TY - JOUR
T1 - Sex differences in associations of plasma metabolites with blood pressure and heart rate variability
T2 - The HELIUS study
AU - Verhaar, Barbara J. H.
AU - Mosterd, Charlotte M.
AU - Collard, Didier
AU - Galenkamp, Henrike
AU - Muller, Majon
AU - Rampanelli, Elena
AU - van Raalte, Daniël H.
AU - Nieuwdorp, Max
AU - van den Born, Bert-Jan H.
N1 - Funding Information: BV is appointed on an Amsterdam Cardiovascular Sciences grant [ ACSPhD2019P003 ]. ER is supported by a Dutch Kidney Foundation Innovation grant and a TKI-PP Health Holland grant. MN is supported by a TransAtlantic Networks of Excellence Program grant ( 33.17CVD01 ) from the Fondation Leducq and a personal ZonMw-VICI grant 2020 [0 9150182010020 ]. Funding Information: The Academic Medical Center (AMC) of Amsterdam and the Public Health Service of Amsterdam (GGD) provided core financial support for HELIUS. The HELIUS study is also funded by research grants of the Dutch Heart Foundation [Hartstichting; 2010T084], the Netherlands Organization for Health Research and Development [ZonMw; 200500003], the European Integration Fund [EIF; 2013EIF013] and the European Union [Seventh Framework Programme , FP-7; 278901]. Funding Information: The Academic Medical Center (AMC) of Amsterdam and the Public Health Service of Amsterdam (GGD) provided core financial support for HELIUS. The HELIUS study is also funded by research grants of the Dutch Heart Foundation [Hartstichting; 2010T084], the Netherlands Organization for Health Research and Development [ZonMw; 200500003], the European Integration Fund [EIF; 2013EIF013] and the European Union [Seventh Framework Programme, FP-7; 278901].BV is appointed on an Amsterdam Cardiovascular Sciences grant [ACSPhD2019P003]. ER is supported by a Dutch Kidney Foundation Innovation grant and a TKI-PP Health Holland grant. MN is supported by a TransAtlantic Networks of Excellence Program grant (33.17CVD01) from the Fondation Leducq and a personal ZonMw-VICI grant 2020 [09150182010020].We would like to thank the AMC Biobank for their support with sample storage and the participants, research nurses and HELIUS staff for their help in data collection. Publisher Copyright: © 2023 The Authors
PY - 2023/11
Y1 - 2023/11
N2 - Background 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.
AB - Background 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.
KW - Blood pressure
KW - Heart rate variability
KW - Hypertension
KW - Metabolomics
KW - Sex differences
UR - http://www.scopus.com/inward/record.url?scp=85161068296&partnerID=8YFLogxK
U2 - https://doi.org/10.1016/j.atherosclerosis.2023.05.016
DO - https://doi.org/10.1016/j.atherosclerosis.2023.05.016
M3 - Article
C2 - 37286456
SN - 0021-9150
VL - 384
JO - Atherosclerosis
JF - Atherosclerosis
M1 - 117147
ER -