Association of Carotid Intima-Medial Thickness and Indices of Arterial Stiffness With Cardiovascular Disease Outcomes in CKD

Background Indices of arterial structure and stiffness are proposed as surrogate markers of cardiovascular disease in patients with chronic kidney disease (CKD), but no study examined multiple markers in the same population. Study Design Prospective observational study. Setting & Participants 315 subjects with stages 4 to 5 CKD, aged 24 to 79 years (mean age, 56.6 ± 13.6 [SD] years), enrolled in the Atherosclerosis and Folic Acid Supplementation Trial. Predictors Carotid arterial intima-medial thickness (IMT; n = 315) and indices of arterial stiffness (n = 207), including aortofemoral pulse wave velocity (PWV[a-f]), systemic arterial compliance (SAC), and carotid-derived augmentation index. Outcomes The primary outcome was a composite of all fatal and nonfatal cardiovascular events. Results During follow-up (median, 3.6 years), 95 cardiovascular events occurred. On Cox proportional-hazard modeling, mean maximum IMT, PWV(a-f), and SAC were predictive of the composite clinical end point of all cardiovascular events, but carotid-derived augmentation index was not (hazard ratio [HR] for every 0.01-mm increase in IMT, 1.09; P = 0.001; 95% confidence interval [CI], 1.03 to 1.14; HR for every 1-m/s increase in PWV(a-f), 1.18; P < 0.001; 95% CI, 1.12 to 1.25; HR for every 0.01-U/mm Hg decrease in SAC, 0.98; P = 0.01; 95% CI, 0.97 to 0.99). After adjustment for age, sex, blood pressure, diabetes, past cardiovascular disease, cholesterol level, and smoking, PWV(a-f) remained a significant independent predictor of cardiovascular events (adjusted HR, 1.12; P = 0.001; 95% CI, 1.05 to 1.20), but IMT and SAC did not. Limitations Study power to analyze differences between predialysis and dialysis stages of CKD. Conclusions PWV(a-f) is the only arterial index independently associated with cardiovascular outcome in patients with CKD.