Torbjørn Omland

• Omland, Torbjørn; Paus, Michael Fredrik; Tveit, Arnljot; Berge, Trygve; Caliskan, Gulser & Brynildsen, Jon [Show all 9 contributors for this article] (2026). Prognostic Value of Cardiac Myosin Binding Protein C in the General Population: The Akershus Cardiac Examination 1950 Study. Clinical Chemistry. ISSN 0009-9147. 72(10), p. 1056–1066. doi: 10.1093/clinchem/hvag082. Full text in Research Archive Show summary

  Background: Cardiac myosin binding protein C (cMyC) is a cardiac-specific biomarker that is released after acute ischemic myocardial injury. Cardiac troponins are established cardiac biomarkers of myocardial injury and provide prognostic information in patients with cardiovascular disease (CVD) and in healthy persons from the general population. There is limited data documenting the prognostic value of cMyC in a general population setting. Accordingly, we assessed the prognostic value of cMyC for incident major adverse cardiovascular events (MACE) and mortality in a general population cohort and contrasted these associations with those of cardiac troponins. Methods: We measured cMyC, high-sensitivity cardiac troponin I (hs-cTnI), and high-sensitivity T (hs-cTnT) in serum samples from 3682 community dwellers born in 1950 at the baseline of the Akershus Cardiac Examination 1950 Study obtained from 2012 to 2015. We assessed the associations of all three biomarkers with a composite MACE outcome (nonfatal myocardial infarction, nonfatal ischemic stroke, nonfatal heart failure, myocardial revascularization, or cardiovascular mortality), as well as with all-cause, cardiovascular and non-cardiovascular mortality separately. Results: The median age was 63.9 years and 1885 were male. After a median follow-up of 8.3 years, we recorded 307 composite MACE outcomes and 191 deaths. cMyC was associated with risk of MACE, as was hs-cTnI and hs-cTnT (all P for log-rank test <0.001). cMyC remained independently associated with MACE (hazard ratio per 1 SD in log-transformed biomarker 1.25, 95% CI, 1.14–1.37) and cardiovascular death (hazard ratio 1.41, 95% CI 1.15–1.72) in adjusted analyses and after further adjustment for hs-cTnI or hs-cTnT. Conclusions: cMyC provides strong prognostic information for incident CVD in the general population, independently of that provided by cardiac troponins.

• Eriksen, Espen Alexander; Wisløff, Ulrik; Welde, Ottar Brohaug; Midttun, Sindre; Skaug, Eli-Anne & Letnes, Jon Magne [Show all 8 contributors for this article] (2026). eHealth-Guided Exercise Improves Peak Oxygen Uptake and Health-Related Quality of Life After COVID-19: A Randomized Controlled Trial. Medicine & Science in Sports & Exercise. ISSN 0195-9131. doi: 10.1249/MSS.0000000000004177. Full text in Research Archive Show summary

  Purpose:Physical activity (PA) levels declined during the COVID-19 pandemic, contributing to reduced fitness and quality of life. eHealth tools may...

• 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
• Daniels, Lori B.; Giannitsis, Evangelos; Mueller, Christian; Meex, Steven J.R.; Buehlmann, David & Kurtoic, Dunja [Show all 27 contributors for this article] (2026). Clinical performance of the next generation Elecsys Troponin T high-sensitivity Gen 6 assay in acute coronary syndrome (PERFORM-TSIX): study design. Clinical Research in Cardiology. ISSN 1861-0684. doi: 10.1007/s00392-025-02842-x. Full text in Research Archive
• Knoll, Marko; Daniels, Lori B.; Mueller, Christian; Mills, Nicholas L.; Giannitsis, Evangelos & Rösser, Alisa F.A. [Show all 26 contributors for this article] (2026). Analytical Performance Evaluation of the Cardiac Troponin T High Sensitivity Gen 6 Assay. The Journal of Applied Laboratory Medicine (JALM). ISSN 2576-9456. 11(5), p. 1009–1025. doi: 10.1093/jalm/jfag031.
• Feng, Xin; Sigurdardottir, Fjola Dögg Hugberg; Arnardottir, Erna Sif; Dammen, Toril; Einvik, Gunnar & Korkalainen, Henri [Show all 15 contributors for this article] (2026). Association of major adverse cardiovascular events with the apnea-hypopnea index, desaturation severity parameters, and cardiac troponins in participants of the Akershus Sleep APnea cohort. Sleep. ISSN 0161-8105. 49(8). doi: 10.1093/sleep/zsag013. Full text in Research Archive Show summary

  Study Objectives: To examine the prognostic value of the apnea-hypopnea index (AHI), desaturation severity parameters, and cardiac troponins alone and combined for major cardiovascular events (MACEs). Methods: MACE data were retrieved in 2021 from the Norwegian Patient Registry for 518 participants in the Akershus Sleep APnea (ASAP) cohort. Baseline polysomnography and fasting blood samples were collected between June 2006 and January 2008. Desaturation duration (DesDur) and severity (DesSev) were calculated using Automatic Blood Oxygen Saturation Analysis software. Cox regression models estimated hazard ratios (HRs) for MACE. Predictive properties of combining troponins and obstructive sleep apnea severity were calculated by comparing established clinical thresholds for cardiac troponin I (cTnI) and T (cTnT) with AHI clinical thresholds of ≥15 and ≥30, respectively. Results: High AHI, DesDur, DesSev, cTnI, and cTnT were associated with increased MACE risk. However, only cTnI independently predicted MACE after adjustment (HR: 1.74, 95% CI: 1.32–2.29). The HR for MACE was 2.68 (95% CI: 1.03–6.97) in patients with both high cTnI and AHI ≥30 events/h. Conclusion: In this 15-year follow-up, cTnI was independently associated with risk of MACE, whereas the AHI, desaturation parameters, and cTnT were not independent predictors. cTnI, especially when combined with AHI, was a stronger MACE predictor than cTnT. Provided our findings are validated in clinical obstructive sleep apnea populations, the measurement of cTnI may be considered for cardiovascular risk stratification.

• Restan, Ingar Ziad; Tew, Yong Yong; Steiro, Ole-Thomas; Li, Ziwen; Tjora, Hilde Lunde & Langørgen, Jørund [Show all 17 contributors for this article] (2026). Exploring Sex-Specific High-Sensitivity Cardiac Troponin Thresholds for Rule-Out of Non-ST-Elevation Myocardial Infarction. Clinical Chemistry. ISSN 0009-9147. 72(8), p. 868–879. doi: 10.1093/clinchem/hvag030. Full text in Research Archive Show summary

  Background: Sex-specific diagnostic thresholds for high-sensitivity cardiac troponin (hs-cTn) assays are recommended by international guidelines for the diagnosis of myocardial infarction (MI). We assessed the performance of sex-specific single-sample rule-out thresholds for identifying low-risk patients in the emergency department. Methods: The derivation cohort comprised patients ≥18 years presenting with suspected MI to 2 Norwegian hospitals between 2015 and 2020 with 0-hour hs-cTnT (Roche) and high-sensitivity cardiac troponin I (Abbott and Siemens) measurements available. The primary endpoint was type 1 MI at index encounter. Diagnoses were adjudicated using assay-specific criteria per the Fourth Universal Definition of Myocardial Infarction. Sex-specific single-sample rule-out thresholds were derived, compared with guideline-recommended uniform thresholds, and externally validated in an independent and comparable British cohort. Results: Among 1896 patients [median age 62 (25th–75th percentile 52–72) years; 39% female], MI occurred in 12.5%–12.8% males and 8.8%–9.2% females, depending on the adjudication assay. For each assay, more females had hs-cTn concentrations below the uniform single-sample thresholds, yet these thresholds did not achieve >99% sensitivity in females. Sex-specific adjustment achieved >99% sensitivity at cutoffs of <4 and <7 ng/L (Roche); <1 and <6 ng/L (Abbott); <2 and <7 ng/L (Siemens) for females and males, respectively. Sex-specific thresholds reduced rule-out proportions in females (from 29%–60% to 10%–32%) and increased them in males (from 17%–53% to 45%–64%). Trends were similar in the validation cohort of 1948 patients. Conclusions: Uniform single-sample rule-out thresholds reveal marked sex differences in MI risk stratification. Sex-specific hs-cTn thresholds could improve safety in females and efficiency in males.

• Gynnild, Mari Nordbø; Mecinaj, Albulena; Wethal, Torgeir; Jakobsen, Even Olav; Vinje-Jakobsen, Victoria & Heck, Siri Lagethon [Show all 12 contributors for this article] (2026). Sacubitril/Valsartan and Right Ventricular and Diastolic Function During Breast Cancer Therapy. JACC: CardioOncology. 8(4), p. 436–436. doi: 10.1016/j.jaccao.2026.06.002. Full text in Research Archive
• Wimalanathan, Thakshani; Sulkowska, Joanna; Melles, Woldegabriel A; Paus, Michael Fredrik; Skranes, Julia Brox & Berge, Trygve [Show all 11 contributors for this article] (2026). Myocardial fibrosis is associated with worse left ventricular strain and synchrony assessed by novel CMR imaging in the general population: data from the Akershus Cardiac examination 1950 study. The International Journal of Cardiovascular Imaging. ISSN 1569-5794. doi: 10.1007/s10554-026-03746-1. Full text in Research Archive
• Myrmel, Gard Mikael Saele; Helseth, Ragnhild Merckoll; Steiro, Ole-Thomas; Tjora, Hilde Lunde; Langørgen, Jørund & Bjørneklett, Rune Oskar [Show all 13 contributors for this article] (2026). Circulating Markers of Neutrophil Extracellular Traps for Long-Term Prognosis in Patients With Acute Chest Pain. Journal of the American Heart Association (JAHA). 15(4). doi: 10.1161/JAHA.125.043680. Full text in Research Archive Show summary

  Background: Neutrophil extracellular traps are released from activated neutrophils and are involved in the pathogenesis of atherosclerotic lesions, atherothrombosis, and myocardial injury. We investigated the prognostic value of circulating neutrophil extracellular trap biomarkers in patients with suspected acute coronary syndrome (ACS). Methods: A total of 1482 patients admitted with suspected non–ST‐segment elevation ACS were included and followed for a median of 4.2 years. The primary end point was a composite of death from any cause, incident myocardial infarction and hospitalization for heart failure. Secondary end points were all‐cause mortality, cardiovascular death, incident myocardial infarction, hospitalization for heart failure, and new‐onset atrial fibrillation. Admission blood samples were analyzed for the neutrophil extracellular trap biomarkers double‐stranded DNA (dsDNA), CitH3 (citrullinated histone H3), and myeloperoxidase‐DNA. Results: A doubling of dsDNA concentration was associated with a hazard ratio (HR) of 3.11 (95% CI, 1.61–5.98, P<0.001) for the primary end point after adjusting for traditional risk factors, cardiac troponin T and N‐terminal pro‐B‐type natriuretic peptide. DsDNA served as a prognostic marker both in patients with (adjusted HR, 5.33 [95% CI, 1.67–17.06], P=0.005) and without ACS (adjusted HR, 2.86 [95% CI, 1.30–6.28], P=0.009). In contrast, CitH3 and myeloperoxidase‐DNA showed no significant prognostic value. Conclusions: In patients with suspected ACS, dsDNA emerged as a long‐term prognostic marker for a composite outcome of death, incident myocardial infarction, or heart failure hospitalization, independent of conventional risk factors. DsDNA can independently from established risk factors identify high‐risk patients with and without ACS who may benefit from risk reduction.

• Schrage, Benedikt; Lackner, Maximilian Karl; Hoshiyar, Aisouda; Lemos, James A. de; Engström, Gunnar & Grossmann, Elisa [Show all 21 contributors for this article] (2026). Emulated Effects of Glucagon-Like Peptide 1 Receptor Agonist Therapy in the General Population. Journal of the American College of Cardiology. ISSN 0735-1097. 87(21), p. 2948–2959. doi: 10.1016/j.jacc.2026.01.055. Full text in Research Archive
• Bonnevie-Svendsen, Martin; Edvardsson, Erle Viktoria; Oppen, Kjersti; Melau, Jørgen; Nyborg, Christoffer & Sæter, Frode Wirum [Show all 9 contributors for this article] (2026). Cardiac troponin patterns in athletes completing Norseman Xtreme Triathlon. BMJ Open sport & exercise medicine. 12(2). doi: 10.1136/bmjsem-2025-002810. Full text in Research Archive
• Grøtting, Nora; Wolford, Brooke N.; Kvaløy, Kirsti; Omland, Torbjørn; Selbæk, Geir & Ernstsen, Linda (2026). APOE genotype, cardiovascular risk, and incident dementia in the Norwegian HUNT study. European Journal of Epidemiology (EJE). ISSN 0393-2990. doi: 10.1007/s10654-026-01412-3. Full text in Research Archive Show summary

  Apolipoprotein E (APOE) genotype and cardiovascular risk are both associated with dementia, but their separate and joint contributions remain uncertain. We examined the independent and combined associations of APOE genotype and cardiovascular disease (CVD) risk with incident dementia in a Norwegian populationbased cohort. In this prospective cohort study, baseline data were obtained from the second Trøndelag Health Study (HUNT2, 1995–97), with follow-up through linkage to specialist health-care records and the Norwegian Cause of Death Registry through Dec 31, 2023. We included 22,108 participants aged 50 years or older who were free of CVD, diabetes, and dementia at baseline. APOE genetic risk and cardiovascular risk based on SCORE2 were each classified into three categories. Adjusted hazard ratios (HRs) for incident dementia were estimated using Cox models. During a median follow-up of 22.0 years, 3,714 incident dementia events occurred. Compared with low APOE genetic risk, adjusted HRs were 1.25(95% CI1.10–1.41) for intermediate risk and 3.09(2.73–3.49) for high risk. Compared with low-to-moderate CVD risk, adjusted HRs were 1.19(1.07–1.32) for high risk and 1.36(1.19–1.55) for very high risk. In joint analyses, the highest risk was observed in participants with high APOE genetic risk and very high cardiovascular risk (HR 3.78, 2.85–5.01). Higher cardiovascular risk was more clearly associated with dementia in participants without high APOE genetic risk, whereas dementia risk was consistently elevated across cardiovascular risk categories among those with high APOE genetic risk. There was no clear evidence of multiplicative interaction (p=0.059). APOE genotype and cardiovascular risk were independently associated with incident dementia, with highest risk among individuals with both high genetic and cardiovascular risk.

• Omland, Torbjørn; Heck, Siri Lagethon; Holte, Espen; Gynnild, Mari Nordbø; Gulati, Geeta & Wethal, Torgeir (2026). Response by Omland et al to Letter Regarding Article, “Sacubitril/Valsartan and Prevention of Cardiac Dysfunction During Adjuvant Breast Cancer Therapy: The PRADA II Randomized Clinical Trial”. Circulation. ISSN 0009-7322. 153(22). doi: 10.1161/circulationaha.126.079810. Full text in Research Archive
• Guldhaug, Nora Alicia; Røys, Eirik Åsen; Viste, Kristin; Alaour, Bashir; Sylte, Marit Sverresdotter & Torsvik, Janniche [Show all 10 contributors for this article] (2026). Biological variation and inter-relation between key calcium homeostasis biomarkers. Clinical Chemistry and Laboratory Medicine. ISSN 1434-6621. 64(5), p. 1124–1132. doi: 10.1515/cclm-2025-1225. Full text in Research Archive Show summary

  Objectives: This study aims to explore the biological variability of calcium homeostasis biomarkers, including calcium, phosphate, magnesium, 25-OH vitamin D, 1,25-OH vitamin D, and parathyroid hormone (PTH), and to develop a model that predicts PTH concentrations based on these parameters. Methods: Thirty healthy volunteers were sampled on a weekly basis over a period of 10 weeks. Each sample was analyzed in duplicate. Statistical methods included estimating within- and between-subject biological variation (CVI, CVG) using ANOVA with outlier removal and a Bayesian model. A linear mixed-effects model (LMM) was used to estimate 95 % prediction intervals for PTH as a function of calcium, phosphate, and 25-OH vitamin D in healthy participants. The effect of applying this prediction model in routine practice was estimated using data from the Laboratory Information System. Results: Estimated CVI from ANOVA and the Bayesian model was: PTH, 18.0 % and 17.4 %; calcium, 1.7 % and 1.6 %; phosphate, 9.3 % and 9.3 %; 25-OH vitamin D, 4.7 % and 7.2 %; and 1,25-OH vitamin D, 16.2 % and 17.1 %. The LMM indicated the best 95 % prediction interval for PTH included calcium (PTH (pmol/L)=exp(3.46−2.67·ln(Ca (mmol/L)) ± Z·0.29)) and did not improve with phosphate and/or 25-OH vitamin D. Compared with conventional reference intervals, this model flagged 56 % vs. 41.6 % of routine PTH/calcium results, respectively. Conclusions: Similar CVI data were obtained using two different methods. A predictive model can be used to predict concentrations for co-regulated biomarkers, potentially enhancing sensitivity in identifying non-physiological results and facilitating clinicians’ awareness of conditions affecting calcium homeostasis.

