Low-Density Lipoprotein Particle Size Distribution in Subjects with Coronary Artery Disease

ABSTRACT

BACKGROUND: Low-density lipoprotein (LDL) cholesterol has been shown to be a major risk factor for coronary artery disease (CAD) in animal studies, clinical trials, and observational epidemiologic studies. It has a hydrated density of 1.019 to 1.063 kg/L, a diameter of 20 to 30 nm, and displays beta-mobility on paper or agarose gel electrophoresis. With technique such as density gradient ultracentrifugation and gel electrophoresis, it is possible to separate lipoproteins accurately on the basis of their density, charge, and particle size. Further, it has been shown that a smaller LDL is associated with an increased risk of coronary artery disease, even when total cholesterol level is only slightly raised. The aim of this study was to analyze LDL particle size distribution in patients with angiographically confirmed coronary artery disease and in control subjects, using nondenaturating gradient polyacrylamide gel electrophoresis, and to investigate the relationship between LDL particle size and the other traditional coronary risk factors. METHODS: Baseline characteristics such as age, sex, body mass index, history of hypertension or NIDDM, smoking habits, and plasma lipoprotein profiles were obtained in 33 and 27 subjects with and without CAD angiographically confirmed, respectively. We determined LDL peak particle diameter (LDL-PPD) using nondenaturating gradient polyacrylmide gel electrophoresis in CAD and control group. 4% to 12% polyacrylamide gradient gels were used for this assay, and the diameters of LDL subclass peaks were calculated by comparison with a standard calibration curve. This procedure permits the assignment according to distribution of particle diameters as exhibiting pattern A, B, or INT. RESULTS: Traditional coronary risk factors (age, sex, body mass index, history of hypertension or NIDDM, smoking habits, plasma triglyceride, HDL-cholesterol, and total to HDL-cholesterol ratio) were found to be significantly different between two groups, except the plasma total cholesterol and LDL-cholesterol. The mean value of LDL-PPD in patients with CAD was significantly lower than that in control subjects (26.110.4 nm versus 27.011.9 nm, p=0.006). LDL-PPD showed relatively strong associations with plasma triglyceride (r= - 0.536, p<0.01), HDL-cholesterol (r=0.497, p<0.01), and total to HDL-cholesterol ratio (r= - 0.516, p<0.01), but showed no relation to total cholesterol (r= - 0.168) or LDL-cholesterol (r= - 0.028). CONCLUSION: These results suggest an association between small LDL and the presence of CAD and also suggest that LDL-PPD may be associated with the plasma lipid levels.