Abstract Body: Background: Whilst there is emerging evidence that the associations of the gut microbiota (GM) with hypertension differ between sexes, it remains uncertain whether the GM 1) is altered with antihypertensive-use, 2) can predict blood pressure (BP) trajectories, and 3) whether these associations are also sex-dependent. We therefore aimed to determine the sex-dependent associations of the GM with baseline hypertensive state in untreated versus treated participants and BP changes over time.
Methods: A total of 451 community-dwelling middle-aged Hong Kong Chinese without symptomatic cardiovascular diseases were recruited (50% men, 14% on antihypertensive agents, mean age, 54.6±6.5 years). Shotgun metagenomic sequencing of stool samples and 24-hour ambulatory blood pressure monitoring (ABPM) were performed. The 24hr-ABPM was repeated on 139 returned subjects after 4 years. Statistical analysis was conducted with 4 covariate models that include age, sex, menopause status, body mass index (BMI), smoking, fasting glucose, triglyceride, cholesterol, sodium intake, and fatty liver status.
Results: Amongst the 389/451 subjects not on antihypertensive agents, 167/389 (42.9%) had newly diagnosed hypertension at baseline. Females drove the significantly different b-diversity of the GM composition (p<0.01) between the normotensives and hypertensives in the baseline study. Multiple GM species were significantly associated with hypertension. In sex stratified analysis, Faecalimonas umbilicate was significantly enriched in hypertensive females while Roseburia sp Am16-25 and Eubacterium ramulus were enriched in hypertensive males (all p<0.05-0.01). When comparing the 62 treated and 167 nontreated hypertensive subjects, the GM abundance, a-, and b-diversity were not significantly different. However, there were significant GM species associated with the use of antihypertensive medication. Notably, Lachnospiraceae bacterium and Flavonifractor plautii were significantly enriched in treated and untreated individuals, respectively (all p<0.05-0.001). During a mean follow up of 51.2±4.5 months, 73.2% of the 71 untreated subjects remained normotensive and were associated with enriched Bacteroides uniformis in their baseline metagenomic data under models adjusted for age, sex, and BMI.
Conclusion: The GM displayed sex-dependent associations with hypertension within untreated and treated individuals and can potentially predict BP trajectory changes within a Chinese population.