• Sulkowska, Joanna; Skranes, Julia Brox; Berge, Trygve; Tveit, Arnljot; Røsjø, Helge Rørvik & Lyngbakken, Magnus Nakrem [Show all 9 contributors for this article] (2026). Mechanical signatures of left ventricular ejection fraction and mass index in a community cohort (ACE 1950). The International Journal of Cardiovascular Imaging. ISSN 1569-5794. doi: 10.1007/s10554-026-03697-7. Full text in Research Archive
• Bhatnagar, Rahul; Lippestad, Kristine; Wisløff, Torbjørn; Berg, Angelica Marianne; Klæboe, Lars Gunnar & Høiseth, Arne Didrik [Show all 9 contributors for this article] (2026). Study Design of the Akershus Cardiac Examination (ACE) 4 Study: Pragmatic Randomized Controlled Trial Assessing the Effect of Early Biomarker Measurements and Structured Feedback in Unselected Patients Hospitalized with Tachypnea. Cardiology. ISSN 0008-6312. p. 1–12. doi: 10.1159/000550049. Full text in Research Archive
• Eriksen, Espen Alexander; Nauman, Javaid; Wisløff, Ulrik; Omland, Torbjørn & Stensvold, Dorthe (2026). Cardiorespiratory fitness and physical activity and risk of SARS-CoV-2 and COVID-19 hospitalization: the HUNT study. BMC Infectious Diseases. 26(1). doi: 10.1186/s12879-026-12684-1. Full text in Research Archive
• Ihle-Hansen, Håkon; Walle-Hansen, Marte; Berge, Trygve; Ihle-Hansen, Hege Beate; Rønningen, Peter Selmer & Omland, Torbjørn [Show all 16 contributors for this article] (2026). Burden of atherosclerosis, cardiovascular risk factors and atrial fibrillation in individuals with covert brain infarcts in late midlife: the Akershus Cardiac Examination 1950 Study. BMJ Open. 16(3). doi: 10.1136/bmjopen-2025-114232. Full text in Research Archive Show summary

  Background Current expert consensus statements generally suggest cardiovascular risk assessment, including atrial fibrillation (AF) screening, on detection of covert brain infarctions (CBIs). However, evidence to guide management of CBI remains limited. In the absence of randomised clinical trials specifically targeting CBI populations, observational studies comparing individuals with and without CBI can provide insights into the prevalence and burden of cardiovascular risk factors. Objectives We aimed to compare the burden of atherosclerosis and cardiovascular risk factors in participants with CBI to those without, and to explore the yield of AF screening in individuals with CBI. Design A prospective population-based birth cohort study including men and women born in 1950 and resident in Akershus County, Norway. Setting The two hospitals serving the population of Akershus county, Norway. Participants Participants included in the Akershus Cardiac Examination (ACE) 1950 study who also underwent a subsequent MRI examination were eligible for this study. Outcome measures Cardiovascular risk assessment was performed at study inclusion (2012–2015). Carotid ultrasound was used to quantify atherosclerosis through a carotid plaque score, and CHA₂DS₂-VA and Systematic COronary Risk Evaluation 2 (SCORE2) scores were calculated to estimate cardiovascular risk. Brain MRI was performed in a randomly selected, blood pressure-stratified subset of participants (2016–2024). CBI was defined as focal lesions consistent with ischaemia in the absence of clinical stroke. Participants with CBI were offered 72-hour ambulatory ECG monitoring for AF detection. Results MRI was performed in 414 of 3706 (11%) participants in the ACE 1950 Study. The mean age at the time of the MRI examination was 70.2±2.3 years, and 165 (41%) were women. CBI was identified in 54 participants (13%), of whom 45 (83%) completed 72-hour ambulatory ECG monitoring. There were no differences in mean carotid plaque score, SCORE2 or CHA₂DS₂-VA score between participants with CBI compared with those with normal MRI findings. AF was detected in one (2%) participant with CBI. Conclusions In this community-based cohort of individuals in late midlife, individuals with CBI did not have an increased cardiovascular risk compared with those without, as indicated by SCORE2, CHA₂DS₂-VA score, age-appropriate carotid plaque burden and a low prevalence of AF. Trial registration number URL: https://www.clinicaltrials.gov . Unique identifier: NCT01555411 .

• Bratholm, Åsmund Olaf; Ihle-Hansen, Håkon; Vigen, Thea; Lyngbakken, Magnus Nakrem; Omland, Torbjørn & Røsjø, Helge Rørvik [Show all 10 contributors for this article] (2026). Association between socioeconomic variables and carotid plaque in middle-aged adults: data from the Akershus Cardiac Examination (ACE) 1950 Study. Open heart. 13(1). doi: 10.1136/openhrt-2025-003865. Full text in Research Archive
• Kvisvik, Brede Alexander Havneraas; Skjørten, Ingunn; Hilde, Janne Mykland; Omland, Torbjørn; Melsom, Morten Nissen & Hummerfeldt, Sjur [Show all 7 contributors for this article] (2025). Six-minute walking distance is a robust predictor of mortality in stable chronic obstructive pulmonary disease without major comorbidities. Respiratory Medicine and Research. 88. doi: 10.1016/j.resmer.2025.101214. Full text in Research Archive Show summary

  Background Most patients with COPD are examined with specific pulmonary function tests and blood samples in addition to six-minute walking distance (6MWD), while few are examined by echocardiography and even fewer by invasive right heart catheterization (RHC). However, the relative prognostic value of these indices of disease remains to be defined. Aim We aimed in the present study to identify predictors of mortality in a cohort of COPD patients who had undergone comprehensive testing of pulmonary function, echocardiography and RHC. Material and methods The study included 97 outpatients with stable COPD in GOLD stages I-IV, after excluding three patients receiving a lung transplant. All patients underwent preinclusion screening where patients with left ventricular disease and other major comorbidities were excluded. Spirometry, blood tests, 6MWD and echocardiography of right and left heart were carried out, and RHC was performed at rest. Results During a mean follow-up of 7.6 ± 0.6 years, 44 patients died. Pulmonary hypertension was diagnosed in 32 patients (33 %) and was associated with mortality (p = 0.029). 6MWD, right ventricular tricuspid annular plane systolic excursion and myocardial performance index, mean pulmonary artery pressure, pulmonary vascular resistance, arterial oxygen tension, forced expiratory volume in one second, and oxygen uptake were all associated with mortality. However, 6MWD was the only significant variable in the multivariable Cox regression model (p = 0.001). Conclusions 6MWD was the most robust prognostic determinant of mortality in a stable COPD population free of major comorbidities.

• Røys, Eirik Åsen; Viste, Kristin; Farrell, Christopher John; Kellmann, Ralf; Alaour, Bashir & Sylte, Marit Sverresdotter [Show all 13 contributors for this article] (2025). A Parametric Empirical Bayes Approach to Personalized Reference Intervals and Reference Change Values. Clinical Chemistry. ISSN 0009-9147. 71(11), p. 1147–1157. doi: 10.1093/clinchem/hvaf092. Full text in Research Archive Show summary

  Background Population-wide reference intervals (RIpop) are commonly used in laboratory medicine but may not reflect an individual’s tightly regulated homeostatic interval. Personalized reference intervals (RIper) could enhance diagnostic precision by accounting for individual variability. A parametric empirical Bayes (PEB) framework stabilizes individual estimates using population parameters, enabling reliable RIper even from a limited number of individual results. Methods We applied the PEB framework to estimate RIper for 9 biomarkers: albumin, creatinine, phosphate, cortisone, cortisol, testosterone, androstenedione, 17-hydroxyprogesterone, and 11-deoxycortisol. The PEB parameters tested were derived from both routine Laboratory Information System (LIS) data and a local biological variation (BV) study. Using serial samples from healthy adults, we assessed the proportion of results flagged with a 95% prediction interval and compared RIper to conventional RIpop and reference change values (RCVs). Results LIS parameters were based on data from 1986 to 185 488 patients. PEB-based RIper were consistently narrower than RIpop while maintaining or reducing the proportion of flagged results. For example, albumin flagging decreased from 4.7% (RIpop) to 0.3% (RIper), phosphate from 5.4% to 3.7%, and cortisone from 7.1% to 3.9%. Conversely, 17-hydroxyprogesterone increased from 0.0% to 5.5% but remained close to the expected 5%. PEB thresholds were narrower than standard RCV estimates by correcting for regression toward the mean without increasing flagged results. Conclusions The PEB framework effectively provides personalized cutoffs for laboratory tests even when few individual patient results are available. PEB parameters can be established using LIS or BV data, offering a feasible and cost-effective implementation pathway.

• Karaji, Iman; Steiro, Ole-Thomas; Myrmel, Gard Mikael Saele; Omland, Torbjørn; Tjora, Hilde Lunde & Langørgen, Jørund [Show all 15 contributors for this article] (2025). Limited incremental value of growth differentiation factor 15 in the initial evaluation of low and intermediate risk acute chest pain patients. Clinical Biochemistry. ISSN 0009-9120. 137. doi: 10.1016/j.clinbiochem.2025.110926. Full text in Research Archive Show summary

  Introduction: Expression of the cytokine growth differentiation factor 15 (GDF-15) is up-regulated in conditions of tissue injury and stress. We evaluated if GDF-15 predicts obstructive coronary artery disease (CAD) or need for revascularization within 30 days and 12 months in low/intermediate risk patients with acute chest pain. Materials and Methods: We included 537 hospitalized patients who had high-sensitivity troponin T (hs-cTnT) < 99th percentile and underwent coronary CT angiography (CCTA). Odds ratios (ORs) and 95 % confidence intervals (CI) were calculated by logistic regression analyses and are reported per standard deviation increment of GDF-15 (log-transformed). Results: The median (25th-75th percentile) age was 56 (49–65) years, 217 (40.4 %) were women, 83 (15.5 %) had obstructive CAD at CCTA. In total 49 (9.1 %) patients underwent revascularization within 30 days and 52 (9.7 %) within 12 months. In age and sex adjusted analysis GDF-15 was a significant predictor with ORs (95 % CI) of 1.35 (1.05–1.73), 1.39 (1.06–1.83) and 1.41 (1.07–1.84) for obstructive CAD, revascularization within 30 days and 12 months, respectively. However, after adjustment for clinical covariables, the ORs of GDF-15 were no longer statistically significant for either outcome (P ≥ 0.07). Adding hs-cTnT levels alone to the age and sex adjusted model also rendered the ORs of GDF-15 non-significant (P ≥ 0.31). Conclusions: In patients with acute chest pain but without acute myocardial infarction, GDF-15 did not substantially improve the identification of obstructive CAD or need for revascularization within 30 days and 12 months. Our findings question the clinical usefulness of GDF-15 for prognostication of low-risk patients with acute chest pain.

• Thulin, Ingrid Viola Lavesson; Jordalen, Silje; Myrmel, Gard Mikael Saele; Lekven, Ole Christian; Krishnapillai, Jeyaseelan & Steiro, Ole-Thomas [Show all 16 contributors for this article] (2025). Effectiveness of Point-of-Care High-Sensitivity Troponin Testing in the Emergency Department: A Randomized Controlled Trial. Annals of Emergency Medicine. ISSN 0196-0644. 86(2), p. 124–135. doi: 10.1016/j.annemergmed.2025.03.005. Full text in Research Archive Show summary

  Study objective To compare the effectiveness of high-sensitivity cardiac troponin (hs-cTn) point-of-care testing to central laboratory hs-cTn measurements when investigating patients presenting to the emergency department (ED) with symptoms of acute coronary syndrome. Methods The WESTCOR point-of-care study was a single-center prospective randomized controlled trial where we randomized patients presenting with possible acute coronary syndrome in a 1:1 fashion to receive either 0/1-hour centralized hs-cTnT measurements (control) or 0/1-hour point-of-care hs-cTnI testing (intervention). We defined length of stay (LOS) in the ED as the primary endpoint and the minimum clinically meaningful difference as 15 minutes. Results We included 1,494 patients in the final analysis, 728 in the point-of-care group, and 766 in the control group. The median (interquartile range) age was 61 (22) years, and 635 (42.5%) were women. Median LOS in the ED was 174 (95% confidence interval [CI] 167 to 181) and 180 (95% CI 175 to 189) minutes in the point-of-care and control group, respectively, resulting in a reduction in median LOS of 6 minutes (95% CI −4 to 17). Acute myocardial infarction, death, or acute revascularization occurred in 83/728 (11.4%) of point-of-care and 72/766 (9.4%) of control patients. Conclusions We found that implementing point-of-care hs-cTnI testing in the ED with a 0/1-hour diagnostic algorithm did not lead to a clinically meaningful reduction in ED LOS. We observed no difference in the incidence of myocardial infarction, acute coronary revascularization, or death during 30 days follow-up.

• Saeed, Nasir; Restan, Ingar Ziad; Steiro, Ole-Thomas; Tjora, Hilde Lunde; Langørgen, Jørund & Skadberg, Øyvind [Show all 18 contributors for this article] (2025). Analytical Error of Cardiac Troponin and Impact on the Performance of Accelerated Diagnostic Protocols in Patients with Acute Chest Pain. Clinical Chemistry. ISSN 0009-9147. 71(12), p. 1243–1256. doi: 10.1093/clinchem/hvaf116. Full text in Research Archive Show summary

  Background This study simulates how assay-specific bias influences the diagnostic performance of 0/1-h accelerated diagnostic protocols (ADPs) for 3 different high-sensitivity cardiac troponin (hs-cTn) assays. Methods We included 1493 patients presenting with chest pain. hs-cTnT (Roche Diagnostics), hs-cTnI from Abbott Diagnostics (hs-cTnI-A), and Siemens Healthineers (hs-cTnI-S) were measured at admission. The absolute total error observed in a state-of-the-art EQA study were added to the admission concentrations, producing 6 new variables being adjusted for maximum possible bias (if analytical variation is 0) (+biasmean, +biasmax95%CI, +biasmin95%CI, −biasmean, −biasmax95%CI, −biasmin95%CI). The influence of this “worst-case scenario” bias was compared after calculating sensitivity, specificity, negative and positive predictive values, and rule-out proportion for 30-day myocardial infarction or death for the observed and bias-adjusted hs-cTn concentrations. Results For 0-h rule-out, hs-cTnI-S and hs-cTnT had a sensitivity of >99.0%, compared to 97.7% for hs-cTnI-A. After adding the bias, sensitivity was unchanged for hs-cTnI-S (99.5%), but lower for hs-cTnT (95.5%), and hs-cTnI-A (96.2%). For the 0-/1-h algorithm, adding bias reduced sensitivity to 95.5% for hs-cTnT, while both hs-cTnI algorithms were unchanged (100.0%). Rule-out proportions for 0 h ranged from 0% to 60.0% for hs-cTnT, 28.2%–62.7% for hs-cTnI-A, and 3.5%–35.5% for hs-cTnI-S. For the 0-/1-h algorithm, ranges were 57.7%–75.8% (hs-cTnT), 52.8%–67.5% (hs-cTnI-A), and 45.7%–61.2% (hs-cTnI-S), Conclusion Analytical bias of hs-cTn assays affects the clinical rule-out rate of the 0/1-h ADPs more than the diagnostic sensitivity. Bias may have a greater influence on the proportion of patients requiring hospital admission and may contribute to the heterogeneity of the reported rule-out rates of current ADPs.

• Jaffe, Allan S.; Sandoval, Yader; Mills, Nicholas L.; Omland, Torbjørn & Aakre, Kristin Moberg (2025). Challenges of using natriuretic peptides to screen for the risk of developing heart failure in patients with diabetes: a report from the International Federation of Clinical Chemistry and Laboratory Medicine (IFCC) Committee on Clinical Applications of Cardiac Bio-Markers (C-CB). Clinical Chemistry and Laboratory Medicine. ISSN 1434-6621. 63(11), p. 2130–2139. doi: 10.1515/cclm-2025-0863. Full text in Research Archive
• Dypvik, Ragnhild; Fjukstad, Katrine Kveli; Lydersen, Stian; Berge, Trygve; Tveit, Arnljot & Røsjø, Helge Rørvik [Show all 9 contributors for this article] (2025). Associations Between Growth Differentiation Factor 15 and Anxiety and Depression in the General Population: The Akershus Cardiac Examination 1950 Study. Biopsychosocial Science and Medicine. ISSN 2998-8748. 87(2), p. 153–159. doi: 10.1097/psy.0000000000001365. Full text in Research Archive Show summary

  Objective Several studies suggest a bidirectional association between inflammation, and anxiety and depression. Elevated inflammatory cytokines generate and aggravate neuroinflammation, which may play a part in developing psychological symptoms. Growth differentiation factor 15 (GDF-15) is a novel biomarker possibly reflecting fibrosis and inflammation. The aim of the current study was to investigate the associations between levels of GDF-15 and symptoms of anxiety and depression in the general population. Methods We measured GDF-15 in middle-aged persons participating in the Akershus Cardiac Examination 1950 Study. Symptoms of anxiety and depression were assessed using the Hospital Anxiety and Depression Scale (HADS), with HADS ≥8 denoting significant symptoms. We used multivariable regression analysis to assess the associations between GDF-15 and HADS, adjusting for levels of C-reactive protein (CRP), demographics, and comorbidities. Results A total of 3638 participants had valid assessment of HADS and measurements of GDF-15 and CRP. The mean age was 63.9 (SD 0.65) years, and 48.8% were women. In adjusted models, levels of GDF-15 were associated with the continuous HADS-D score ( β = 0.27, 95% confidence interval [CI] = 0.12 to 0.43) and HADS-D score ≥8 (odds ratio = 1.41, 95% CI = 1.12 to 1.78), but not with the continuous HADS-A score ( β = 0.06, 95% CI = −0.12 to 0.24) or HADS-A score ≥8 (odds ratio = 1.06, 95% CI = 0.88 to 1.27). Conclusions Levels of GDF-15 are independently associated with symptoms of depression in the general population. Our results reinforce the notion that inflammation may be a contributing factor for the development of clinical depression. Registration ClinicalTrials.gov identifier NCT01555411 (Akershus Cardiac Examination [ACE] 1950 Study), https://clinicaltrials.gov/study/NCT01555411

• Ottesen, Anett Hellebø; Røsjø, Helge Rørvik & Omland, Torbjørn (2025). Secretoneurin as a novel cardiovascular biomarker and potential therapeutic strategy. Expert Review of Cardiovascular Therapy. ISSN 1477-9072. 24(1), p. 21–27. doi: 10.1080/14779072.2025.2604574. Full text in Research Archive Show summary

  Introduction Secretoneurin (SN) is a prognostic biomarker in cardiovascular disease (CVD), and circulating SN concentrations have been associated with clinical outcomes in various cohort of CVDs. SN reflects other cellular pathways than established CV biomarkers, and SN provides incremental prognostic information to established CV risk indices. SN has been found to have several beneficial properties and SN could have potential as a future therapeutic strategy in CVD. Areas covered This review discusses SN as a novel cardiovascular biomarker and a potential therapeutic strategy in cardiovascular medicine. The authors have considered relevant papers identified by PubMed. Expert opinion SN is a prognostic biomarker in CVD, and unraveling the underlying pathophysiology of SN will be important to advance SN as a biomarker and potential future therapy in CVD. The future for SN as a biomarker and therapy is attractive and could be of future clinical relevance.

