A Nested Case-Control Study of Association between Metabolome and Hypertension Risk

Abstract

We aimed to explore novel small metabolites that associated with hypertension risk in a population-based nested case-control study. Among 460 individuals with optimal blood pressure (<120/80 mmHg) at baseline, 55 progressed to hypertension during 5 years of follow-up. Twenty-nine cases of incident hypertension and 29 controls, matched for age, sex, and baseline systolic blood pressure, were included in this study. Serum metabolites were measured by gas chromatography-tandem mass spectrometry. t-test and logistic regression analysis were applied to investigate the association between metabolites and incident hypertension. Among the 241 metabolites identified in this study, baseline levels of 26 metabolites were significantly different between hypertension and control groups. After adjusting for body mass index, smoking, and drinking, 16 out of the 26 metabolites were still associated with hypertension risk including four amino acids. Amino acids were negatively associated with risk of future hypertension, with odds ratio (OR) ranging from 0.33 to 0.53. Two of these amino acids were essential amino acids including threonine and phenylalanine. Higher level of lyxose, a fermentation product of gut microbes, was associated with higher risk of hypertension. Our study identified multiple metabolites that associated with hypertension risk. These findings implied that low amino acid levels and gut microbiome might play an important role in the pathogenesis of hypertension.

Sleep fragmentation increases blood pressure and is associated with alterations in the gut microbiome and fecal metabolome in rats

“…Therefore, in addition to characterization of the gut microbiome, we analyzed the fecal metabolome in a subset of rats before SF (baseline day −1 ) and on intervention days 27 and 34 (7 days after SF was stopped). Higher fecal levels of SCFAs have been correlated with adiposity and hypertension in human studies ( 22 , 39 , 43 ) and high-salt diet in animal research ( 12 ). We observed increased succinate metabolite levels and increased grouped putative succinate-producing bacteria during recovery/rest in the SF rats, which corresponded to a twofold increase in Faecalibacterium sp.…”

“…The metabolites of bacterial carbohydrate fermentation in the colon affect blood pressure ( 31 , 68 , 78 ), suggesting an important role for the gut microbiota in cardiovascular health and disease ( 22 , 39 ). Short chain fatty acids (SCFAs), which include butyrate, propionate, and acetate, are produced by fermentative intestinal microbes, and these metabolites enter the circulation via the portal vein ( 15 ).…”

Metabolomics profiling in hypertension and blood pressure regulation: a review

“…a YDYHS and YYDS -"Yin-deficiency and Yang-hyperactivity syndrome" and "Yin-Yang deficiency syndrome" respectively pressure (120/80 mmHg) at baseline was conducted to explore metabolites that are associated with hypertension [14]. A total of 241 metabolites were detected with baseline levels of 26 of them being significantly different for the hypertension group compared with the control.…”

A Bayesian approach to Mendelian randomization with multiple pleiotropic variants

“…Many of these studies compared small groups of individuals with large differences in adiposity, and it remains unclear whether those deviations are also observed in the general population. One putative molecular signature of obesity is the α -aminoacid phenylalanine (PHE) (Jones, 1996; Droyvold and others , 2005; Shah and others , 2012; Moore and others , 2014; Wuertz and others , 2015; Hao and others , 2016). Recent research also highlights PHE as a putative mediator of the causal effect of body fat on blood pressure.…”