Sex differences in associations of plasma metabolites with blood pressure and heart rate variability: The HELIUS study

Elsevier

Available online 28 May 2023

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Sphingomyelins and conjugated bile acids were more predictive of blood pressure in men, while metabolites from acylcarnitine and catecholamine pathways were better predictors in women.

Several metabolites were associated with gut microbiota composition, providing potential targets for intervention.

Our analyses underline that plasma metabolites could have sex-dependent effects on blood pressure and are often only associated with blood pressure in either men or women. Therefore, future studies on the role of plasma metabolites in hypertension should consider sex stratification.

AbstractBackground and aims

Since plasma metabolites can modulate blood pressure (BP) and vary between men and women, we examined sex differences in plasma metabolite profiles associated with BP and sympathicovagal balance. Our secondary aim was to investigate associations between gut microbiota composition and plasma metabolites predictive of BP and heart rate variability (HRV).

Methods

From the HELIUS cohort, we included 196 women and 173 men. Office systolic BP and diastolic BP were recorded, and heart rate variability (HRV) and baroreceptor sensitivity (BRS) were calculated using finger photoplethysmography. Plasma metabolomics was measured using untargeted LC-MS/MS. Gut microbiota composition was determined using 16S sequencing. We used machine learning models to predict BP and HRV from metabolite profiles, and to predict metabolite levels from gut microbiota composition.

Results

In women, best predicting metabolites for systolic BP included dihomo-lineoylcarnitine, 4-hydroxyphenylacetateglutamine and vanillactate. In men, top predictors included sphingomyelins, N-formylmethionine and conjugated bile acids. Best predictors for HRV in men included phenylacetate and gentisate, which were associated with lower HRV in men but not in women. Several of these metabolites were associated with gut microbiota composition, including phenylacetate, multiple sphingomyelins and gentisate.

Conclusions

Plasma metabolite profiles are associated with BP in a sex-specific manner. Catecholamine derivatives were more important predictors for BP in women, while sphingomyelins were more important in men. Several metabolites were associated with gut microbiota composition, providing potential targets for intervention.

Keywords

Sex differences

Metabolomics

Blood pressure

Hypertension

Heart rate variability

© 2023 The Authors. Published by Elsevier B.V.

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