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Prognostic Utility of Novel Biomarkers of Cardiovascular Stress: The Framingham Heart Study
Open accessAbstract
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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“Elevated serum GDF15 level have also been found in patients with heart failure”
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Metadata
- 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
- Venue
- Circulation
- Published
- 2012-09-25
- Volume
- 126
- Issue
- 13
- Pages
- 1596-1604
- ISSN
- 0009-7322 (ISSN-L)
- 1524-4539
- 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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