Impact of inflammatory biomarkers on relation of high density lipoprotein-cholesterol with incident coronary heart disease: Cardiovascular Health Study

Background: Inflammatory factors and low HDL-C relate to CHD risk, but whether inflammation attenuates any protective association of high HDL-C is unknown. Objective: Investigate inflammatory markers' individual and collective impact on the association of HDL-C with incident coronary heart disease (CHD). Methods: In 3888 older adults without known cardiovascular disease (CVD), we examined if the inflammatory markers C-reactive protein (CRP), interleukin-6 (IL-6), and lipoprotein-associated phospholipase A2 (Lp-PLA₂) modify the relation of HDL-C with CHD. HDL-C, CRP, IL-6, and Lp-PLA₂ values were grouped as using gender-specific tertiles. Also, an inflammation index of z-score sums for CRP, IL-6, and Lp-PLA₂ was categorized into tertiles. We calculated CHD incidence for each HDL-C/inflammation group and performed Cox regression, adjusted for standard CVD risk factors and triglycerides to examine the relationship of combined HDL-C-inflammation groups with incident events. Results: CHD incidence (per 1000 person years) was higher for higher levels of CRP, IL-6, and the index, and lower for higher levels of HDL-C. Compared to high HDL-C/low-inflammation categories (referent), adjusted HRs for incident CHD were increased for those with high HDL-C and high CRP (HR=1.50, p<0.01) or highest IL-6 tertile (HR=1.40, p<0.05), but not with highest Lp-PLA₂ tertile. Higher CHD incidence was similarly seen for those with intermediate or low HDL-C accompanied by high CRP, high IL-6, or a high inflammatory index. Conclusion: The protective relation of high HDL-C for incident CHD appears to be attenuated by greater inflammation.