C-reactive protein as a predictor of total arteriosclerotic outcomes in type 2 diabetic nephropathy

The inflammatory marker C-reactive protein (CRP) has been found in most, but not all, prospective studies to be associated with future cardiovascular outcomes. However, CRP has not been tested in the high-cardiovascular risk population of type 2 diabetic nephropathy.

We studied the independent relationship between CRP and the subsequent development of incident or recurrent arteriosclerotic outcomes (primary) and congestive heart failure events (secondary) in 1560 individuals with diabetic nephropathy, overt proteinuria, and hypertension enrolled in the prospective Irbesartan Diabetic Nephropathy Trial.

Traditional cardiac risk factors were highly prevalent, CRP levels were high overall [quintiles (mg/L) 1st, 0 to 1.2; 2nd, 1.3 to 2.5; 3rd, 2.6 to 5.0; 4th, 5.1 to 10.0; and 5th, >10), and subsequent cardiovascular events were very common. A univariate relationship existed between CRP and total arteriosclerotic outcomes (P < 0.0001). However, after adjusting for study intervention and traditional risk factors, the relationship no longer remained. In fact, controlling for previous cardiovascular disease alone caused the association to become nonsignificant. The secondary analysis found a significant univariate relationship between CRP and congestive heart failure events (P= 0.007) that persisted in multivariate analyses (P= 0.006). However, this relationship was confined to the highest CRP quintile [RR (95% CI) 2.0 (1.27, 3.16)].

In diabetic patients with nephropathy, CRP does not add predictive information above and beyond that provided by traditional established risk factors. Whether this holds true for other populations with similar risk burdens is an important public health question that should be addressed. A secondary finding of a link between CRP and congestive heart failure requires further confirmation.