Sex differences in vascular dysfunction and cardiovascular outcomes: The cardiac, endothelial function, and arterial stiffness in ESRD (CERES) study

Abstract

Introduction: Recent studies suggest that women with end-stage renal disease (ESRD) may have higher rates of mortality than men, but it is unknown whether sex differences in vascular function explain this disparity. The cardiac, endothelial function, and arterial stiffness in ESRD (CERES) study is an ongoing, prospective observational study designed to investigate vascular function, myocardial injury, and cardiovascular outcomes in ESRD.Methods: Among 200 CERES participants (34% women), we evaluated arterial wave reflections as augmentation index normalized to a heart rate of 75 (AIx75), arterial stiffness as pulse wave velocity, and macro-and microvascular endothelial dysfunction as flow-mediated dilation and velocity time integral (VTI). Over a median of 14 months, participants were followed for the composite outcome of cardiovascular hospitalization or all-cause death.Findings: Women had higher arterial wave reflection (Mean, SD AIx75 30% 6 9% for women vs. 21% 6 10% for men; P < 0.001) and worse microvascular function (VTI 55 6 30 cm for women vs. 70 6 27 cm for men; P 5 0.007). After multivariable adjustment, female sex remained associated with a 0.5-SD higher AIx75 (95% CI [0.01, 0.9]) and 0.3-SD lower VTI (95%CI [0.1, 0.7]). Women experienced higher adjusted rates of the composite outcome (HR 2.5; 95%CI [1.1, 5.6]; P 5 0.03), and further adjustment for arterial wave reflection attenuated this risk. Discussion: Vascular dysfunction may partly explain the association of female sex with higher cardiovascular risk and mortality in patients with ESRD. Further studies are needed to explore whether sex differences in vascular function predict long-term outcomes, and whether hormonal or inflammatory factors explain these associations.

Differential biomechanics in resistance arteries of male compared with female Dahl hypertensive rats

“…Arterial stiffness and the resultant hemodynamic changes are now considered to be predictors of increase in morbidity and mortality; vascular stiffness is positively associated with increased risk of cardiovascular disease, including hypertension, myocardial infarction, heart failure, stroke [38][39][40][41][42]. Moreover, differential characteristics of the development of arterial stiffness between men and women appear to involve sex-specific mechanisms [43][44][45][46][47].…”

Modulation of endothelium function by fatty acids

“…Endothelial dysfunction is a significant feature in atherosclerosis, hypertension, diabetes, and cardiovascular disorders [ 7 , 23 ]. Defective endothelium results in leukocyte adhesion, activation of platelets, pro-oxidation of mitogens, dysregulated synthesis of PGI 2 , NO, and endothelium-derived hyperpolarizing factor (EDHF), and other vasoconstriction factors such as Ang II and PGH 2 , resulting in atherosclerosis and thrombosis [ 24 ].…”

Relationship between sex and cardiovascular mortality in chronic kidney disease: A systematic review and meta-analysis

“…myocardial infarction; MI) and all-cause cardiovascular mortality is higher in women than men [ 9 ]. Moreover, more recent data from 2018 suggests that women with CKD have a higher annual risk of cardiovascular hospitalisations and death than men [ 10 ]. Thus the collective evidence regarding the role of sex on cardiovascular mortality among CKD patients is inconsistent and inconclusive.…”