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Hypertension. 2013 Aug;62(2):398-403. doi: 10.1161/HYPERTENSIONAHA.113.01166. Epub 2013 Jun 17.

Metabolomics and incident hypertension among blacks: the atherosclerosis risk in communities study.

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  • 1Division of Epidemiology, Human Genetics and Environmental Sciences, University of Texas Health Science Center at Houston, TX, USA.


Development of hypertension is influenced by genes, environmental effects, and their interactions, and the human metabolome is a measurable manifestation of gene-environment interaction. We explored the metabolomic antecedents of developing incident hypertension in a sample of blacks, a population with a high prevalence of hypertension and its comorbidities. We examined 896 black normotensives (565 women; aged, 45-64 years) from the Atherosclerosis Risk in Communities study, whose metabolome was measured in serum collected at the baseline examination and analyzed by high-throughput methods. The analyses presented here focus on 204 stably measured metabolites during a period of 4 to 6 weeks. Weibull parametric models considering interval censored data were used to assess the hazard ratio for incident hypertension. We used a modified Bonferroni correction accounting for the correlations among metabolites to define a threshold for statistical significance (P<3.9 × 10(-4)). During 10 years of follow-up, 38% of baseline normotensives developed hypertension (n=344). With adjustment for traditional risk factors and estimated glomerular filtration rate, each +1SD difference in baseline 4-hydroxyhippurate, a product of gut microbial fermentation, was associated with 17% higher risk of hypertension (P=2.5 × 10(-4)), which remained significant after adjusting for both baseline systolic and diastolic blood pressure (P=3.8 × 10(-4)). After principal component analyses, a sex steroids pattern was significantly associated with risk of incident hypertension (highest versus lowest quintile hazard ratio, 1.72; 95% confidence interval, 1.05-2.82; P for trend, 0.03), and stratified analyses suggested that this association was consistent in both sexes. Metabolomic analyses identify novel pathways in the pathogenesis of hypertension.


blacks; hypertension; metabolomics; risk factors

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