Prognostic utility of novel biomarkers of cardiovascular stress: the Framingham Heart Study

Circulation. 2012 Sep 25;126(13):1596-604. doi: 10.1161/CIRCULATIONAHA.112.129437. Epub 2012 Aug 20.

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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Biomarkers / blood
  • C-Reactive Protein / metabolism
  • Cardiovascular Diseases / blood*
  • Cardiovascular Diseases / diagnosis*
  • Cardiovascular Diseases / epidemiology
  • Follow-Up Studies
  • Growth Differentiation Factor 15 / blood*
  • Heart Failure / epidemiology
  • Humans
  • Interleukin-1 Receptor-Like 1 Protein
  • Male
  • Middle Aged
  • Natriuretic Peptide, Brain / blood
  • Prognosis
  • Proportional Hazards Models
  • Receptors, Cell Surface / blood*
  • Retrospective Studies
  • Risk Factors
  • Troponin I / blood*

Substances

  • Biomarkers
  • Growth Differentiation Factor 15
  • IL1RL1 protein, human
  • Interleukin-1 Receptor-Like 1 Protein
  • Receptors, Cell Surface
  • Troponin I
  • Natriuretic Peptide, Brain
  • C-Reactive Protein