• Paus, Michael Fredrik; Lyngbakken, Magnus Nakrem; Tveit, Arnljot; Steine, Kjetil; Berge, Trygve & Skranes, Julia Brox [Show all 14 contributors for this article] (2025). Determinants of Cardiac Myosin Binding Protein C in the General Population. Clinical Chemistry. ISSN 0009-9147. 71(4), p. 484–496. doi: 10.1093/clinchem/hvaf013. Full text in Research Archive Show summary

  Background: Cardiac myosin binding protein C (cMyC) is a novel, cardiac-specific biomarker with an early release profile after acute ischemic myocardial injury. Whether cMyC reflects chronic myocardial injury and left ventricular remodelling in the general population is unknown. The aims of the study were to test the hypotheses that cMyC concentrations are associated with cardiovascular risk factors, biomarkers of chronic myocardial injury, and imaging biomarkers of cardiac anatomy, function, and fibrosis. Methods: Circulating cMyC and cardiac troponin I and T concentrations were measured in 3672 individuals from the general population, born in 1950, who underwent echocardiography. One-hundred-ninety-nine participants with measured cMyC completed a cardiovascular magnetic resonance (CMR) examination for assessment of myocardial fibrosis. Results: Circulating cMyC was measurable in 99.6% of study participants and in 99.0% of CMR substudy participants. cMyC was positively associated with left ventricular mass and left atrial volume and inversely associated with renal function and indices of left ventricular systolic and diastolic function. In participants with available late gadolinium enhancement images for the assessment of focal fibrosis (n = 197), cMyC was positively associated with indices of focal myocardial fibrosis. Conclusions: In the general population, circulating cMyC concentrations are associated with cardiovascular risk factors, reflect left ventricular remodelling, including focal myocardial fibrosis, and systolic and diastolic dysfunction independently of traditional risk factors.

• Shah, Anoop S.V.; Keene, Spencer J.; Pennells, Lisa; Kaptoge, Stephen; Kimenai, Dorien M. & Walker, Matthew [Show all 56 contributors for this article] (2025). Cardiac Troponins and Cardiovascular Disease Risk Prediction: An Individual-Participant-Data Meta-Analysis. Journal of the American College of Cardiology. ISSN 0735-1097. 85(14), p. 1471–1484. doi: 10.1016/j.jacc.2025.02.016. Full text in Research Archive
• Gynnild, Mari Nordbø; Holtrop, Joris; Hageman, Steven H J; Vinje, Victoria; Dorresteijn, Jannick A N & Visseren, Frank L J [Show all 10 contributors for this article] (2025). External validation of the systematic coronary risk evaluation 2 (SCORE2) and SCORE2-older persons in cancer patients. European Journal of Preventive Cardiology (EJPC). ISSN 2047-4873. doi: 10.1093/eurjpc/zwaf356. Full text in Research Archive Show summary

  Aims The 2022 European Society of Cardiology cardio-oncology guidelines recommend cardiovascular disease (CVD) risk stratification for cancer patients and suggest using SCORE2 and SCORE2-OP. However, these models have not been validated or specifically adapted for cancer populations. Our aim was to refine the SCORE2 and SCORE2-OP models to accurately predict 10-year fatal and non-fatal CVD risk in cancer patients. Methods and results We included 1622 patients from the HUNT3 study (2006–08) who were diagnosed with cancer within 4 years after their enrolment and followed until 2023 linked to national registries. The primary outcome was a composite of myocardial infarction (MI), stroke, or CVD mortality. Model performance was assessed using Harrel’s C-statistic and calibration curves. Both models were recalibrated by applying a multiplicative adjustment factor based on expected–observed (E/O) ratios. The most prevalent cancers were gastrointestinal (23%), prostate (17%), and breast (14%). Mean age was 65.2 years, 52% were female. During a median follow-up of 8.8 years [inter-quartile range 1.9–12.6], 252 CVD events (39% MI, 36% stroke, 25% CVD deaths) and 708 non-CVD deaths occurred. SCORE2 initially underestimated CVD risk (E/O ratio for men and women: 0.91 and 0.63, respectively) but showed adequate agreement after recalibration. C-statistics for SCORE2 was 0.693 [95% confidence interval (CI) 0.643–0.743], and 0.730 (95% CI 0.676–0.784) after excluding those not surviving the first 2 years. For SCORE2-OP, the C-statistics were 0.586 (95% CI 0.529–0.643) and 0.648 (95% CI 0.577–0.720). Conclusion SCORE2 underestimated CVD risk in cancer patients. After recalibration, the model may serve as a valuable tool for risk stratification in cancer patients.

• Gynnild, Mari Nordbø; Vinje-Jakobsen, Victoria; Holtrop, Joris; Hageman, Steven H.J.; Holte, Espen & Gulati, Geeta [Show all 14 contributors for this article] (2025). Prognostic Performance of a Modified HFA-ICOS Tool for Prediction of Cardiovascular Complications in Cancer Patients. JACC: Advances. 4(12). doi: 10.1016/j.jacadv.2025.102344. Full text in Research Archive Show summary

  Background The 2022 European Society of Cardiology Cardio-oncology Guidelines recommend the Heart Failure Association and International Cardio-Oncology Society risk stratification tool to predict cardiovascular disease (CVD) risk in cancer patients. Developed from expert consensus rather than mathematical derivation, its quantitative prognostic value in unselected cancer populations remains uncertain. Objectives The objective of the study was to assess the prognostic utility of a modified Heart Failure Association and International Cardio-Oncology Society tool, excluding biomarkers and imaging, in predicting CVD complications in cancer patients, thereby providing a quantitative correlate to an expert consensus-based method. Methods We included 2,290 cancer patients from the third follow-up of the Trøndelag Health study, diagnosed within 4 years of participation, and followed through 2023. Cancer therapy details were obtained from the Norwegian Cancer Registry. The primary outcome was a composite of myocardial infarction, heart failure hospitalization, stroke, or CVD mortality, identified via national registries. Results The mean age was 65.8 years; 48% were female. The most common cancers were gastrointestinal (23%), prostate (19%), and breast (12%). The median follow-up was 6.9 years. The modified tool classified 28% as low-, 35% moderate-, 34% high-, and 3% very high-risk. CVD incidence rose across categories: 7%, 21%, 29%, and 37% (P < 0.001). The C-statistic was 0.696 (95% CI: 0.674-0.718), and 0.746 (95% CI: 0.676-0.812) among anthracycline-treated patients. Within the low-to-moderate group, event rates ranged from 6% to 8% (0-1 points) to 24% to 27% (3-4 points). Conclusions The tool stratifies CVD risk in cancer patients and may guide tailored follow-up and cardioprotection. Heterogeneity within moderate-risk patients highlights the need for refinement to improve individualized assessment.

• Chadwick, Jessica; Berry, Colin; Carpenter, Meredith A.; Gulati, Geeta; Heck, Siri Lagethon & Hinterberg, Michael A. [Show all 18 contributors for this article] (2025). Utilization of Proteomic Measures for Early Detection of Drug Benefits and Adverse Effects. Journal of clinical pharmacology. ISSN 0091-2700. 65(11), p. 1460–1473. doi: 10.1002/jcph.70077. Full text in Research Archive Show summary

  Recognition of benefits and adverse effects of therapies in earlier clinical trial phases could improve the safety, efficiency, and cost of clinical trials. Using four clinical trials representing a diverse set of diseases and drug classes (EXSCEL: exenatide/GLP‐1 RA, SUGAR‐DM‐HF: empagliflozin/SGLT2i, PRADA: epirubicin/anthracycline, and AMPLE: abatacept/immunomodulator and adalimumab/TNF inhibitor), we hypothesized that previously validated proteomic measures for cardiometabolic outcomes could enable the detection of beneficial and adverse drug effects in fewer participants over a shorter follow‐up period. Changes in SomaSignal TM proteomic tests over time in response to treatment were assessed in the EXSCEL (baseline vs 1 year; once‐weekly exenatide (EQW) (n) = 1812 vs control (n) = 1787), SUGAR‐DM‐HF (baseline vs 12 weeks and 36 weeks; empagliflozin (n) = 45 vs control (n) = 52), AMPLE (baseline vs 85 days and 1 year; abatacept (n) = 210, adalimumab (n) = 222), and PRADA (baseline vs 7–10 days and 3 months, n = 120) trial. Improvement of cardiovascular risk and cardiometabolic traits with EQW was detectable within 1 year ( P = .002) in sample sizes significantly smaller than the original study. Cardio‐ and kidney‐protective ( P = .06, P = .037) effects of empagliflozin were detectable within 36 weeks in a small sample size (n ∼ 50). Abatacept and adalimumab treatment demonstrated significant improvements in cardiovascular risk ( P ≤ .001, P ≤ .001) and cardiorespiratory fitness ( P ≤ .001, P ≤ .001) within 85 days. In contrast, anthracycline treatment led to significant increases in heart failure mortality risk ( P ≤ 0.001) and cardiovascular risk ( P = .004) after the first cycle of chemotherapy treatment. These findings provide preliminary evidence that proteomics may provide a powerful tool for optimizing drug pipelines by predicting the effects of novel therapeutics in smaller, shorter trials.

• Zhang, Jianying; Wang, Heling; Lautrup, Sofie Hindkjær; Nilsen, Hilde; Treebak, Jonas T. & Watne, Leiv Otto [Show all 28 contributors for this article] (2025). Emerging strategies, applications and challenges of targeting NAD+ in the clinic. Nature Aging. 5(9), p. 1704–1731. doi: 10.1038/s43587-025-00947-6. Full text in Research Archive Show summary

  Beyond their classical functions as redox cofactors, recent fundamental and clinical research has expanded our understanding of the diverse roles of nicotinamide adenine dinucleotide (NAD) and nicotinamide adenine dinucleotide phosphate (NADP) in signaling pathways, epigenetic regulation and energy homeostasis. Moreover, NAD and NADP influence numerous diseases as well as the processes of aging, and are emerging as targets for clinical intervention. Here, we summarize safety, bioavailability and efficacy data from NAD+-related clinical trials, focusing on aging and neurodegenerative diseases. We discuss the established NAD+ precursors nicotinic acid and nicotinamide, newer compounds such as nicotinamide riboside and nicotinamide mononucleotide, and emerging precursors. We also discuss technological advances including in industrial-scale production and real-time detection, which are facilitating NAD+ research and clinical translation. Finally, we emphasize the need for further large-scale studies to determine optimal dose, administration routes and frequency, as well as long-term safety and interindividual variability in response.

• Omland, Torbjørn; Heck, Siri Lagethon; Holte, Espen; Mecinaj, Albulena; Gynnild, Mari Nordbø & Fagerland, Morten [Show all 13 contributors for this article] (2025). Sacubitril/Valsartan and Prevention of Cardiac Dysfunction During Adjuvant Breast Cancer Therapy: The PRADA II Randomized Clinical Trial. Circulation. ISSN 0009-7322. 152(16), p. 1136–1145. doi: 10.1161/circulationaha.125.076616. Full text in Research Archive Show summary

  Background: Anthracycline- and trastuzumab-associated cardiotoxicity may lead to cardiac dysfunction and dose reduction or halt in potentially life-saving adjuvant cancer therapy. Whether angiotensin receptor neprilysin inhibitors can prevent cancer therapy-related cardiac dysfunction and injury remains to be established. Methods: PRADA II was a randomized, parallel-group, placebo-controlled, double-blind multicenter trial conducted at 4 academic medical centers in Norway that evaluated the cardioprotective effect of sacubitril-valsartan vs. placebo administered concomitantly with anthracycline-containing breast cancer therapy and continued for 18 months. The target dose was 97/103 mg b.i.d. The primary outcome was change in left ventricular ejection fraction by cardiovascular magnetic resonance from prior to initiation of chemotherapy to 18 months after. Secondary outcomes included change in echocardiographic global longitudinal strain, circulating cardiac troponins, and N-terminal pro-B-type natriuretic peptide (NT-proBNP). Results: In total, 138 women (mean (±SD) age: 54.0 ± 9.4 years) were randomized. The overall decline in left ventricular ejection fraction from baseline to 18 months was 2.2 percentage points (95% confidence interval [CI], 1.1 to 3.3) in the placebo group and 1.1 percentage points (95% CI, -0.01 to 2.2) in the sacubitril-valsartan group. The between-group difference was 1.1 percentage points (95% CI, -0.4 to 2.7; P=0.16). Left ventricular global longitudinal strain was normal and remained stable in the sacubitril-valsartan group throughout the study (change from baseline to 18 months -0.32 [95% CI, -0.80 to 0.15]). In contrast, there was a progressive decline in the placebo group (change from baseline to 18 months 0.53 [95% CI, 0.05 to 1.00]). The between-group difference was -0.85 (95% CI, -1.52 to -0.18). The mean increases in NT-proBNP and cardiac troponin I concentrations from baseline to 18 months were greater in the placebo than in the sacubitril-valsartan group (log difference 0.303 (95% CI 0.0547 to 0.552) for NT-proBNP and 0.534 (95% CI 0.114 to 0.954) for cardiac troponin I). Conclusions: Anthracycline-based treatment for early breast cancer is associated with a reduction in left ventricular ejection fraction that was not significantly attenuated by sacubitril-valsartan.

• Magnussen, Christina; Alegre-Diaz, Jesus; Al-Nasser, Lubna A.; Amouyel, Philippe; Aviles-Santa, Larissa & Bakker, Stephan J. L. [Show all 126 contributors for this article] (2025). Global Effect of Cardiovascular Risk Factors on Lifetime Estimates. New England Journal of Medicine. ISSN 0028-4793. 393(2), p. 125–138. doi: 10.1056/NEJMoa2415879. Full text in Research Archive Show summary

  Background Five risk factors account for approximately 50% of the global burden of cardiovascular disease. How the presence or absence of classic risk factors affects lifetime estimates of cardiovascular disease and death from any cause remains unclear. Methods We harmonized individual-level data from 2,078,948 participants across 133 cohorts, 39 countries, and 6 continents. Lifetime risk of cardiovascular disease and death from any cause was estimated up to 90 years of age according to the presence or absence of arterial hypertension, hyperlipidemia, underweight and overweight or obesity, diabetes, and smoking at 50 years of age. Differences in life span (in terms of additional life-years free of cardiovascular disease or death from any cause) according to the presence or absence of these risk factors were also estimated. Risk-factor trajectories were analyzed to predict lifetime differences according to risk-factor variation. Results The lifetime risk of cardiovascular disease was 24% (95% confidence interval [CI], 21 to 30) among women and 38% (95% CI, 30 to 45) among men for whom all five risk factors were present. In the comparison between participants with none of the risk factors and those with all the risk factors, the estimated number of additional life-years free of cardiovascular disease was 13.3 (95% CI, 11.2 to 15.7) for women and 10.6 (95% CI, 9.2 to 12.9) for men; the estimated number of additional life-years free of death was 14.5 (95% CI, 9.1 to 15.3) for women and 11.8 (95% CI, 10.1 to 13.6) for men. As compared with no changes in the presence of all risk factors, modification of hypertension at an age of 55 to less than 60 years was associated with the most additional life-years free of cardiovascular disease, and modification of smoking at an age of 55 to less than 60 years was associated with the most additional life-years free of death. Conclusions The absence of five classic risk factors at 50 years of age was associated with more than a decade greater life expectancy than the presence of all five risk factors, in both sexes. Persons who modified hypertension and smoking in midlife had the most additional life-years free of cardiovascular disease and death from any cause, respectively.

