Cited by 482GDF15 and Related BiomarkersHeart Failure Treatment and ManagementAcute Myocardial Infarction Research

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Prognostic Utility of Novel Biomarkers of Cardiovascular Stress: The Framingham Heart Study

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Wang, Thomas J., Wollert, Kai C., Larson, Martin G., Coglianese, Erin, McCabe, Elizabeth L., Cheng, Susan, Ho, Jennifer E., Fradley, Michael G., Ghorbani, Anahita, Xanthakis, Vanessa, Kempf, Tibor, Benjamin, Emelia J., Levy, Daniel, Vasan, Ramachandran S., Januzzi, James L.·2012·Circulation

DOI 10.1161/circulationaha.112.129437PMC PMC3656719

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Abstract

BACKGROUND: Biomarkers for predicting cardiovascular events in community-based populations have not consistently added information to standard risk factors. A limitation of many previously studied biomarkers is their lack of cardiovascular specificity. METHODS AND RESULTS: To determine the prognostic value of 3 novel biomarkers induced by cardiovascular stress, we measured soluble ST2, growth differentiation factor-15, and high-sensitivity troponin I in 3428 participants (mean age, 59 years; 53% women) in the Framingham Heart Study. We performed multivariable-adjusted proportional hazards models to assess the individual and combined ability of the biomarkers to predict adverse outcomes. We also constructed a "multimarker" score composed of the 3 biomarkers in addition to B-type natriuretic peptide and high-sensitivity C-reactive protein. During a mean follow-up of 11.3 years, there were 488 deaths, 336 major cardiovascular events, 162 heart failure events, and 142 coronary events. In multivariable-adjusted models, the 3 new biomarkers were associated with each end point (P<0.001) except coronary events. Individuals with multimarker scores in the highest quartile had a 3-fold risk of death (adjusted hazard ratio, 3.2; 95% confidence interval, 2.2-4.7; P<0.001), 6-fold risk of heart failure (6.2; 95% confidence interval, 2.6-14.8; P<0.001), and 2-fold risk of cardiovascular events (1.9; 95% confidence interval, 1.3-2.7; P=0.001). Addition of the multimarker score to clinical variables led to significant increases in the c statistic (P=0.005 or lower) and net reclassification improvement (P=0.001 or lower). CONCLUSION: Multiple biomarkers of cardiovascular stress are detectable in ambulatory individuals and add prognostic value to standard risk factors for predicting death, overall cardiovascular events, and heart failure.

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Chow, S. L., Maisel, A. S., Anand, I. S., Bozkurt, B., de Boer, R. A., Felker, G. M., Fonarow, G. C., Greenberg, B., Januzzi, J. L., Kiernan, M. S., et al. (2017) · Circulation · doi:10.1161/cir.0000000000000490 · Cited by 626

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Authors: Wang, T. J., Wollert, K. C., Larson, M. G., Coglianese, E., McCabe, E. L., Cheng, S., Ho, J. E., Fradley, M. G., Ghorbani, A., Xanthakis, V., Kempf, T., Benjamin, E. J., Levy, D., Vasan, R. S., & Januzzi, J. L.
Affiliations: Boston University (US)
ORCID: Wang, Thomas J.
Wollert, Kai C.
Larson, Martin G.
Coglianese, Erin
Cheng, Susan
Ho, Jennifer E.
Fradley, Michael G.
Ghorbani, Anahita
Xanthakis, Vanessa
Kempf, Tibor
Benjamin, Emelia J.
Levy, Daniel
Vasan, Ramachandran S.
Januzzi, James L.
Venue: Circulation
Publisher: Ovid Technologies (Wolters Kluwer Health)
Published: 2012-09-25
Volume: 126
Issue: 13
Pages: 1596-1604
ISSN: 0009-7322 (ISSN-L)
1524-4539
DOI: 10.1161/circulationaha.112.129437
PMC: PMC3656719
OpenAlex: W2163917890
Cited by: 482
References: 65
Citations by year: 2026: 16 · 2025: 16 · 2024: 29 · 2023: 33 · 2022: 25 · 2021: 32 · 2020: 40 · 2019: 42 · 2018: 31 · 2017: 42 · 2016: 45 · 2015: 38 · 2014: 44 · 2013: 43 · 2012: 6
FWCI: 32.23
Type: journal article
Language: en
Open access: green
www.ncbi.nlm.nih.gov
Locations: Circulation (publishedVersion)
PubMed (publishedVersion)
Europe PMC (PubMed Central) (acceptedVersion)
PubMed Central (acceptedVersion)
Funders: National Institutes of Health (n01hc25195-41-0-1)
National Heart, Lung, and Blood Institute (R01HL086875, N01‐HC25195, K99HL107642, R01-HL-08675, N01-HC-025195)
Topics: Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › GDF15 and Related Biomarkers
Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Heart Failure Treatment and Management
Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Acute Myocardial Infarction Research
Keywords: soluble ST2, growth differentiation factor 15, high-sensitivity troponin I, cardiovascular mortality, heart failure, major cardiovascular events, brain natriuretic peptide, C-reactive protein, prognostic value, Framingham Heart Study
MeSH terms: Interleukin-1 Receptor-Like 1 Protein, Aged, C-Reactive Protein, Cardiovascular Diseases, Follow-Up Studies, Heart Failure, Humans, Male, Middle Aged, Prognosis, Receptors, Cell Surface, Retrospective Studies, Risk Factors, Biomarkers, Proportional Hazards Models, Troponin I, Natriuretic Peptide, Brain, Growth Differentiation Factor 15

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Prognostic Utility of Novel Biomarkers of Cardiovascular Stress: The Framingham Heart Study

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