Prognostic Utility of Novel Biomarkers of Cardiovascular Stress

TLDR

Biomarkers for predicting cardiovascular events in community populations have not consistently added information beyond standard risk factors, partly because many lack cardiovascular specificity. The study aimed to determine the prognostic value of three novel cardiovascular stress biomarkers—soluble ST2, GDF‑15, and hs‑troponin I—in a large community cohort. Multivariable‑adjusted proportional hazards models were used to evaluate each biomarker and a multimarker score—including the three novel markers plus BNP and hs‑CRP—for predicting adverse outcomes. Over 11.3 years, the three biomarkers were independently associated with death, cardiovascular events, and heart failure, and individuals in the highest multimarker quartile had 3‑fold higher death risk, 6‑fold higher heart failure risk, and 2‑fold higher cardiovascular event risk; adding the multimarker score improved discrimination and reclassification.

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.