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

TitleMetabolomics and incident hypertension among blacks: the atherosclerosis risk in communities study.
Publication TypeJournal Article
Year of Publication2013
AuthorsZheng, Y, Yu, B, Alexander, D, Mosley, TH, Heiss, G, Nettleton, JA, Boerwinkle, E
Date Published2013 Aug
KeywordsAfrican Continental Ancestry Group, Atherosclerosis, Female, High-Throughput Screening Assays, Humans, Hypertension, Male, Metabolomics, Middle Aged, Principal Component Analysis, Risk Factors

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.

Alternate JournalHypertension
PubMed ID23774226
PubMed Central IDPMC3789066
Grant ListHHSN268201100012C / HL / NHLBI NIH HHS / United States
HHSN268201100009I / HL / NHLBI NIH HHS / United States
HHSN268201100010C / HL / NHLBI NIH HHS / United States
HHSN268201100008C / HL / NHLBI NIH HHS / United States
HHSN268201100005G / HL / NHLBI NIH HHS / United States
HHSN268201100008I / HL / NHLBI NIH HHS / United States
HHSN268201100005C / / PHS HHS / United States
HHSN268201100007C / HL / NHLBI NIH HHS / United States
HHSN268201100009C / / PHS HHS / United States
3U01HG004402-02S1 / HG / NHGRI NIH HHS / United States
HHSN268201100011I / HL / NHLBI NIH HHS / United States
HHSN268201100011C / HL / NHLBI NIH HHS / United States
U01 HG004402 / HG / NHGRI NIH HHS / United States
HHSN268201100010C / / PHS HHS / United States
HHSN268201100006C / HL / NHLBI NIH HHS / United States
HHSN268201100008C / / PHS HHS / United States
HHSN268201100005I / HL / NHLBI NIH HHS / United States
HHSN268201100007C / / PHS HHS / United States
HHSN268201100009C / HL / NHLBI NIH HHS / United States
HHSN268201100011C / / PHS HHS / United States
HHSN268201100005C / HL / NHLBI NIH HHS / United States
HHSN268201100007I / HL / NHLBI NIH HHS / United States
K01 DK082729 / DK / NIDDK NIH HHS / United States
HHSN268201100006C / / PHS HHS / United States

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