ApoB lipoproteins containing apoC3 and recurrent coronary events in diabetic patients.

摘要

We hypothesize that apoB lipoproteins containing apoC3 (apoC3+) are particularly atherogenic because apoC3 inhibits lipolysis and lipoprotein clearance. The apoB, cholesterol, and triglyceride levels were measured in lipoprotein particle types that were isolated with anti-apoE and anti-apoC3 immunoaffinity chromatography (E+C3+, E−C3+, and E−C3−).; The levels of apoC3+ VLDL and IDL particles were associated with hypertriglyceridemia and hyperglycemia but were not associated with diabetes status per se. These finding suggest that diabetes-related dyslipidemia that causes coronary heart disease may not be different from diabetes-unrelated dyslipidemia in relation to the metabolism of apoC3+ lipoproteins. We also found that the levels of apoC3+ LDL were strong predictors of recurrent coronary events in 244 diabetic patients from the Cholesterol and Recurrent Events (CARE) trial. The relative risks for the 4th compared to 1st quartile of the apoB of apoC3+ LDL were 2.95–3.18 (p .05) in models that included baseline risk factors and LDL-C, HDL-C and triglyceride. The apoC3+ LDL compared to the apoC3− LDL was enriched in both triglyceride and cholesterol. Furthermore, the apoC3+ LDL may be particularly atherogenic, more so than the major type of LDL that does not contain apoC3 (apoC3−), since a small increase of concentration, 5 mg/dl (from 2–7 mg/dl), is associated with a threefold increase in risk, similar to that associated with a 45 mg/dl increase (from 45–90 mg/dl) in the major apoC3− LDL fraction. Finally, we investigated the effects of pravastatin, an HMG CoA reductase inhibitor, on apoC3+ LDL after 1 year of treatment. Compared with placebo, pravastatin reduced LDL apoB levels by 42% (E+C3+, p = 0.02), 17% (E−C3+, p = 0.74), and 29% (E−C3−, p = 0.002), commensurate with the reduction of LDL cholesterol concentrations in particle types by 29% (E+C3+, p = 0.002), 25% (E−C3+, p = 0.21) 36% (E−C3−, p 0.0001), respectively. The levels of apoC3+ LDL that had characteristics of atherogenic remnants were strong predictors of coronary events and their levels were reduced after 1 year of pravastatin therapy. The benefits derived from reducing apoC3+ LDL could be as important as reducing LDL E−C3− that represents 85–90% of total LDL particles.