• Myrmel, Gard Mikael Saele; Saeed, Nasir; Steiro, Ole-Thomas; Tjora, Hilde Lunde; Langørgen, Jørund & Bjørneklett, Rune Oskar [Show all 13 contributors for this article] (2025). Sex Differences in the Prognostic Value of Circulating Biomarkers in Patients Presenting With Acute Chest Pain. JACC: Advances. 4(2). doi: 10.1016/j.jacadv.2024.101567. Full text in Research Archive
• Riveland, Egil Aarstad; Ushakova, Anastasia; Valborgland, Torstein; Karlsen, Trine; Dalen, Håvard & Prescott, E. [Show all 12 contributors for this article] (2025). Cardiac myosin binding protein C correlate with cardiac troponin I during an exercise training program in patients with HFrEF. ESC Heart Failure. 12(3), p. 2382–2386. doi: 10.1002/ehf2.15222. Full text in Research Archive Show summary

  Background: Cardiac myosin binding protein C (cMyC) is an emerging new biomarker of myocardial injury rising earlier and cleared faster than cardiac troponins. It has discriminatory power similar to high-sensitive troponins in diagnosing myocardial infarction in patients presenting with chest pain. It is also associated with outcome in patients with acute heart failure. It is currently unclear how it relates to cardiac troponins in patients with chronic heart failure undergoing exercise training. Methods and results: This is a post hoc analysis of symptomatic heart failure patients in the multicentre randomized SMARTEX trial. Patients were randomized to one of three arms: high-intensity interval training, moderate continuous training and recommendation of regular exercise serving as control group (CG) for 12 weeks. As the training load in the two intervention arms was similar, these patients were merged and constituted the intervention group (IG). Clinical data and measurements were obtained at baseline and at 12 weeks. In 205 patients, serum was available for cMyC testing and in 196 patients, serum was available for hs-cTni testing. Due to non-normal distribution, cMyC and hs-cTnI measurements were log-transformed. A Bland–Altman plot was employed to evaluate the agreement of cMyC with hs-cTnI measurements. Lastly, a linear regression model was applied. No significant differences were observed in the change of cMyC levels between the groups throughout the intervention period (∆ cMyC IG: −0.5 [IQR: −3.4; 2.1] vs. ∆ cMyC CG: −0.7 [IQR: −2.7; 2.6]). The change in log hs-cTnI was significantly correlated with the change in log cMyC during the 12-week intervention period, with a Pearson correlation coefficient of R = 0.52 (95% CI 0.37–0.66, P < 0.001). For every 10% increase in cMyC levels, hs-cTnI levels rose by approximately 5%. Conclusions: Changes in levels of the novel biomarker cMyC were significantly associated with hs-cTnI serum levels in patients with symptomatic chronic HFrEF during a structured 12-week exercise training programme. This may indicate that cMyC has a role as a future marker of subclinical myocardial damage.

• Ihle-Hansen, Håkon; Walle-Hansen, Marte; Hagberg, Guri; Berge, Trygve; Ihle-Hansen, Hege Beate & Rønningen, Peter Selmer [Show all 11 contributors for this article] (2025). Applying the 2024 European Society of Cardiology Guidelines for the management of elevated blood pressure and hypertension to a Norwegian general population cohort from age 40: data from the Akershus Cardiac Examination 1950 study. Heart. ISSN 1355-6037. 111(23), p. 1119–1123. doi: 10.1136/heartjnl-2025-325770. Full text in Research Archive
• Berge, Kristian; Janssen, Sylvan L.J.E.; Velthuis, Birgitta K.; Myhre, Peder Langeland; Mosterd, Arend & Omland, Torbjørn [Show all 8 contributors for this article] (2025). Predictors of coronary atherosclerosis in middle-aged and older athletes: the MARC-2 study. European Heart Journal-Cardiovascular Imaging. ISSN 2047-2404. 26(3), p. 461–470. doi: 10.1093/ehjci/jeae317. Full text in Research Archive Show summary

  Aims Exercise improves cardiovascular health, but high-volume high-intensity exercise is associated with increased coronary artery calcification (CAC). We aimed to identify predictors of CAC in athletes. Methods and results We assessed the association of traditional and non-traditional cardiovascular risk factors with CAC using linear and logistic regression. A total of 289 male athletes from the MARC-2 study were included, with a median age of 60 (Q1–3 56–66) years, lifelong weekly training load of 26 (17–35) metabolic equivalent of task hours, body mass index of 24.5 (22.9–26.6) kg/m2, systolic blood pressure of 139 ± 18 mmHg, and reported 0.0 (0.0–8.0) smoking pack years. Thirty-one per cent had a CAC score > 100 and 13% > 400. Among traditional cardiovascular risk factors, higher age, systolic blood pressure, smoking pack years, and family history of coronary artery disease independently predicted greater CAC scores, while body mass index, low-density lipoprotein cholesterol, and diabetes mellitus did not. Among non-traditional risk factors, higher training loads, serum phosphate, and lower adjusted energy intake and fat percentage of energy intake independently predicted greater CAC scores. The full model with all traditional and non-traditional risk factors had higher accuracy in predicting CAC > 100 [receiver operating characteristic area under the curve 0.76, 95% confidence interval (0.70–0.82)] and CAC > 400 [0.85 (0.77–0.92)] than traditional cardiovascular risk factors alone [0.72 (0.65–0.78), P = 0.012, and 0.81 (0.74–0.90), P = 0.038, respectively]. Conclusion Non-traditional risk factors, including training load, dietary patterns, and serum phosphate, were independently associated with CAC in aging male athletes. Prediction accuracy for CAC increased when including these variables in a prediction model with traditional risk factors.

• Bakker, Marie de; Welsh, Paul; Sattar, Naveed; Lindahl, Bertil; Hammarsten, Ola & Omland, Torbjørn [Show all 12 contributors for this article] (2025). Cardiac Troponin I and T Ratio and Risk of Cardiovascular or Non-Cardiovascular Events in a General Population. Clinical Chemistry. ISSN 0009-9147. 71(5), p. 599–608. doi: 10.1093/clinchem/hvaf016. Full text in Research Archive Show summary

  Background Emerging evidence suggests that the ratio between cardiac troponin (cTn) I and T may provide information on the risk of adverse outcomes in individuals with cardiovascular disease. Whether the cTn I/T ratio provides prognostic insights in the general population is unknown. Methods The cTn I/T ratio was calculated in 8855 participants (43% female, median age 56 years) from the Generation Scotland Study where both cTnI and cTnT concentrations were above the limit of blank. Multivariable cause-specific Cox proportional hazard models were used to estimate the associations between cTn I/T ratio and the primary outcome of cardiovascular or non-cardiovascular death. Results The median cTn I/T ratio was 0.5 (25th–75th percentile, 0.3–0.8) and median follow-up was 11.4 (10.8–12.7) years. Individuals in the highest ratio tertile (≥0.64) were more likely to be male, have a higher body mass index and systolic blood pressure, and a history of cardiovascular disease. Those in the lowest ratio tertile (<0.38) were more likely to be smokers or have diabetes. After adjustment for cardiovascular risk factors, the cTn I/T ratio was positively associated with cardiovascular death (per doubling increase, adjusted hazard ratio [HR] 1.16 [95% CI, 1.05–1.28]), while an inverse association was observed for non-cardiovascular death (HR 0.89 [95% CI, 0.81–0.99]). Conclusions The cTn I/T ratio is positively associated with cardiovascular death in the general population, while inversely associated with non-cardiovascular death. Future research is needed to unravel underlying mechanisms and determine whether the cTn I/T ratio provides valuable information regarding risk of cardiovascular and non-cardiovascular mortality to guide further management.

• Røsjø, Helge Rørvik; Rugolo, Ilde; Berg, Angelica Marianne; Faaren, Arne L; Frantzen, Frank & Christensen, Geir [Show all 11 contributors for this article] (2025). Secretoneurin Concentrations Measured with a High-Throughput Assay and Clinical Outcomes in Patients Hospitalized with Acute Dyspnea: Data from the Akershus Cardiac Examination 2 Study. The Journal of Applied Laboratory Medicine (JALM). ISSN 2576-9456. 10(3), p. 691–703. doi: 10.1093/jalm/jfaf011. Full text in Research Archive Show summary

  Background High-throughput assays are required for novel biomarkers to have clinical potential. Secretoneurin (SN) is a candidate biomarker, and the performance of a new high-throughput SN assay is not known. Methods We measured SN concentrations with a prototype chemiluminescent immunoassay (CLIA) in 299 patients hospitalized with acute dyspnea. We compared the results with a CE-marked SN enzyme linked immunosorbent assay (ELISA). We adjudicated the cause of dyspnea as heart failure (HF) or non-HF, and we obtained information on all-cause mortality during follow-up. Results SN concentrations measured with CLIA and ELISA were closely correlated: rho = 0.81, P < 0.001. SN CLIA concentrations were higher in HF patients (n = 129) compared to patients with non-HF-related dyspnea (n = 170): median 51 (quartile 1–3 40–69) vs 41 (32–54) pmol/L, P < 0.001. The area under the curve (AUC) of SN CLIA to diagnose HF was 0.64 (95% CI, 0.58–0.71) and the AUC of N-terminal pro-B-type natriuretic peptide (NT-proBNP) was 0.85 (0.81–0.89). During median 818 days follow-up, 110 patients died (37%). There was a nonlinear association between SN CLIA concentrations and mortality with optimal cutpoint 53 pmol/L. SN CLIA concentrations >53 pmol/L were associated with mortality after adjusting for clinical variables and NT-proBNP and cardiac troponin T concentrations: hazard ratio 1.7 (95% CI, 1.1–2.7), AUC 0.67 (0.61–0.74). We found similar results for SN ELISA for diagnosis and prognosis with AUC 0.63 (0.57–0.70) for the prediction of mortality. Conclusion The high-throughput SN CLIA correlates with the SN ELISA and provides independent prognostic information over established biomarkers in patients with acute dyspnea.

• Liboriussen, Caroline; Nygaard, Louis; Lyngbakken, Magnus Nakrem; Bakkan, Sara Marie Engelsvold; Jensen, Jens Dam & Glerup, Rie Io [Show all 9 contributors for this article] (2025). Secretoneurin is not associated with cardiovascular events or mortality in patients treated with hemodialysis: A prospective multicenter cohort study. Clinical Biochemistry. ISSN 0009-9120. 136. doi: 10.1016/j.clinbiochem.2025.110899. Full text in Research Archive Show summary

  Introduction Secretoneurin (SN) is a novel cardiac biomarker with an upper reference limit of ∼60 pmol/L in healthy individuals. High SN concentrations have been associated with an increased risk of mortality in various cardiac diseases. We investigated the association between SN and the risk of cardiovascular (CV) events and all-cause mortality in patients treated with maintenance hemodialysis (HD). Materials and Methods Prospective multicenter cohort study with five years of follow-up. Serum SN (pmol/L) was measured at baseline. Outcomes were CV events (composite outcome) and all-cause mortality. The population was divided into tertiles according to SN concentrations: tertile 1 < 110.7 pmol/L, tertile 2 110.7–143 pmol/L, and tertile 3 > 143 pmol/L. The association between SN tertiles and outcomes was examined using Cox regression analysis. Results The study included 336 patients treated with HD. Median SN concentration was 126 (100–153) pmol/L. During a median follow-up of 5.05 (5.02–5.07) years, 42 % had a CV event and 60 % died. Despite overall high SN concentrations, neither SN tertile 2 nor SN tertile 3 was associated with the risk of CV events (HRtertile2 1.27 (95 % CI 0.84–1.93) and HRtertile3 1.20 (95 % CI 0.76–1.90)) or all-cause mortality (HRtertile2 0.84 (95 % CI 0.60–1.18) and HRtertile3 0.90 (95 % CI 0.62–1.31)), when compared to tertile 1. Conclusions Patients treated with HD have high SN concentrations; however, SN was not associated with CV events or all-cause mortality after five years of follow-up. High concentrations of SN, possibly explained by both impaired renal clearance and a high prevalence of cardiomyopathy, may limit its prognostic relevance in patients treated with maintenance HD.

• Restan, Ingar Ziad; Steiro, Ole-Thomas; Pickering, John W.; Tjora, Hilde Lunde; Langørgen, Jørund & Omland, Torbjørn [Show all 15 contributors for this article] (2025). Clinical derivation and data simulated validation of rule-out and rule-in algorithms for the Siemens Atellica IM high-sensitivity cardiac troponin I assay. European Heart Journal: Acute Cardiovascular Care. ISSN 2048-8726. 14(3), p. 155–168. doi: 10.1093/ehjacc/zuaf017. Full text in Research Archive Show summary

  Aims: This prospective, two-centre study derived and validated predictive algorithms for the Siemens Atellica IM high-sensitivity cardiac troponin I (hs-cTnI) assay in the emergency department (ED). Methods and results: Algorithms for predicting 30-day myocardial infarction (MI) Types 1 and 2 and death or non-ST-elevation MI (NSTEMI, Types 1 and 2) at index admission were developed from a derivation cohort of 1896 patients and validated using a synthetic data set with nearly 1 million patient cases. Performance was compared with the European Society of Cardiology algorithms for hs-cTnT (Roche Diagnostics) and hs-cTnI (Abbott Diagnostics). An admission hs-cTnI concentration < 5 ng/L had a negative predictive value (NPV) and sensitivity for 30-day MI or death of 99.5–99.7% and 98.1–98.8%, respectively, in the derivation cohort and validation data set. The NPV and sensitivity were ≥99.7% and ≥98.8% for ruling out index NSTEMI. A 0- to 1-h algorithm with baseline hs-cTnI concentration < 10 ng/L and Δ change < 3 ng/L had NPV of ≥99.5% and sensitivity ≥ 97.3% for predicting 30-day MI or death and a ≥99.5% sensitivity and NPV for index NSTEMI. Rule-in algorithms of either 0-h hs-cTnI ≥ 120 ng/L or 0- to 1-h Δ change ≥ 12 ng/L had positive predictive value ≥ 73% and specificity > 96% for 30-day MI or death and index NSTEMI. The results were comparable with established hs-cTn algorithms. Conclusion: This study presents Siemens Atellica hs-cTnI algorithms for diagnosis and risk prediction in the ED with performance comparable with established hs-cTnT (Roche) and hs-cTnI (Abbott) algorithms.

• Røys, Eirik Åsen; Viste, Kristin; Kellmann, Ralf; Guldhaug, Nora Alicia; Alaour, Bashir & Sylte, Marit Sverresdotter [Show all 13 contributors for this article] (2025). Estimating Reference Change Values Using Routine Patient Data: A Novel Pathology Database Approach. Clinical Chemistry. ISSN 0009-9147. 71(2), p. 307–318. doi: 10.1093/clinchem/hvae166. Full text in Research Archive Show summary

  Background: The reference change value (RCV) is calculated by combining the within-subject biological variation (CVI) and local analytical variation (CVA). These calculations do not account for the variation seen in preanalytical conditions in routine practice or CVI in patients presenting for treatment. As a result, the RCVs may not reflect routine practice or align with clinicians’ experiences. We propose a novel RCV approach based on routine patient data that is potentially more clinically relevant. Methods: This study used the refineR algorithm to determine RCVs using serial patient data extracted from a local Laboratory Information System (LIS). The model was applied to biomarkers with a range of result ratio distributions varying from normal to log-normal. Results were compared against conventional formula-based RCVs using CVI estimates from a state-of-the-art biological variation study. Monte Carlo simulations were also used to validate the LIS data approach. Results: The RCVs estimated from LIS data were: 11-deoxycortisol (men): −70%/+196%, 17-hydroxyprogesterone (men): −49%/+100%, albumin: −10%/+11%, androstenedione (men): −47%/+96%, cortisol (men): −54%/+51%, cortisone (men): −32%/+51%, creatinine: −16%/+14%, phosphate (women): −23%/+29%, phosphate (men): −27%/+29%, testosterone (men): −38%/+60%. The formula-based RCV estimates showed similar but slightly lower results, and the Monte Carlo simulations confirmed the applicability of the new approach. Conclusions: RCVs may be estimated from patient results without prior assumptions about the shape of the ratios between serial results. Laboratories can determine RCVs based on local practice and population.

• 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.

