Prognostic Value of Cardiovascular Biomarkers in the Population
: 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
Publisher: American Medical Association
: 2024
: JAMA: Journal of the American Medical Association
: JAMA
: JAMA
: 331
: 22
: 1898
: 1909
: 0098-7484
: 1538-3598
DOI: https://doi.org/10.1001/jama.2024.5596
: https://jamanetwork.com/journals/jama/fullarticle/2818624
: https://pmc.ncbi.nlm.nih.gov/articles/PMC11091824/
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.
:
This study was supported by the European Union project euCanSHare (Horizon 2020, No. 847770). The KORA study was initiated and financed by the Helmholtz Zentrum München–German Research Center for Environmental Health, which is funded by the German Federal Ministry of Education and Research and by the State of Bavaria. Data collection in the KORA study is done in cooperation with the University Hospital of Augsburg. The Malmö Diet and Cancer and Malmö Preventive project were supported by Lund University infrastructure grant (STYR 2019/2046). The MORGAM Project has received funding from European Union projects MORGAM (Biomed, BMH4-CT98-3183), GenomEUtwin (FP5, QLG2-CT-2002-01254), ENGAGE (FP7, HEALTH-F4-2007-201413), CHANCES (FP7, HEALTH-F3-2010-242244), BiomarCaRE (FP7, HEALTH-F2-2011-278913), euCanSHare (Horizon 2020, No. 825903), AFFECT-EU (Horizon 2020, No. 847770), and Medical Research Council, London (G0601463, No. 80983; Biomarkers in the MORGAM populations). This funding has supported central coordination, workshops, and part of the activities of the MORGAM data center, the MORGAM laboratories, and the MORGAM participating centers. The MONICA project is funded by Umeå University, the county councils in Norr and Västerbotten, and the King Gustaf V and Queen Victoria’s Foundation of Freemasons. Dr Neumann is supported by the Heisenberg programme of the Deutsche Forschungsgemeinschaft (German Research Foundation). Dr Benjamin received funding from grants HHSN268201500001I, 75N92019D00031, R01 HL092577, R01 HL64753, R01 HL076784, and R01 AG028321 from the National Institutes of Health. Dr Lewis was funded by a National Heart Foundation of Australia Future Leader Fellowship (ID: 107323). Dr Niiranen was supported by the Finnish Foundation for Cardiovascular Research, the Research Council of Finland (grants 321351 and 354447) and the Sigrid Jusélius Foundation. The Trøndelag Health Study (HUNT Study) is a collaboration between the HUNT Research Centre (Faculty of Medicine and Health Sciences, Norwegian University of Science and Technology), the Trøndelag County Council, the Central Norway Regional Health Authority, and the Norwegian Institute of Public Health. We acknowledge generous support from the KG Jebsen Center for Cardiac Biomarkers (grant SKGJ-MED-024 awarded to Drs Lyngbakken and Omland). Dr Zeller is funded by the German Centre for Cardiovascular Research (grants 81Z0710101 and 81Z0710102).
