HDL particle size and the risk of coronary heart disease in apparently healthy men and women: the EPIC-Norfolk prospective population study.

Objective: To evaluate the association between HDL particle size measured by gradient gel electrophoresis and risk of incident coronary heart disease (CHD) in apparently healthy men and women.
Methods: We performed a prospective case-control study nested in the EPIC-Norfolk cohort. Cases were apparently healthy men and women aged 45-79 years who developed fatal or nonfatal CHD (n=1035). They were matched to 1920 controls who remained free of CHD over the follow-up period of 6 years.
Results: Participants with the smallest HDL particles had the most unfavourable cardiometabolic risk profile whereas those with the largest HDL particles had the most favourable risk profile. Plasma HDL cholesterol levels were found to be the best correlate of HDL particle size (r=0.58 and r=0.62, respectively, for men and women, p<0.001). Men in the highest quartile of HDL particle size had an unadjusted odds ratio (OR) for future CHD of 0.75 (95% CI, 0.57-0.97) compared to those in the bottom quartile. For women, the equivalent OR was 0.50 (0.35-0.71). After additional adjustment for diabetes, body mass index, systolic blood pressure, LDL and HDL cholesterol levels, the ORs were 1.43 (1.01-2.03) in men and 0.84 (0.52-1.35) in women.
Conclusions: A decreased HDL particle size is associated with an adverse cardiometabolic risk profile. Small HDL particle size was also associated with an increased CHD risk, but this association was largely explained by traditional risk factors.