Predictors of fatal and nonfatal cardiovascular events in patients with type 2 diabetes mellitus, chronic kidney disease, and anemia: an analysis of the Trial to Reduce cardiovascular Events with Aranesp (darbepoetin-alfa) Therapy (TREAT)

Aims: This study aims to examine predictors of cardiovascular mortality and morbidity in patients with chronic kidney disease (CKD). Individuals with the triad of diabetes, CKD, and anemia represent a significant proportion of patients with cardiovascular disease and are at particularly high risk for adverse outcomes.

Methods and results: Using Cox proportional hazards models, we identified independent predictors of the composite of cardiovascular death, myocardial infarction, stroke, hospitalization for myocardial ischemia, or heart failure (HF) in 3,847 patients in the TREAT, 961 (25%) of whom experienced this outcome. The predictors (ranked by χ(2) value) were prior HF (hazard ratio [HR] 1.74, 95% CI 1.51-2.01), age (HR 1.03, 95% CI 1.02-1.04 per year), log urine protein/creatinine ratio (HR 1.19, 95% CI 1.13-1.26 per log unit ), C-reactive protein ≥6.6 mg/L (HR 1.44, 95% CI 1.23-1.69, compared with C-reactive protein ≤3.0 mg/L), and abnormal electrocardiogram (HR 1.42, 95% CI 1.21-1.66 ), all P < .0001. Addition of cardiac-derived biomarkers (subset of first 1,000 patients enrolled) significantly enhanced risk estimation, with N-terminal pro B-type natriuretic peptide becoming the highest ranked predictor of outcome (HR 1.30, 95% CI 1.15-1.46 per log unit, P < .001) and troponin T providing additional predictive information. These biomarkers improved risk classification in 17.8% (9.4%-26.2%) of patients.

Conclusion: In patients with diabetes, CKD, and anemia, cardiovascular risk is most strongly predicted by age, history of HF, C-reactive protein, urinary protein/creatinine ratio, abnormal electrocardiogram, and 2 specific cardiac biomarkers, serum N-terminal pro B-type natriuretic peptide and troponin T, which are elevated in many. These findings suggest ways to improve cardiovascular risk stratification of patients with predialysis CKD, support the concept of cardiorenal syndrome, and may help target therapy.