Circulating short-chain fatty acids in hypertension: a reflection of various hypertensive phenotypes

Hypertension is the most common chronic condition globally, contributing to an increased risk of cardiovascular disease and premature death. Despite advances in treatment options, approximately 10% of patients have resistant hypertension, characterized by elevated blood pressure that does not respond to treatment. The gut microbiome is now increasingly recognized to play a role in the development and pathogenesis of several diseases, including hypertension, although the exact mechanisms remain unclear.The aim of the present study was to investigate circulating levels of short-chain fatty acids, metabolites produced by gut bacteria, in essential ( n = 168) and resistant hypertensive ( n = 27) patients, compared with healthy controls ( n = 38).Serum acetate was significantly lower in the resistant hypertensive population, compared with both the normotensive controls and those with essential hypertension (748 ± 89 versus 1335 ± 61 and 1171 ± 22 nmol/ml, P < 0.0001). Acetate was also significantly lower in treated versus untreated hypertensive patients or controls (1112 ± 27 versus 1228 ± 40 and 1327 ± 63 nmol/l, P < 0.01), with this finding more pronounced with increasing number of antihypertensive therapies. In contrast, propionate was lower and butyrate significantly higher in those with essential hypertension compared with controls (propionate: 25.2 ± 7.5 versus 58.6 ± 7.6 nmol/ml, P < 0.0001; butyrate: 46.5 ± 3.5 versus 14.7 ± 9.9 nmol/ml, P < 0.01). A novel and perhaps clinically relevant observation was the significant difference in acetate and propionate levels between patients taking ACE inhibitors or angiotensin-receptor blockers.The present study has highlighted differences in circulating short-chain fatty acids in different hypertensive phenotypes and a possible influence of drug number and class. Although further research is necessary, this may represent a novel therapeutic target, particularly in patients with resistant hypertension.