Search

Background: American and European guidelines define hypertension differently and are sex agnostic. Our aim was to assess the impact of different hypertension thresholds at the age of 40 on 30-year stroke risk and to examine sex differences., Methods: We included 2608 stroke-free individuals from the Akershus Cardiac Examination 1950 Study, a Norwegian regional study conducted in 2012-2015 of the 1950 birth cohort, who had previously participated in the Age 40 Program, a nationwide health examination study conducted in 1990-1993. We categorised participants by systolic blood pressure (SBP) at age 40 (<120 mm Hg (reference), 120-129 mm Hg, 130-139 mm Hg and ≥140 mm Hg) and compared stroke risk using Cox proportional hazard regressions adjusted for age, sex, smoking, cholesterol, physical activity, obesity and education. Fatal and non-fatal strokes were obtained from the Norwegian Cardiovascular Disease Registry from 1 January 2012 to 31 December 2020, in addition to self-reported strokes., Results: The mean age was 40.1±0.3 years (50.4% women) and mean SBP was 128.3±13.5 mm Hg (mean±SD). Stroke occurred in 115 (4.4%) individuals (32 (28%) women and 83 (72%) men) during 29.4±2.9 years of follow-up. SBP between 130 and 139 mm Hg was not associated with stroke (adjusted HR 1.71, 95% CI 0.87 to 3.36) while SBP ≥140 mm Hg was associated with increased stroke risk (adjusted HR 3.11, 95% CI 1.62 to 6.00). The adjusted HR of stroke was 4.32 (95% CI 1.66 to 11.26) for women and 2.66 (95% CI 1.03 to 6.89) for men, with non-significant sex interactions., Conclusions: SBP ≥140 mm Hg was significantly associated with 30-year stroke risk in both sexes. A small subgroup of women had SBP ≥140 mm Hg and systolic hypertension was a strong risk factor for stroke in these women., Trial Registration Number: NCT01555411., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Objectives: The impact of antibiotics in patients with positive polymerase chain reaction (PCR) for respiratory viruses without evidence of a respiratory bacterial co-infection is largely unknown. The aim of this study was to assess the association of antibiotics on 30-day mortality and length of hospital stay in patients with an acute respiratory infection and PCR documented presence of respiratory viruses., Methods: We conducted a retrospective cohort study of adult patients admitted to hospital between 2012 and 2021 with positive PCR for influenza virus (H3N2, H1N1, influenza B), respiratory syncytial virus, human metapneumovirus or severe acute respiratory syndrome coronavirus 2. We used logistic regression, the Kaplan-Meier estimator and Poisson's regression to assess the impact of antibiotic therapy on outcomes., Results: Among 3979 patients, 67.7% received antibiotics. In adjusted analyses, antibiotics initiated in the emergency department (adjusted OR 1.23, 95% CI 0.77-1.96) and days of antibiotic therapy (adjusted OR per day of therapy 0.98, 95% CI 0.95-1.00) had no significant impact on mortality, whereas antibiotics initiated later during admission (adjusted OR 2.25, 95% CI 1.26-4.02) was associated with increased mortality. Patients prescribed antibiotics had longer duration of hospital admission., Conclusions: We observed no protective association between in-hospital antibiotic therapy and outcomes, suggesting overuse of antibiotics in respiratory infections with proven respiratory viruses. A restrictive antibiotic strategy may be warranted.

Importance: Identification of individuals at high risk for atherosclerotic cardiovascular disease within the population is important to inform primary prevention strategies., Objective: To evaluate the prognostic value of routinely available cardiovascular biomarkers when added to established risk factors., Design, Setting, and Participants: Individual-level analysis including data on cardiovascular biomarkers from 28 general population-based cohorts from 12 countries and 4 continents with assessments by participant age. The median follow-up was 11.8 years., Exposure: Measurement of high-sensitivity cardiac troponin I, high-sensitivity cardiac troponin T, N-terminal pro-B-type natriuretic peptide, B-type natriuretic peptide, or high-sensitivity C-reactive protein., Main Outcomes and Measures: The primary outcome was incident atherosclerotic cardiovascular disease, which included all fatal and nonfatal events. The secondary outcomes were all-cause mortality, heart failure, ischemic stroke, and myocardial infarction. Subdistribution hazard ratios (HRs) for the association of biomarkers and outcomes were calculated after adjustment for established risk factors. The additional predictive value of the biomarkers was assessed using the C statistic and reclassification analyses., Results: The analyses included 164 054 individuals (median age, 53.1 years [IQR, 42.7-62.9 years] and 52.4% were women). There were 17 211 incident atherosclerotic cardiovascular disease events. All biomarkers were significantly associated with incident atherosclerotic cardiovascular disease (subdistribution HR per 1-SD change, 1.13 [95% CI, 1.11-1.16] for high-sensitivity cardiac troponin I; 1.18 [95% CI, 1.12-1.23] for high-sensitivity cardiac troponin T; 1.21 [95% CI, 1.18-1.24] for N-terminal pro-B-type natriuretic peptide; 1.14 [95% CI, 1.08-1.22] for B-type natriuretic peptide; and 1.14 [95% CI, 1.12-1.16] for high-sensitivity C-reactive protein) and all secondary outcomes. The addition of each single biomarker to a model that included established risk factors improved the C statistic. For 10-year incident atherosclerotic cardiovascular disease in younger people (aged <65 years), the combination of high-sensitivity cardiac troponin I, N-terminal pro-B-type natriuretic peptide, and high-sensitivity C-reactive protein resulted in a C statistic improvement from 0.812 (95% CI, 0.8021-0.8208) to 0.8194 (95% CI, 0.8089-0.8277). The combination of these biomarkers also improved reclassification compared with the conventional model. Improvements in risk prediction were most pronounced for the secondary outcomes of heart failure and all-cause mortality. The incremental value of biomarkers was greater in people aged 65 years or older vs younger people., Conclusions and Relevance: Cardiovascular biomarkers were strongly associated with fatal and nonfatal cardiovascular events and mortality. The addition of biomarkers to established risk factors led to only a small improvement in risk prediction metrics for atherosclerotic cardiovascular disease, but was more favorable for heart failure and mortality.

Purpose: To assess left atrial (LA) function in individuals with known paroxysmal atrial fibrillation (AF) compared with healthy and nonhealthy individuals without atrial fibrillation., Methods: The Akershus Cardiac Examination 1950 Study included 3,706 individuals all born in 1950. LA strain assessment of reservoir (LASr), conduit (LAScd) and contractile (LASct) functions were performed in all participants by investigators blinded to clinical data. Participants with cardiovascular disease, obesity, diabetes, pulmonary or renal disease were defined as nonhealthy, and those without as healthy. Patients with paroxysmal AF were identified through medical history and ECG documentation., Results: LA strain assessment was feasible in 3,229 (87%) of the participants (50% women). The healthy group (n = 758) had significantly higher LASr and LAScd than the nonhealthy (n = 2,376), but LASct was similar between the groups. Participants with paroxysmal AF had significantly lower values of all strain parameters than the other groups. Multivariable logistic regression showed a significantly reduced probability of having AF per standard deviation increase in LASr and LASct. A nonlinear restricted cubic spline model fitted better with the association of LASr with paroxysmal AF than the linear model, and LA strain values below the population mean associated with an increased probability of having AF, but for values above the population mean no such association was present., Conclusion: Compared to participants without AF, those with known paroxysmal AF had significantly lower values of all LA strain parameters during sinus rhythm. Lower values of LA strain were associated with a significantly increased probability of having AF., (© 2024 The Author(s). Echocardiography published by Wiley Periodicals LLC.)

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.

Objectives: Secretoneurin (SN) is a novel cardiac biomarker that associates with the risk of mortality and dysfunctional cardiomyocyte Ca 2+ 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., (© 2024 the author(s), published by De Gruyter, Berlin/Boston.)

