title: Association of lecithin-cholesterol acyltransferase activity measured as a serum cholesterol esterification rate and low-density lipoprotein heterogeneity with cardiovascular risk: a cross-sectional study.
abstract: The cholesterol-esterifying enzyme, lecithin-cholesterol acyltransferase (LCAT), is believed to play a key role in reverse cholesterol transport. However, recent investigations have demonstrated that higher LCAT activity levels increase the formation of triglyceride (TG)-rich lipoproteins (TRLs) and atherogenesis. We hypothesized that higher LCAT activity measured as a serum cholesterol esterification rate by the endogenous substrate method might increase the formation of TRLs and thereby alter low-density lipoprotein (LDL) heterogeneity. The estimated LDL particle size [relative LDL migration (LDL-Rm)] was measured by polyacrylamide gel electrophoresis with the LipoPhor system (Joko, Tokyo, Japan) in 538 consecutive patients with at least risk factor for atherosclerosis. Multivariate regression analysis after adjustments for traditional risk factors identified elevated TRL-related marker (TG, remnant-like particle cholesterol, apolipoprotein C-II, and apolipoprotein C-III) levels as independent predictors of smaller-sized LDL particle size, both in the overall subject population and in the subset of patients with serum LDL cholesterol levels of <100 mg/dL. Area under the receiver operating characteristic curve of the LCAT activity (0.79; sensitivity 60 %; specificity 84.8 %) was observed for the evaluation of the indicators of an LDL-Rm value of ≥0.40, which suggests the presence of large amounts of small-dense LDL. The results lend support to the hypothesis that increased LCAT activity may be associated with increased formation of TRLs, leading to a reduction in LDL particle size. Therefore, to reduce the risk of atherosclerotic cardiovascular disease, it may be of importance to pay attention not only to a quantitative change in the serum LDL-C, but also to the LCAT activity which is possibly associated with LDL heterogeneity.
authors.affiliation: Department of Health Planning Center, Nihon University Hospital, 1-6 Kanda-Surugadai, Chiyoda-ku, Tokyo, 101-8309, Japan. tani.shigemasa@nihon-u.ac.jp.|Division of Cardiology, Department of Medicine, Nihon University School of Medicine, Tokyo, Japan. tani.shigemasa@nihon-u.ac.jp.
authors.forename: Shigemasa
authors.initials: S
authors.lastname: Tani
authors.affiliation: Department of Health Planning Center, Nihon University Hospital, 1-6 Kanda-Surugadai, Chiyoda-ku, Tokyo, 101-8309, Japan.|Division of Cardiology, Department of Medicine, Nihon University School of Medicine, Tokyo, Japan.
authors.forename: Atsuhiko
authors.initials: A
authors.lastname: Takahashi
authors.affiliation: Division of Cardiology, Department of Medicine, Nihon University School of Medicine, Tokyo, Japan.
authors.forename: Ken
authors.initials: K
authors.lastname: Nagao
authors.affiliation: Division of Cardiology, Department of Medicine, Nihon University School of Medicine, Tokyo, Japan.
authors.forename: Atsushi
authors.initials: A
authors.lastname: Hirayama
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D019540:Area Under Curve; D050197:Atherosclerosis / Q000097:blood* / Q000175:diagnosis / Q000201:enzymology / Q000209:etiology; D015415:Biomarkers / Q000097:blood; D016009:Chi-Square Distribution; D002784:Cholesterol / Q000097:blood*; D003430:Cross-Sectional Studies; D018450:Disease Progression; D004951:Esterification; D005260:Female; D006801:Humans; D008077:Lipoproteins, LDL / Q000097:blood*; D016015:Logistic Models; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D010316:Particle Size; D007862:Phosphatidylcholine-Sterol O-Acyltransferase / Q000097:blood*; D011237:Predictive Value of Tests; D012372:ROC Curve; D012307:Risk Factors; D014280:Triglycerides / Q000097:blood; D015854:Up-Regulation
chemical_list: D015415:Biomarkers; D008077:Lipoproteins, LDL; D014280:Triglycerides; C032607:low density lipoprotein triglyceride; D002784:Cholesterol; D007862:Phosphatidylcholine-Sterol O-Acyltransferase
keywords: Atherosclerosis; LDL particle size; Lecithin–cholesterol acyltransferase; Triglyceride-rich lipoproteins