HDLs Containing Apolipoproteins A-I and A-II (LpA-I:A-II) as Markers of Coronary Artery Disease in Men With Non–Insulin- Dependent Diabetes Mellitus

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Abstract
Background Abnormalities in HDL and an increased risk of coronary artery disease (CAD) coexist in non–insulin-dependent diabetes mellitus (NIDDM). HDLs can be separated by their apolipoprotein (apo) content into particles containing apoA-I but not apoA-II (LpA-I) and those containing both apoA-I and apoA-II (LpA-I:A-II). The LpA-I particles have been suggested to be more effective in conferring protection against CAD than the LpA-I:A-II particles. However, data are sparse, and no studies have defined the role of these two classes of particles in NIDDM. Methods and Results LpA-I and LpA-I:A-II particles were quantified by a differential electroimmunoassay in four groups of men with similar age and body mass index (BMI) distributions. Group 1 consisted of 50 patients with NIDDM and angiographically verified CAD; group 2, 50 men with CAD but no diabetes; group 3, 50 men with NIDDM but no CAD; and group 4, 31 healthy men. Serum apoA-I and apoA-II concentrations were measured by immunoturbidimetry, and HDL 2 and HDL 3 were separated by ultracentrifugation. Concentrations of LpA-I:A-II particles in group 1 were 13.8%, 18.3%, and 26.9% lower than in groups 2 through 4, respectively. In a two-by-two factorial ANOVA, adjusted for age and BMI, the differences were significant for both CAD ( P <.001) and NIDDM ( P <.001), with no interaction between the factors. These results were confirmed by comparable differences in the serum concentrations of apoA-I and apoA-II. LpA-I particles were related to the presence or absence of CAD ( P =.013), but the difference was lost in a multivariate analysis. A low HDL 3 cholesterol concentration characterized both CAD ( P =.002) and NIDDM ( P =.024). HDL 2 cholesterol differed significantly with regard to the presence of NIDDM ( P =.033) but only borderline with respect to CAD ( P =.073). Conclusions ApoA-II–containing lipoproteins and HDL 3 cholesterol are powerful markers of CAD in men with NIDDM.