Do associations with C-Reactive protein and extent of coronary artery disease account for the increased cardiovascular risk of renal insufficiency?

Objectives We sought to determine whether the association of higher C-reactive protein levels (CRP) and more extensive coronary artery disease (CAD) explains the high cardiovascular risk of renal insufficiency (RI). Background Renal insufficiency and renal failure (RF) have been associated with increased cardiovascular risk in several studies, and it has been suggested that this association may be due to higher CRP levels and greater extent of CAD. To what extent CRP or severity of CAD explains this risk is uncertain. Methods A total of 1,484 patients without myocardial infarction (MI) undergoing angiography were entered and followed for 3.0 ± 1.6 years; RI and RF were defined as estimated glomerular filtration rates (GFR) of 30 to 60 and <30 ml/min; CRP was measured by immunoassay and ≥ 1.0 mg/dl defined as elevated. A CAD score was determined by extent and severity of angiographic disease. Multivariate Cox regressions were performed using seven standard risk factors, homocysteine, GFR, CRP, and CAD score. Results Mean age was 64 years, and 67% were men; CAD was absent in 24%, mild in 11%, and severe (≥70% stenosis) in 60%; CRP and CAD scores increased with declining renal function (median CRP: 1.2, 1.4, 2.2 mg/dl, p < 0.001 and CAD score: 8.1, 8.7, 9.3, p = 0.008 for no-RI, RI, and RF). During follow-up, 208 patients (15%) died or had nonfatal MI. Unadjusted hazard ratio (HR) for death/MI was 2.3 for RI and 5.1 for RF (p < 0.0001). Adjustment for CRP (HR, 2.2, 4.5), CAD score (HR, 2.1, 5.1), and all other risk factors (HR, 1.7, 4.5) had minimal or modest impact on RI and RF risk; HR increased to 5.4 (p < 0.001) for presence of both elevated CRP and RI/RF. Conclusions Renal insufficiency, CRP, and angiographic CAD, although correlated, are largely independent predictors of cardiovascular risk, suggesting the importance of both inflammation and as yet undefined RI-related risk factors.