Objective: To compare mortality and length of hospital stay between patients with ESBL-producing E. coli bloodstream infections (BSIs) and patients with non-ESBL E. coli BSIs. We also aimed at describing risk factors for ESBL-producing E. coli BSIs and time to effective antibiotic treatment for the two groups., Methods: A retrospective case-control study among adults admitted between 2014 and 2021 to a Norwegian University Hospital., Results: A total of 468 E. coli BSI episodes from 441 patients were included (234 BSIs each in the ESBL- and non-ESBL group). Among the ESBL-producing E. coli BSIs, 10.9% (25/230) deaths occurred within 30 days compared to 9.0% (21/234) in the non-ESBL group. The adjusted 30-day mortality OR was 1.6 (95% CI 0.7-3.7, p  = 0.248). Effective antibiotic treatment was administered within 24 hours to 55.2% (129/234) in the ESBL-group compared to 86.8% (203/234) in the non-ESBL group. Among BSIs of urinary tract origin ( n  = 317), the median length of hospital stay increased by two days in the ESBL group (six versus four days, p  < 0.001). No significant difference in the length of hospital stay was found for other sources of infection ( n  = 151), with a median of seven versus six days ( p  = 0.550) in the ESBL- and non-ESBL groups, respectively., Conclusion: There was no statistically significant difference in 30-day mortality in ESBL-producing E. coli compared to non-ESBL E. coli BSI, despite a delay in the administration of an effective antibiotic in the former group. ESBL-production was associated with an increased length of stay in BSIs of urinary tract origin.

Background: Five modifiable risk factors are associated with cardiovascular disease and death from any cause. Studies using individual-level data to evaluate the regional and sex-specific prevalence of the risk factors and their effect on these outcomes are lacking., Methods: We pooled and harmonized individual-level data from 112 cohort studies conducted in 34 countries and 8 geographic regions participating in the Global Cardiovascular Risk Consortium. We examined associations between the risk factors (body-mass index, systolic blood pressure, non-high-density lipoprotein cholesterol, current smoking, and diabetes) and incident cardiovascular disease and death from any cause using Cox regression analyses, stratified according to geographic region, age, and sex. Population-attributable fractions were estimated for the 10-year incidence of cardiovascular disease and 10-year all-cause mortality., Results: Among 1,518,028 participants (54.1% of whom were women) with a median age of 54.4 years, regional variations in the prevalence of the five modifiable risk factors were noted. Incident cardiovascular disease occurred in 80,596 participants during a median follow-up of 7.3 years (maximum, 47.3), and 177,369 participants died during a median follow-up of 8.7 years (maximum, 47.6). For all five risk factors combined, the aggregate global population-attributable fraction of the 10-year incidence of cardiovascular disease was 57.2% (95% confidence interval [CI], 52.4 to 62.1) among women and 52.6% (95% CI, 49.0 to 56.1) among men, and the corresponding values for 10-year all-cause mortality were 22.2% (95% CI, 16.8 to 27.5) and 19.1% (95% CI, 14.6 to 23.6)., Conclusions: Harmonized individual-level data from a global cohort showed that 57.2% and 52.6% of cases of incident cardiovascular disease among women and men, respectively, and 22.2% and 19.1% of deaths from any cause among women and men, respectively, may be attributable to five modifiable risk factors. (Funded by the German Center for Cardiovascular Research (DZHK); ClinicalTrials.gov number, NCT05466825.)., (Copyright © 2023 Massachusetts Medical Society.)

Background: Concentrations of cardiac troponin predict risk of cardiovascular disease and death in the general population. There is limited evidence on changing patterns of cardiac troponin in the years preceding cardiovascular events., Methods: We analyzed cardiac troponin I (cTnI) with a high-sensitivity assay in 3272 participants in the Trøndelag Health (HUNT) Study at study visit 4 (2017-2019). Of these, 3198 had measurement of cTnI at study visit 2 (1995-1997), 2661 at study visit 3, and 2587 at all 3 study visits. We assessed the trajectories of cTnI concentrations in the years prior to cardiovascular events using a generalized linear mixed model, with adjustment for age, sex, cardiovascular risk factors, and comorbidities., Results: At HUNT4 baseline, median age was 64.8 (range 39.4-101.3) years, and 55% were women. Study participants who were admitted because of heart failure or died from cardiovascular cause on follow-up had a steeper increase in cTnI compared with study participants with no events (P < .001). The average yearly change in cTnI was 0.235 (95% confidence interval, 0.192-0.289) ng/L for study participants with heart failure or cardiovascular death, and -0.022 (95% confidence interval, -0.022 to -0.023) ng/L for study participants with no events. Study participants who experienced myocardial infarction, ischemic stroke, or noncardiovascular mortality exhibited similar cTnI patterns., Conclusions: Fatal and nonfatal cardiovascular events are preceded by slowly increasing concentrations of cardiac troponin, independently of established cardiovascular risk factors. Our results support the use of cTnI measurements to identify at-risk subjects who progress to subclinical and later overt cardiovascular disease., (Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.)

Purpose: Coronary atherosclerosis is the leading cause of sudden death among athletes >35 yr old, but current cardiovascular risk prediction algorithms have not been validated for athletes. Advanced glycation end products (AGE) and dicarbonyl compounds have been associated with atherosclerosis and rupture-prone plaques in patients and ex vivo studies. The detection of AGE and dicarbonyl compounds might be a novel screening tool for high-risk coronary atherosclerosis in older athletes., Methods: Concentrations of three different AGE and the dicarbonyl compounds methylglyoxal, glyoxal, and 3-deoxyglucosone were measured in plasma with ultraperformance liquid chromatography tandem mass spectrometry in athletes from the Measuring Athletes' Risk of Cardiovascular Events 2 study cohort. Coronary plaques, plaque characteristics (calcified, noncalcified or mixed), and coronary artery calcium (CAC) scores were assessed with coronary computed tomography, and potential associations with AGE and dicarbonyl compounds were analyzed using linear and logistic regression., Results: A total of 289 men were included (60 [quartiles 1-3 = 56-66] yr old, body mass index = 24.5 [22.9-26.6] kg·m -2 ), with a weekly exercise volume of 41 (25-57) MET-hours. Coronary plaques were detected in 241 participants (83%), with a dominant plaque type of calcified plaques in 42%, noncalcified plaques in 12% and mixed plaques in 21%. No AGE or dicarbonyl compounds were associated with total number of plaques or any of the plaque characteristics in adjusted analyses. Similarly, AGE and dicarbonyl compounds were not associated with CAC score., Conclusions: Concentrations of plasma AGE and dicarbonyl compounds do not predict the presence of coronary plaques, plaque characteristics or CAC scores, in middle-age and older athletes., (Copyright © 2023 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the American College of Sports Medicine.)

Background: High-sensitivity cardiac troponin testing is a promising tool for cardiovascular risk prediction, but whether serial testing can dynamically predict risk is uncertain. We evaluated the trajectory of cardiac troponin I in the years prior to a cardiovascular event in the general population, and determine whether serial measurements could track risk within individuals., Methods: In the Whitehall II cohort, high-sensitivity cardiac troponin I concentrations were measured on three occasions over a 15-year period. Time trajectories of troponin were constructed in those who died from cardiovascular disease compared to those who survived or died from other causes during follow up and these were externally validated in the HUNT Study. A joint model that adjusts for cardiovascular risk factors was used to estimate risk of cardiovascular death using serial troponin measurements., Results: In 7,293 individuals (mean 58 ± 7 years, 29.4% women) cardiovascular and non-cardiovascular death occurred in 281 (3.9%) and 914 (12.5%) individuals (median follow-up 21.4 years), respectively. Troponin concentrations increased in those dying from cardiovascular disease with a steeper trajectory compared to those surviving or dying from other causes in Whitehall and HUNT (P interaction  < 0.05 for both). The joint model demonstrated an independent association between temporal evolution of troponin and risk of cardiovascular death (HR per doubling, 1.45, 95% CI,1.33-1.75)., Conclusions: Cardiac troponin I concentrations increased in those dying from cardiovascular disease compared to those surviving or dying from other causes over the preceding decades. Serial cardiac troponin testing in the general population has potential to track future cardiovascular risk., (© 2023. The Author(s).)

