Endothelial function and cardiovascular events in chronic kidney disease

BackgroundAs patients with chronic kidney disease (CKD) are at high risk of developing coronary artery disease (CAD), it is important to stratify their cardiovascular risk. We investigated whether peripheral endothelial dysfunction is associated with the presence of CAD in patients with CKD and is a predictor of cardiovascular events.MethodsWe enrolled 383 CKD patients with at least one coronary risk factor. Peripheral endothelial function was assessed by reactive hyperemia peripheral arterial tonometry index (RHI). The presence of CAD was determined by coronary angiography. Cardiovascular events were assessed during follow-up.ResultsLn-RHI was significantly lower in risk factor-matched CKD patients (n = 323) than risk factor-matched non-CKD patients (n = 323) (0.527 ± 0.192 vs. 0.580 ± 0.218, p = 0.001). In CKD patients (n = 383), Ln-RHI was significantly lower in CAD (0.499 ± 0.183, n = 262) than non-CAD (0.582 ± 0.206, n = 121) (p < 0.001) patients. Multivariate logistic regression analysis identified Ln-RHI as an independent factor associated with the presence of CAD (p = 0.001). During a mean follow-up period of 30 months, 90 cardiovascular events were recorded in CKD patients. Multivariate Cox hazard analysis identified low-Ln-RHI as an independent predictor of cardiovascular events (hazard ratio = 2.70, 95% confidence interval = 1.62-4.51, p < 0.001). The predictive value of combined Ln-RHI and Framingham risk score (FRS) was evaluated by net reclassification index (NRI) and C-statistics, which showed significant improvement (NRI = 22%, p < 0.001) (C-statistics: FRS = 0.49, FRS + Ln-RHI = 0.62, p = 0.005).ConclusionsEndothelial function was significantly impaired in CKD patients and correlated with the presence of CAD. Severe endothelial dysfunction was an independent and incremental predictor of cardiovascular events in CKD.