Prognostic value of multiple emerging biomarkers in cardiovascular risk prediction in patients with stable cardiovascular disease

Atherosclerosis. 2013 Jun;228(2):478-84. doi: 10.1016/j.atherosclerosis.2013.03.017. Epub 2013 Mar 26.

Abstract

Background: Few studies have examined simultaneously the prognostic value of traditional and emerging biomarkers including atrial natriuretic peptide (ANP) and brain-type natriuretic peptide (BNP), for major cardiovascular disease (CVD) outcomes in patients with stable CVD, and results are equivocal.

Design: and

Methods: Mid-regional pro-ANP (MR-proANP) and N-Terminal pro-BNP (NT-proBNP), CRP and homocysteine were measured in stable CVD patients (n = 1456; age: 61.8 y) at inclusion in the SU.FOL.OM3 cohort. Prospective association of biomarkers with risk of heart failure, major cardiovascular (non-fatal myocardial infarction, ischemic stroke or death from CVD) or overall cardiovascular event were examined with Cox proportional-hazards analyses. Increase in prediction risk upon addition of biomarker(s) to the traditional risk model was examined by change in C-statistic, NRI and IDI.

Results: During follow-up (median: 4.7 y), 40 heart failure, 145 major cardiovascular and 493 overall cardiovascular events were diagnosed. In models adjusted for age, sex, smoking, diabetes, serum creatinine and CVD inclusion criteria, NT-proBNP and CRP associated significantly with heart failure. Both natriuretic peptides predicted the risk of major cardiovascular events in adjusted models; Hazard ratio (HR) and 95% CI for each SD increase in MR-proANP and NT-proBNP were 1.24 (1.04-1.47), and 1.31 (1.09-1.57), respectively. The addition of NT-proBNP to a traditional risk model increased significantly the area-under-curve for heart failure and overall cardiovascular events (by 6 and 12%, respectively); addition of MR-proANP or homocysteine yielded modest (2%) but statistically significant increase for major cardiovascular events.

Conclusion: NT-proBNP consistently predicted CVD outcomes and may be useful singly or in combination with MR-proANP for risk-stratification in high-risk patients.

Publication types

  • Comparative Study
  • Multicenter Study
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Atrial Natriuretic Factor / blood*
  • Biomarkers / blood
  • C-Reactive Protein / analysis
  • Cardiovascular Diseases / blood*
  • Cardiovascular Diseases / diagnosis
  • Cardiovascular Diseases / mortality
  • Chi-Square Distribution
  • Disease Progression
  • Double-Blind Method
  • Female
  • France
  • Homocysteine / blood
  • Humans
  • Kaplan-Meier Estimate
  • Male
  • Middle Aged
  • Natriuretic Peptide, Brain / blood*
  • Peptide Fragments / blood*
  • Prognosis
  • Proportional Hazards Models
  • Prospective Studies
  • Risk Assessment
  • Risk Factors
  • Time Factors

Substances

  • Biomarkers
  • Peptide Fragments
  • midregional pro-atrial natriuretic peptide, human
  • pro-brain natriuretic peptide (1-76)
  • Homocysteine
  • Natriuretic Peptide, Brain
  • Atrial Natriuretic Factor
  • C-Reactive Protein

Associated data

  • ISRCTN/ISRCTN41926726