Objective: Atrial fibrillation is a common arrhythmia associated with risk of stroke, heart failure and death. We aimed to elucidate the associations of cardiac biomarkers, echocardiographic left atrial volumetric indices and risk of prevalent and incident atrial fibrillation in the general population., Methods: We assessed cardiac troponin T (cTnT), N-terminal pro-B-type natriuretic peptide (NT-proBNP), growth differentiation factor 15 (GDF-15), maximum (LAVi max ) and minimum (LAVi min ) indexed left atrial volumes and left atrial emptying fraction (LAEF) in subjects born in 1950 participating in the prospective observational cohort, Akershus Cardiac Examination 1950 Study. The Cohorts for Heart and Ageing Research in Genomic Epidemiology for Atrial Fibrillation risk score and sex was used to adjust for residual risk of atrial fibrillation., Results: Out of 3487 subjects, 157 (4.5%) had prevalent and 123 (3.5%) had incident atrial fibrillation. Echocardiographic left atrial volumes and cardiac biomarkers associated with prevalent atrial fibrillation, but GDF-15 was non-significant in adjusted analysis. Incident atrial fibrillation was predicted by LAVi max (adjusted HR 1.51, 95% CI 1.30 to 1.75), LAVi min (adjusted HR 1.52, 95% CI 1.35 to 1.72), LAEF (adjusted HR 1.24, 95% CI 1.04 to 1.48) and NT-proBNP (adjusted HR 1.57, 95% CI 1.32 to 1.85). cTnT and NT-proBNP provided incremental prognostic information to left atrial volumes, but GDF-15 demonstrated no prognostic value for incident atrial fibrillation., Conclusions: In the general population, echocardiographic left atrial volumetric indices and NT-proBNP, but not cTnT and GDF-15, associate with prevalent atrial fibrillation and with risk of incident atrial fibrillation. cTnT and NT-proBNP provide incremental prognostic information to echocardiography., Competing Interests: Competing interests: TO has served on advisory boards for Abbott Diagnostics, Roche Diagnostics and Bayer, and has received research support from Abbott Diagnostics, Novartis, Roche Diagnostics, Singulex and SomaLogic via Akershus University Hospital, and speaker’s or consulting honoraria from Roche Diagnostics, Siemens Healthineers and CardioNor. TB has received speaker fees from Bayer, Boehringer Ingelheim, BMS and Pfizer (non-related to the submitted work). All other authors have no competing interests., (© Author(s) (or their employer(s)) 2023. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: Hypertension is a risk factor for the development of cardiovascular disease. Whether serial blood pressure (BP) measurements are more closely associated with subclinical left ventricular (LV) remodelling and better predict risk of cardiovascular events over individual BP measurements are not known., Methods: We assessed systolic BP, diastolic BP and pulse pressure at several time points during adulthood in 1333 women and 1211 men participating in the Akershus Cardiac Examination 1950 Study. We defined serial BP measurements as the sum of averaged BPs from adjacent consecutive visits indexed to total exposure time between measurements. We assessed the associations between serial and individual BP measurements and (1) LV structure, function and volumes and (2) incident myocardial infarction, ischemic stroke, heart failure and cardiovascular death., Results: All indices of higher serial BP measurements were associated with increased indexed LV mass, and the associations were stronger than those of individual BP measurements. Serial diastolic BP pressure was strongly and inversely associated with LV systolic function, while higher serial systolic BP was primarily associated with higher LV volumes. Both serial systolic (incidence rate ratio [IRR] 1.10, 95% CI 1.03 to 1.17) and diastolic BPs (IRR 1.14, 95% CI 1.02 to 1.27) were associated with increased incidence of clinical events., Conclusion: In healthy community dwellers without established cardiovascular disease, different serial BP indices associate strongly with LV remodelling and cardiovascular outcomes. Whether the use of serial BP indices for guiding treatment is superior to individual measurements should be explored in additional prospective studies., (© 2022 The Authors. European Journal of Clinical Investigation published by John Wiley & Sons Ltd on behalf of Stichting European Society for Clinical Investigation Journal Foundation.)

Objectives: Hypertension in midlife is a risk factor for cognitive impairment. Still, the ideal midlife blood pressure (BP) remains unknown. We examined associations between different systolic blood pressure (SBP) levels at the age of 40-43 years and change in SBP over a 25-year period with cognitive function at age 62-65 years., Methods: We included 2424 individuals born in 1950 who had participated both in the Age 40 Program (1990-1993) and the Akershus Cardiac Examination (ACE) 1950 Study (2012-2015). The exposure was SBP at age 40-43 years and the outcome was cognitive function at age 62-65 years, assessed with Montreal Cognitive Assessment, Delayed recall trial from the Consortium to Establish a Registry for Alzheimer's Disease Word List Memory Task, and Trail Making Test part B (TMT B)., Results: Participants were 40.1 ± 0.3 years old with mean SPB 128 ± 13 mmHg at the Age 40 Program, and 63.9 ± 0.6 years old with mean SPB 138 ± 18 at the ACE 1950 Study. Adjusted linear regressions showed no associations between SBP and subsequent cognitive function. In logistic regressions, individuals with SBP ≥140 mmHg, compared to individuals with SBP <120 mmHg (odds ratio 2.29, 95% confidence interval 1.28-4.10, P-value 0.005) had increased risk of an abnormal TMT B-score. Change in SBP during the 25-year follow-up was not associated with cognitive function., Conclusions: SBP ≥140 mmHg at age 40-43 was associated with reduced capacity on TMT B, a domain specific cognitive test sensitive to vascular impairment. No other associations were found between SBP, or change in SBP, and cognitive function., (Copyright © 2022 Wolters Kluwer Health, Inc. All rights reserved.)

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 &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., (© 2023 The Author(s). Published by S. Karger AG, Basel.)

Subarachnoid hemorrhage (SAH) is a serious condition, and a myocardial injury or dysfunction could contribute to the outcome. We assessed the prevalence and prognostic impact of cardiac involvement in a cohort with SAH. This is a prospective observational multicenter study. We included 192 patients treated for non-traumatic subarachnoid hemorrhage. We performed ECG recordings, echocardiographic examinations, and blood sampling within 24 h of admission and on days 3 and 7 and at 90 days. The primary endpoint was the evidence of cardiac involvement at 90 days, and the secondary endpoint was to examine the prevalence of a myocardial injury or dysfunction. The median age was 54.5 (interquartile range [IQR] 48.0-64.0) years, 44.3% were male and the median World Federation of Neurological Surgeons (WFNS) score was 2 (IQR 1-4). At day 90, 22/125 patients (17.6%) had left ventricular ejection fractions ≤ 50%, and 2/121 patients (1.7%) had evidence of a diastolic dysfunction as defined by mitral peak E-wave velocity by peak e' velocity (E/e') > 14. There was no prognostic impact from echocardiographic evidence of cardiac complications on neurological outcomes. The overall prevalence of cardiac dysfunction was modest. We found no demographic or SAH-related factors associated with 90 days cardiac dysfunction., (© 2022. The Author(s).)

Background Echocardiographic measures of left atrial volumes are powerful predictors of cardiovascular events and important for assessing diastolic dysfunction. Despite this, there is limited knowledge of factors influencing left atrial remodeling. In particular, the impact of blood pressure in those in their early 40s on left atrial volumes later in life has not been sufficiently elucidated. Methods and Results We linked data from individuals born in 1950 who participated in the Age 40 Program, and the ACE (Akershus Cardiac Examination) 1950 Study. We divided the study population into quartiles of systolic blood pressure in their early 40s and assessed the proportion of individuals with an enlarged left atrium in their mid-60s. The associations between blood pressure and left atrial volumes were assessed in linear regression analyses. Of the 2591 individuals included in this study, 1302 (50.3%) were women, and the mean age in the Age 40 Program was 40.1±0.3 years. Systolic blood pressure was 128.1±13.6 mm Hg and diastolic blood pressure was 78.3±9.5 mm Hg. Mean age in the ACE 1950 Study was 64.0±0.6 years. The proportion of individuals with an enlarged left atrium increased across the quartiles of systolic blood pressure ( P =0.001). Systolic blood pressure was independently associated with left atrial volumes; the end-systolic volume was 0.09 mL (95% CI, 0.04-0.14 mL) larger per 1-mm Hg higher systolic blood pressure. Conclusions Our findings suggest that increased blood pressure in those in their early 40s is relevant for left atrial remodeling later in life. Registration URL: https://www.clinicaltrials.gov; Unique identifier: NCT01555411.

