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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.

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.)

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.)

Purpose: To compare the diagnostic and prognostic value of mid-regional pro-ANP (MR-proANP) and N-terminal pro-B-type natriuretic peptide (NT-proBNP) in patients with acute dyspnea., Methods: MR-proANP and NT-proBNP were measured with commercial immunoassays at hospital admission (n = 313), on day 2 (n = 234), and before discharge (n = 91) and compared for diagnosing acute heart failure (HF; n = 143) and to predict mortality among patients with acute HF and acute exacerbation of chronic obstructive pulmonary disease (AECOPD; n = 84) separately., Results: The correlation coefficient between MR-proANP and NT-proBNP was 0.89 (p < 0.001) and the receiver-operating area under the curve (AUC) was 0.85 (95% CI 0.81-0.89) for MR-proANP and 0.86 (0.82-0.90) for NT-proBNP to diagnose acute HF. During a median follow-up of 816 days, mortality rates were 46% in acute HF patients and 42% in AECOPD patients. After adjustment for other risk variables by multivariate Cox regression analysis, MR-proANP and NT-proBNP concentrations were associated with mortality in patients with acute HF, but only MR-proANP were associated with mortality among patients with AECOPD: hazard ratio ( ln MR-proANP) 1.98 (95% CI 1.17-3.34)., Conclusion: MR-proANP and NT-proBNP concentrations provide similar diagnostic and prognostic information in patients with acute HF. In contrast to NT-proBNP, MR-proANP measurements also provided independent prognostic information in AECOPD patients.

Background: European System for Cardiac Operative Risk Evaluation II (EuroSCORE II) is used for risk stratification before cardiac surgery, but whether N-terminal pro-B-type natriuretic peptide (NT-proBNP) and high-sensitivity troponin T (hs-TnT) may add prognostic information to EuroSCORE II is not known., Methods: Preoperative (n=640) and postoperative (n=629) blood samples were available from cardiac surgical patients with 961-day follow-up (FINNAKI Heart study; cohort #1). The accuracy of a parsimonious risk model with NT-proBNP measurements was also tested in 90 patients with respiratory failure after cardiac surgery (FINNALI study; cohort #2)., Results: Sixty-one patients (9.5%) died during follow-up in cohort #1. Preoperative NT-proBNP and hs-TnT concentrations correlated (rho=0.58; p<0.001) and were higher in non-survivors compared to survivors: median 2027 (Q1-3 478-5387) vs. 373 (134-1354) ng/L [NT-proBNP] and 39 (16-191) vs. 13 (8-32) ng/L [hs-TnT]; p<0.001 for both. Preoperative NT-proBNP concentrations were associated with time to death after adjustment for EuroSCORE II (HR [ ln NT-proBNP] 1.33 [95% CI 1.08-1.64]), p=0.008 and reclassified patients on top of EuroSCORE II (net reclassification index 0.39 [95% CI 0.14-0.64], p=0.003). Pre- and postoperative NT-proBNP concentrations were closely correlated (rho=0.80, p<0.001) and postoperative NT-proBNP concentrations were also associated with long-term mortality after adjustment for EuroSCORE II. A parsimonious risk model that included age, creatinine clearance, chronic pulmonary disease, and NT-proBNP measurements provided comparable prognostic accuracy as EuroSCORE II in cohort #1 and #2 for risk of long-term mortality. hs-TnT measurements did not add to NT-proBNP measurements CONCLUSION: NT-proBNP measurements could improve and simplify risk prediction in cardiac surgical patients., (Copyright © 2018 The Canadian Society of Clinical Chemists. Published by Elsevier Inc. All rights reserved.)