Background: Epidemiological studies suggest that levels of C-reactive protein(CRP)predict cardiovascular disease(CVD). We have evaluated the relationship bet ween 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 caroti d artery, and CRP were obtained on all subjects. Results: C-reactive protein is positively and significantly associated with female sex, body mass index, and s moking and is negatively and significantly associated with age and statin use. G eneralized estimating equations were used to test whether CRP was associated wit h each subclinical CVD measure(presence/absence of CAC, quantity of CAC, and IMT )adjusting for covariates and correlation among siblings. Stratified analyses we re conducted to examine whether these associations differed across sex and stati n use. In the overall analysis, CRP was not significantly associated with IMT or presence of CAC but was negatively and significantly associated with quantity o f CAC(P=.01). When covariates were added, the relationship was no longer signifi cant. 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 populati on at high risk for CVD, there was no evidence of incremental association of CRP levels with measures of subclinical CVD. Background: Epidemiological studies suggest that levels of C-reactive protein (CRP) predict cardiovascular disease (CVD). We have evaluated the relationship bet ween 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 soking and is negatively and significantly associated with age and statin use G eneralized estimating equations were used to test whether CRP was associated wit h each subclinical CVD measure (presence / absence of CAC, quantity of CAC, and IMT) adjusted for covariates and correlation among siblings. Stratified analyzes we re conducted to examine whether these associations differed across sex and stati n 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 signifi cant. The same patterns were observed in stratified analyzes 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 populati on at high risk for CVD, there was no evidence of incremental association of CRP levels with measures of subclinical CVD.