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Identification of Serum Metabolites Associated With Incident Hypertension in the European Prospective Investigation
Stefan Dietrich1, Anna Floegel2, Cornelia Weikert2
1From the Department of Epidemiology, German Institute of Human Nutrition, Potsdam-Rehbruecke (DIfE), Nuthetal, Germany (S.D., A.F., H.B., D.D.); Department of Food Safety, Federal Institute for Risk Assessment, Berlin, Germany (C.W.); Institute for Social Medicine, Epidemiology, and Health Economics, Charité University Medical Center, Berlin, Germany (C.W.); DZHK (German Center for Cardiovascular Research), Partner Site Berlin, Germany (C.W., T.P.); Molecular Epidemiology Group, Max Delbrück Center for Molecular Medicine (MDC) Berlin-Buch, Berlin, Germany (T.P.); Charité-Universiätsmedizin Berlin, Berlin, Germany (T.P.); and AOK Research Institute (WIdO), AOK Bundesverband, Berlin, Germany (D.D.). stefan.dietrich@dife.de.
Abstract:
Metabolomics is a promising tool to gain new insights into early metabolic alterations preceding the development of hypertension in humans. We therefore aimed to identify metabolites associated with incident hypertension using measured data of serum metabolites of the European Prospective Investigation Into Cancer and Nutrition (EPIC)-Potsdam study. Targeted metabolic profiling was conducted on serum blood samples of a randomly drawn EPIC-Potsdam subcohort consisting of 135 cases and 981 noncases of incident hypertension, all of them being free of hypertension and not on antihypertensive therapy at the time of blood sampling. Mean follow-up was 9.9 years. A validated set of 127 metabolites was statistically analyzed with a random survival forest backward selection algorithm to identify predictive metabolites of incident hypertension taking into account important epidemiological hypertension risk markers. Six metabolites were identified to be most predictive for the development of hypertension. Higher concentrations of serine, glycine, and acyl-alkyl-phosphatidylcholines C42:4 and C44:3 tended to be associated with higher and diacyl-phosphatidylcholines C38:4 and C38:3 with lower predicted 10-year hypertension-free survival, although visualization by partial plots revealed some nonlinearity in the above associations. The identified metabolites improved prediction of incident hypertension when used together with known risk markers of hypertension. In conclusion, these findings indicate that metabolic alterations occur early in the development of hypertension. However, these alterations are confined to a few members of the amino acid or phosphatidylcholine metabolism, respectively.