Sex-Divergent Blood Pressure Associations With Multiorgan System Metabolic Stress.

Abstract

Background: Women experience excess cardiovascular risk compared with men in the setting of similar metabolic disease burden. We aimed to examine sex differences in the vascular response to various forms of metabolic stress.

Methods: We conducted an observational study of 4299 adult participants (52% women, aged 59±13 years) of the National Health and Nutrition Examination Survey 2017 to 2018 cohort and 110 225 adult outpatients (55% women, aged 64±16 years) from the Cedars-Sinai Medical Center in 2019. We used natural splines to examine the association of systemic and organ-specific measures of metabolic stress including body mass index, hemoglobin A1c, hepatic FIB-4 score, and CKD-EPI estimated glomerular filtration rate with systolic blood pressure (SBP). Piecewise linear models were generated using normal value thresholds (body mass index <25 kg/m², hemoglobin A1c <5.7%, FIB-4 <1.3, and estimated glomerular filtration rate ≥90 mL/min), which approximated observed spline break points. The primary outcome was an increase in SBP in association with increase in each metabolic measure.

Results: Women compared with men demonstrated larger magnitudes and an earlier onset of increase in SBP per increment increase across all metabolic stress measures. The slope of SBP increase per increment of each metabolic measure was greater for women than men particularly for metabolic measures within the normal range, with slope differences of 1.86 mm Hg per kg/m² of body mass index, 12.48 mm Hg per %hemoglobin A1c, 6.87 mm Hg per FIB-4 unit, and 0.44 mm Hg per mL/min decrement of estimated glomerular filtration rate in the National Health and Nutrition Examination Survey cohort (P difference <0.05 for all). Overall results were consistent in the Cedars-Sinai Medical Center cohort.

Conclusions: Women exhibited greater SBP alteration in the setting of multiple types of metabolic stress, particularly in periods representing the transition from metabolic health to disease. These findings suggest potential benefit of early metabolic health interventions as part of efforts to mitigate vascular risks in both women and men.