• Johannes Tobias Neumann, Raphael Twerenbold, Jessica Weimann, Christie M Ballantyne, Emelia J Benjamin, Simona Costanzo, James A de Lemos, Christopher R deFilippi, Augusto Di Castelnuovo, Chiara Donfrancesco, Marcus Dörr, Kai M Eggers, Gunnar Engström, Stephan B Felix, Marco M Ferrario, Ron T Gansevoort, Simona Giampaoli, Vilmantas Giedraitis, Pär Hedberg, Licia Iacoviello, Torben Jørgensen, Frank Kee, Wolfgang Koenig, Kari Kuulasmaa, Joshua R Lewis, Thiess Lorenz, Magnus N Lyngbakken, Christina Magnussen, Olle Melander, Matthias Nauck, Teemu J Niiranen, Peter M Nilsson, Michael H Olsen, Torbjorn Omland, Viktor Oskarsson, Luigi Palmieri, Anette Peters, Richard L Prince, Vazhma Qaderi, Ramachandran S Vasan, Veikko Salomaa, Susana Sans, J Gustav Smith, Stefan Söderberg, Barbara Thorand, Andrew M Tonkin, Hugh Tunstall-Pedoe, Giovanni Veronesi, Tetsu Watanabe, Masafumi Watanabe, Andreas M Zeiher, Tanja Zeller, Stefan Blankenberg, and Francisco Ojeda.
• Department of Cardiology, University Heart and Vascular Center Hamburg, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.
• JAMA. 2024 Jun 11; 331 (22): 189819091898-1909.

ImportanceIdentification of individuals at high risk for atherosclerotic cardiovascular disease within the population is important to inform primary prevention strategies.ObjectiveTo evaluate the prognostic value of routinely available cardiovascular biomarkers when added to established risk factors.Design, Setting, And ParticipantsIndividual-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.ExposureMeasurement 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 MeasuresThe 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.ResultsThe 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 RelevanceCardiovascular 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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