Baseline Metabolomic Profiles Predict Cardiovascular Events in Patients at Risk for Coronary Artery Disease

Am Heart J. 2012 May;163(5):844-850.e1. doi: 10.1016/j.ahj.2012.02.005.

Abstract

Background: Cardiovascular risk models remain incomplete. Small-molecule metabolites may reflect underlying disease and, as such, serve as novel biomarkers of cardiovascular risk.

Methods: We studied 2,023 consecutive patients undergoing cardiac catheterization. Mass spectrometry profiling of 69 metabolites and lipid assessments were performed in fasting plasma. Principal component analysis reduced metabolites to a smaller number of uncorrelated factors. Independent relationships between factors and time-to-clinical events were assessed using Cox modeling. Clinical and metabolomic models were compared using log-likelihood and reclassification analyses.

Results: At median follow-up of 3.1 years, there were 232 deaths and 294 death/myocardial infarction (MI) events. Five of 13 metabolite factors were independently associated with mortality: factor 1 (medium-chain acylcarnitines: hazard ratio [HR] 1.12 [95% CI, 1.04-1.21], P = .005), factor 2 (short-chain dicarboxylacylcarnitines: HR 1.17 [1.05-1.31], P = .005), factor 3 (long-chain dicarboxylacylcarnitines: HR 1.14 [1.05-1.25], P = .002); factor 6 (branched-chain amino acids: HR 0.86 [0.75-0.99], P = .03), and factor 12 (fatty acids: HR 1.19 [1.06-1.35], P = .004). Three factors independently predicted death/MI: factor 2 (HR 1.11 [1.01-1.23], P = .04), factor 3 (HR 1.13 [1.04-1.22], P = .005), and factor 12 (HR 1.18 [1.05-1.32], P = .004). For mortality, 27% of intermediate-risk patients were correctly reclassified (net reclassification improvement 8.8%, integrated discrimination index 0.017); for death/MI model, 11% were correctly reclassified (net reclassification improvement 3.9%, integrated discrimination index 0.012).

Conclusions: Metabolic profiles predict cardiovascular events independently of standard predictors.

Publication types

  • Comparative Study

MeSH terms

  • Adult
  • Age Distribution
  • Analysis of Variance
  • Biomarkers / blood
  • Blood Chemical Analysis
  • Cardiac Catheterization / methods
  • Cardiac Catheterization / statistics & numerical data
  • Cardiovascular Diseases / diagnosis
  • Cardiovascular Diseases / epidemiology
  • Cardiovascular Diseases / metabolism*
  • Cohort Studies
  • Confidence Intervals
  • Coronary Artery Disease / diagnosis
  • Coronary Artery Disease / epidemiology*
  • Coronary Artery Disease / metabolism*
  • Female
  • Humans
  • Lipids / blood
  • Male
  • Metabolomics / methods*
  • Middle Aged
  • Multivariate Analysis
  • Predictive Value of Tests
  • Prevalence
  • Prognosis
  • Retrospective Studies
  • Risk Assessment
  • Severity of Illness Index
  • Sex Distribution
  • Stroke Volume
  • Survival Analysis

Substances

  • Biomarkers
  • Lipids