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Neumann, J.T.* ; Twerenbold, R.* ; Weimann, J.* ; Ballantyne, C.M.* ; Benjamin, E.J.* ; Costanzo, S.* ; de Lemos, J.A.* ; deFilippi, C.R.* ; Di Castelnuovo, A.* ; Donfrancesco, C.* ; Dörr, M.* ; Eggers, K.M.* ; Engström, G.* ; Felix, S.B.* ; Ferrario, M.M.* ; Gansevoort, R.T.* ; Giampaoli, S.* ; Giedraitis, V.* ; Hedberg, P.* ; Iacoviello, L.* ; Jørgensen, T.* ; Kee, F.* ; Koenig, W.* ; Kuulasmaa, K.* ; Lewis, J.R.* ; Lorenz, T.* ; Lyngbakken, M.N.* ; Magnussen, C.* ; Melander, O.* ; Nauck, M.* ; Niiranen, T.J.* ; Nilsson, P.M.* ; Olsen, M.H.* ; Omland, T.* ; Oskarsson, V.* ; Palmieri, L.* ; Peters, A. ; Prince, R.L.* ; Qaderi, V.* ; Vasan, R.S.* ; Salomaa, V.* ; Sans, S.* ; Smith, J.G.* ; Söderberg, S.* ; Thorand, B. ; Tonkin, A.M.* ; Tunstall-Pedoe, H.* ; Veronesi, G.* ; Watanabe, T.* ; Watanabe, M.* ; Zeiher, A.M.* ; Zeller, T.* ; Blankenberg, S.* ; Ojeda, F.*

Prognostic value of cardiovascular biomarkers in the population.

JAMA, DOI: 10.1001/jama.2024.5596 (2024)
Publ. Version/Full Text Postprint DOI PMC
Open Access Green
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.
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Publication type Article: Journal article
Document type Scientific Article
Corresponding Author
Keywords Sensitivity Cardiac Troponin; General-population; Risk Prediction; Validation; Models; Impact
ISSN (print) / ISBN 0098-7484
e-ISSN 1538-3598
Journal JAMA: Journal of the American Medical Association
Publisher American Medical Association
Publishing Place 330 N Wabash Ave, Ste 39300, Chicago, Il 60611-5885 Usa
Non-patent literature Publications
Reviewing status Peer reviewed
Institute(s) Institute of Epidemiology II (EPI2)
Grants German Centre for Cardiovascular Research
County council in Vasterbotten
County council in Norr
Umea University
Medical Research Council, London
Lund University
State of Bavaria
Helmholtz Zentrum Munchen-German Research Center for Environmental Health - German Federal Ministry of Education and Research
King Gustaf V andQueen Victoria's Foundation of Freemasons
MORGAM data center
KG Jebsen Center for Cardiac Biomarkers
Sigrid Juselius Foundation
Research Council of Finland
Finnish Foundation for Cardiovascular Research
National Heart Foundation of Australia Future Leader Fellowship
National Institutes of Health
Heisenberg programme of the Deutsche Forschungsgemeinschaft (German Research Foundation)
European Union