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

Abstract

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. 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). 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. 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.