Abstract
BackgroundThe low-density lipoprotein cholesterol/apolipoprotein B (LDL-C/apoB) ratio has conventionally been used as an index of the LDL-particle size. Smaller LDL-particle size is associated with triglyceride (TG) metabolism disorders, often leading to atherogenesis. We investigated the association between the LDL-C/apoB ratio and TG metabolism in coronary artery disease (CAD) patients with diabetes mellitus (DM).MethodsIn the cross-sectional study, the LDL-C/apoB ratio, which provides an estimate of the LDL-particle size, was calculated in 684 consecutive patients with one additional risk factor. The patients were classified into 4 groups based on the presence or absence of CAD and DM, as follows: CAD (−) DM (−) group, n = 416; CAD (−) DM (+) group, n = 118; CAD (+) DM (−) group, n = 90; CAD (+) DM (+) group, n = 60.ResultsA multi-logistic regression analysis after adjustments for coronary risk factors revealed that the CAD (+) DM (+) condition was an independent predictor of the smallest LDL-C/apoB ratio among the four groups. Furthermore, multivariate regression analyses identified elevated TG-rich lipoprotein (TRL)-related markers (TG, very-LDL fraction, remnant-like particle cholesterol, apolipoprotein C-II, and apolipoprotein C-III) as being independently predictive of a smaller LDL-particle size in both the overall subject population and a subset of patients with a serum LDL-C level < 100 mg/dL. In the 445 patients followed up for at least 6 months, multi-logistic regression analyses identified increased levels of TRL-related markers as being independently predictive of a decreased LDL-C/apoB ratio, which is indicative of smaller LDL-particle size.ConclusionsThe association between disorders of TG metabolism and LDL heterogeneity may account for the risk of CAD in patients with DM. Combined evaluation of TRL-related markers and the LDL-C/apoB ratio may be of increasing importance in the risk stratification of CAD patients with DM. Further studies are needed to investigate the useful clinical indices and outcomes of these patients.Clinical Trial Registration UMIN (http://www.umin.ac.jp/) Study ID: UMIN000028029 retrospectively registered 1 July 2017
Highlights
The serum non-high-density lipoprotein (HDL)-C level was significantly lower in the coronary artery disease (CAD) (+) group than in the CAD (−) group, probably reflecting the statin treatment that is given to many patients of the CAD (+) group
The low-density lipoprotein cholesterol (LDL-C)/apoB ratio was significantly lower in the CAD (+) group than in the CAD (−) group, and TG/high-density lipoprotein cholesterol (HDL-C) ratio was higher in the CAD (+) group than in the CAD (−) group, this difference was not statistically
This study evaluated the risk of CAD in diabetes mellitus (DM) by means of a cross-sectional and longitudinal design that focused on LDL-particle size and TG metabolism, the results may indicate the necessity of monitoring the qualitative changes in LDL-C, in addition to the quantitative changes, especially in CAD patients with DM
Summary
Progression of coronary atherosclerosis in patients with diabetes mellitus (DM) is characterized by increased frequency, extent, complexity, and rate of progress compared to that in non-DM patients [1,2,3].In a meta-analysis that assessed the preventive effect of statins on cardiovascular (CV) events, the preventive effect on CV mortality was found to be no more than 20% even when the serum low-density lipoprotein cholesterol (LDL-C) level was controlled with a statin [4], and among the residual risks of statin therapy, insulin resistance, Impaired glucose tolerance, and lipid metabolism abnormalities [5], especially defective triglyceride (TG) metabolism, was found to cause a decrease in LDL-particle size, which has a powerful atherogenic effect [6].TG metabolites, i.e., chylomicrons, very low density lipoprotein (VLDL), and remnant-like particle cholesterol (RLP-C), which are TG-rich lipoproteins (TRLs), and, apolipoprotein (apo) C-II and apo C-III which are involved in the metabolic process, etc., have been demonstrated to be involved in the progression of atherosclerosis [6].Density gradient ultracentrifugation, nondenaturing gradient gel electrophoresis, and nuclear magnetic resonance spectroscopy are the methods that are usually employed to measure LDL-particle diameter; these methods present problems in clinical settings due to their cost and complexity [7]. TG metabolites, i.e., chylomicrons, very low density lipoprotein (VLDL), and remnant-like particle cholesterol (RLP-C), which are TG-rich lipoproteins (TRLs), and, apolipoprotein (apo) C-II and apo C-III which are involved in the metabolic process, etc., have been demonstrated to be involved in the progression of atherosclerosis [6]. The apoB concentration represents the plasma number of LDL-particles. The LDL-C/apoB ratio reflects indirectly the LDL-particle size [7]. The low-density lipoprotein cholesterol/apolipoprotein B (LDL-C/apoB) ratio has conventionally been used as an index of the LDL-particle size. Smaller LDL-particle size is associated with triglyceride (TG) metabolism disorders, often leading to atherogenesis. We investigated the association between the LDL-C/apoB ratio and TG metabolism in coronary artery disease (CAD) patients with diabetes mellitus (DM)
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