EFFECTS OF LOVASTATIN ON APOA-CONTAINING AND APOB-CONTAINING LIPOPROTEINS - FAMILIES IN A SUBPOPULATION OF PATIENTS PARTICIPATING IN THE MONITORED ATHEROSCLEROSIS REGRESSION STUDY (MARS)

To establish whether lovastatin, an inhibitor of 3-hydroxy-3-methylglutaryl coenzyme A (HMG CoA) reductase, exhibits a specific effect on apolipoprotein (ape) A- and apoB-containing lipoproteins, 63 subjects, a subset of the 270 Monitored Atherosclerosis Regression Study (MARS) patients with hypercholesterolemia (190 to 295 mg/dL) and documented coronary artery disease, were randomized into either lovastatin 40 mg twice daily or matching placebo tablets twice daily. Both groups consumed a diet containing 27% calories as fat (polyunsaturated fat/saturated fat ratio, 2.85) and a daily cholesterol intake of less than 250 mg. The plasma lipid and apolipoprotein profiles were determined at the time of randomization and after 2 years of treatment, and the levels of apoA- and apoB-containing lipoprotein families were measured after 2 years of treatment. After this treatment period, the drug group was characterized in comparison with the placebo group by significantly reduced levels of total cholesterol (33%), triglycerides (30%), very-low-density lipoprotein cholesterol (36%), low-density lipoprotein cholesterol (43%), apoB (36%), apoC-III (18%), and apoE (17%) and slightly but insignificantly increased levels of high-density lipoprotein cholesterol (6%) and apoA-I (1%). The 2-year levels of lipoprotein containing apoA-I but no apoA-II (LpA-I) and lipoprotein containing both apoA-I and apoA-II (LpA-I/A-II) particles separated by immunoaffinity chromatography on an anti-apoA-II immunosorber did not differ between the two treatment groups. However, the apoB-containing lipoprotein (Lp) families defined by apolipoprotein composition and separated by immunoaffinity chromatography on anti-apoA-II and anti-apoC-III immunosorbers were affected in a selective manner. Compared with the placebo group, lovastatin subjects had significantly lower levels of cholesterol-rich LpB particles (40%), but there was no difference in the levels of intact and/or partially delipidized triglyceride-rich LpB/C+LpB/C/E and LpA-II/B/C/D/E families. We conclude that the reducing effect of lovastatin on apoB-containing lipoproteins is mediated through its selective decrease of cholesterol-rich LpB particles. Lovastatin is a potent agent for lowering the levels of potentially atherogenic LpB particles but a less effective drug for reducing other forms of apoB-containing lipoproteins or for increasing the levels of putative nonatherogenic apoA-containing lipoproteins.