title: The role of triglyceride-rich lipoprotein families in the progression of atherosclerotic lesions as determined by sequential coronary angiography from a controlled clinical trial.
abstract: We have demonstrated previously in a subset of Monitored Atherosclerosis Regression Study (MARS) subjects with hypercholesterolemia (190 to 295 mg/dL) and documented coronary artery disease that lovastatin significantly reduces cholesterol-rich lipoprotein B (LpB) but has little effect on complex, triglyceride-rich apolipoprotein (apo) B-containing LpBc (the sum of LpB:C, LpB:C:E and LpA-II:B:C:D:E) particles defined by their apolipoprotein composition. This differential effect of lovastatin on apoB-containing lipoprotein families offered the opportunity to determine in the same subset of MARS subjects the independent relationship of LpB and LpBc with the progression of coronary artery disease. Subjects randomized to either lovastatin (40 mg twice daily) or matching placebo were evaluated by coronary angiography before randomization and after 2 years of treatment, and the overall coronary status was judged by a coronary global change score. In the lovastatin-treated group, there were 22 nonprogressors (69%) and 10 progressors (31%), while in the placebo group 13 subjects (42%) were nonprogressors and 18 (58%) were progressors (P < .03). In the lovastatin-treated group, lipid and lipoprotein parameters did not differ between progressors and nonprogressors except for LpBc and LpA-II:B:C:D:E particle levels, which were statistically higher in progressors (P = .02). In the placebo-treated group, progressors differed from nonprogressors by having significantly higher levels of triglycerides (P = .03) and apoC-III in VLDL + LDL (P = .05), the characteristic constituents of triglyceride-rich lipoproteins. In the placebo- and lovastatin-treated groups combined, progressors had significantly higher on-trial levels of triglycerides (P = .003), VLDL cholesterol (P = .005), apoC-III in VLDL + LDL (P = .008), apoC-III (P = .01), apoB (P = .03), and total cholesterol (P = .04) than nonprogressors. Even after adjustment for treatment group, progressors in the combined placebo- and lovastatin-treated groups had significantly higher levels of LpBc, LpA-II:B:C:D:E, triglycerides, and apoC-III in VLDL + LDL than nonprogressors. Progressors in the placebo-treated, lovastatin-treated, and combined treatment groups had lower levels of LpA-1 but not LpA-I:A-II than non-progressors, and this difference reached statistical significance (P = .047) in the combined sample adjusted for treatment group. Results of this study show that elevated levels of triglyceride-rich LpBc in general and LpA-II:B:C:D:E in particular contribute significantly to the progression of coronary artery disease. Furthermore, they provide additional evidence for the potentially protective role of LpA-I particles in the atherogenic process and suggest that apolipoprotein-defined lipoprotein families may be more specific prognosticators of coronary artery atherosclerosis progression than lipids and apolipoproteins.
authors.affiliation: Lipid and Lipoprotein Laboratory, Okalhoma Medical Research Foundation, Oklahoma City, USA.
authors.forename: P
authors.initials: P
authors.lastname: Alaupovic
authors.forename: W J
authors.initials: WJ
authors.lastname: Mack
authors.forename: C
authors.initials: C
authors.lastname: Knight-Gibson
authors.forename: H N
authors.initials: HN
authors.lastname: Hodis
mesh_terms: D000328:Adult; D000368:Aged; D001053:Apolipoproteins / Q000097:blood; D001161:Arteriosclerosis / Q000473:pathology*; D017023:Coronary Angiography; D005260:Female; D006801:Humans; D006937:Hypercholesterolemia / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology; D008074:Lipoproteins / Q000097:blood / Q000378:metabolism*; D008148:Lovastatin / Q000627:therapeutic use; D008297:Male; D008875:Middle Aged; D016017:Odds Ratio; D013997:Time Factors; D014280:Triglycerides / Q000378:metabolism*
chemical_list: D001053:Apolipoproteins; D008074:Lipoproteins; D014280:Triglycerides; D008148:Lovastatin