Metabolite Profiling and Cardiovascular Event Risk: A Prospective Study of Three Population-Based Cohorts | Journal Scan

Study Questions:

Using a serum nuclear magnetic resonance (NMR) metabolite profiling, what circulating biomarkers are predictive of cardiovascular risk during long-term follow-up?


This observational study examined metabolite associations with incident cardiovascular events. Biomarker discovery was conducted in the FINRISK study, a general population survey conducted to monitor the health of the Finnish population among persons aged 25-74 years at recruitment. For those who had serum samples collected in 1997 available, metabolic profiling by high-throughput NMR was measured in 2012. The main endpoint was the first incidence of a major cardiovascular event during follow-up. Metabolic biomarker candidates were replicated in two additional population-based cohorts; fasting serum samples from the Southall and Brent Revisited Study (SABRE) and the British Women’s Heart and Health Study (BWHHS) were profiled with the same NMR platform as employed in FINRISK.


The discovery cohort from the FINRISK study included 7,256 individuals. From analysis of 68 lipids and metabolites, 33 measures were associated with incident cardiovascular events in analyses adjusted for age, sex, blood pressure, smoking, diabetes, and medication (at p < 0.0007). After adjustment for lipid measures, four metabolites were predictive of future cardiovascular events. Higher phenylalanine and monounsaturated fatty acid (MUFA)% levels were associated with increased cardiovascular risk; whereas higher concentrations of omega-6 fatty acids, total concentration of polyunsaturated fat, and docosahexaenoic acid (DHA) were associated with lower risk.


The authors concluded that in large prospective cohorts, phenylalanine and monounsaturated fats were predictive of cardiovascular risk.


This is an important, thoughtfully conducted analysis of data from three large prospective cohorts. As the authors indicate, the blood levels of MUFA and phenylalanine have not been previously associated with risk for incident cardiovascular disease. Although much study will be necessary to understand the biological pathways through which these metabolites are associated with cardiovascular risk and to establish the clinical value of these biomarkers, the authors do draw attention to the benefits of metabolic profiling for biomarker discovery.

Clinical Topics: Dyslipidemia, Lipid Metabolism, Nonstatins, Statins

Keywords: Biological Markers, Cardiovascular Diseases, Docosahexaenoic Acids, Fatty Acids, Monounsaturated, Fatty Acids, Omega-6, Phenylalanine, Lipids, Magnetic Resonance Spectroscopy, Prospective Studies, Risk

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