Sodium Reduction, Metabolomic Profiling, and Cardiovascular Disease Risk in Untreated Black Hypertensives

Abstract

Dietary sodium restriction has multiple beneficial effects on cardiovascular health. The underlying mechanisms are not fully understood, and the roles of metabolomics have been rarely studied. We aimed to test the hypothesis that the reduction in dietary sodium intake would induce changes in metabolomic profiling among black hypertensives, and the changes would be associated with reduced blood pressure (BP) and improved skin capillary density. A total of 64 untreated black hypertensives were included from a randomized, double-blind, placebo-controlled cross-over trial of sodium reduction. The participants were given either 9 slow sodium tablets (10 mmol sodium per tablet) or placebo tablets daily for 6 weeks, they then crossed over to receive the other tablets for another 6 weeks, while on reduced sodium diet aiming at achieving daily sodium intake around 2.0 g. Untargeted metabolomic profiling was performed in paired serum samples, which were collected at the end of each period, so were BP and capillary density. Mixed-effects models were used. There were 34 metabolites identified with raw P's<0.05. Among those, 2 metabolites including β-hydroxyisovalerate and methionine sulfone were significantly increased with sodium reduction (false discovery rate =0.006 and 0.099, respectively). Increased β-hydroxyisovalerate was associated with reduced office systolic BP and ambulatory daytime systolic BP, whereas increased methionine sulfone was associated with reduced 24-hour diastolic BP, ambulatory nighttime diastolic BP, and increased skin capillary density. Our results suggest that dietary sodium reduction increases the circulating levels of β-hydroxyisovalerate and methionine sulfone. Further studies are warranted. Clinical Trial Registration- URL: http://www.clinicaltrials.gov . Unique identifier: NCT00152074.

Keywords: blood pressure; hypertension; metabolomics; methionine.

Conflict of interest statement

Disclosures

None.

Figures

Figure 1.. Plot of −log10Ps for the metabolomic profiles in response to the sodium reduction.

Ps were calculated based on the mixed effects models adjusted for age, sex and BMI as confounding variables. Associations with raw ps<0.01 are labeled with chemical names.