Background: Chronic obstructive pulmonary disease (COPD) is often misdiagnosed. We aimed to estimate the prevalence of misdiagnosed COPD in middle-aged Norwegians, and to assess potentially treatable clinical traits in over- and undiagnosed individuals., Methods and Findings: The Akershus Cardiac Examination (ACE) 1950 Study is a population-based study of the 1950 birth cohort of Akershus county including 3706 participants aged 62-65 years at baseline. COPD was defined as a forced expiratory volume in 1 second (FEV 1 ) to forced vital capacity (FVC) ratio < lower limit of normal (LLN). Misdiagnosed COPD was defined according to self-reported COPD. A total of 259 (7.1%) participants had spirometry confirmed COPD. Of these, only 72 (28%) reported having COPD, thus 187 (72%) were undiagnosed. A total of 92 (2.5%) of the 164 particpants who reported having COPD had an FEV 1 /FVC ratio ≥ LLN and were overdiagnosed. They had lower lung function, and more respiratory symptoms, self-reported asthma, eosinophils, and sleep apnea than other non-COPD participants . The main predictor of being overdiagnosed was overweight. Spirometry in participants reporting wheezing or cough and current smokers or participants with ≥20 tobacco pack-year history would have identified 85% of the undiagnosed cases., Conclusion: Both over- and underdiagnosis of COPD is frequent. Undiagnosed individuals have better lung function and less symptoms, but similar prevalence of comorbidities and systemic inflammation. Overdiagnosed individuals have treatable traits including asthma, eosinophilic inflammation, and sleep apnea. The main predictor of being overdiagnosed was being overweight., (JCOPDF © 2022.)

Objective: Patients hospitalised with acute dyspnoea due to acute heart failure (AHF) have a grave prognosis, but the European Society of Cardiology guidelines recommend no system to risk stratify these patients. The prognostic value of combining National Early Warning Score (NEWS) 2 and established cardiac biomarkers is not known., Methods: We measured high-sensitivity cardiac troponin T (hs-cTnT) and N-terminal pro-B-type natriuretic peptide (NT-proBNP) and calculated NEWS2 in 314 patients with acute dyspnoea within 24 hours of hospitalisation. Their prognostic merits were assessed in the total cohort and for the subgroup with AHF separately., Results: The median age was 73 (quartile (Q) 1-3, 63-81) years, 48% were women and 143 patients (46%) were hospitalised with AHF. The 114 patients (36%) who died during follow-up (median 823 days, Q1-3, 471-998) had higher concentrations of hs-cTnT (62 vs 33 ng/L, p<0.001) and NT-proBNP (6995 vs 2605 ng/L, p<0.001), and higher NEWS2 (6.1 vs 4.5 points, p<0.001), compared with survivors. Patients with increased vs low NEWS2 clinical risk had higher mortality rates in adjusted analyses in the total cohort (HR 2.11, 95% CI 1.28 to 3.48) and in patients with AHF (HR 2.00, 95% CI 1.54 to 2.60). NEWS2 provided incremental prognostic information compared with biomarkers alone for the total cohort: area under the curve 0.72 vs 0.70, p=0.042, and for the subpopulation with AHF: 0.70 vs 0.67, p=0.014., Conclusion: NEWS2 predicts long-term mortality in patients hospitalised due to acute dyspnoea and the subgroup with AHF and provide incremental prognostic information to hs-cTnT and NT-proBNP., Competing Interests: Competing interests: TO has received speaker’s honoraria from Abbott Diagnostics, Siemens Healthcare Diagnostics and Roche Diagnostics; research grant support from Abbott Diagnostics and Roche Diagnostics through Akershus University Hospital and a grant from the Norwegian Research Council to perform the ACE 2 Study. HR has received honoraria from CardiNor AS, SpinChip Diagnostics, Thermo Fisher BRAHMS and Novartis., (© Author(s) (or their employer(s)) 2022. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: Obesity is associated with subclinical myocardial injury as quantified by concentrations of cardiac troponin T, but whether lifetime excess weight history is associated with increased concentrations of cardiac troponin I (cTnI) and how indices of abdominal adiposity and glycemic dysregulation affect these associations remain unclear., Methods: We analyzed cTnI with a high-sensitivity assay in 9739 participants in the Trøndelag Health (HUNT) Study at study visit 4 (2017-2019). BMI was assessed at study Visit 1 (1984-1986), 2 (1995-1997), 3 (2006-2008), and 4., Results: Median age at visit 4 was 68.7 years and 59% were women. Concentrations of cTnI were detectable in 84.1% of study participants, with a median of 2.5 (1.5-4.5 ng/L). We identified three clusters of BMI trajectories from visit 1 to 4, (1) stable normal weight, (2) stable overweight, and (3) stable obesity. Participants in clusters 2 and 3 were at increased risk of elevated concentrations of cTnI at visit 4 (odds ratio 1.27, 95% CI 1.09-1.47, and odds ratio 1.70, 95% CI 1.33-2.17, p for trend <0.001). Participants in cluster 3 had 22.0 (95% CI 14.1-29.9) higher concentrations of cTnI compared to participants in cluster 1 (p for trend <0.001). Dysregulated glucose metabolism and abdominal obesity did not influence our results., Conclusions: Individuals with stable overweight or obesity are at increased risk of subclinical myocardial injury, independently of glycemic dysregulation and abdominal adiposity. Our data support a direct detrimental effect of long-standing obesity on cardiovascular health., (© 2021 The Authors. Journal of Internal Medicine published by John Wiley & Sons Ltd on behalf of Association for Publication of The Journal of Internal Medicine.)

Aims: Mechanical dispersion measures left ventricular contraction heterogeneity and is associated with the risk of sudden cardiac death. However, the associations between mechanical dispersion and cardiovascular risk factors in early mid-life, and established biomarkers of sub-clinical myocardial injury and dysfunction are not known. We aimed to examine this in the general population., Methods and Results: During 2012-15, we included 2527 Norwegian individuals from the general population born in 1950, with measurements of mechanical dispersion by 2D speckle tracking echocardiography and concentrations of high-sensitivity cardiac troponin T (hs-cTnT) and N-terminal pro-B-type natriuretic peptide (NT-proBNP) available. Mechanical dispersion was calculated as the standard deviation of the contraction duration of 17 strain segments. We assessed the associations between mechanical dispersion, concentrations of hs-cTnT and NT-proBNP, and cardiovascular risk factors collected at a national health screening survey two decades earlier. At echocardiography baseline, median age was 64 (interquartile range 63.5-64.5) years, 49.8% were women, 59.1% had hypertension, and 5.9% reported established coronary artery disease. Median mechanical dispersion was 38.0 (29.5-47.0) ms, median hs-cTnT concentration 6 (4-8) ng/L, and the median NT-proBNP concentration 54 (34-93) ng/L. Mechanical dispersion was associated with both hs-cTnT and NT-proBNP concentrations in multivariable models adjusted for clinical and echocardiographic variables. High body mass index, serum triglyceride concentrations, and low resting heart rate at Age 40 were independently associated with increased mechanical dispersion two decades later., Conclusion: Established risk factors at Age 40 are associated with mechanical dispersion two decades later, and mechanical dispersion is cross-sectionally associated with biomarkers of subclinical myocardial injury and dysfunction., (© The Author(s) 2022. Published by Oxford University Press on behalf of the European Society of Cardiology.)

