Plasma levels of lecithin:cholesterol acyltransferase and risk offuture coronary artery disease in apparently healthy men and women: aprospective case-control analysis nested in the EPIC-Norfolk populationstudy

Abstract

LCAT plays a key role in the maturation of HDL, as evidenced by lowHDL-cholesterol levels in carriers of deleterious mutations inLCAT. However, the role of LCAT in atherosclerosis isunclear. We set out to study this in a prospective study. Plasma LCAT levels,which strongly correlate with LCAT activity, were measured in baselinenonfasting samples of 933 apparently healthy men and women who developedcoronary artery disease (CAD) and 1,852 matched controls who remained free ofCAD during 6 year follow-up. LCAT levels did not differ between cases andcontrols but were higher in women than men. Stratification into LCAT quartilesrevealed a positive association with plasma LDL-cholesterol and triglyceridelevels in the unexpected absence of an association with HDL-cholesterol. Inmixed-gender analyses, the odds ratio (OR) for future CAD in the highest LCATquartile versus the lowest was 1.00 [confidence interval (CI): 0.76–1.29,P for linearity = 0.902], although opposite trendswere observed in men and women. In fact, high LCAT levels were associated withan increased CAD risk in women (unadjusted OR 1.45, CI: 0.94–2.22,P for linearity = 0.036). In contrast to our studiesin carriers of LCAT mutations, the current data show that lowLCAT plasma levels are not associated with increased atherosclerosis in thegeneral population.

Keywords

• high-density lipoprotein cholesterol
• atherosclerosis
• lipoproteins
• epidemiology
• European Prospective Investigation into Cancer and Nutrition