• Omland, Torbjørn; Røsjø, Helge Rørvik; Wisløff, Torbjørn; Bernard, Michael L.; Hiltbold, A.Elise & Khatib, Sammy [Show all 9 contributors for this article] (2025). Serial secretoneurin measurement and risk of ventricular arrhythmias and death in patients with left ventricular systolic dysfunction. Clinical Biochemistry. ISSN 0009-9120. 135. doi: 10.1016/j.clinbiochem.2024.110868. Full text in Research Archive Show summary

  Background Secretoneurin, a member of the granin protein family, is associated with the risk of mortality in patients with acute and chronic heart failure. Secretoneurin may play an important role in cardiomyocyte calcium handling, suggesting that it may influence cardiac arrhythmia risk. We hypothesized that baseline and serial measurements of circulating secretoneurin are associated with the risk of incident ventricular tachyarrhythmias (VA) and death, and that serial measurement would provide prognostic information beyond baseline values. Methods We measured circulating secretoneurin concentrations in blood samples obtained at 3-month intervals for one year in a prospectively enrolled cohort of ambulatory patients with left ventricular ejection fraction (LVEF) ≤ 35 % and a primary-prevention implanted cardioverter defibrillator (ICD). Associations between secretoneurin modeled as a time-dependent variable and the incidences of VA and death were assessed. Results 154 patients (66 ± 14 years, LVEF 23 ± 8 %) were included in the analysis. During one-year follow-up, 26 (17 %) patients experienced VA, and 16 (10 %) died. Adjusting for age, sex, eGFR, and LVEF, baseline secretoneurin concentration was associated with the risk of death (hazard ratio (HR) per 10 pmol/L increase: 1.14 (95 % CI: 1.02–1.27), p = 0.020) but not VA (HR: 0.98 (0.81–1.19), p = 0.856). Using serial measurements at 3-month intervals, time-varying secretoneurin was associated with a similarly higher risk of death (HR: 1.14 (1.02–1.27), p = 0.017) but not of VA (HR: 0.97 (0.81–1.17), p = 0.776). Conclusion In stable ambulatory patients with reduced LV systolic function and a primary prevention indication for ICD, secretoneurin concentration was associated with the risk of death but not ventricular tachyarrhythmia.

• Bhatnagar, Rahul; Berge, Kristian; Høiseth, Arne Didrik; Omland, Torbjørn; Lyngbakken, Magnus Nakrem & Røsjø, Helge Rørvik (2024). Associations between Chest Pain, Diagnosis, and Clinical Outcome in Patients Hospitalized with Acute Dyspnea: Data from the ACE 2 Study. Cardiology. ISSN 0008-6312. 150(3), p. 242–242. doi: 10.1159/000541897. Full text in Research Archive Show summary

  <p>Introduction: Patients hospitalized due to dyspnea sometimes also report concomitant chest pain. Whether co-existing chest pain in patients with acute dyspnea associates with specific diagnosis and clinical outcome is not known. Method: We included 313 patients admitted to Akershus University Hospital with acute dyspnea and asked the patients directly on hospital admission whether they had experienced chest pain during the last 24 h. We examined the associations between chest pain and (1) diagnosis of the index hospitalization and (2) clinical outcome during follow-up. The diagnosis for the index hospitalization was adjudicated as acute heart failure (HF) or non-HF etiology of acute dyspnea by two experts working independently. Non-HF patients were further sub-grouped into chronic obstructive pulmonary disease (COPD) or non-COPD etiology. Results: In total, 143 patients were admitted with acute HF (46% of the population), 83 patients with COPD (26% of the population), and 87 patients with non-HF, non-COPD-related dyspnea (28% of the population). Ninety-six patients (31%) with acute dyspnea reported chest pain during the last 24 h prior to hospital admission. The prevalence of chest pain was not statistically different for patients who were hospitalized with acute HF (n = 42, 44%), acute exacerbation of COPD (n = 22, 23%), or non-HF, non-COPD-related dyspnea (n = 32, 33%), p > 0.05 for all comparisons between groups. During median of 823 days follow-up, 114 patients died (36%). Patients with dyspnea and concomitant chest pain did not have different outcome compared to patients with dyspnea and no chest pain (log-rank test: p = 0.09). Chest pain prior to admission was neither associated with all-cause mortality in any of the adjudicated diagnosis groups. Conclusions: Chest pain was reported in 31% of patients hospitalized with acute dyspnea but the prevalence did not differ according to adjudicated diagnosis. Patients with dyspnea and chest pain did not have worse outcome compared to patients with dyspnea and no chest pain. </p>

• 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
• Vigen, Rebecca; Ayers, Colby; Berry, Jarett; Rohatgi, Anand; Nambi, Vijay & Ballantyne, Christie M. [Show all 9 contributors for this article] (2024). Individual and Joint Associations of High-Sensitivity Troponin I and High-Sensitivity Troponin T with Cardiac Phenotypes and Outcomes in the General Population: An Analysis From the Dallas Heart Study. Journal of the American Heart Association (JAHA). 13(13). doi: 10.1161/JAHA.124.034549. Full text in Research Archive Show summary

  Background High‐sensitivity troponin I (hs‐cTnI) and T (hs‐cTnT) provide complementary information regarding cardiovascular disease risk. The explanation for their distinct risk profiles is incompletely understood. Methods and Results hs‐cTnI and hs‐cTnT were measured in Dallas Heart Study participants. Associations of hs‐cTnI and hs‐cTnT with demographics and phenotypes were assessed using linear regression. Associations with incident heart failure, atherosclerotic cardiovascular disease, global cardiovascular disease, and cardiovascular and all‐cause mortality were assessed using Cox models. Among 3276 participants (56% women, 50% Black persons, median age 43 years), the correlation between hs‐cTnI and hs‐cTnT was modest (Spearman rho=0.35). Variables associated with hs‐cTnI but not hs‐cTnT included hypertension, higher body mass index and total cholesterol, and lower high‐density lipoprotein and cholesterol efflux capacity. Older age, male sex, and diabetes were positively associated, and smoking was negatively associated, with hs‐cTnT but not hs‐cTnI. Hs‐cTnI and hs‐cTnT were associated with heart failure (hazard ratio [HR] per SD log hs‐cTnI 1.53 [95% CI, 1.30–1.81] and HR per SD log hs‐cTnT 1.65 [95% CI, 1.40–1.95]), global cardiovascular disease (HR, 1.22 [95% CI, 1.10–1.34] and HR, 1.27 [95% CI, 1.15–1.32]), and all‐cause mortality (HR, 1.12 [95% CI, 1.01–1.25], and HR, 1.17 [95% CI, 1.06–1.29]). After adjustment for N‐terminal pro‐B‐type natriuretic peptide and the alternative troponin, both remained associated with heart failure (HR per SD log hs‐cTnI 1.32 [95% CI, 1.1–1.58] and HR per log hs‐cTnT 1.27 [95% CI, 1.06–1.51]). Conclusions Hs‐cTnI and hs‐cTnT are modestly correlated, demonstrate differential associations with cardiac and metabolic phenotypes, and provide complementary information regarding heart failure risk.

• Shah, Amil M.; Myhre, Peder Langeland; Arthur, Victoria; Dorbala, Pranav; Rasheed, Humaira & Buckley, Leo F. [Show all 22 contributors for this article] (2024). Large scale plasma proteomics identifies novel proteins and protein networks associated with heart failure development. Nature Communications. 15(1). doi: 10.1038/s41467-023-44680-3. Full text in Research Archive Show summary

  Heart failure (HF) causes substantial morbidity and mortality but its pathobiology is incompletely understood. The proteome is a promising intermediate phenotype for discovery of novel mechanisms. We measured 4877 plasma proteins in 13,900 HF-free individuals across three analysis sets with diverse age, geography, and HF ascertainment to identify circulating proteins and protein networks associated with HF development. Parallel analyses in Atherosclerosis Risk in Communities study participants in mid-life and late-life and in Trøndelag Health Study participants identified 37 proteins consistently associated with incident HF independent of traditional risk factors. Mendelian randomization supported causal effects of 10 on HF, HF risk factors, or left ventricular size and function, including matricellular (e.g. SPON1, MFAP4), senescence-associated (FSTL3, IGFBP7), and inflammatory (SVEP1, CCL15, ITIH3) proteins. Protein co-regulation network analyses identified 5 modules associated with HF risk, two of which were influenced by genetic variants that implicated trans hotspots within the VTN and CFH genes.

• Saeed, Nasir; Steiro, Ole-Thomas; Langørgen, Jørund; Tjora, Hilde Lunde; Bjørneklett, Rune Oskar & Skadberg, Øyvind [Show all 13 contributors for this article] (2024). Diagnosing Myocardial Injury in an Acute Chest Pain Cohort; Long-Term Prognostic Implications of Cardiac Troponin T and i. Clinical Chemistry. ISSN 0009-9147. 70(10), p. 1241–1255. doi: 10.1093/clinchem/hvae110. Full text in Research Archive Show summary

  Background There are limited data regarding the utility of follow-up cardiac troponin (cTn) measurements after admission for acute chest pain and how long-term stability of myocardial injury and prognostic value differ when using cardiac troponin T (cTnT) or I (cTnI). Methods We measured high-sensitivity (hs)-cTnT (Roche Diagnostics) and hs-cTnI (Siemens Healthineers) during hospitalization for acute chest pain and after 3 months. Acute myocardial injury was defined as concentrations > sex-specific upper reference limit (URL) during hospitalization and ≤URL at 3-months. Chronic myocardial injury (CMI) was defined as concentrations > URL at both time points. Patients were followed from the 3-month sampling point for a median of 1586 (IQR 1161–1786) days for a primary composite endpoint of all-cause mortality, myocardial infarction (MI), revascularization, and heart failure, and a secondary endpoint of all-cause mortality. Results Among 754 patients, 33.8% (hs-cTnT) and 19.2% (hs-cTnI) had myocardial injury during hospitalization. The rate of CMI was 5 times higher by hs-cTnT (20%) assay than hs-cTnI (4%), while acute myocardial injury was equally common; 14% (hs-cTnT) and 15% (hs-cTnI), respectively (6% and 5% when excluding index non-ST-elevation MI (NSTEMI). For hs-cTnT, peak index concentration, 3-month concentration and classification of CMI predicted the primary endpoint; hazard ratios (HRs) 1.38 (95% CI 1.20–1.58), 2.34 (1.70–3.20), and 2.31 (1.30–4.12), respectively. For hs-cTnI, peak index concentration predicted the primary endpoint; HR 1.14 (1.03–1.25). This association was nonsignificant after excluding index NSTEMI. Conclusions Acute myocardial injury is equally frequent, whereas CMI is more prevalent using hs-cTnT assay than hs-cTnI. Measuring hs-cTnT 3 months after an acute chest pain episode could assist in further long-term risk assessment.

• Bhatnagar, Rahul; Berge, Kristian; Høiseth, Arne Didrik; Omland, Torbjørn; Lyngbakken, Magnus Nakrem & Røsjø, Helge Rørvik (2024). Associations between Chest Pain, Diagnosis, and Clinical Outcome in Patients Hospitalized with Acute Dyspnea: Data from the ACE 2 Study. Cardiology. ISSN 0008-6312. doi: 10.1159/000541897. Full text in Research Archive Show summary

  Introduction: Patients hospitalized due to dyspnea sometimes also report concomitant chest pain. Whether co-existing chest pain in patients with acute dyspnea associates with specific diagnosis and clinical outcome is not known. Method: We included 313 patients admitted to Akershus University Hospital with acute dyspnea and asked the patients directly on hospital admission whether they had experienced chest pain during the last 24 h. We examined the associations between chest pain and (1) diagnosis of the index hospitalization and (2) clinical outcome during follow-up. The diagnosis for the index hospitalization was adjudicated as acute heart failure (HF) or non-HF etiology of acute dyspnea by two experts working independently. Non-HF patients were further sub-grouped into chronic obstructive pulmonary disease (COPD) or non-COPD etiology. Results: In total, 143 patients were admitted with acute HF (46% of the population), 83 patients with COPD (26% of the population), and 87 patients with non-HF, non-COPD-related dyspnea (28% of the population). Ninety-six patients (31%) with acute dyspnea reported chest pain during the last 24 h prior to hospital admission. The prevalence of chest pain was not statistically different for patients who were hospitalized with acute HF (n = 42, 44%), acute exacerbation of COPD (n = 22, 23%), or non-HF, non-COPD-related dyspnea (n = 32, 33%), p > 0.05 for all comparisons between groups. During median of 823 days follow-up, 114 patients died (36%). Patients with dyspnea and concomitant chest pain did not have different outcome compared to patients with dyspnea and no chest pain (log-rank test: p = 0.09). Chest pain prior to admission was neither associated with all-cause mortality in any of the adjudicated diagnosis groups. Conclusions: Chest pain was reported in 31% of patients hospitalized with acute dyspnea but the prevalence did not differ according to adjudicated diagnosis. Patients with dyspnea and chest pain did not have worse outcome compared to patients with dyspnea and no chest pain.

• Riveland, Egil Aarstad; Valborgland, Torstein; Ushakova, Anastasia; Skadberg, Øyvind; Karlsen, Trine & Hole, Torstein Laurits [Show all 19 contributors for this article] (2024). Exercise training and high-sensitivity cardiac troponin-I in patients with heart failure with reduced ejection fraction. ESC Heart Failure. 11(2), p. 1121–1132. doi: 10.1002/ehf2.14674. Full text in Research Archive Show summary

  Aims: The aims of this sub-study of the SMARTEX trial were (1) to evaluate the effects of a 12-week exercise training programme on serum levels of high sensitivity cardiac troponin I (hs-cTnI) in patients with moderate chronic heart failure (CHF), in New York Heart Association class II-III with reduced ejection fraction (HFrEF) and (2) to explore the associations with left ventricular remodelling, functional capacity and filling pressures measured with N-terminal pro brain natriuretic peptide (NT-proBNP). Methods and results: In this sub-study, 196 patients were randomly assigned to high intensity interval training (HIIT, n = 70), moderate continuous training (MCT, n = 59) or recommendation of regular exercise (RRE), (n = 67) for 12 weeks. To reveal potential difference between structured intervention and control, HIIT and MCT groups were merged and named supervised exercise training (SET) group. The RRE group constituted the control group (CG). To avoid contributing factors to myocardial injury, we also evaluated changes in patients without additional co-morbidities (atrial fibrillation, hypertension, diabetes mellitus, and chronic obstructive pulmonary disease). The relationship between hs-cTnI and left ventricular end-diastolic diameter (LVEDD), VO2peak, and NT-proBNP was analysed by linear mixed models. At 12 weeks, Hs-cTnI levels were modestly but significantly reduced in the SET group from median 11.9 ng/L (interquartile ratio, IQR 7.1–21.8) to 11.5 ng/L (IQR 7.0–20.7), P = 0.030. There was no between-group difference (SET vs. CG, P = 0.116). There was a numerical but not significant reduction in hs-cTnI for the whole population (P = 0.067) after 12 weeks. For the sub-group of patients without additional co-morbidities, there was a significant between-group difference: SET group (delta −1.2 ng/L, IQR −2.7 to 0.1) versus CG (delta −0.1 ng/L, IQR −0.4 to 0.7), P = 0.007. In the SET group, hs-cTnI changed from 10.9 ng/L (IQR 6.0–22.7) to 9.2 ng/L (IQR 5.2–20.5) (P = 0.002), whereas there was no change in the CG (6.4 to 5.8 ng/L, P = 0.64). Changes in hs-cTnI (all patients) were significantly associated with changes in; LVEDD, VO2peak, and NT-proBNP, respectively. Conclusions: In patients with stable HFrEF, 12 weeks of structured exercise intervention was associated with a modest, but significant reduction of hs-cTnI. There was no significant difference between intervention group and control group. In the sub-group of patients without additional co-morbidities, this difference was highly significant. The alterations in hs-cTnI were associated with reduction of LVEDD and natriuretic peptide concentrations as well as improved functional capacity.

• Neumann, Johannes Tobias; Twerenbold, Raphael; Weimann, Jessica; Ballantyne, Christie M.; Benjamin, Emelia J. & Costanzo, Simona [Show all 54 contributors for this article] (2024). Prognostic Value of Cardiovascular Biomarkers in the Population. Journal of the American Medical Association (JAMA). ISSN 0098-7484. 331(22), p. 1898–1909. doi: 10.1001/jama.2024.5596. Full text in Research Archive
• Wimalanathan, Thakshani; Paus, Michael Fredrik; Skranes, Julia Brox; Berge, Trygve; Tveit, Arnljot & Røsjø, Helge Rørvik [Show all 9 contributors for this article] (2024). Associations between Growth Differentiation Factor 15, Cardiac Troponin T, and N-terminal pro-B-type Natriuretic Peptide, and Future Myocardial Fibrosis Assessed by Cardiac Magnetic Resonance Imaging: Data from the Akershus Cardiac Examination 1950 Study. The Journal of Applied Laboratory Medicine (JALM). ISSN 2576-9456. 10(2), p. 392–405. doi: 10.1093/jalm/jfae145. Full text in Research Archive Show summary

  Background Myocardial fibrosis is associated with a poor outcome for patients with cardiovascular disease (CVD). Growth differentiation factor 15 (GDF-15) concentrations predict the risk of death in patients with CVD, but the underlying pathophysiological mechanisms are poorly understood. We aimed to assess the associations between biomarkers of cellular stress and inflammation (GDF-15), cardiac injury (cardiac troponin T [cTnT]), and stretch (N-terminal pro-B-type natriuretic peptide [NT-proBNP]), and subsequent focal and diffuse myocardial fibrosis assessed by cardiac magnetic resonance (CMR) imaging. Methods We measured GDF-15, cTnT, and NT-proBNP in 200 study participants without known coronary artery disease or renal dysfunction from the population-based Akershus Cardiac Examination 1950 Study at baseline in 2012 to 2015. Focal myocardial scars and diffuse fibrosis were assessed by late gadolinium enhancement imaging and septal extracellular volume fraction (ECV) by CMR 4 to 7 years later. The relationships between cardiac biomarkers and CMR parameters were assessed by logistic regression analysis adjusted for common cardiovascular risk factors. Results The median age was 63.9 (interquartile range 63.4–64.5) years and 49% were women. GDF-15 (adjusted odds ratio [aOR] 4.40, 95% CI 1.09–17.72) and cTnT (aOR 1.59, 95% CI 1.01–2.50) were associated with nonischemic scars in the fully adjusted model. cTnT (aOR 2.45, 95% CI 1.41–4.25) and NT-proBNP (aOR 3.12, 95% CI 1.55–6.28) were associated with ischemic scars. None of the biomarkers were significantly associated with elevated ECV. Conclusions In a general population cohort, GDF-15, an emerging biomarker of cellular stress and inflammation, associates with nonischemic scars. Biomarkers of myocardial injury and stretch associate with ischemic scars, while no biomarker was associated with diffuse fibrosis as assessed by CMR.

