Abstract
Background: Measurement of cholesterol levels in small LDL particles represents a novel metabolic marker that might add to the coronary risk prediction attributed to LDL cholesterol and LDL particle size taken separately. We examined, in a nested case-control study performed in the prospective EPIC-Norfolk cohort, the association of LDL cholesterol in small LDL particles to future CHD in apparently healthy men and women aged 45 to 79 years who developed fatal or nonfatal CHD over 10-year follow-up. Methods and results: Cases (n=1035) were matched to 1920 controls who remained free of CHD, by age, gender and enrollment time. Electrophoretic characteristics of LDL particles were measured using 2–16% nondenaturing polyacrylamide gradient gel electrophoresis. Cholesterol levels in small LDL particles (<255 Å) were higher in cases than in controls (1.26 ± 0.87 vs. 1.07 ± 0.78 mmol/l, P<0.001) Participants in the top tertile of cholesterol concentrations in small LDL particles were characterized by the highest waist circumference, by the highest triglyceride, C-reactive protein and apolipoprotein B levels and by the lowest HDL cholesterol concentrations. These participants had an unadjusted odds ratio (OR) for future CHD of 1.72 (95% CI, 1.42 to 2.09; P<0.001) which remained significant after adjustment for classical risk factors such as age, smoking, diabetes, body mass index, systolic blood pressure and LDL cholesterol concentrations (OR, 1.43; 95% CI, 1.16 to 1.76; P=0.001). However, after further adjustments for triglyceride and HDL cholesterol levels, the association between cholesterol in small LDL particles and CHD was no longer significant (OR, 1.18; 95% CI, 0.95 to 1.48; NS). Conclusions: Cholesterol concentrations in different LDL subclasses show different relationships with CHD incidence in a European cohort representative of a contemporary Western population.
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