Prognostic Value of Cardiovascular Biomarkers in the Population
Authors: Neumann Johannes Tobias , Twerenbold Raphael , Weimann Jessica , Ballantyne Christie M. , Benjamin Emelia J. , Costanzo Simona , de Lemos James A. , deFilippi Christopher R. , Di Castelnuovo Augusto , Donfrancesco Chiara , Dörr Marcus , Eggers Kai M. , Engström Gunnar , Felix Stephan B. , Ferrario Marco M. , Gansevoort Ron T. , Giampaoli Simona , Giedraitis Vilmantas , Hedberg Pär , Iacoviello Licia , Jørgensen Torben , Kee Frank , Koenig Wolfgang , Kuulasmaa Kari , Lewis Joshua R. , Lorenz Thiess , Lyngbakken Magnus N. , Magnussen Christina , Melander Olle , Nauck Matthias , Niiranen Teemu J. , Nilsson Peter M. , Olsen Michael H. , Omland Torbjorn , Oskarsson Viktor , Palmieri Luigi , Peters Anette , Prince Richard L. , Qaderi Vazhma , Vasan Ramachandran S. , Salomaa Veikko , Sans Susana , Smith J. Gustav , Söderberg Stefan , Thorand Barbara , Tonkin Andrew M. , Tunstall-Pedoe Hugh , Veronesi Giovanni , Watanabe Tetsu , Watanabe Masafumi , Zeiher Andreas M. , Zeller Tanja , Blankenberg Stefan , Ojeda Francisco 
Published: May 2024

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 &amp;lt;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.