Background Cardiac troponins represent a sensitive index of subclinical myocardial injury and are associated with increased risk of cardiovascular events in the general population. Despite positive associations with cardiovascular risk of both cardiac troponins and cigarette smoking, concentrations of cardiac troponin I measured by high-sensitivity assays (hs-cTnI) are paradoxically lower in current smokers than in never-smokers. The impact of smoking intensity and time from smoking cessation on hs-cTnI remains unknown. Methods and Results hs-cTnI concentrations were measured in 32028 subjects free from cardiovascular disease enrolled in the prospective, population-based HUNT (Trøndelag Health Study). Tobacco habits were self-reported and classified as never (n=14 559), former (n=14 248), and current (n=3221) smokers. Current smokers exhibited significantly lower concentrations of hs-cTnI than never-smokers ( P <0.001). In adjusted models, both current smoking (-17.3%; 95% CI, -20.6 to -13.9%) and former smoking (-6.6%; 95% CI, -8.7 to -4.5%) were associated with significantly lower hs-cTnI concentrations. Among former smokers, higher smoking burden (>10 pack-years) were associated with lower concentrations of hs-cTnI. Time since smoking cessation was associated with increasing concentrations of hs-cTnI in a dose-dependent manner ( P for trend<0.001), and subjects who quit smoking >30 years ago had concentrations of hs-cTnI comparable with those of never-smokers. Conclusions In the general population, both current and former cigarette smoking is associated with lower concentrations of hs-cTnI. In former smokers, there was a dose-response relationship between pack-years of smoking, and hs-cTnI. Time since smoking cessation was associated with increasing concentrations of hs-cTnI, indicating a continuum of hs-cTnI from current smoker to never-smokers.

Background: Coronavirus disease 2019 (COVID-19) may cause myocardial injury and myocarditis, and reports of persistent cardiac pathology after COVID-19 have raised concerns of long-term cardiac consequences. We aimed to assess the presence of abnormal cardiovascular resonance imaging (CMR) findings in patients recovered from moderate-to-severe COVID-19, and its association with markers of disease severity in the acute phase., Methods: Fifty-eight (49%) survivors from the prospective COVID MECH study, underwent CMR median 175 [IQR 105-217] days after COVID-19 hospitalization. Abnormal CMR was defined as left ventricular ejection fraction (LVEF) <50% or myocardial scar by late gadolinium enhancement. CMR indices were compared to healthy controls (n = 32), and to circulating biomarkers measured during the index hospitalization., Results: Abnormal CMR was present in 12 (21%) patients, of whom 3 were classified with major pathology (scar and LVEF <50% or LVEF <40%). There was no difference in the need of mechanical ventilation, length of hospital stay, and vital signs between patients with vs without abnormal CMR after 6 months. Severe acute respiratory syndrome coronavirus 2 viremia and concentrations of inflammatory biomarkers during the index hospitalization were not associated with persistent CMR pathology. Cardiac troponin T and N-terminal pro-B-type natriuretic peptide concentrations on admission, were higher in patients with CMR pathology, but these associations were not significant after adjusting for demographics and established cardiovascular disease., Conclusions: CMR pathology 6 months after moderate-to-severe COVID-19 was present in 21% of patients and did not correlate with severity of the disease. Cardiovascular biomarkers during COVID-19 were higher in patients with CMR pathology, but with no significant association after adjusting for confounders., Trial Registration: COVID MECH Study ClinicalTrials.gov Identifier: NCT04314232., (Copyright © 2021 The Author(s). Published by Elsevier Inc. All rights reserved.)

Circulating cardiac troponin proteins are associated with structural heart disease and predict incident cardiovascular disease in the general population. However, the genetic contribution to cardiac troponin I (cTnI) concentrations and its causal effect on cardiovascular phenotypes are unclear. We combine data from two large population-based studies, the Trøndelag Health Study and the Generation Scotland Scottish Family Health Study, and perform a genome-wide association study of high-sensitivity cTnI concentrations with 48 115 individuals. We further use two-sample Mendelian randomization to investigate the causal effects of circulating cTnI on acute myocardial infarction (AMI) and heart failure (HF). We identified 12 genetic loci (8 novel) associated with cTnI concentrations. Associated protein-altering variants highlighted putative functional genes: CAND2, HABP2, ANO5, APOH, FHOD3, TNFAIP2, KLKB1 and LMAN1. Phenome-wide association tests in 1688 phecodes and 83 continuous traits in UK Biobank showed associations between a genetic risk score for cTnI and cardiac arrhythmias, metabolic and anthropometric measures. Using two-sample Mendelian randomization, we confirmed the non-causal role of cTnI in AMI (5948 cases, 355 246 controls). We found indications for a causal role of cTnI in HF (47 309 cases and 930 014 controls), but this was not supported by secondary analyses using left ventricular mass as outcome (18 257 individuals). Our findings clarify the biology underlying the heritable contribution to circulating cTnI and support cTnI as a non-causal biomarker for AMI in the general population. Using genetically informed methods for causal inference helps inform the role and value of measuring cTnI in the general population., (© The Author(s) 2021. Published by Oxford University Press.)

Pragmatic clinical trials are based on data from unselected patients recruited from common clinical practice. These trials therefore bridge the gap between evidence-based medicine and clinical practice.

Insomnia symptoms are associated with increased risk of heart failure (HF) and cardiovascular (CV) mortality. We hypothesised that insomnia symptoms are cross-sectionally associated with increased cardiac troponin I (cTnI), a biomarker of subclinical myocardial injury, and that phenotyping by insomnia symptoms and cTnI enhances longitudinal risk stratification in the general population. In a population-based study, cTnI was measured in 8,398 participants (median age 49 years, 55% women), who had answered questionnaires regarding insomnia symptoms. Association between cTnI and insomnia symptoms was assessed by linear regression analysis for each response category of a sleep questionnaire. Insomnia symptoms were defined as having difficulty falling asleep almost every night, difficulty maintaining sleep almost every night, and/or non-restorative sleep once a week or more. The primary outcome measure was a composite endpoint of CV mortality or first admission for HF. In all, 844 participants reported insomnia symptoms, 585 (69%) were women. Those with insomnia symptoms had marginally, but significantly higher median cTnI than those without insomnia symptoms, (median [interquartile range] 3.4 [2.4-5.2] ng/L versus 3.2 [2.2-4.9] ng/L; p = .014), but there was no association between any insomnia symptom and cTnI in unadjusted linear regression models (β 0.06, 95% confidence interval [CI] -0.01 to 0.12). In adjusted analyses, participants with insomnia symptoms and increased cTnI were at increased risk of the composite endpoint (hazard ratio 1.71, 95% CI 1.04-2.79) compared to participants with insomnia symptoms and low cTnI. In the general population, insomnia symptoms are not associated with biochemical evidence of subclinical myocardial injury., (© 2021 The Authors. Journal of Sleep Research published by John Wiley & Sons Ltd on behalf of European Sleep Research Society.)

Aims: Concentrations of cardiac troponin I (cTnI) are associated with incident ischemic stroke and predict the presence and severity of coronary atherosclerosis. Accordingly, we hypothesized that concentrations of cTnI measured with a very high sensitivity (hs-) assay would be associated with subclinical stages of carotid atherosclerosis in the general population., Methods: We measured hs-cTnI on the Singulex Clarity System in 1745 women and 1666 men participating in the prospective observational Akershus Cardiac Examination 1950 Study. All study participants were free from known coronary heart disease and underwent extensive cardiovascular phenotyping at baseline, including carotid ultrasound. We quantified carotid atherosclerosis by the carotid plaque score, carotid intima-media thickness (cIMT) and the presence of hypoechoic plaques., Results: Concentrations of hs-cTnI were measurable in 99.8% of study participants and were significantly associated with increased carotid plaque score (odds ratio for quartile 4 of hs-cTnI 1.59, 95% CI 1.22 to 2.07, p for trend < 0.001) and cIMT (odds ratio for quartile 4 of hs-cTnI 1.57, 95% CI 1.02 to 2.42, p for trend = 0.036), but not with the presence of hypoechoic plaques. hs-cTnI concentrations significantly improved reclassification and discrimination models in predicting carotid plaques when added to cardiovascular risk factors, no improvements were evident in predicting cIMT or hypoechoic plaques., Conclusion: Concentrations of cTnI measured with a very high sensitivity assay are predictive of carotid atherosclerotic burden, a phenomenon likely attributable to common risk factors of subclinical myocardial injury, coronary and carotid atherosclerosis., (Copyright © 2021 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: MicroRNA (miR)-210 expression is induced by acute and chronic hypoxia and provides prognostic information in patients with aortic stenosis and acute coronary syndrome. We hypothesized that circulating miR-210 concentrations could provide diagnostic and prognostic information in patients with acute heart failure (HF)., Methods: We measured miR-210 concentrations in serum samples on admission from 314 patients hospitalized for acute dyspnea and 9 healthy control subjects. The diagnostic and prognostic properties of miR-210 were tested in patients after adjudication of all diagnoses and with median follow-up of 464 days., Results: All patients and control subjects had miR-210 concentrations within the range of detection, and the analytical variation was low as the coefficient of variation of synthetic spike-in RNA was 4%. Circulating miR-210 concentrations were increased in patients with HF compared to healthy control subjects, but miR-210 concentrations did not separate patients with acute HF (n = 143) from patients with non-HF-related dyspnea (n = 171): the area under the curve was 0.50 (95% CI 0.43-0.57). Circulating miR-210 concentrations were associated with mortality (n = 114) after adjustment for clinical risk factors (hazard ratio 1.65 [95% CI 1.03-2.62] per unit miR-210 increase), but this association was attenuated and not significant after adjustment for established cardiac protein biomarkers., Conclusions: Circulating miR-210 concentrations are associated with mortality, but do not add to established protein biomarkers for diagnosis or prognosis in patients with acute dyspnea., (© American Association for Clinical Chemistry 2021.)

