Objective-Lecithin:cholesterol acyltransferase (LCAT) is thought to be important in reverse cholesterol transport. However, its association with coronary heart disease (CHD) and sudden death is controversial. Approach and Results-We prospectively studied 1927 individuals from the general population. Serum concentrations of apolipoprotein A-I, A-II, B, C-II, C-III, E, and LCAT activity measured as a serum cholesterol esterification rate were evaluated. We documented 61 events of CHD and sudden death during 10.9 years of follow-up. After adjustment for age and sex, LCAT activity was significantly associated with the risk of CHD and sudden death (hazard ratio, 3.02; 95% confidence interval, 1.49−6.12; P=0.002). In multivariate analysis adjusted for age, sex, current smoking status, history of diabetes mellitus, body mass index, systolic blood pressure, serum total cholesterol, and serum high-density lipoprotein cholesterol concentrations, the hazard ratio of LCAT activity for the risk of CHD and sudden death remained significant (hazard ratio, 3.07; 95% confidence interval, 1.35−7.01; P=0.008). However, when it was analyzed for men and women separately, this association remained significant only in women. Conclusions-Increased LCAT activity measured as a serum cholesterol esterification rate was a risk for CHD and sudden death in a Japanese general population. Key Words: cohort study ◼ coronary heart disease ◼ lecithin:cholesterol acyltransferase ◼ sex differences ◼ sudden death
Increased Serum Cholesterol Esterification Rates Predict Coronary Heart Disease and Sudden Death in a General PopulationShin-ichiro Tanaka
Tanaka et al LCAT Activity Predicts CHD and Sudden Death 1099measured by the exogenous substrate method. However, this relationship was not significant after adjustment for lipids. 21 Thus, the number of prospective studies in humans is still limited, and the results are controversial. 12 Here, we report that increased LCAT activity measured as a serum cholesterol esterification rate by the endogenous substrate method is significantly associated with a future risk of CHD and sudden death in a community-based cohort study.
Materials and MethodsMaterials and Methods are available in the online-only Supplement.
ResultsBaseline characteristics of the study cohort are presented in Table 1. Women had higher concentrations of total cholesterol (TC), HDL-C, and non-HDL-C than men (all tests for trend, P<0.001). Men had higher proportions of current smokers (P<0.001) and patients with a history of diabetes mellitus (P=0.03), a higher serum concentration of triglycerides (TG) (P<0.001), and a higher level of serum thiobarbituric acid reactive substances (TBARS) (P=0.001), than Women.During the 19 866 person-years of follow-up (median followup period, 10.9 years), we documented 19 cases of myocardial infarction (15 in men and 4 in women); 12 cases of angina pectoris, coronary artery bypass, and angioplasty procedures (10 in men and 2 in women); and 30 cases of sudden deaths (13 in men and 17 in women). Thus, the t...