title: Metabolomics and incident hypertension among blacks: the atherosclerosis risk in communities study.
abstract: 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.
authors.affiliation: Division of Epidemiology, Human Genetics and Environmental Sciences, University of Texas Health Science Center at Houston, TX, USA.
authors.forename: Yan
authors.initials: Y
authors.lastname: Zheng
authors.forename: Bing
authors.initials: B
authors.lastname: Yu
authors.forename: Danny
authors.initials: D
authors.lastname: Alexander
authors.forename: Thomas H
authors.initials: TH
authors.lastname: Mosley
authors.forename: Gerardo
authors.initials: G
authors.lastname: Heiss
authors.forename: Jennifer A
authors.initials: JA
authors.lastname: Nettleton
authors.forename: Eric
authors.initials: E
authors.lastname: Boerwinkle
mesh_terms: D050197:Atherosclerosis / Q000209:etiology*; D044383:Black People; D005260:Female; D057166:High-Throughput Screening Assays; D006801:Humans; D006973:Hypertension / Q000208:ethnology / Q000209:etiology*; D008297:Male; D055432:Metabolomics; D008875:Middle Aged; D025341:Principal Component Analysis; D012307:Risk Factors
keywords: blacks; hypertension; metabolomics; risk factors