Background Diabetes mellitus (DM) is associated with left ventricular remodeling and incident heart failure, but the association between glycated hemoglobin A1c (HbA1c) and subclinical cardiac disease is not established. We aimed to determine the associations between HbA1c and (1) echocardiographic measures of left ventricular structure and function, and (2) cardiovascular biomarkers: cardiac troponin T, NT-proBNP (N-terminal pro-B-type natriuretic peptide), and CRP (C-reactive protein). Methods and Results Participants (n=3688) born in 1950 from the population-based ACE (Akershus Cardiac Examination) 1950 Study were classified as DM (HbA1c≥6.5% or self-reported DM), pre-DM (HbA1c 5.7%-6.5%), and no-DM (HbA1c<5.7%). DM, pre-DM, and no-DM were classified in 380 (10%), 1630 (44%), and 1678 (46%) participants, respectively. Mean age was 63.9±0.7 years, mean body mass index was 27.2±4.4 kg/m 2 , and 49% were women. Higher HbA1c was associated with worse left ventricular systolic (ejection fraction and global longitudinal strain) and diastolic (E/e'-ratio) function, myocardial injury (cardiac troponin T), inflammation (CRP), and impaired neurohormonal homeostasis (NT-proBNP) ( P <0.001 in unadjusted and P <0.01 in adjusted analysis for all). The associations between HbA1c and cardiovascular biomarkers were independent of the echocardiographic variables, and vice versa. Associations were nonlinear ( P <0.05 for nonlinearity) and appeared stronger in the pre-DM range of HbA1c than the no-DM and DM range. Conclusions HbA1c was associated with indexes of subclinical cardiovascular disease, and this was more pronounced in pre-DM. Our results suggest that cardiovascular preventive measures should be considered also in subjects with hyperglycemia and HbA1c below the established DM cutoff. Registration clinicaltrials.gov. Identifier: NCT01555411.

Substantial COVID-19 research investment has been allocated to randomized clinical trials (RCTs) on hydroxychloroquine/chloroquine, which currently face recruitment challenges or early discontinuation. We aim to estimate the effects of hydroxychloroquine and chloroquine on survival in COVID-19 from all currently available RCT evidence, published and unpublished. We present a rapid meta-analysis of ongoing, completed, or discontinued RCTs on hydroxychloroquine or chloroquine treatment for any COVID-19 patients (protocol: https://osf.io/QESV4/ ). We systematically identified unpublished RCTs (ClinicalTrials.gov, WHO International Clinical Trials Registry Platform, Cochrane COVID-registry up to June 11, 2020), and published RCTs (PubMed, medRxiv and bioRxiv up to October 16, 2020). All-cause mortality has been extracted (publications/preprints) or requested from investigators and combined in random-effects meta-analyses, calculating odds ratios (ORs) with 95% confidence intervals (CIs), separately for hydroxychloroquine and chloroquine. Prespecified subgroup analyses include patient setting, diagnostic confirmation, control type, and publication status. Sixty-three trials were potentially eligible. We included 14 unpublished trials (1308 patients) and 14 publications/preprints (9011 patients). Results for hydroxychloroquine are dominated by RECOVERY and WHO SOLIDARITY, two highly pragmatic trials, which employed relatively high doses and included 4716 and 1853 patients, respectively (67% of the total sample size). The combined OR on all-cause mortality for hydroxychloroquine is 1.11 (95% CI: 1.02, 1.20; I² = 0%; 26 trials; 10,012 patients) and for chloroquine 1.77 (95%CI: 0.15, 21.13, I² = 0%; 4 trials; 307 patients). We identified no subgroup effects. We found that treatment with hydroxychloroquine is associated with increased mortality in COVID-19 patients, and there is no benefit of chloroquine. Findings have unclear generalizability to outpatients, children, pregnant women, and people with comorbidities.

Background: To assess if cardiac troponins can improve diagnostics of acute heart failure (AHF) and provide prognostic information in patients with acute dyspnea., Methods: We measured cardiac troponin T with a high-sensitivity assay (hs-cTnT) in 314 patients hospitalized with acute dyspnea. The index diagnosis was adjudicated and AHF patients were stratified into AHF with reduced or preserved ejection fraction (HFrEF/HFpEF). The prognostic and diagnostic merit of hs-cTnT was compared to the merit of N-terminal pro-B-type natriuretic peptide (NT-proBNP)., Results: In the total population, median age was 73 (quartile [Q] 1-3 63-81) years and 48% were women. One-hundred-forty-three patients were categorized as AHF (46%) and these patients had higher hs-cTnT concentrations than patients with non-AHF-related dyspnea: median 38 (Q1-3 22-75) vs. 13 (4-25) ng/L; p < 0.001. hs-cTnT concentrations were similar between patients with HFrEF and HFpEF (p = 0.80), in contrast to NT-proBNP, which was higher in HFrEF (p < 0.001). C-statistics for discriminating HFpEF from non-AHF-related dyspnea was 0.80 (95% CI 0.73-0.86) for hs-cTnT, 0.79 (0.73-0.86) for NT-proBNP, and 0.83 (0.76-0.89) for hs-cTnT and NT-proBNP in combination. Elevated hs-cTnT remained associated with HFpEF in logistic regression analysis after adjusting for demographics, comorbidities and renal function. During median 27 months of follow-up, 114 (36%) patients died in the total population. Higher hs-cTnT concentrations were associated with increased risk of all-cause mortality after adjustment for clinical variables and NT-proBNP: hazard ratio 1.30 (95% CI 1.07-1.58), p = 0.009., Conclusion: hs-cTnT measurements improve diagnostic accuracy for HFpEF and provide independent prognostic information in unselected patients with acute dyspnea., (Copyright © 2020 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: Concentrations of B-type natriuretic peptide (BNP) reflect myocardial distension and stress, and are associated with poor prognosis in patients with cardiovascular disease. Accordingly, we hypothesized that concentrations of BNP would be associated with indices of adverse left ventricular (LV) remodeling and early stages of LV systolic and diastolic dysfunction in healthy participants from the general population., Methods: We measured BNP in 1757 women and 1677 men free from known coronary heart disease participating in the prospective observational Akershus Cardiac Examination 1950 Study. All study participants underwent extensive cardiovascular phenotyping at baseline, including detailed echocardiography with assessment of indexed LV mass (LVMI), diastolic [tissue Doppler e', E/e' ratio, indexed left atrial volume (LAVI), maximal tricuspid regurgitation velocity (TRVmax), and E/A ratio], and systolic [global longitudinal strain (GLS) and LV ejection fraction (LVEF)] function., Results: Study participants with the highest BNP concentrations had higher GLS, LVMI, e', E/e' ratio, LAVI, TRVmax, and E/A ratio. In adjusted analyses, both GLS and LVEF exhibited significant nonlinear associations with BNP, with reduced LV systolic function observed in both the low and high concentration range of BNP., Conclusions: In healthy participants recruited from the general population, concentrations of BNP exhibit nonlinear associations with LV systolic function, and both low and high concentrations are associated with reduced LV systolic function. This supports the notion that natriuretic peptides are beneficial and elicit cardioprotective effects, and may have important implications for the interpretation of BNP measurements in the general population., (© American Association for Clinical Chemistry 2020.)

