Abstract MP48: Sex Difference, Circulating Short-chain Fatty Acids, Dietary Sodium Reduction in Untreated Hypertensives: A Randomized, Double-Blind, Placebo-Controlled Trial

Abstract

Introduction: Short-chain fatty acids (SCFAs) are products from the fermentative activity of gut bacteria and almost all circulating SCFAs are microbial in origin. Emerging evidence suggests that circulating SCFAs play a role in blood pressure (BP) control through the host receptors. Animal studies demonstrate that high salt diet modulates the gut microbiome and SCFAs. Moreover, gut microbiome contributes to sex differences in BP regulation. Hypothesis: We tested the hypothesis that the modest sodium reduction would alter circulating SCFAs among untreated hypertensives, and the changes in SCFAs would be associated with reduced blood pressure (BP) and improved cardiovascular phenotypes. Moreover, there would be sex differences in circulating SCFA response to sodium reduction. Methods: A total of 145 subjects (42% blacks, 19% Asian, 34% females) were included from a completed randomized, double-blind, placebo-controlled crossover trial of sodium restriction with slow sodium or placebo, each for 6 weeks. Targeted circulating SCFA profiling was performed in paired serum samples, which were collected at the end of each period, so as all outcome measures. Two-level mixed-effects linear regression models were used to assess the differences in SCFAs between sodium and placebo tablets while incorporating repeated measured data and controlling for age, sex and BMI as confounding variables. We further tested whether the changes in the SCFAs were associated with the changes in BPs, and cardiovascular phenotypes using mixed-effects models. Results: Sodium reduction increased all 8 SCFAs, among which the increases in 2-methylbutyrate, butyrate, hexanoate, isobutyrate, and valerate were statistically significant ( p <0.05). The increased SCFAs were associated with decreased BP and improved capillary density. There were significant sex differences of SCFAs in response to sodium reduction ( p <0.05). When stratified by sex, the increases in butyrate, hexanoate, isobutyrate, isovalerate, and valerate were significant only in women ( p <0.05), but none were significantly changed in men ( p >0.05). In women, increased isobutyrate, isovalerate, and 2-methylbutyrate were inversely associated with reduced BPs ( p <0.05). Additionally, increased valerate was associated with decreased carotid-femoral pulse wave velocity (cf-PWV) ( p =0.04). Conclusions: Our results show that dietary sodium reduction increases SCFAs, suggesting that dietary sodium may influence the gut microbiome in humans given almost all SCFAs are microbial in origin. Moreover, increased circulating SCFAs are associated with decreased BPs, improved arterial compliance, and increased capillary density. The sex differences in SCFA response to dietary sodium reduction warrants further investigation.