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...