• Sulkowska, Joanna; Melles, Woldegabriel A; Skranes, Julia Brox; Berge, Trygve; Tveit, Arnljot & Røsjø, Helge Rørvik [Show all 9 contributors for this article] (2024). Cardiac troponin T associates with left ventricular function and synchrony assessed by CMR in the general population: results from the Akershus Cardiac Examination 1950 Study. European Heart Journal – Imaging Methods and Practice (EHJ-IMP). 2(3). doi: 10.1093/ehjimp/qyae078. Full text in Research Archive Show summary

  Background and aim Cardiac troponin T (cTnT) is a blood biomarker of myocardial injury that is associated with future adverse cardiovascular events in the general population. Left ventricular (LV) global longitudinal strain (GLS) and mechanical dispersion (MD) are metrics of systolic function and synchrony that can be obtained from cardiac imaging. Studies suggest an association between cTnT and echocardiographically assessed GLS and MD, but it is unknown whether cTnT relates to these metrics when assessed by cardiac magnetic resonance (CMR). We hypothesized that cTnT associates with GLS and with MD assessed by CMR feature tracking (CMR-FT) in the general population. Methods and results cTnT and CMR-FT measurements were performed in 186 community dwellers from the Akershus Cardiac Examination 1950 Study. The participants’ age ranged from 68 to 70 years. Median cTnT concentration was 7.0 ng/L (interquartile interval 5.0–12.6 ng/L), median absolute value of GLS was 17.3% (interquartile interval 15.7–18.8%), and median MD was 80.7 milliseconds (interquartile interval 61.8–105.0 milliseconds). In multivariable linear regression models adjusted for common clinical risk factors of cardiovascular disease, with GLS and MD as outcome and cTnT as the predictor variable of interest, log10 transformed cTnT was significantly associated with both absolute GLS [β-coefficient −1.65, confidence interval (−2.84, −0.46)] and MD [β-coefficient 28.56, confidence interval (12.14, 44.92)]. Conclusion In older adults from the general population, higher cTnT concentrations are associated with worse systolic function and synchrony assessed by CMR-FT LV GLS and MD, adding information about myocardial function to traditional risk factors.

• Røsjø, Helge Rørvik; Solberg, Ole Geir; Aaberge, Lars; Bosse, Gerhard; Omland, Torbjørn & Stavem, Knut [Show all 7 contributors for this article] (2024). Trans-Cardiac Gradient of Secretoneurin in Patients with Takotsubo Syndrome. Cardiology. ISSN 0008-6312. 149(5), p. 466–471. doi: 10.1159/000539094. Full text in Research Archive
• Sharma, Archana; Birkeland, Kåre Inge; Nermoen, Ingrid; Sommer, Christine; Qvigstad, Elisabeth & Lee-Ødegård, Sindre [Show all 11 contributors for this article] (2024). N-terminal pro-B-type natriuretic peptide levels vary by ethnicity and are associated with insulin sensitivity after gestational diabetes mellitus. Cardiovascular Diabetology. 23(1). doi: 10.1186/s12933-024-02349-1. Full text in Research Archive Show summary

  Background Individuals of South Asian origin have a greater risk of cardiovascular disease after gestational diabetes mellitus (GDM) than European individuals. B-type natriuretic peptide (BNP) and the amino-terminal fragment of its prohormone (NT-proBNP) are commonly used for heart failure screening and diagnosis, but biologically BNP exerts several beneficial cardiovascular effects primarily by counteracting the renin-angiotensin-aldosterone-system. We asked whether ethnic differences in circulating NT-proBNP levels could be explained by the differences in cardiometabolic and inflammatory risk markers? Methods We examined 162 South Asian and 107 Nordic women in Norway 1–3 years after GDM with a clinical examination, fasting blood samples and an oral glucose tolerance test. We measured the levels of NT-proBNP, high-sensitivity cardiac troponin T, high-sensitivity C-reactive protein (hsCRP), interleukin-6 (IL-6), leptin, adiponectin and markers of insulin sensitivity, such as the Matsuda insulin sensitivity index (ISI). Finally, we tried to identify which independent covariate best mediated the ethnic differences in NT-proBNP. Results The mean (SD) age was 35.3 (4.5) years, BMI 29.1 (6.0) kg/m2, waist-height ratio 0.60 (0.08) and 164 women (61%) had prediabetes/diabetes. Notably, South Asian women had lower levels of NT-proBNP than Nordic women in both the normoglycemic and prediabetes/diabetes groups (median (IQR) 26  (15–38)  vs. 42 (22–66) ng/L, p < 0.001). Higher NT-proBNP levels were associated with greater insulin sensitivity in both South Asian and Nordic women (p = 0.005 and p < 0.001). South Asian women had higher levels of hsCRP (median (IQR) 2.2 (1.1–4.4) vs. 1.2 (0.3–4.2) mg/L), IL-6 (2.3 (1.5–3.2) vs. 1.5 (1.5–2.5) pg/mL), leptin (1647 (1176–2480) vs. 1223 (876–2313) pmol/L), and lower adiponectin levels (7.2 (5.3–9.3) vs. 10.0 (7.2–13.5) mg/L) and Matsuda ISI (2.4 (1.7–3.7) vs. 4.2 (2.9–6.1), pall<0.01) than Nordic women. Even after adjusting for these differences, higher NT-proBNP levels remained associated with insulin sensitivity (22% higher NT-proBNP per SD Matsuda ISI, p = 0.015). Insulin sensitivity and adiponectin mediated 53% and 41% of the ethnic difference in NT-proBNP. Conclusions NT-proBNP levels are lower in South Asian than in Nordic women after GDM. Lower NT-proBNP levels correlate with impaired insulin sensitivity. Lower NT-proBNP levels in South Asian women could, therefore, be attributed to impaired insulin sensitivity rather than total body fat.

• Young, Juliet; Lyngbakken, Magnus Nakrem; Hveem, Kristian; Røsjø, Helge Rørvik & Omland, Torbjørn (2024). Systolic Blood Pressure, Diastolic Blood Pressure and Pulse Pressure and the Risk of Subclinical Myocardial Injury: The HUNT Study. Journal of the American Heart Association (JAHA). 13(9). doi: 10.1161/JAHA.123.031107. Full text in Research Archive Show summary

  Background: Subclinical myocardial injury expressed as higher cardiac troponin concentrations may represent an important intermediary between hypertension and the risk of cardiovascular disease. The study aimed to assess the relative strength of associations between systolic blood pressure (BP), diastolic BP, and pulse pressure, and subclinical myocardial injury, and how change in BP variables over time associates with subclinical myocardial injury. Methods and Results: cTnl (cardiac troponin I) was measured in 32 968 participants of the fourth wave of the population‐based cohort HUNT4 (Trøndelag Health Study) without a history of cardiovascular disease. An additional longitudinal analysis included participants from HUNT4 with BP measurements from HUNT3 (n=18 681). Associations between BP variables and cTnI concentrations were assessed by linear and logistic regression analyses. The median cTnI concentration was 1.6 ng/L (25th–75th percentiles, 0.6–3.1 ng/L), median age was 52 years (39.1–65.6 years), and 57% were female subjects. Cross‐sectionally, only systolic BP categories ≥130 mm Hg associated with higher cTnI concentrations, compared with a reference systolic BP of <110 mm Hg. All categories of diastolic BP and pulse pressure were positively associated with higher cTnI concentrations when diastolic BP 70 to 79 mm Hg and pulse pressure <40 mm Hg were used as references, respectively. When comparing systolic BP, diastolic BP, and pulse pressure as continuous variables, cross‐sectionally, pulse pressure most strongly associated with cTnI concentrations (P for all comparisons <0.001), whereas longitudinally, change in diastolic BP was most strongly associated with cTnI concentrations (P for all comparisons <0.05). Conclusions: Subjects with high pulse pressure and longitudinal increase in diastolic BP are at higher risk for subclinical myocardial injury.

• Mecinaj, Albulena; Gulati, Geeta; Ree, Anne Hansen; Gravdehaug, Berit; Røsjø, Helge Rørvik & Steine, Kjetil [Show all 10 contributors for this article] (2024). Impact of the ESC Cardio-Oncology Guidelines Biomarker Criteria on Incidence of Cancer Therapy–Related Cardiac Dysfunction. JACC: CardioOncology. 6(1), p. 83–95. doi: 10.1016/j.jaccao.2023.10.008. Full text in Research Archive Show summary

  Background The impact of recent consensus definitions of cancer therapy–related cardiac dysfunction (CTRCD) from the European Society of Cardiology cardio-oncology guidelines on the reported incidence of CTRCD has not yet been assessed. Objectives The aim of this study was to assess the: 1) cumulative incidence; 2) point prevalence during and after adjuvant therapy; and 3) prognostic value of CTRCD as defined by different asymptomatic CTRCD guideline criteria. Methods The cumulative incidence and point prevalence of CTRCD were retrospectively assessed in 118 patients participating in the PRADA (Prevention of Cardiac Dysfunction During Adjuvant Breast Cancer Therapy) trial. Asymptomatic CTRCD was assessed using alternative cardiac troponin (cTn) 99th percentile upper reference limits (URLs) to define cTnT and cTnI elevation. Results The cumulative incidence of moderate or severe CTRCD was low (1.7%), whereas the cumulative incidence of mild asymptomatic CTRCD was higher and differed markedly according to the biomarker criteria applied, ranging from 49.2% of patients when cTnT greater than the sex-specific 99th percentile URL was used to define cTn elevation to 9.3% when sex-neutral cTnI was used. The point prevalence of CTRCD was highest at the end of anthracycline therapy (47.8%) and was driven primarily by asymptomatic cTn elevation. CTRCD during adjuvant therapy was not prognostic for CTRCD at extended follow-up of 24 months (Q1-Q3: 21-29 months) after randomization. Conclusions Mild asymptomatic CTRCD during adjuvant breast cancer therapy was frequent and driven mainly by cTn elevation and was not prognostic of subsequent CTRCD. The incidence of mild, asymptomatic CTRCD differed markedly depending on the cTn assay and whether sex-neutral or sex-dependent URLs were applied. (Prevention of Cardiac Dysfunction During Adjuvant Breast Cancer Therapy [PRADA]; NCT01434134)

• Aakre, Kristin Moberg; Lyngbakken, Magnus Nakrem; Faaren, Arne L.; Røsjø, Helge Rørvik; Dalen, Håvard & Omland, Torbjørn (2024). Reference intervals of circulating secretoneurin concentrations determined in a large cohort of community dwellers: the HUNT study. Clinical Chemistry and Laboratory Medicine. ISSN 1434-6621. 62(10), p. 2030–2036. doi: 10.1515/cclm-2024-0154. Full text in Research Archive Show summary

  Objectives Secretoneurin (SN) is a novel cardiac biomarker that associates with the risk of mortality and dysfunctional cardiomyocyte Ca2+ handling in heart failure patients. Reference intervals for SN are unknown. Methods SN was measured with a CE-marked ELISA in healthy community dwellers from the fourth wave of the Trøndelag Health Study (HUNT4) conducted in 2017–2019. The common, sex and age specific 90th, 95th, 97.5th and 99th percentiles were calculated using the non-parametric method and outlier exclusion according to the Reed test. The applicability of sex and age specific reference intervals were investigated using Harris and Boyd test. We also estimated the percentiles in a subset with normal findings on echocardiographic screening. Results The total cohort included 887 persons (56.4 % women). After echocardiographic screening 122 persons were excluded, leaving a total of 765 persons (57.8 % women). The 97.5th percentile (95 % CI in brackets) of SN was 59.7 (57.5–62.1) pmol/L in the total population and 58.6 (57.1–62.1) pmol/L after echocardiography screening. In general, slightly higher percentiles were found in women and elderly participants, but less than 4 % in these subgroups had concentrations deviating from the common 97.5th percentile. Low BMI or eGFR was also associated with higher concentrations of SN. Conclusions Upper reference limits for SN were similar amongst healthy adult community dwellers regardless of prescreening including cardiac echocardiography or not. Women and elderly showed higher concentrations of SN, but the differences were not sufficiently large to justify age and sex stratified upper reference limits

• Øvrebotten, Tarjei; Mecinaj, Albulena; Stavem, Knut; Ghanima, Waleed; Brønstad, Eivind & Durheim, Michael Thomas [Show all 14 contributors for this article] (2024). Trajectory of cardiac troponin T following moderate-to-severe COVID-19 and the association with cardiac abnormalities. BMC Cardiovascular Disorders. 24(1). doi: 10.1186/s12872-024-03854-7. Full text in Research Archive Show summary

  Background COVID-19 has been associated with cardiac troponin T (cTnT) elevations and changes in cardiac structure and function, but the link between cardiac dysfunction and high-sensitive cardiac troponin T (hs-cTnT) in the acute and convalescent phase is unclear. Objective To assess whether hs-cTnT concentrations are associated with cardiac dysfunction and structural abnormalities after hospitalization for COVID-19, and to evaluate the performance of hs-cTnT to rule out cardiac pathology. Methods Patients hospitalized with COVID-19 had hs-cTnT measured during the index hospitalization and after 3-and 12 months, when they also underwent an echocardiographic study. A subset also underwent cardiovascular magnetic resonance imaging (CMR) after 6 months. Cardiac abnormalities were defined as left ventricular hypertrophy or dysfunction, right ventricular dysfunction, or CMR late gadolinium. Results We included 189 patients with hs-cTnT concentrations measured during hospitalization for COVID-19, and after 3-and 12 months: Geometric mean (95%CI) 13 (11–15) ng/L, 7 (6–8) ng/L and 7 (6–8) ng/L, respectively. Cardiac abnormalities after 3 months were present in 45 (30%) and 3 (8%) of patients with hs-cTnT ≥ and < 5 ng/L at 3 months, respectively (negative predictive value 92.3% [95%CI 88.5–96.1%]). The performance was similar in patients with and without dyspnea. Hs-cTnT decreased from hospitalization to 3 months (more pronounced in intensive care unit-treated patients) and remained unchanged from 3 to 12 months, regardless of the presence of cardiac abnormalities. Conclusion Higher hs-cTnT concentrations in the convalescent phase of COVID-19 are associated with the presence of cardiac pathology and low concentrations (< 5 ng/L) may support in ruling out cardiac pathology following the infection.

• Sourour, Nur; Riveland, Egil Aarstad; Næsgaard, Patrycja; Kjekshus, Harald; Larsen, Alf Inge & Røsjø, Helge Rørvik [Show all 8 contributors for this article] (2024). Associations Between Biomarkers of Myocardial Injury and Systemic Inflammation and Risk of Incident Ventricular Arrhythmia. JACC: Clinical Electrophysiology. ISSN 2405-500X. 10(9), p. 2021–2032. doi: 10.1016/j.jacep.2024.04.017. Full text in Research Archive
• Røsjø, Helge Rørvik; Meessen, Jennifer; Ottesen, Anett Hellebø; Latini, Roberto & Omland, Torbjørn (2023). Prognostic value of secretoneurin in chronic heart failure. Data from the GISSI-Heart Failure trial. Clinical Biochemistry. ISSN 0009-9120. 118. doi: 10.1016/j.clinbiochem.2023.110595. Full text in Research Archive Show summary

  Background Circulating secretoneurin (SN) concentrations have been found to provide prognostic information in patients with acute heart failure. We wanted to assess whether SN would improve prognostication also in patients with chronic heart failure (HF) in a large multicenter trial. Methods We measured plasma SN concentrations at randomization (n = 1224) and after 3 months (n = 1103) in patients with chronic, stable HF from the GISSI-HF study. The co-primary endpoints were (1) time to death or (2) admission to hospital for cardiovascular reasons. Results Mean age was 67 years and 80% were male. Median (quartile 1–3) SN concentrations were 42.6 (35.0–62.8) pmol/L on randomization and 42.0 (34.5–53.1) pmol/L after 3 months, which are higher than SN concentrations in healthy subjects. Higher SN concentrations at randomization were associated with lower body-mass index (BMI), lower systolic blood pressure, lower estimated glomerular filtration rate (eGFR), higher B-type natriuretic peptide (BNP) concentrations, and diagnosis of chronic obstructive pulmonary disease. During median follow-up of 3.9 years, 344 patients (27.0%) died. After adjusting for age, sex, left ventricular ejection fraction, BMI, functional class, ischemic etiology, heart rate, blood pressure, eGFR, bilirubin, comorbidities, and BNP concentrations, logarithmically transformed SN concentrations on randomization were associated with mortality (HR 2.60 (95% CI 1.01–6.70), p = 0.047). SN concentrations were also associated with admission to hospital for cardiovascular reasons, but the association was attenuated and no longer significant in multivariable analysis. Conclusion Plasma SN concentrations provided incremental prognostic information to established risk indices and biomarkers in a large cohort of chronic HF patients.

