Distribution of ApoA-I–Containing HDL Subpopulations in Patients With Coronary Heart Disease

Abstract

Abstract-High density lipoproteins (HDLs) and their subspecies play a role in the development of coronary heart disease (CHD). HDL subpopulations were measured by 2-dimensional nondenaturing gel electrophoresis in 79 male control subjects and 76 male CHD patients to test the hypothesis that greater differences in apolipoprotein (apo)A-I-containing HDL subpopulations would exist between these 2 groups than for traditional lipid levels. In CHD subjects, HDL cholesterol (HDL-C) was lower (Ϫ14%, PϽ0.001), whereas total cholesterol and the low density lipoprotein cholesterol/HDL-C ratio were higher (9% [PϽ0.05] and 21% [PϽ0.01], respectively) compared with control levels. No significant differences were found for low density lipoprotein cholesterol, triglyceride, and apoA-I levels. In CHD subjects, there were significantly (PϽ0.001) lower concentrations of the large lipoprotein (Lp)A-I ␣ 1 (Ϫ35%), pre-␣ 1 (Ϫ50%), pre-␣ 2 (Ϫ33%), and pre-␣ 3 (Ϫ31%) subpopulations, whereas the concentrations of the small LpA-I/A-II ␣ 3 particles were significantly (PϽ0.001) higher (20%). Because ␣ 1 was decreased more than HDL-C and plasma apoA-I concentrations in CHD subjects, the ratios of HDL-C to ␣ 1 and of apoA-I to ␣ 1 were significantly (PϽ0.001) higher by 36% and 57%, respectively, compared with control values. Subjects with low HDL-C levels (Յ35 mg/dL) have different distributions of apoA-I-containing HDL subpopulations than do subjects with normal HDL-C levels (Ͼ35 mg/dL). Therefore, we stratified participants according to HDL-C concentrations into low and normal groups. The differences in lipid levels between controls and HDL-C-matched cases substantially decreased; however, the significant differences in HDL subspecies remained. Our research findings support the concept that compared with control subjects, CHD patients not only have HDL deficiency but also have a major rearrangement in the HDL subpopulations with significantly lower ␣ 1 and pre- Key Words: HDL subpopulations Ⅲ coronary heart disease Ⅲ lipids Ⅲ lipoproteins Ⅲ apolipoproteins C oronary heart disease (CHD) remains the leading cause of death and disability in the United States. Approximately 14 million people have CHD, and 1.5 million individuals experience a myocardial infarction annually, leading to Ϸ500 000 deaths per year. 1 Atherosclerosis is a multifactorial disease affected by lifestyle and genetic factors. 2 Independent risk factors for CHD as defined by the National Cholesterol Education Program (NCEP) Adult Treatment Panel II include the following: age, sex, hypertension, smoking, diabetes, family history of premature CHD, elevated plasma levels of LDL cholesterol (LDL-C Ն160 mg/dL), and low levels of HDL (HDL-C Ͻ35 mg/dL). 3-10 The NCEP panel classified an HDL-C level Ն60 mg/dL (Ͼ1.55 mmol/L) as protective against the development of CHD. 3 Many prospective epidemiological studies have indicated that a decreased HDL-C level is a significant independent risk factor for heart disease. [5][6][7]9,11,12 HDL is found in human plasma at a density of 1.063 t...

Physical Fitness and Reverse Cholesterol Transport

“…It is, however, premature to draw conclusions regarding the relationship between pre␤ 1 -HDL concentration and atherosclerosis. Asztalos et al reported either no difference in pre␤ 1 -HDL between men with or without CAD 24 or a higher pre␤ 1 -HDL/␣ 1 -HDL ratio in subjects with more severe coronary artery stenosis. 25 Miida et al have reported higher pre␤ 1 -HDL values among Japanese men with CAD.…”

Effects of Atorvastatin on Nuclear Magnetic Resonance-Defined Lipoprotein Subclasses and Inflammatory Markers in Patients with Hypercholesterolemia

“…Indeed, in vivo kinetic studies demonstrated the decreased production as well as increased clearance of VLDL, an observation consistent with the inhibition of VLDL secretion via the strong inhibition of HMG-Co reductase activity and increased direct uptake by an up-regulated LDL receptor 12,13) . Cardioprotective HDL is heterogeneous in size and apolipoprotein composition, which would, in turn, affect atherosclerosis differently; for example, large HDL, but not small HDL, is a predictor of cardiovascular risk [14][15][16] . In this context, atorvastatin may exert a cardioprotective effect by increasing large HDL (HDL4).…”

Pitavastatin Decreases Plasma Pre.BETA.1-HDL Concentration and Might Promote its Disappearance Rate in Hypercholesterolemic Patients

“…Increased HDL2 might promote non-specific cholesterol efflux from the cells 24) . In regard to the clinical significance of the plasma pre 1-HDL concentration and its disappearance, supposing conversion to -HDL, accumulating evidence suggests that impaired conversion of pre 1-HDL resulting in high plasma pre 1-HDL concen- tration is involved in the initiation and progression of atherosclerosis [25][26][27] . In this study, pitavastatin also significantly decreased plasma pre 1-HDL concentration, but significantly increased the disappearance rate of pre 1-HDL.…”