The relationship between HDL particle size and concentration and the risk of coronary artery disease (CAD) was investigated in a nested case-control analysis of the EPIC-Norfolk study. During the mean follow-up of 6 years, 822 initially healthy men and women developed CAD and were matched to 1,410 controls by sex, age and enrolment time. HDL size was measured by gradient gel electrophoresis as well as by nuclear magnetic resonance (NMR) spectroscopy, while HDL particle concentration was measured by NMR. HDL particle size and concentration were significantly higher in control subjects than in case patients. Although significant, the relationship between HDL particle size and concentration was weak, irrespective of the method used to determine HDL size. Moreover, HDL particle size was associated with some features of the metabolic syndrome, whereas a weak or no relationship was observed between HDL concentration and features of the metabolic syndrome. After adjusting for features of the metabolic syndrome, the association between HDL size and CAD risk was no longer significant (odds ratio=1.00, 95% CI: 0.71-1.39), but the relationship between HDL concentration and CAD risk remained highly significant (odds ratio=0.50, 95% CI: 0.37-0.66).
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