• Sæther, Julie Caroline; Vesterbekkmo, Elisabeth Kleivhaug; Taraldsen, Maria Dalen; Gigante, Bruna; Follestad, Turid & Røsjø, Helge Rørvik [Show all 10 contributors for this article] (2023). Associations between circulating microRNAs and lipid-rich coronary plaques measured with near-infrared spectroscopy. Scientific Reports. 13(1). doi: 10.1038/s41598-023-34642-6. Full text in Research Archive Show summary

  Lipid-rich coronary atherosclerotic plaques often cause myocardial infarction (MI), and circulating biomarkers that reflect lipid content may predict risk of MI. We investigated the association between circulating microRNAs (miRs) are lipid-rich coronary plaques in 47 statin-treated patients (44 males) with stable coronary artery disease undergoing percutaneous coronary intervention. We assessed lipid content in non-culprit coronary artery lesions with near-infrared spectroscopy and selected the 4 mm segment with the highest measured lipid core burden index (maxLCBI4mm). Lipid-rich plaques were predefined as a lesion with maxLCBI4mm ≥ 324.7. We analyzed 177 circulating miRs with quantitative polymerase chain reaction in plasma samples. The associations between miRs and lipid-rich plaques were analyzed with elastic net. miR-133b was the miR most strongly associated with lipid-rich coronary plaques, with an estimated 18% increase in odds of lipid-rich plaques per unit increase in miR-133b. Assessing the uncertainty by bootstrapping, miR-133b was present in 82.6% of the resampled dataset. Inclusion of established cardiovascular risk factors did not attenuate the association. No evidence was found for an association between the other analyzed miRs and lipid-rich coronary plaques. Even though the evidence for an association was modest, miR-133b could be a potential biomarker of vulnerable coronary plaques and risk of future MI. However, the prognostic value and clinical relevance of miR-133b needs to be assessed in larger cohorts.

• Tveit, Sjur Hansen; Myhre, Peder Langeland & Omland, Torbjørn (2023). The clinical importance of high-sensitivity cardiac troponin measurements for risk prediction in non-cardiac surgery. Expert Review of Molecular Diagnostics. ISSN 1473-7159. 23(6), p. 535–544. doi: 10.1080/14737159.2023.2211267. Full text in Research Archive Show summary

  Introduction The global healthcare burden associated with surgery is substantial, with many patients experiencing perioperative complications. Cardiac troponin I and T measured with high-sensitivity assays are cardiac specific biomarkers that associate closely with adverse outcomes in most patient populations. Perioperative physiological stress can induce troponin release from cardiomyocytes, a condition known as perioperative myocardial injury (PMI). PMI is associated with increased risk of poor short- and long-term outcomes, and current European guidelines recommend screening for PMI in at-risk individuals undergoing non-cardiac surgery. Areas covered In this review we summarize current knowledge of the prognostic attributes of cardiac troponins, as well as the challenges associated with their application as biomarkers in the perioperative phase. Expert opinion Measurement of circulating levels of cardiac troponins identify individuals at increased risk of poor postoperative outcomes. Systematic screening of at-risk individuals undergoing non-cardiac surgery will result in a large proportion of patients in need of further diagnostic workup to establish the exact nature of their PMI. The lack of concrete evidence of clinical benefit and the increased cost associated with such a strategy is concerning and underscore the need for further research.

• Myrmel, Gard Mikael Saele; Steiro, Ole-Thomas; Tjora, Hilde Lunde; Langørgen, Jørund; Bjørneklett, Rune Oskar & Skadberg, Øyvind [Show all 12 contributors for this article] (2023). Growth Differentiation Factor 15: A Prognostic Marker in Patients with Acute Chest Pain without Acute Myocardial Infarction. Clinical Chemistry. ISSN 0009-9147. 69(6), p. 649–660. doi: 10.1093/clinchem/hvad015. Full text in Research Archive Show summary

  Background Acute chest pain is associated with an increased risk of death and cardiovascular events even when acute myocardial infarction (AMI) has been excluded. Growth differentiation factor-15 (GDF-15) is a strong prognostic marker in patients with acute chest pain and AMI, but the prognostic value in patients without AMI is uncertain. This study sought to investigate the ability of GDF-15 to predict long-term prognosis in patients presenting with acute chest pain without AMI. Methods In total, 1320 patients admitted with acute chest pain without AMI were followed for a median of 1523 days (range: 4 to 2208 days). The primary end point was all-cause mortality. Secondary end points included cardiovascular (CV) death, future AMI, heart failure hospitalization, and new-onset atrial fibrillation (AF). Results Higher concentrations of GDF-15 were associated with increased risk of death from all causes (median concentration in non-survivors vs survivors: 2124 pg/mL vs 852 pg/mL, P < 0.001), and all secondary end points. By multivariable Cox regression, GDF-15 concentration ≥4th quartile (compared to <4th quartile) remained an independent predictor of all-cause death (adjusted hazard ratio (HR): 2.75; 95% CI, 1.69–4.45, P < 0.001), CV death (adjusted HR: 3.74; 95% CI, 1.31–10.63, P = 0.013), and heart failure hospitalization (adjusted HR: 2.60; 95% CI, 1.11–6.06, P = 0.027). Adding GDF-15 to a model consisting of established risk factors and high-sensitivity cardiac troponin T (hs-cTnT) led to a significant increase in C-statistics for prediction of all-cause mortality. Conclusions Higher concentrations of GDF-15 were associated with increased risk of mortality from all causes and risk of future CV events.

• Bhatnagar, Rahul; Berge, Kristian; Røysland, Ragnhild; Høiseth, Arne Didrik; Brynildsen, Jon & Christensen, Geir [Show all 9 contributors for this article] (2023). Cardiac Troponin T and NT-proBNP for Prediction of 30-Day Readmission or Death in Patients with Acute Dyspnea: Data from the Akershus Cardiac Examination 2 Study. Cardiology. ISSN 0008-6312. 148(6), p. 506–516. doi: 10.1159/000533266. Full text in Research Archive Show summary

  Introduction: N-terminal pro-B-type natriuretic peptide (NT-proBNP) and cardiac troponin T (cTnT) measurements are recommended in patients with acute dyspnea. We aimed to assess the prognostic merit of cTnT compared to NT-proBNP for 30-day readmission or death in patients hospitalized with acute dyspnea. Methods: We measured cTnT and NT-proBNP within 24 h in 314 patients hospitalized with acute dyspnea and adjudicated the cause of the index admission. Time to first event of readmission or death ≤30 days after hospital discharge was recorded, and cTnT and NT-proBNP measurements were compared head-to-head. Results: Patients who died (12/314) or were readmitted (71/314) within 30 days had higher cTnT concentrations (median: 32.6, Q1–Q3: 18.4–74.2 ng/L vs. median: 19.4, Q1–Q3: 8.4–36.1 ng/L; p for comparison &amp;lt;0.001) and NT-proBNP concentrations (median: 1,753.6, Q1–Q3: 464.2–6,862.0 ng/L vs. median 984, Q1–Q3 201–3,600 ng/L; for comparison p = 0.027) compared to patients who survived and were not readmitted. cTnT concentrations were associated with readmission or death within 30 days after discharge both in the total cohort (adjusted hazard ratio [aHR]: 1.64, 95% confidence interval [CI]: 1.30–2.05) and in patients with heart failure (HF) (aHR: 1.58, 95% CI: 1.14–2.18). In contrast, NT-proBNP concentrations were not associated with short-term events, neither in the total cohort (aHR: 1.10, 95% CI: 0.94–1.30) nor in patients with adjudicated HF (aHR: 1.06, 95% CI: 0.80–1.40). Conclusion: cTnT concentrations are associated with 30-day readmission or death in patients hospitalized with acute dyspnea, as well as in patients adjudicated HF.

• Røys, Eirik Åsen; Guldhaug, Nora Alicia; Viste, kristin; Jones, Graham Dallas; Alaour, Bashir & Sylte, Marit Sverresdotter [Show all 13 contributors for this article] (2023). Sex Hormones and Adrenal Steroids: Biological Variation Estimated Using Direct and Indirect Methods. Clinical Chemistry. ISSN 0009-9147. 69(1), p. 100–109. doi: 10.1093/clinchem/hvac175. Full text in Research Archive Show summary

  Background: Biological variation (BV) data may be used to develop analytical performance specifications (APS), reference change values (RCV), and support the applicability of population reference intervals. This study estimates within-subject BV (CVI) for several endocrine biomarkers using 3 different methodological approaches. Methods: For the direct method, 30 healthy volunteers were sampled weekly for 10 consecutive weeks. Samples were analyzed in duplicate for 17-hydroxyprogesterone (17-OHP), androstenedione, cortisol, cortisone, estradiol, follicle-stimulating hormone (FSH), luteinizing hormone (LH), sex hormone-binding globulin (SHBG), and testosterone. A CV-ANOVA with outlier removal and a Bayesian model were applied to derive the CVI. For estradiol, FSH and LH, only the male subgroup was included. In the indirect method, using the same analytes and groups, pairs of sequential results were extracted from the laboratory information system. The total result variation for individual pairs was determined by identifying a central gaussian distribution in the ratios of the result pairs. The CVI was then estimated by removing the effect of analytical variation. Results: The estimated CVI from the Bayesian model (μCVP(i)) in the total cohort was: 17-OHP, 23%; androstenedione, 20%; cortisol, 18%; cortisone, 11%; SHBG, 7.4%; testosterone, 16%; and for the sex hormones in men: estradiol, 14%; FSH, 8%; and LH, 26%. CVI-heterogeneity was present for most endocrine markers. Similar CVI data were estimated using the CV-ANOVA and the indirect method. Conclusions: Similar CVI data were obtained using 2 different direct and one indirect method. The indirect approach is a low-cost alternative ensuring implementation of CVI data applicable for local conditions.

• Jaffe, Allan S.; Body, Richard; Mills, Nicholas L.; Aakre, Kristin Moberg; Collinson, Paul O. & Saenger, Amy [Show all 12 contributors for this article] (2023). Single Troponin Measurement to Rule Out Myocardial Infarction: JACC Review Topic of the Week. Journal of the American College of Cardiology. ISSN 0735-1097. 82(1), p. 60–69. doi: 10.1016/j.jacc.2023.04.040. Full text in Research Archive

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• Zühlke, Stephanie; Hjort, Rebecka; Moksnes, Marta Riise; Lyngbakken, Magnus Nakrem; Alam, Mohammad Sayeef & Haug, Eirin Beate [Show all 10 contributors for this article] (2026). Traditional risk factors underestimate cardiovascular risk in individuals with coeliac disease in the Trondelag Health Study (HUNT4). European Heart Journal. ISSN 0195-668X. 47. Full text in Research Archive
• 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

• Gynnild, Mari Nordbø; Gulati, Geeta; Mecinaj, Albulena; Wethal, Torgeir; Holte, Espen & Vinje-Jakobsen, Victoria [Show all 11 contributors for this article] (2026). Baseline and early changes in cardiac biomarkers as predictors of global longitudinal strain deterioration during breast cancer therapy: a PRADAII substudy. Full text in Research Archive Show summary

  Background: Cardiac biomarkers are recommended for risk stratification before and during potentially cardiotoxic cancer therapy, but the prognostic value of baseline levels and early changes for subsequent left ventricular (LV) dysfunction remains unclear. Objectives: To evaluate whether baseline and early changes in high-sensitivity cardiac troponins (hs-cTnI, hs-cTnT) and N-terminal pro–B-type natriuretic peptide (NT-proBNP) predict changes in global longitudinal strain (GLS) over 18 months. Methods: In the randomized PRADAII, 138 women treated with anthracyclines (±trastuzumab) received sacubitril/valsartan or placebo and underwent serial biomarker sampling and cardiac imaging at baseline, post-anthracycline, and 18 months. Longitudinal changes in GLS and left ventricular ejection fraction (LVEF) were analyzed using adjusted linear mixed models, including exploratory analyses of combined, persistent, and peak biomarker elevations. Results: Mean age was 54.0±9.4 years. At baseline, no patients had hs-cTnI values above the sex-specific 99th percentile, 6 (4%) had hs-cTnT >99th percentile, and 16 (12%) had NT-proBNP >125 ng/L. Mean baseline GLS was −19.5±2.1% and CMR- and echocardiography-derived LVEF was 60.3±4.8% and 58.3±6.2%, respectively. GLS declined modestly over follow-up, with less deterioration in the sacubitril/valsartan group than in the placebo group (ΔΔ −1.26, 95% CI −2.19 to −0.33). Both hs-cTnI and hs-cTnT increased markedly after anthracycline therapy, with 16.7% and 71.7% exceeding the sex-specific 99th percentile at peak, whereas NT-proBNP showed modest changes with wide inter-individual variability. Transient and persistent troponin elevation occurred in 60.1% and 11.6%, respectively; corresponding NT-proBNP elevations in 5.1% and 7.3%, and combined troponin and NT-proBNP elevation in 9.4%. Baseline biomarker levels were not associated with GLS deterioration, and no biomarker–treatment interactions were observed (all p for interaction >0.27). Early post-anthracycline changes in hs-cTnI, hs-cTnT, or NT-proBNP were not predictive of subsequent GLS decline, nor were peak or persistent elevations (Table 1, Figure 1). No significant associations were observed between baseline or early biomarker levels and changes in LVEF assessed by echocardiography or CMR. Conclusions: In our breast cancer cohort with preserved baseline LV function, baseline levels and early changes in hs-cTnI, hs-cTnT, and NT-proBNP were not associated with subsequent deterioration in GLS over 18 months. Larger studies including higher-risk patients and clinical endpoints are needed to clarify the role of cardiac biomarkers in individualized cardiotoxicity risk stratification.

• Gynnild, Mari Nordbø; Gulati, Geeta; Mecinaj, Albulena; Wethal, Torgeir; Holte, Espen & Vinje-Jakobsen, Victoria [Show all 11 contributors for this article] (2026). Baseline and early changes in cardiac biomarkers as predictors of global longitudinal strain deterioration during breast cancer therapy: a PRADAII substudy. European Heart Journal, Supplement. ISSN 1520-765X. 28(Supplement_8). doi: 10.1093/eurheartjsupp/suag097.089. Full text in Research Archive Show summary

  Abstract Background Cardiac biomarkers are recommended for risk stratification before and during potentially cardiotoxic cancer therapy, but the prognostic value of baseline levels and early changes for subsequent left ventricular (LV) dysfunction remains unclear. Objectives To evaluate wheter baseline and early changes in high-sensitivity cardiac troponins (hs-cTnI, hs-cTnT) and N-terminal pro–B-type natriuretic peptide (NT-proBNP) predict changes in global longitudinal strain (GLS) over 18 months. Methods In the randomized PRADAII, 138 women treated with anthracyclines (±trastuzumab) received sacubitril/valsartan or placebo and underwent serial biomarker sampling and cardiac imaging at baseline, post-anthracycline, and 18 months. Longitudinal changes in GLS and left ventricular ejection fraction (LVEF) were analyzed using adjusted linear mixed models, including exploratory analyses of combined, persistent, and peak biomarker elevations. Results Mean age was 54.0±9.4 years. At baseline, no patients had hs-cTnI values above the sex-specific 99th percentile, 6 (4%) had hs-cTnT &gt;99th percentile, and 16 (12%) had NT-proBNP &gt;125 ng/L. Mean baseline GLS was −19.5±2.1% and CMR- and echocardiography-derived LVEF was 60.3±4.8% and 58.3±6.2%, respectively. GLS declined modestly over follow-up, with less deterioration in the sacubitril/valsartan group than in the placebo group (ΔΔ −1.26, 95% CI −2.19 to −0.33). Both hs-cTnI and hs-cTnT increased markedly after anthracycline therapy, with 16.7% and 71.7% exceeding the sex-specific 99th percentile at peak, whereas NT-proBNP showed modest changes with wide inter-individual variability. Transient and persistent troponin elevation occurred in 60.1% and 11.6%, respectively; corresponding NT-proBNP elevations in 5.1% and 7.3%, and combined troponin and NT-proBNP elevation in 9.4%. Baseline biomarker levels were not associated with GLS deterioration, and no biomarker–treatment interactions were observed (all p for interaction &gt;0.27). Early post-anthracycline changes in hs-cTnI, hs-cTnT, or NT-proBNP were not predictive of subsequent GLS decline, nor were peak or persistent elevations (Table 1, Figure 1). No significant associations were observed between baseline or early biomarker levels and changes in LVEF assessed by echocardiography or CMR. Conclusions In our breast cancer cohort with preserved baseline LV function, baseline levels and early changes in hs-cTnI, hs-cTnT, and NT-proBNP were not associated with subsequent deterioration in GLS over 18 months. Larger studies including higher-risk patients and clinical endpoints are needed to clarify the role of cardiac biomarkers in individualized cardiotoxicity risk stratification.  

