Abstract 15751: Metabolite Profiling Identifies Novel Biomarkers for Cardiovascular Disease Risk Across Multiple Population-Studies and Profiling Platforms
Introduction: Metabolomics holds promise to elucidate mechanisms of atherogenesis and improve cardiovascular risk prediction. The consistency of metabolite biomarker identification across different profiling technologies and populations remains unclear. We applied metabolomics approaches to three cohorts to identify systemic biomarkers reflective of the risk for first cardiovascular event during >10 years of follow-up.
Method: Metabolite profiles were quantified by serum NMR spectroscopy in FINRISK (n=7,520, 713 events) and the British Women’s Heart and Health Study (n=4,282, 450 events), and by liquid chromatography-tandem mass spectrometry in the Framingham Heart Study (n=2,289, 466 events). Metabolite biomarkers were assessed for association with incident cardiovascular events (fatal or nonfatal coronary or stroke events) during 13-year follow-up in FINRISK. The biomarkers highlighted in FINRISK were validated in the two independent cohorts using different metabolomics platforms.
Results: Six circulating metabolites were predictive of incident cardiovascular events independently of established risk factors in the FINRISK study (P<0.05 after multiple testing correction). Phenylalanine, alpha-1-acid glycoprotein and pyruvate were associated with increased risk, while glutamine was associated with decreased cardiovascular risk. Circulating levels of both omega-3 and omega-6 fatty acids were inversely associated with cardiovascular disease development. The majority of the biomarker associations replicated in age- and sex-adjusted analyses in both validation studies, albeit hazard ratios were weaker. Differences in population structure as well as fasting vs. non-fasting may underpin some of the differences in the biomarker associations.
Conclusion: Aromatic amino acids, glycolysis substrates and polyunsaturated fatty acids are reflective of cardiovascular disease risk in general population settings. The metabolite biomarkers highlighted by high-throughput profiling were consistent in multiple populations despite quantification with different technologies.
- © 2013 by American Heart Association, Inc.