title: Sex differences in vascular dysfunction and cardiovascular outcomes: The cardiac, endothelial function, and arterial stiffness in ESRD (CERES) study.
abstract: 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.
  
  
  
  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.
  
  
  
  Women had higher arterial wave reflection (Mean, SD AIx75 30% ± 9% for women vs. 21% ± 10% for men; P < 0.001) and worse microvascular function (VTI 55 ± 30 cm for women vs. 70 ± 27 cm for men; P = 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 = 0.03), and further adjustment for arterial wave reflection attenuated this risk.
  
  
  
  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.
authors.affiliation: Division of Nephrology, San Francisco VA Medical Center, University of California, San Francisco, California, USA.
authors.forename: Isabella
authors.initials: I
authors.lastname: Guajardo
authors.affiliation: Division of Nephrology, San Francisco VA Medical Center, University of California, San Francisco, California, USA.
authors.forename: Amrita
authors.initials: A
authors.lastname: Ayer
authors.affiliation: Division of Nephrology, San Francisco VA Medical Center, University of California, San Francisco, California, USA.
authors.forename: Alexander D
authors.initials: AD
authors.lastname: Johnson
authors.affiliation: Division of Cardiology, Center for Vascular Excellence, San Francisco General Hospital, University of California, San Francisco, California, USA.
authors.forename: Peter
authors.initials: P
authors.lastname: Ganz
authors.affiliation: Division of Cardiology, Center for Vascular Excellence, San Francisco General Hospital, University of California, San Francisco, California, USA.
authors.forename: Claire
authors.initials: C
authors.lastname: Mills
authors.affiliation: Division of Cardiology, Center for Vascular Excellence, San Francisco General Hospital, University of California, San Francisco, California, USA.
authors.forename: Catherine
authors.initials: C
authors.lastname: Donovan
authors.affiliation: Division of Nephrology, San Francisco VA Medical Center, University of California, San Francisco, California, USA.
authors.forename: Rebecca
authors.initials: R
authors.lastname: Scherzer
authors.affiliation: Division of Cardiology, Department of Medicine, Northwestern University Feinberg School of Medicine, Chicago, Illinois, USA.
authors.forename: Sanjiv J
authors.initials: SJ
authors.lastname: Shah
authors.affiliation: Division of Nephrology, Kidney Health Research Collaborative, San Francisco VA Medical Center/University of California, San Francisco, California, USA.
authors.forename: Carmen A
authors.initials: CA
authors.lastname: Peralta
authors.affiliation: Division of Nephrology, San Francisco VA Medical Center, University of California, San Francisco, California, USA.
authors.forename: Ruth F
authors.initials: RF
authors.lastname: Dubin
mesh_terms: D002318:Cardiovascular Diseases / Q000453:epidemiology* / Q000473:pathology; D004730:Endothelium, Vascular / Q000503:physiopathology*; D005260:Female; D006801:Humans; D007676:Kidney Failure, Chronic / Q000503:physiopathology*; D008297:Male; D008875:Middle Aged; D059289:Vascular Stiffness / Q000502:physiology*
keywords: Arterial stiffness; cardiovascular; chronic hemodialysis; end-stage renal disease