Aims: Morbid obesity is a risk factor for cardiovascular disease. The relative effects of Roux-en-Y gastric bypass surgery (GBS) and intensive lifestyle intervention (ILI) on subclinical myocardial injury, the activity of the cardiac natriuretic system, and systemic inflammation remain unclear., Methods: In a 59-week non-randomized clinical trial that included 131 patients with morbid obesity, we compared the effects ofGBS and ILI on concentrations of cardiac troponin T (cTnT) and I (cTnI), N-terminal pro-B-type natriuretic peptide (NT-proBNP) and C-reactive protein (CRP)., Results: In the GBS and ILI group, median body mass index (BMI) was reduced by 14.4 kg/m 2 versus 3.9 kg/m 2 , respectively (p value < 0.001). Cardiac troponins decreased after GBS, p = 0.014 (cTnT) and p = 0.065 (cTnI) and increased significantly in those treated with ILI (p values ≤ 0.021) (between-group differences for deltas: p ≤ 0.003). NT-proBNP increased in both groups, but significantly more in the GBS than in the ILI group (between-group differences for deltas: p = 0.008). CRP decreased significantly within the GBS and the ILI group, with this change significantly greater in the GBS group (between-group differences for deltas p < 0.001). The dominating mediator of the biomarker changes was weight loss. Prior coronary artery disease and diabetes were predictive of the magnitude of the changes in cTnI and NT-proBNP, respectively., Conclusion: Compared to ILI, GBS was associated with reduced subclinical myocardial injury and systemic inflammation, and enhancement of the cardiac natriuretic peptide system. The biomarker changes were predominantly mediated by weight loss., (Copyright © 2020. Published by Elsevier Inc.)

Background: A high intake of linoleic acid (LA), the major dietary polyunsaturated fatty acid (PUFA), has previously been associated with reduced cardiovascular (CV) morbidity and mortality in observational studies. However, recent secondary analyses from clinical trials of LA-rich diet suggest harmful effects of LA on CV health., Methods: A total of 3706 participants, all born in 1950, were included in this cross-sectional study. We investigated associations between plasma phospholipid levels of LA and CV risk factors in a Norwegian general population, characterized by a relative low LA and high marine n-3 PUFA intake. The main statistical approach was multivariable linear regression., Results: Plasma phospholipid LA levels ranged from 11.4 to 32.0 wt%, with a median level of 20.8 wt% (interquartile range 16.8-24.8 wt%). High plasma LA levels were associated with lower serum low-density lipoprotein cholesterol levels (standardized regression coefficient [Std. β-coeff.] -0.04, p = 0.02), serum triglycerides (Std. β-coeff. -0.10, p < 0.001), fasting plasma glucose (Std. β-coeff. -0.10, p < 0.001), body mass index (Std. β-coeff. -0.13, p < 0.001), systolic and diastolic blood pressure (Std. β-coeff. -0.04, p = 0.03 and Std. β-coeff. -0.02, p = 0.02, respectively) and estimated glomerular filtration rate (Std. β-coeff. -0.09, p < 0.001). We found no association between plasma LA levels and high-density lipoprotein cholesterol levels, glycated hemoglobin, carotid intima-media thickness, or C-reactive protein., Conclusion: High plasma LA levels were favorably associated with several CV risk factors in this study of a Norwegian general population.

Here, we randomized 53 patients hospitalized with coronavirus disease 2019 (COVID-19) to hydroxychloroquine therapy (at a dose of 400 mg twice daily for seven days) in addition to standard care or standard care alone (ClinicalTrials.gov Identifier, NCT04316377). All severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) positive patients 18 years of age or older were eligible for study inclusion if they had moderately severe COVID-19 at admission. Treatment with hydroxychloroquine did not result in a significantly greater rate of decline in SARS-CoV-2 oropharyngeal viral load compared to standard care alone during the first five days. Our results suggest no important antiviral effect of hydroxychloroquine in humans infected with SARS-CoV-2.

Background: Cardiac troponin T (cTnT) and I (cTnI) concentrations provide strong prognostic information in anticoagulated patients with atrial fibrillation (AF). Whether the associations between cardiac troponin concentrations and mortality and morbidity differ by sex is not known., Objectives: To assess whether men and women have different concentrations and prognostic value of cTnT and cTnI measurements in anticoagulated patients with AF., Methods: cTnT and cTnI concentrations were measured with high-sensitivity (hs) assays in EDTA plasma samples obtained from the multicentre ARISTOTLE trial, which randomized patients with AF and at least one risk factor for stroke or systemic embolic event to warfarin or apixaban. Patients were stratified according to sex and the associations between hs-troponin concentrations, and all-cause death, cardiac death, myocardial infarction, stroke or systemic embolic event and major bleeding were assessed in multivariable regression models., Results: We found higher cardiac troponin concentrations in men (n = 9649) compared to women (n = 5331), both for hs-cTnT (median 11.8 [Q1-3 8.1-18.0] vs. 9.6 [6.7-14.3] ng L -1 , P < 0.001) and hs-cTnI (5.8 [3.4-10.8] vs. 4.9 [3.1-8.8] ng L -1 , P < 0.001). Adjusting for baseline demographics, comorbidities and medications, men still had significantly higher hs-troponin concentrations than women. C-reactive protein and N-terminal pro-B-type natriuretic peptide concentrations were higher in female patients. Both hs-cTnT and hs-cTnI concentrations were associated with all clinical outcomes similarly in men and women (p-value for interaction >0.05 for all end-points)., Conclusion: Men have higher hs-troponin concentrations than women in AF. Regardless of sex, hs-troponin concentrations remain similarly associated with adverse clinical outcomes in anticoagulated patients with AF., (© 2020 The Authors. Journal of Internal Medicine published by John Wiley & Sons Ltd on behalf of Association for Publication of The Journal of Internal Medicine.)

Purpose: A high intake of marine n-3 polyunsaturated fatty acids (PUFAs) might improve cardiovascular (CV) health. We conducted a cross-sectional study to investigate associations between plasma phospholipid levels of marine n-3 PUFAs and CV risk factors, educational level, physical activity and smoking habits., Methods: A total of 3706 individuals from a general population, all born in 1950 and residing in Akershus County, Norway, were included in this study. The main statistical approach was multivariable adjusted linear regression., Results: Plasma marine n-3 PUFA levels ranged from 2.7 to 20.3 wt%, with a median level of 7.7 wt% (interquartile range 4.3-11.1 wt%). High levels of plasma marine n-3 PUFAs were associated with lower serum triglycerides [Standardized regression coefficient (Std.β-coeff.) - 0.14, p < 0.001], body mass index (Std. β-coeff. -0.08, p < 0.001), serum creatinine (Std. β-coeff. -0.03, p = 0.05), C-reactive protein levels (Std. β-coeff. - 0.03, p = 0.04), higher levels of serum high-density lipoprotein cholesterol (Std. β-coeff. 0.08, p < 0.001) and low-density lipoprotein cholesterol (Std. β-coeff. 0.04, p = 0.003). High levels of plasma marine n-3 PUFAs were also associated with lower glycated hemoglobin (Std. β-coeff. - 0.04, p = 0.01), however, only in individuals without diabetes. We found no associations between plasma marine n-3 PUFA levels and fasting plasma glucose or carotid intima-media thickness. High levels of plasma marine n-3 PUFAs were associated with higher educational level, more physical activity and lower prevalence of smoking., Conclusion: In this cross-sectional study of Norwegian individuals born in 1950, high levels of plasma marine n-3 PUFAs were favourably associated with several CV risk factors, suggesting that fish consumption might improve CV health.

