Abstract
BackgroundLecithin-cholesterol acyltransferase (LCAT) is believed to be involved in reverse cholesterol transport, which is known to play a key role in suppression of atherosclerosis. However, recent investigations have demonstrated that higher LCAT activity, measured in terms of the serum cholesterol esterification rate by an endogenous substrate method, is associated with increased formation of triglyceride (TG)-rich lipoproteins (TRLs), leading to a decrease in the low-density lipoprotein (LDL) particle size. The purpose of this hospital-based longitudinal study was to clarify the causal relationship between changes in the LCAT activity and changes in the LDL-particle size.MethodsThe subjects were a total of 335 patients, derived from our previous study cohort, with one or more risk factors for atherosclerotic cardiovascular disease (ASCVD). For this study, we measured the LDL-particle size (relative LDL migration [LDL-Rm value]) by polyacrylamide gel electrophoresis in the subjects, along with the changes in the LCAT activity, at the end of a follow-up period of at least 1 year.ResultsThe results revealed that the absolute change (Δ) in the LDL-particle size increased significantly as the quartile of Δ LCAT activity increased (p = 0.01). A multi-logistic regression adjusted-analysis revealed that Δ LCAT activity in the fourth quartile as compared to that in the first quartile was independently predictive of an increased LDL-particle size (odds ratio [95% confidence interval]: 2.03 [1.02/4.04], p = 0.04). Moreover, the ∆ LCAT activity was also positively correlated with ∆ TRL-related markers (i.e., TG, remnant particle-like cholesterol [RLP-C], apolipoprotein B, apolipoprotein C-2, and apolipoprotein C-3).ConclusionsThe results lend support to the hypothesis that increased LCAT activity may be associated with increased formation of TRLs, leading to a reduction in the LDL-particle size in patients at a high risk for ASCVD. To reduce the risk of ASCVD, it may be important to focus not only on the quantitative changes in the serum LDL-cholesterol levels, but also on the LCAT activity.Trial registrationUMIN (https://upload.umin.ac.jp/cgi-bin/ctr/ctr_reg_list.cgi) Study ID: UMIN000033228 retrospectively registered 2 July 2018.
Highlights
Lecithin-cholesterol acyltransferase (LCAT) is believed to be involved in reverse cholesterol transport, which is known to play a key role in suppression of atherosclerosis
The primary endpoint was to evaluate the association between the absolute changes (Δ) in the LCAT activity and the Δ low-density lipoprotein (LDL)-particle size using a multi-logistic regression analysis with adjustments for confounding factors, and the secondary endpoint was to investigate the associations between the Δ LCAT activity and Δ TG-rich lipoprotein (TRL)-related markers, which are closely associated with TG metabolism
Among the subjects of this cross-sectional study [7], we investigated the association between the Δ LCAT activity, as classified into quartiles, and the Δ Relative LDL migration (LDL-Rm) values in the 335 patients who could be followed up for at least 1 year
Summary
Lecithin-cholesterol acyltransferase (LCAT) is believed to be involved in reverse cholesterol transport, which is known to play a key role in suppression of atherosclerosis. Recent investigations have demonstrated that higher LCAT activity, measured in terms of the serum cholesterol esterification rate by an endogenous substrate method, is associated with increased formation of triglyceride (TG)-rich lipoproteins (TRLs), leading to a decrease in the low-density lipoprotein (LDL) particle size The purpose of this hospital-based longitudinal study was to clarify the causal relationship between changes in the LCAT activity and changes in the LDL-particle size. We reported that increased LCAT activity, as measured in terms of the serum cholesterol esterification rate by the endogenous substrate method, might be associated with a decrease in the LDL-particle size via its association with an increase in the serum levels of TRL-related markers in patients at a high risk for progression of atherosclerosis [5] Because this aforementioned study was designed as a cross-sectional study, and not as a longitudinal study or an interventional study, it was difficult to arrive at any definitive conclusions about the causal relationships based on the results. We designed this longitudinal study in an attempt to verify the hypothesis that elevation of the LCAT activity is associated with an increase in the serum levels of TRL-related markers, involved in disordered TG metabolism (i.e., TG, remnant particle-like cholesterol [RLP-C], apolipoprotein (apo) B, apo C-2, and apo C-3) [6], and is thereby involved in a reduction of the LDL-particle size
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