• 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.

• Zühlke, Stephanie; Hjort, Rebecka; Moksnes, Marta Riise; Lyngbakken, Magnus Nakrem; Alam, Mohammad Sayeef & Aksaas, Anne Kristin [Show all 10 contributors for this article] (2026). Kardiovaskulær risiko hos individer med cøliaki i HUNT4. Full text in Research Archive
• Young, Juliet; Lyngbakken, Magnus Nakrem; Zühlke, Stephanie; Andersen, Ina Lervåg; Lukina, Polina & Hveem, Kristian [Show all 8 contributors for this article] (2025). Celiac disease, systemic inflammation, and the risk of subclinical myocardial injury. European Heart Journal. ISSN 0195-668X. 46(Supplement_1). doi: 10.1093/eurheartj/ehaf784.4220. Full text in Research Archive Show summary

  Abstract Background Celiac disease (CeD) is a prevalent disorder due to an immunologic reaction to the ingestion of gluten. CeD is characterized by inflammation, antibodies to transglutaminase, small intestinal villous atrophy, and subsequent malabsorption. Studies have indicated an increased risk of cardiovascular disease (CVD) in patients with CeD, potentially mediated by inflammation, yet the results are inconsistent. Studies assessing the impact of CeD on the heart and CVD risk are thus warranted. Subclinical myocardial injury can be assessed as increased concentrations of cardiac troponin I (cTnI) and is associated with an increased risk of CVD. Purpose To assess the association between CeD, systemic inflammation, and subclinical myocardial injury, expressed as increased C-reactive protein (CRP) and circulating concentrations of cTnI, respectively. Methods We cross-sectionally measured CRP and cTnI in 37 559 participants (mean age 55 years, 45% male) in the fourth wave of the population-based cohort, the Trøndelag Health Study (HUNT4). Study participants were serologically screened for CeD with transglutaminase 2 (TG2) IgA and IgG antibodies, and all seropositive participants without known CeD were invited to endoscopy with duodenal biopsies during 2019-2023 for verification of a potential CeD diagnosis (clinicaltrials.gov identifier: NCT04041622). Participants were categorized into no CeD, potential CeD, known CeD prior to the study, and newly diagnosed CeD following the current study. The association between the categories of CeD diagnosis, CRP, and cTnI concentrations, were assessed using linear regression analysis. Results In total, 336 (0.89%) of the participants in the current study were diagnosed with a new CeD diagnosis, an additional 268 (0.71%) had a known CeD diagnosis prior to the study, 170 (0.45%) were categorized as potential CeD, and 36 785 (97.94%) did not have CeD. Participants with a new CeD had lower median CRP concentrations than participants without CeD (1.0mg/L, 25th-75th percentiles, 0.6-2.2mg/L versus 1.3mg/L, 0.6-2.8mg/L; p &lt; 0.01). Median cTnI concentrations were also lower in participants with a new or known CeD diagnosis compared to participants without CeD (1.5ng/L, 0.6-3.1ng/L, and 1.5ng/L, 0.6-3.1ng/L, respectively, versus 1.7ng/L, 0.6-3.5ng/L; all p &lt; 0.05) (Table 1). In the fully adjusted regression models, CRP was not associated with CeD. Only a known CeD diagnosis was associated with lower cTnI concentrations compared to no CeD (B -0.154, 95% Confidence Interval -0.260, -0.049; p = 0.004) (Table 2). Conclusions In this large, contemporary general population study, a known CeD diagnosis, but not a new CeD diagnosis, was associated with lower cTnI concentrations, potentially suggesting a cardioprotective effect of gluten free diet in patients with CeD. However, no association between CeD and CRP concentrations was observed, suggesting that systemic inflammation may not be a prominent feature of CeD.  

• 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
• Thulin, Ingrid Viola Lavesson; Myrmel, Gard Mikael Saele; Collinson, Paul O; Apple, Fred S; Vikenes, Kjell & Bjørneklett, Rune Oskar [Show all 8 contributors for this article] (2025). Diagnostic Accuracy of a Novel 0/1-H Algorithm Using Point-of-Care High-Sensitivity Troponin in the Emergency Department. Clinical Chemistry. ISSN 0009-9147. 71(9), p. 1005–1008. doi: 10.1093/clinchem/hvaf078. Full text in Research Archive
• Zühlke, Stephanie; Hjort, Rebecka; Moksnes, Marta Riise; Lyngbakken, Magnus Nakrem; Alam, Mohammad Sayeef & Aksaas, Anne Kristin [Show all 10 contributors for this article] (2025). CARDIOVASCULAR RISK IN INDIVIDUALS WITH COELIAC DISEASE IN THE TRØNDELAG HEALTH STUDY (HUNT4). United European Gastroenterology Journal (UEG Journal). ISSN 2050-6406. 13(S8), p. 483–484. doi: https:/onlinelibrary.wiley.com/toc/20506414/2025/13/S8. Full text in Research Archive
• Zühlke, Stephanie; Hjort, Rebecka; Moksnes, Marta Riise; Lyngbakken, Magnus Nakrem; Alam, Mohammad Sayeef & Aksaas, Anne Kristin [Show all 10 contributors for this article] (2025). Cardiovascular Risk in Individuals with Coeliac Disease in the Trøndelag Health Study (HUNT4). Full text in Research Archive
• Gynnild, Mari Nordbø; Hageman, Steven; Holtrop, Joris; Holte, Espen; Dalen, Håvard & Wethal, Torgeir [Show all 7 contributors for this article] (2025). Improved risk stratification with SCORE2 on top of HFA-ICOS in cancer patients without previous cardiovascular disease. European Heart Journal, Supplement. ISSN 1520-765X. doi: 10.1093/eurheartj/ehaf784.4088. Full text in Research Archive
• Gynnild, Mari Nordbø; Hageman, Steven; Holtrop, Joris; Holte, Espen; Dalen, Håvard & Wethal, Torgeir [Show all 7 contributors for this article] (2025). Improved risk stratification with SCORE2 on top of HFA-ICOS in cancer patients without previous cardiovascular disease. Full text in Research Archive
• Zühlke, Stephanie; Hjort, Rebecka; Moksnes, Marta Riise; Lyngbakken, Magnus Nakrem; Alam, Mohammad Sayeef & Aksaas, Anne Kristin [Show all 10 contributors for this article] (2025). Cardiovascular Risk in Individuals with Coeliac Disease in the Trøndelag Health Study (HUNT4). Hjerteforum. ISSN 0802-1465. Full text in Research Archive Show summary

  Introduction: Coeliac disease (CeD) is a chronic immune-mediated enteropathy driven by dietary gluten proteins. Previous studies indicate an increased risk of cardiovascular disease (CVD) in individuals with CeD [1-3]. However, results are inconsistent and guidelines on the management of CVD risk for individuals with CeD do not exist. Here, we compare the distribution of CVD risk factors in CeD patients and non-CeD controls from a population-based cohort. Methods: We performed an anti-transglutaminase-2-based CeD screening of 54,541 serum samples from adult participants in HUNT4 [4]. Seropositive participants were invited to gastroscopy for diagnosis confirmation. Seronegative participants with CeD were identified by linkage of hospital records and the Norwegian Patient Registry. We calculated SCORE2(-OP) and analysed samples for lipoprotein (a), NTproBNP, FGF-23, IL-6, IL1RL1/ST2 and GDF-15 [5-9]. Individuals with a previous diagnosis (“known CeD”), CeD diagnosed in HUNT4 (“new CeD”), as well as the combination of the two subgroups (“CeD”) were compared to non-CeD controls (“no CeD”). Results: 468 (0.8%) individuals received a CeD diagnosis in HUNT4, while 309 (0.6%) seronegative individuals had known CeD. Newly diagnosed individuals are younger, better educated, and have lower blood lipids compared to controls. Individuals with CeD have smoked less, have a lower BMI, lower HbA1c, serum creatinine, and hsCRP levels compared to controls. NORRISK2 and SCORE2 are lower in CeD cases (p<0.05 for all variables mentioned, see Table). Lipoprotein (a) does not differ between groups, while NTproBNP is increased in individuals with known CeD (484 vs. 566 pg/mL, p<0.05) compared to newly diagnosed ones. Individuals with CeD have higher levels of GDF-15 in serum. Conclusions: Individuals with CeD have a lower CVD risk compared to controls. In line with that, both NORRISK2 and SCORE2(-OP) were lower. However, GDF-15, an emerging biomarker of cellular stress and inflammation associated with nonischemic scars [7, 9], is upregulated in individuals with CeD.

• Zühlke, Stephanie; Hjort, Rebecka; Moksnes, Marta Riise; Lyngbakken, Magnus Nakrem; Alam, Mohammad Sayeef & Aksaas, Anne Kristin [Show all 10 contributors for this article] (2025). CARDIOVASCULAR RISK IN INDIVIDUALS WITH COELIAC DISEASE IN THE TRØNDELAG HEALTH STUDY (HUNT4). Full text in Research Archive
• Dahl, Tuva Børresdatter; Aftab, Friha; Prebensen, Christian Haugland; Berdal, Jan-Erik; Ueland, Thor & Barratt-Due, Andreas [Show all 15 contributors for this article] (2025). Imidazole propionate is increased in severe COVID-19 and correlates with cardiac involvement. Journal of Infection. ISSN 0163-4453. 90(6). doi: 10.1016/j.jinf.2025.106494. Full text in Research Archive
• Brandão, Luiz Eduardo Mateus; Zhang, Lei; Grip, Anastasia; Hong, Mun-Gwan; Kåks, Emil & Benfeitas, Rui [Show all 14 contributors for this article] (2025). The overlooked trio: sleep duration, sampling time and physical exercise alter levels of olink-assessed blood biomarkers of cardiovascular risk. Biomarker Research. 13(1). doi: 10.1186/s40364-025-00776-0. Full text in Research Archive Show summary

  Biomarker profiling from biofluids such as blood are widely measured in clinical research, using for example Olink proteomics panels. One such research focus area is cardiovascular disease (CVD), for which chronic sleep restriction (SR) is a risk factor. However, it remains unclear whether blood levels of commonly measured CVD biomarkers are sensitive to acute dynamic factors such as SR, physical exercise (PEx), and time of day. In this crossover design, 16 normal-weight, healthy men underwent three highly standardized in-lab nights of SR (4.25 h/night) and normal sleep (NS, 8.5 h/night) in randomized order, with 88 CVD blood protein biomarkers quantified using the Olink technology (and selected validation using ELISA) in the morning, evening, and immediately before and repeatedly after 30 min of high-intensity exercise. We found significant time-of-day-dependent changes in several CVD biomarkers. Whereas several proteins were exercise-induced across sleep conditions (such as the canonical exerkines IL- 6 and BDNF), exercise-induced proteomic dynamics differed in response to recurrent SR, compared with following NS. Moreover, SR compared with NS resulted in a biomarker profile previously associated with increased prospective risk of several CVDs across large-scale cohorts (such as higher circulating levels of IL-27 and LGALS9). Our findings highlight how dynamic physiology can modulate CVD biomarker levels. These results also underscore the need to consider sleep duration as a key determinant of cardiovascular health—an emphasis reflected in recent American Heart Association guidelines. Further studies in women, older individuals, and patients with prior CVD, and across different chronotypes and dietary schedules are warranted.

• Gynnild, Mari Nordbø; Holtrop, Joris; Dalen, Håvard; Dorresteijn, Jannick; Visseren, Frank & Holte, Espen [Show all 9 contributors for this article] (2025). Validation of the LIFE-CVD2 model for lifetime cardiovascular risk prediction in cancer survivors. European Journal of Preventive Cardiology (EJPC). ISSN 2047-4873. doi: 10.1093/eurjpc/zwaf236.207. Full text in Research Archive
• Gynnild, Mari Nordbø; Holtrop, Joris; Dorresteijn, Jannick A. N.; Visseren, F.L.J.; Dalen, Håvard & Holte, Espen [Show all 9 contributors for this article] (2025). Validation of the LIFE-CVD2 model for lifetime cardiovascular risk prediction in cancer survivors. Full text in Research Archive
• Gynnild, Mari Nordbø; Holtrop, Joris; Hageman, Steven HJ; Vinje, Victoria; Dorresteijn, Jannick AN & Visseren, Frank [Show all 10 contributors for this article] (2024). External validation of the HFA-ICOS risk stratification tool for prediction of cardiovascular complications after cancer treatment. European Heart Journal, Supplement. ISSN 1520-765X. doi: 10.1093/eurheartj/ehae666.2693. Full text in Research Archive
• Gynnild, Mari Nordbø; Holtrop, Joris; Hageman, Steven; Vinje, Victoria; Dorresteijn, Jannick & Visseren, Frank [Show all 10 contributors for this article] (2024). External validation of the Systematic COronary Risk Evaluation 2 (SCORE2) model in cancer patients. Full text in Research Archive
• Gynnild, Mari Nordbø; Holtrop, Joris; Hageman, Steven; Vinje, Victoria; Dorresteijn, Jannick A.N. & Visseren, Frank [Show all 10 contributors for this article] (2024). External validation of the HFA-ICOS risk stratification tool for prediction of cardiovascular complications after cancer treatment. Full text in Research Archive
• Gynnild, Mari Nordbø; Holtrop, Joris; Hageman, Steven HJ; Vinje, Victoria; Dorresteijn, Jannick AN & Visseren, Frank [Show all 10 contributors for this article] (2024). External validation of the Systematic COronary Risk Evaluation 2 (SCORE2) model in cancer patients. European Heart Journal, Supplement. ISSN 1520-765X. doi: 10.1093/eurheartj/ehae666.2692. Full text in Research Archive
• Myhre, Peder Langeland; Omland, Torbjørn & Shah, Amil M. (2024). Ongoing Enigma of NT-proBNP in HFpEF: Insights from Proteomics. Circulation: Heart Failure. ISSN 1941-3289. 17(2), p. 126–128. doi: 10.1161/CIRCHEARTFAILURE.123.011428. Full text in Research Archive
• Guldhaug, Nora Alicia; Røys, Eirik Åsen; Viste, kristin; Thorsby, Per Medbøe; Sylte, Marit Sverresdotter & Torsvik, Janniche [Show all 11 contributors for this article] (2023). Week-to-week within-subject and between-subject biological variation of copeptin. Clinical Chemistry and Laboratory Medicine. ISSN 1434-6621. 62(2), p. e29–e33. doi: 10.1515/cclm-2023-0673. Full text in Research Archive
• Thulin, Ingrid Viola Lavesson; Jordalen, Silje Marie Farestveit; Lekven, Ole Christian; Krishnapillai, Jeyaseelan; Steiro, Ole-Thomas & Collinson, Paul [Show all 14 contributors for this article] (2023). Aiming toWards Evidence baSed inTerpretation of Cardiac biOmarkers in patients pResenting with chest pain using Point of Care Testing (WESTCOR- POC): study design. Scandinavian Cardiovascular Journal. ISSN 1401-7431. 57(1). doi: 10.1080/14017431.2023.2272585. Full text in Research Archive Show summary

  Objectives: Patients presenting with symptoms suggestive of acute coronary syndrome (ACS) contribute to a high workload and overcrowding in the Emergency Department (ED). Accelerated diagnostic protocols for non-ST-elevation myocardial infarction have proved challenging to implement. One obstacle is the turnaround time for analyzing high-sensitivity cardiac troponin (hs-cTn). In the WESTCOR-POC study (Clinical Trials number NCT05354804) we aim to evaluate safety and efficiency of a 0/1 h hs-cTn algorithm utilizing a hs-cTnI point of care (POC) instrument in comparison to central laboratory hs-cTnT measurements. Design: This is a prospective single-center randomized clinical trial aiming to include 1500 patients admitted to the ED with symptoms suggestive of ACS. Patients will receive standard investigations following the European Society of Cardiology 0/1h protocols for centralized hs-cTnT measurements or the intervention using a 0/1h POC hs-cTnI algorithm. Primary end-points are 1) Safety; death, myocardial infarction or acute revascularization within 30 days 2) Efficiency; length of stay in the ED, 3) Cost- effectiveness; total episode cost, 4) Patient satisfaction, 5) Patient symptom burden and 6) Patients quality of life. Secondary outcomes are 12-months death, myocardial infarction or acute revascularization, percentage discharged after 3 and 6 h, total length of hospital stay and all costs related to hospital contact within 12 months. Conclusion: Results from this study may facilitate implementation of POC hs-cTn testing assays and accelerated diagnostic protocols in EDs, and may serve as a valuable resource for guiding future investigations for the use of POC high sensitivity troponin assays in outpatient clinics and prehospital settings.

• Prebensen, Christian Haugland; Lefol, Yohan Pierre; Myhre, Peder Langeland; Lüders, Torben; Jonassen, Christine M & Blomfeldt, Anita [Show all 9 contributors for this article] (2023). Author Correction: Longitudinal whole blood transcriptomic analysis characterizes neutrophil activation and interferon signaling in moderate and severe COVID-19 (Scientific Reports, (2023), 13, 1, (10368), 10.1038/s41598-023-37606-y). Scientific Reports. 13(1). doi: 10.1038/s41598-023-39872-2. Full text in Research Archive

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