Prognostic Utility of Novel Biomarkers of Cardiovascular Stress: The Framingham Heart Study
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 3,428 participants (mean age 59, 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 endpoint (p<0.001) except for coronary events. Individuals with multimarker scores in the highest quartile had a 3-fold risk of death (adjusted hazard ratio, 3.2, 95% CI, 2.2-4.7; p<0.001), 6-fold risk of heart failure (6.2, 95% CI, 2.6-14.8; p<0.001), and 2-fold risk of cardiovascular events (1.9, 95% CI, 1.3-2.7; p=0.001). Addition of the multimarker score to clinical variables led to significant increases in the c-statistic (p=0.007 or lower) and net reclassification improvement (p=0.001 or lower).
Conclusions—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.
- Received February 3, 2012.
- Accepted August 6, 2012.
- Copyright © 2012, American Heart Association, Inc. All rights reserved. Unauthorized use prohibited