Metabolomic Markers Improve Cardiovascular Risk Prediction
Metabolite profiling has identified four new biomarkers that improve the prediction of the risk for heart attack or stroke within the next 15 years, according to a study published online Jan. 8 in Circulation. Phenylalanine and three measures of fatty acids independently predict future cardiovascular events and could, the authors say, provide a low-cost means […]
Metabolite profiling has identified four new biomarkers that improve the prediction of the risk for heart attack or stroke within the next 15 years, according to a study published online Jan. 8 in Circulation. Phenylalanine and three measures of fatty acids independently predict future cardiovascular events and could, the authors say, provide a low-cost means of improving risk assessment. “These new biomarkers can help to better assess the complex molecular processes behind the development of cardiovascular disease," said lead author Peter Würtz, Ph.D., in a statement. "The improved prediction of cardiovascular risk also suggests cost savings in healthcare by advanced biomarker profiling." Profiling metabolic status, the researchers say, may provide insights into the underlying mechanisms associated with atherosclerosis formation. The international group of researchers used a high-throughput nuclear magnetic resonance (NMR) spectroscopy platform to qualitatively identify biomarkers tied to incident cardiovascular disease over long-term follow-up. NMR spectroscopy allows for assessment of over 200 metabolism-related markers from a single blood sample. Biomarker discovery was conducted using data from the FINRISK study (n=7,256; 800 cardiovascular events) with validation occurring using data from the SABRE study (n=2,622; 573 events) and British Women’s Health and Heart Study (BWHHS; n=3,563; 368 events).
The researchers found that 33 out of 68 lipid and metabolite measures tested were significantly associated with incident cardiovascular events, after adjusting for age, sex, blood pressure, smoking, diabetes, and medication. Four metabolites emerged as associated with future cardiovascular events when analyses further adjusted for routine lipids. Specifically, higher serum phenylalanine and monounsaturated fatty acid levels were associated with increased cardiovascular risk, while higher omega-6 fatty acids and docosahexaenoic acid levels were associated with lower risk. A risk score, incorporating these four biomarkers, was then developed. Risk reclassification was improved with the addition of the biomarker risk score among individuals who did not experience a cardiovascular event. Net reclassification improvement for the whole study population was 7.6 percent in SABRE and 5.3 percent in BWHHS. However, there was a substantial upclassification with inclusion of the biomarker score for persons classified in the intermediate risk range (5 percent to 10 percent). "Novel biomarkers for risk prediction are primarily needed for persons in the intermediate risk range, for whom treatment decisions are most challenging," Würtz writes in the study. "The four biomarkers proved particularly helpful in correctly reclassifying individuals in the 5 percent to 10 percent risk grey zone." Takeaway: Identification of biomarkers through metabolomic analyses may improve individual's risk classification for future cardiovascular events. The researchers are optimistic that this high-throughput biomarker profiling may be a cost-effective means of improving cardiovascular disease prevention.