The relationship between C-reactive protein and subclinical cardiovascular disease in the Diabetes Heart Study (DHS)

Background Epidemiological studies suggest that levels of C-reactive protein (CRP) predict cardiovascular disease (CVD). We have evaluated the relationship between CRP and subclinical CVD in a study cohort at high risk of CVD. Methods The DHS is a single-center, family-based study of the genetic and environmental components of CVD in type 2 diabetes mellitus (T2DM). We evaluated 666 subjects (551 T2DM affected and 115 unaffected) with an average age of 61 years. Measures of coronary artery calcium (CAC), intimal-medial thickness (IMT) of the common carotid artery, and CRP were obtained on all subjects. Results C-reactive protein is positively and significantly associated with female sex, body mass index, and smoking and is negatively and significantly associated with age and statin use. Generalized estimating equations were used to test whether CRP was associated with each subclinical CVD measure (presence/absence of CAC, quantity of CAC, and IMT) adjusting for covariates and correlation among siblings. Stratified analyses were conducted to examine whether these associations differed across sex and statin use. In the overall analysis, CRP was not significantly associated with IMT or presence of CAC but was negatively and significantly associated with quantity of CAC (P = .01). When covariates were added, the relationship was no longer significant. Similar patterns were observed in stratified analyses based on sex, statin use, and diabetes status: weak but negative association of CAC with CRP, which became nonsignificant with adjustment for covariates. Conclusions In a population at high risk for CVD, there was no evidence of incremental association of CRP levels with measures of subclinical CVD.