Cholesterol levels in small LDL particles predict the risk of coronary heart disease in the EPIC-Norfolk prospective population study

Aims To evaluate the association of low-density lipoprotein cholesterol (LDL-C) levels in small and large LDL particles with risk of incident coronary heart disease (CHD). Methods and results 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 non-fatal CHD (n = 1035), and who were matched by age, gender, and enrollment time to 1920 controls who remained free of CHD. Electrophoretic characteristics of LDL particles were measured using 2-16% polyacrylamide gradient gel electrophoresis. Concentrations of LDL-C-<255 angstrom were higher in cases than controls in men (1.34 +/- 0.88 vs. 1.15 +/- 0.80 mmol/ L, P < 0.001) as well as in women (1.12 +/- 0.84 vs. 0.94 +/- 0.74 mmol/ L, P < 0.001). The unadjusted odds ratio (OR) for future CHD in men of the top tertile of LDL-C-<255 angstrom was 1.68 (95% CI, 1.33 -2.13; P < 0.001) whereas in women the unadjusted OR was 1.53 (95% CI, 1.13 -2.07; P < 0.001). However, after further adjustments for confounding variables, the association between LDL-C, 255 A and CHD was no longer signi. cant in men and in women. Conclusion Cholesterol concentrations in different LDL subclasses show different relationships with CHD risk in this European cohort.