Intake of industrially produced trans fatty acids (iTFAs) has previously been associated with dyslipidemia, insulin resistance, hypertension and inflammation, as well as increased cardiovascular (CV) morbidity and mortality. iTFA intake declined in Norway after the introduction of legislative bans against iTFA consumption. However, the relationship between the current iTFA intake and CV health is unclear. The aim of the present study was to investigate the association between current iTFA intake, reflected by plasma iTFA levels, and established CV risk factors. We also examined the associations between plasma ruminant TFA levels and CV risk factors. In this cross-sectional study, we included 3706 participants from a Norwegian general population, born in 1950 and residing in Akershus County, Norway. The statistical method was multivariable linear regression. Plasma iTFA levels were inversely associated with serum triglycerides ( p < 0.001), fasting plasma glucose ( p < 0.001), body mass index ( p < 0.001), systolic and diastolic blood pressure ( p = 0.001 and p = 0.03) and C-reactive protein ( p = 0.001). Furthermore, high plasma iTFA levels were associated with higher education and less smoking and alcohol consumption. We found that plasma ruminant trans fatty acids (rTFA) levels were favorably associated with CV risk factors. Furthermore, plasma iTFA levels were inversely associated with CV risk factors. However, our results might have been driven by lifestyle factors. Overall, our findings suggest that the current low intake of iTFAs in Norway does not constitute a threat to CV health., Competing Interests: The authors have no conflict of interest to declare. Funders were not involved in organizing the study; collecting, analyzing, or interpreting the data; preparing the manuscript; or in the decision to publish the final results. Findings in the present study are unpublished and are not under consideration for publication elsewhere.

Background: Concentrations of cardiac troponin I (cTnI) and T (cTnT) are associated with clinical cardiac outcomes, but do not correlate closely in subjects recruited from the general population. Accordingly, we hypothesized that cTnI and cTnT concentrations would be influenced by different cardiovascular (CV) and non-CV risk factors and reflect different CV phenotypes., Methods: We measured cTnI and cTnT with last generation assays in 1236 women and 1157 men with no known CV disease participating in the prospective observational Akershus Cardiac Examination 1950 Study. All study participants underwent extensive CV phenotyping at baseline, including detailed echocardiography., Results: Concentrations of cTnI were measurable in 60.3% and cTnT in 72.5% of study participants (P < 0.001), and correlated moderately (r = 0.53; P < 0.001). cTnI was more strongly associated with male sex (P = 0.018), higher education (P < 0.001), history of hypertension (P < 0.001), and age (P < 0.001), whereas cTnT was more strongly associated with eGFR (P = 0.015). Both cTnI and cTnT were inversely associated with global longitudinal strain and positively associated with LV mass index (LVMI) in analyses adjusted for CV risk factors. The association between cTnI and LVMI was stronger than the association between cTnT and LVMI (P = 0.035). Concentrations of cTnI improved diagnostic accuracy for LV hypertrophy when added to established CV risk factors, but concentrations of cTnT did not improve these models further., Conclusions: In a large community-based cohort examined with extensive echocardiography, concentrations of cTnI and cTnT are associated with subclinical LV hypertrophy and dysfunction. Concentrations of cTnI appear superior to cTnT in predicting subclinical LV hypertrophy., (© American Association for Clinical Chemistry 2020. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Background and Purpose: Pulsatility index (PI) in the middle cerebral artery (MCA) is considered a measure of peripheral vascular resistance. Several established cardiovascular risk factors are common for both MCA PI and carotid atherosclerosis. Accordingly, in the present study we hypothesized an association between ultrasound-derived indices of carotid atherosclerosis and MCA PI., Methods: All residents in Akershus County, born in 1950, were invited to a cardiovascular examination, The Akershus Cardiac Examination (ACE) 1950 Study (2012-2015). A thorough ultrasound examination was performed to assess indices of atherosclerosis in the carotid arteries, and PI in the MCAs. In all, 3154 (85.1%) had adequate transcranial and carotid data. Associations between indices of carotid atherosclerosis and MCA PI were assessed by regression analyses adjusted for established cardiovascular risk factors., Results: Mean age was 64 (standard deviation [SD]: .6) years, and 1,357 (43%) were women. Mean MCA PI was .97 (SD: .17). Participants in the upper quartile of MCA PI had higher pulse pressure, more frequently hypertension, diabetes mellitus, and a history of coronary artery disease. Both carotid plaque score (B .007 [95% CI: .003-.010]) and carotid intimamedia thickness (B .173 [95% CI: .120-.226]) were significantly associated with MCA PI in adjusted analysis. The model R 2 was .055., Conclusion: In a population-based sample of middle-aged adults, ultrasound-derived indices of carotid atherosclerosis were independently associated with MCA PI. However, the overall explained variance of MCA PI was low, suggesting other factors than atherosclerosis and cardiovascular risk factors to play an important role for MCA PI., (© 2019 The Authors. Journal of Neuroimaging published by Wiley Periodicals, Inc. on behalf of American Society of Neuroimaging.)

Aims: Increased left ventricular mechanical dispersion by 2D speckle tracking echocardiography predicts ventricular arrhythmias in ischaemic heart disease and heart failure. However, little is known about mechanical dispersion in the general population. We aimed to study mechanical dispersion in the general population and in diseases associated with increased risk of cardiovascular disease., Methods and Results: The present cross-sectional study consists of 2529 subjects born in 1950 included in the Akershus Cardiac Examination (ACE) 1950 study. Global longitudinal strain (GLS) was assessed from 17 strain segments, and mechanical dispersion calculated as the standard deviation of contraction duration of all segments. The cohort was divided according to the median value of mechanical dispersion, and multivariable linear regression models were performed with mechanical dispersion as the dependent variable. The prevalence of coronary artery disease (CAD), hypertension, obesity, and diabetes (P < 0.01 for all) was significantly higher in subjects with supra-median mechanical dispersion. In a multivariable clinical model, CAD (B = 7.05), hypertension (B = 4.15; both P < 0.001), diabetes (B = 3.39), and obesity (B = 1.89; both P < 0.05) were independently associated with increasing mechanical dispersion. When echocardiographic indices were added to the multivariable model, CAD (B = 4.38; P < 0.01) and hypertension (B = 2.86; P < 0.001) remained significant in addition to peak early diastolic tissue velocity e' (B = -2.00), GLS (B = 1.68), and ejection fraction (B = 0.22; P < 0.001 for all)., Conclusion: In a general middle-aged population, prevalent CAD and hypertension were associated with increasing mechanical dispersion, possibly indicating elevated risk of fatal arrhythmias and sudden cardiac death. Albeit weaker, systolic and diastolic dysfunction, were also associated with increasing mechanical dispersion., (Published on behalf of the European Society of Cardiology. All rights reserved. © The Author(s) 2019. For permissions, please email: journals.permissions@oup.com.)

Objective: We assessed the impact of a single time-point measurement of SBP, DBP and pulse pressure at the age of 40, on carotid plaque burden, echolucent plaques and carotid intima-media thickness late midlife., Methods: Individuals participating in two separate studies, 23 years apart, defined our cohort (n = 2714). 'The Age 40 Program', a nationwide Norwegian cardiovascular screening survey, performed 1985-1999, assessed cardiovascular risk factors and lifestyle variables at age 40. 'The ACE 1950 Study', a population-based cohort study on individuals born in 1950, performed 2012-2015, included ultrasound examinations of the carotid arteries. Blood pressure (BP) determinants of carotid atherosclerosis were assessed by regression models adjusted for cardiovascular risk factors at age 40, and late midlife BP., Results: The participants, 50.3% women, had a mean age of 40 (SD 0.3) years in the first study, and 64 (SD 0.6) years in the second. At age 40, mean SBP was 128 (SD 14) mmHg, mean DBP was 78 (SD 10) mmHg and mean pulse pressure was 50 (SD 9) mmHg. SBP and DBP at age 40 predicted carotid plaque burden in late midlife. Only DBP predicted echolucent plaques, and none of the BP components predicted carotid intima-media thickness., Conclusion: A single time-point measurement of SBP and DBP at age 40 is associated with carotid plaque burden late midlife, also after adjustment for other cardiovascular risk factors at age 40, and of late midlife BP. Our findings emphasize the strong association between BP and atherosclerosis.