High-Density Lipoprotein Cholesterol, High-Sensitivity C-Reactive Protein, and Cardiovascular Disease in United States Adults

High-density lipoprotein (HDL) cholesterol is inversely associated with the risk of cardiovascular disease (CVD). However, whether the protective effect of HDL becomes impaired by elevated high-sensitivity C-reactive protein (hs-CRP) is not well-established. We evaluated 13,572 United States adults aged ≥18 years who participated in the cross-sectional National Health and Nutrition Examination Survey 1999–2008. The subjects were classified according to the recognized cutpoints of HDL cholesterol elevations of ≥60 mg/dl, hs-CRP of >3 mg/L, and by a history of self-reported coronary heart disease (CHD) or CVD. Multivariate logistic regression analysis was used to assess the odds of prevalent CHD and CVD according to HDL cholesterol/hs-CRP group, after adjusting for known risk factors. Those with HDL cholesterol of ≥60 mg/dl and CRP >3 mg/L versus HDL cholesterol <60 mg/dl and CRP ≤3 mg/L had as high or a greater prevalence of CHD (5.5% and 5.3%, respectively) and CVD (8.6% and 6.9%, respectively). Compared to those with HDL cholesterol of ≥60 mg/dl and CRP ≤3 mg/L, those with HDL cholesterol ≥60 mg/dl and hs-CRP >3 mg/L had a 1.38 (95% confidence interval 0.94 to 2.02) adjusted odds of CHD and 1.38 (95% confidence interval 1.00 to 1.90) adjusted odds of CVD. Those with an HDL cholesterol <60 mg/dl and CRP >3 mg/L had the greatest adjusted odds of both CHD (1.75, 95% confidence interval 1.28 to 2.38) and CVD (1.74, 95% confidence interval 1.33 to 2.28). In conclusion, an hs-CRP >3 mg/L in the presence of HDL cholesterol of ≥60 mg/dl is associated with an attenuation in the protective association of HDL cholesterol ≥60 mg/dl and CRP of ≤3 mg/L with CHD and CVD.