Associations of microvascular dysfunction with cardiovascular outcomes: The cardiac, endothelial function and arterial stiffness in ESRD (CERES) cohort

Hemodial Int. 2019 Jan;23(1):58-68. doi: 10.1111/hdi.12675. Epub 2019 Feb 6.

Abstract

Introduction: Patients with end-stage renal disease (ESRD) have reduced endothelial function, but whether macro- and microvascular endothelial function correlate with baseline risk factors and cardiovascular outcomes in this population is not well understood.

Methods: Among 146 participants of the Cardiac, Endothelial Function and Arterial Stiffness in ESRD (CERES) study, we evaluated macro- and microvascular endothelial dysfunction as flow-mediated dilation (FMD) and velocity time integral (VTI), respectively. We examined cross-sectional correlations of baseline characteristics, inflammatory and cardiac markers with FMD and VTI. We followed participants for the composite outcome of cardiovascular hospitalization or all-cause death over fourteen months. Cox survival analyses were adjusted for demographics, comorbidities, medications, systolic blood pressure, inflammation, high-sensitivity troponin T (hs-TnT), and N-terminal pro B-type natriuretic peptide (NT-proBNP).

Findings: Impaired VTI was associated with older age and Black race (P < 0.05), as well as female gender, atherosclerosis, and hemodialysis (as opposed to peritoneal dialysis) (P < 0.2). Myocardial injury, measured as hs-TnT, inflammatory markers and NT-proBNP correlated with impaired VTI. In unadjusted analyses, VTI was significantly associated with the composite outcome (HR per SD VTI 0.65 [95%CI 0.45, 0.95]), but FMD was not (HR per SD FMD 0.97 [95%CI 0.69, 1.4]). When VTI was calculated as the ratio of (hyperemic VTI-baseline VTI)/baseline VTI, its association with the outcome persisted after multivariable adjustment.

Discussion: Microvascular function was associated with higher rates of cardiovascular hospitalizations and all-cause mortality among individuals with ESRD on dialysis. Further research is needed to learn whether novel therapies that target microvascular endothelial function could improve outcomes in this high-risk population.

Keywords: Cardiovascular; end-stage renal disease; endothelial function.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Cardiovascular Diseases / etiology*
  • Cohort Studies
  • Cross-Sectional Studies
  • Female
  • Humans
  • Kidney Failure, Chronic / complications*
  • Kidney Failure, Chronic / therapy
  • Male
  • Middle Aged
  • Renal Dialysis / methods*
  • Risk Factors
  • Vascular Stiffness / physiology*