Yoshihisa Ban

Small dense LDL phenotype is associated with postprandial increases of large VLDL and remnant-like particles in patients with acute myocardial infarction

BACKGROUND The small dense low-density lipoprotein (LDL) phenotype (pattern B), high concentrations of remnant-like particles (RLPs), and postprandial lipemia are newly recognized risk factors for coronary heart disease (CHD). However, the associations of these lipoprotein abnormalities remain unclear. The aim of this study was to investigate the relationships among LDL phenotype, very-low-density lipoprotein (VLDL) subclasses, and postprandial lipoprotein metabolism in CHD patients. METHOD We performed an oral fat tolerance test in 32 patients with acute myocardial infarction and compared the following parameters between patients characterized by either large buoyant LDL (pattern A) versus pattern B: lipids and apolipoproteins (apo) in the plasma and Svedberg flotation rates (Sf) >400 (chylomicron), Sf 60-400 (large VLDL), and Sf 20-60 (small VLDL) fractions. RESULT Fasting levels of triglyceride, RLP-cholesterol and RLP-triglyceride were slightly higher in the pattern B patients. Postprandial increases of RLP-cholesterol and the cholesterol and triglyceride of large VLDL fractions were significantly greater in the pattern B patients. The areas under the curves of cholesterol, triglyceride, and apo-B in large VLDL fractions were significantly higher in pattern B, while those in small VLDL were not. RLP-cholesterol and RLP-triglyceride in fasting and fed states correlated very highly with the corresponding cholesterol and triglyceride concentrations in large VLDL fractions. CONCLUSION These results suggest that postprandial increase of large VLDL fractions and RLPs contribute to the formation of small dense LDL in CHD patients.

Comparison Between Small Dense LDL-Cholesterol and LDL-Cholesterol to Predict Coronary Events in Stable Coronary Heart Disease

Recent evidence suggests that small dense low-density lipoprotein (sd-LDL) particles are more atherogenic than large-LDLs in spite of their lower cholesterol contents. This study aimed to determine whether sd-LDL-cholesterol (sd-LDL-C) is superior to LDL-C as a biomarker of the severe coronary heart disease (CHD). We compared the LDL particle size by gradient gel electrophoresis and sd-LDL-C concentrations quantified by heparin-magnesium precipitation in two groups: 482 consecutive patients with stable CHD who had undergone coronary arteriography and 389 non-diabetic subjects without CHD who were not receiving any lipid-lowering drugs. The LDL size, large-LDL-C (estimated by subtracting the sd-LDL-C concentration from the LDL-C concentration), and HDL-C were significantly lower in the CHD subjects than in the healthy subjects, and the sd-LDL-C was significantly higher, in both men and women. The LDL-C was modestly higher and the sd-LDL-C was significantly higher in 258 patients with coronary events (defined as coronary revascularization therapy) than in the patients without events, irrespective of treatment by LDL-lowering drugs. Large-LDL-C, in contrast, was similar between the two groups. Multivariate logistic regression analysis revealed that sd-LDL-C levels were significantly associated with coronary events independently of LDL-C, HDL-C, and high-sensitivity CRP. The sd-LDL-C levels are more powerful than LDL-C levels as disease markers for the determination of high-risk patients among patients with stable CHD.

Significance of Small Dense Low-Density Lipoproteins in Coronary Heart Disease

Low-density lipoprotein (LDL) particles are heterogeneous with respect to their size, density, and lipid composition, and the size of LDL particles is chiefly determined by their lipid contents. Small dense LDL particles have been suggested to be highly atherogenic compared to large buoyant LDL. Our case-control studies have shown that the LDL particle size determined by gradient gel electrophoresis was remarkably smaller in patients with coronary heart disease (CHD), irrespective of the presence of diabetes and the differences in clinical situation and severity of CHD. In addition, small dense LDL-cholesterol concentration evaluated by heparin magnesium precipitation was significantly higher in severe stable CHD and acute coronary syndrome compared with non-CHD subjects and patients with mild CHD, while large LDL-cholesterol estimated by subtracting the small dense LDL-cholesterol concentration from the LDLcholesterol concentration, were somewhat lower in stable CHD compared with healthy subjects. Furthermore, reduced LDL particle size and elevated small dense LDL-cholesterol levels were significantly associated with metabolic dyslipidemia in Metabolic syndrome. These suggest that the predominance of small dense LDL and high levels of small dense LDLcholesterol are very promising risk marker for CHD.