Prognostic Value of Cardiovascular Biomarkers in the Population (2024)

• ¹Department of Cardiology, University Heart and Vascular Center Hamburg, University Medical Center Hamburg-Eppendorf, Hamburg, Germany

• ²Center for Population Health Innovation, University Heart and Vascular Center Hamburg, University Medical Center Hamburg-Eppendorf, Hamburg, Germany

• ³German Center for Cardiovascular Research, Partner Site Hamburg/Kiel/Lübeck, Hamburg, Germany

• ⁴Department of Epidemiology and Preventive Medicine, School of Public Health and Preventive Medicine, Monash University, Melbourne, Australia

• ⁵Center for Cardiometabolic Disease Prevention, Department of Medicine, College of Medicine, Baylor University, Houston, Texas

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• ⁶Department of Medicine, Boston Medical Center, Chobanian and Avedisian School of Medicine, Boston University, Boston, Massachusetts

• ⁷Department of Epidemiology, School of Public Health, Boston University, Boston, Massachusetts

• ⁸Department of Epidemiology and Prevention, IRCCS Neuromed, Pozzilli, Italy

• ⁹Department of Internal Medicine, UT Southwestern Medical Center, Dallas, Texas

• ¹⁰Inova Heart and Vascular Institute, Falls Church, Virginia

• ¹¹Mediterranea Cardiocentro, Naples, Italy

• ¹²Department of Cardiovascular, Endocrine-Metabolic Diseases, and Aging, National Institute of Health, Rome, Italy

• ¹³Department of Internal Medicine B, University Greifswald, Greifswald, Germany

• ¹⁴German Center for Cardiovascular Research, Partner Site Greifswald, University Medicine, Greifswald, Germany

• ¹⁵Departments of Medical Sciences and Cardiology, Uppsala University, Uppsala, Sweden

• ¹⁶Department of Clinical Sciences, Lund University, Malmö, Sweden

• ¹⁷Research Centre in Epidemiology and Preventive Medicine, Department of Medicine and Surgery, University of Insubria, Varese, Italy

• ¹⁸Department of Nephrology, University Medical Center Groningen, Groningen, the Netherlands

• ¹⁹Istituto Superiore di Sanità, Rome, Italy

• ²⁰Department of Public Health and Caring Sciences/Geriatrics, Uppsala University, Uppsala, Sweden

• ²¹Department of Clinical Physiology and Centre for Clinical Research, Västmanland County Hospital, Uppsala University, Västerås, Sweden

• ²²Department of Medicine and Surgery, Libera Università Mediterranea, Casamassima, Italy

• ²³Department of Public Health, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark

• ²⁴Centre for Clinical Research and Prevention, BFH Hospital, Copenhagen, Denmark

• ²⁵UKCRC Centre of Excellence for Public Health, Queens University of Belfast, Belfast, Northern Ireland

• ²⁶German Heart Center, Technical University of Munich, Munich, Germany

• ²⁷Institute of Epidemiology and Medical Biometry, University of Ulm, Ulm, Germany

• ²⁸German Center for Cardiovascular Disease Research, Partner Site Munich Heart Alliance, Munich, Germany

• ²⁹Finnish Institute for Health and Welfare, Helsinki, Finland

• ³⁰Nutrition and Health Innovation Research Institute, School of Medical and Health Sciences, Edith Cowan University, Perth, Australia

• ³¹Medical School, University of Western Australia, Perth

• ³²Centre for Kidney Research, Children’s Hospital at Westmead, School of Public Health, Sydney Medical School, University of Sydney, Sydney, Australia

• ³³Division of Medicine, Department of Cardiology, Akershus University Hospital, Lørenskog, Norway

• ³⁴K. G. Jebsen Center for Cardiac Biomarkers, Institute of Clinical Medicine, Faculty of Medicine, University of Oslo, Oslo, Norway

• ³⁵Institute for Clinical Chemistry and Laboratory Medicine, University Medicine Greifswald, Greifswald, Germany

• ³⁶Division of Medicine, Turku University Hospital, Turku, Finland

• ³⁷Department of Internal Medicine, University of Turku, Turku, Finland

• ³⁸Cardiology Section, Department of Internal Medicine, Holbaek Hospital, Holbaek, Denmark

• ³⁹Department of Regional Health, University of Southern Denmark, Odense

• ⁴⁰Department of Public Health and Clinical Medicine, Section of Medicine, Umeå University, Umeå, Sweden

• ⁴¹Institute of Epidemiology, Helmholtz Zentrum München, German Research Center for Environmental Health, Neuherberg, Germany

• ⁴²Institute for Medical Information Processing, Biometry, and Epidemiology, Faculty of Medicine, Ludwig-Maximilians-Universität, Munich, Germany

• ⁴³University of Texas School of Public Health and the University of Texas Health Science Center, San Antonio

• ⁴⁴Catalan Department of Health, Barcelona, Spain

• ⁴⁵Wallenberg Laboratory and Department of Molecular and Clinical Medicine, Institute of Medicine, Gothenburg University, Gothenburg, Sweden

• ⁴⁶Cardiovascular Epidemiology Unit, Institute of Cardiovascular Research, University of Dundee, Dundee, Scotland

• ⁴⁷Department of Cardiology, Pulmonology, and Nephrology, School of Medicine, Yamagata University, Yamagata, Japan

• ⁴⁸Institute for Cardiovascular Regeneration, Goethe University, Frankfurt, Germany

• ⁴⁹German Center for Cardiovascular Disease Research, Partner Site Rhine-Main, Mainz, Germany

Key Points

Question What is the value of cardiovascular biomarkers when added to established risk factors to predict incident cardiovascular events in the population?

Findings In this large, individual-level data analysis from 28 general population–based cohorts from 12 countries, high-sensitivity cardiac troponins I and T, B-type natriuretic peptide, and high-sensitivity C-reactive protein were associated with fatal and nonfatal events.

Meaning The addition of biomarkers to established risk factors leads to only a small improvement in risk prediction metrics for atherosclerotic cardiovascular disease, but was more favorable for heart failure and mortality.

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.

Genetics and Genomics Heart Failure Neurogenetics Cardiology Acute Coronary Syndromes Ischemic Heart Disease Cerebrovascular Disease Neurology Stroke Cerebrovascular Infarction

Citation

Neumann JT, Twerenbold R, Weimann J, et al. Prognostic Value of Cardiovascular Biomarkers in the Population. JAMA. Published online May 13, 2024. doi:10.1001/jama.2024.5596

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