7 contributors for this article] (2022). Sex differences in the associations between physical activity, left atrial size and atrial fibrillation: The Tromsø Study. Full text in Research Archive
• Hämäläinen, Soile; Musial, Frauke; Graff, Ola; Schirmer, Henrik; Olsen, Torjer Andreas & Salamonsen, Anita [Show all 7 contributors for this article] (2022). Kan joik være bra for helsa? Presentasjon av samlet forskning fra fire publikasjoner. Full text in Research Archive
• Hämäläinen, Soile; Musial, Frauke; Graff, Ola; Schirmer, Henrik; Salamonsen, Anita & Mehus, Grete (2022). The art of yoik in care: Sami caregivers’ experiences in dementia care in Northern Norway. Full text in Research Archive
• Tiwari, Sweta; Cerin, Ester; Wilsgaard, Tom; Løvsletten, Ola; Njølstad, Inger & Grimsgaard, Sameline [Show all 11 contributors for this article] (2021). Risk factors for cardiovascular disease and psycho-socioeconomic determinants according to various living areas with lifestyle factors as mediators. The Tromsø Study. Dr.med. - Norwegian Journal of Epidemiology. Suppl.. 29, p. 36–36. Full text in Research Archive
• Hämäläinen, Soile Päivikki; Musial, Frauke; Graff, Ola; Schirmer, Henrik; Salamonsen, Anita & Mehus, Grete (2021). The art of yoik in care: Sami caregivers’ experiences in dementia care in Northern Norway. 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
• Hämäläinen, Soile; Mehus, Grete; Musial, Frauke; Schirmer, Henrik; Olsen, Torjer Andreas & Graff, Ola [Show all 7 contributors for this article] (2021). Kan joik være bra for helsa? En sammenfatning av våre publiserte studier. Full text in Research Archive
• Hämäläinen, Soile; Musial, Frauke; Graff, Ola; Schirmer, Henrik; Salamonsen, Anita & Mehus, Grete (2021). The art of yoik in care: Sami caregivers’ experiences in dementia care in Northern Norway. Full text in Research Archive
• Hämäläinen, Soile Päivikki; Musial, Frauke; Graff, Ola; Schirmer, Henrik; Salamonsen, Anita & Mehus, Grete (2021). The art of yoik in care: Sami caregivers’ experiences in dementia care in Northern Norway. Full text in Research Archive
• Pedersen, Elisabeth; Garcia, Beate Hennie; Halvorsen, Kjell H.; Eggen, Anne Elise; Schirmer, Henrik & Waaseth, Marit (2021). Correction to: Adherence to prescription guidelines and achievement of treatment goals among persons with coronary heart disease in Tromsø 7 (BMC Cardiovascular Disorders, (2021), 21, 1, (44), 10.1186/s12872-021-01866-1). BMC Cardiovascular Disorders. 21(1). doi: 10.1186/s12872-021-02214-z. Full text in Research Archive
• Opdal, Ida Marie; Larsen, Lill Sverresdatter; Hopstock, Laila Arnesdatter; Schirmer, Henrik & Lorem, Geir F (2021). Correction to: A prospective study on the effect of self-reported health and leisure time physical activity on mortality among an ageing population: results from the Tromsø study. BMC Public Health. 21. doi: 10.1186/s12889-021-10840-7. Full text in Research Archive
• Stenhede, Elias; Ranjbar, Arian & Schirmer, Henrik (2026). Trustworthy AI-ECG for heart failure detection. Universitetet i Oslo. ISSN 9788234808760. Full text in Research Archive Show summary

  Heart failure has a worse prognosis than most cancers, yet despite the existence of effective treatment, the condition often goes unnoticed with current diagnostic tools. This thesis shows that artificial intelligence applied to electrocardiograms (AI–ECG) can detect heart failure both with reduced and preserved ejection fraction. This work focuses on the development and validation of AI–ECG models for heart failure detection and on tools that convert paper ECGs into digital signals. Together, they enable the use of AI in healthcare settings with varying degrees of digital infrastructure. The AI–ECG model showed strong performance across both internal and external cohorts, and the AI–ECG risk of heart failure was closely related to echocardiographic measures of cardiac structure and function. The strongest correlation was found for global longitudinal strain, suggesting that the model might detect early myocardial dysfunction. All models and digitisation software have been released openly to support reproducibility and clinical use. Together, this work establishes AI–ECG as a scalable tool that can complement current diagnostic pathways and enable earlier detection of heart failure.

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