TY - JOUR
T1 - Prognostic Value of Cardiovascular Biomarkers in the Population
AU - Neumann, Johannes Tobias
AU - Twerenbold, Raphael
AU - Weimann, Jessica
AU - Ballantyne, Christie M.
AU - Benjamin, Emelia J.
AU - Costanzo, Simona
AU - De Lemos, James A.
AU - Defilippi, Christopher R.
AU - Di Castelnuovo, Augusto
AU - Donfrancesco, Chiara
AU - Dörr, Marcus
AU - Eggers, Kai M.
AU - Engström, Gunnar
AU - Felix, Stephan B.
AU - Ferrario, Marco M.
AU - Gansevoort, Ron T.
AU - Giampaoli, Simona
AU - Giedraitis, Vilmantas
AU - Hedberg, Pär
AU - Iacoviello, Licia
AU - Jørgensen, Torben
AU - Kee, Frank
AU - Koenig, Wolfgang
AU - Kuulasmaa, Kari
AU - Lewis, Joshua R.
AU - Lorenz, Thiess
AU - Lyngbakken, Magnus N.
AU - Magnussen, Christina
AU - Melander, Olle
AU - Nauck, Matthias
AU - Niiranen, Teemu J.
AU - Nilsson, Peter M.
AU - Olsen, Michael H.
AU - Omland, Torbjorn
AU - Oskarsson, Viktor
AU - Palmieri, Luigi
AU - Peters, Anette
AU - Prince, Richard L.
AU - Qaderi, Vazhma
AU - Vasan, Ramachandran S.
AU - Salomaa, Veikko
AU - Sans, Susana
AU - Smith, J. Gustav
AU - Söderberg, Stefan
AU - Thorand, Barbara
AU - Tonkin, Andrew M.
AU - Tunstall-Pedoe, Hugh
AU - Veronesi, Giovanni
AU - Watanabe, Tetsu
AU - Watanabe, Masafumi
AU - Zeiher, Andreas M.
AU - Zeller, Tanja
AU - Blankenberg, Stefan
AU - Ojeda, Francisco
N1 - Publisher Copyright:
© 2024 American Medical Association. All rights reserved.
PY - 2024/6/11
Y1 - 2024/6/11
N2 - 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 164054 individuals (median age, 53.1 years [IQR, 42.7-62.9 years] and 52.4% were women). There were 17211 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.
AB - 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 164054 individuals (median age, 53.1 years [IQR, 42.7-62.9 years] and 52.4% were women). There were 17211 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.
UR - http://www.scopus.com/inward/record.url?scp=85193277267&partnerID=8YFLogxK
U2 - 10.1001/jama.2024.5596
DO - 10.1001/jama.2024.5596
M3 - Article
C2 - 38739396
AN - SCOPUS:85193277267
SN - 0098-7484
VL - 331
SP - 1898
EP - 1909
JO - JAMA
JF - JAMA
IS - 22
ER -