THE ROLE OF TRIGLYCERIDE-RICH LIPOPROTEIN FAMILIES IN THE PROGRESSIONOF ATHEROSCLEROTIC LESIONS AS DETERMINED BY SEQUENTIAL CORONARY ANGIOGRAPHY FROM A CONTROLLED CLINICAL-TRIAL

We have demonstrated previously in a subset of Monitored Atheroscleros is Regression Study (MARS) subjects with hypercholesterolemia (190 to 295 mg/dL) and documented coronary artery disease that lovastatin sign ificantly reduces cholesterol-rich lipoprotein B (LpB) but has little effect on complex, triglyceride-rich apolipoprotein (ape) B-containing LpB(c) (the sum of LpB:C, LpB:C:E and LpA-II:B:C:D:E) particles defin ed by their apolipoprotein composition. This differential effect of lo vastatin on apoB-containing lipoprotein families offered the opportuni ty to determine in the same subset of MARS subjects the independent re lationship of LpB and LpB(c) with the progression of coronary artery d isease. Subjects randomized to either lovastatin (40 mg twice daily) o r matching placebo were evaluated by coronary angiography before rando mization and after 2 years of treatment, and the overall coronary stat us was judged by a coronary global change score. In the lovastatin-tre ated group, there were 22 nonprogressors (69%) and 10 progressors (31% ), while in the placebo group 13 subjects (42%) were nonprogressors an d 18 (58%) were progressors (P<.03). In the lovastatin-treated group, lipid and lipoprotein parameters did not differ between progressors an d nonprogressors except for LpB(c) and LpA-II:B:C:D:E particle levels, which were statistically higher in progressors (P=.02). In the placeb o-treated group, progressors differed from nonprogressors by having si gnificantly higher levels of triglycerides (P=.03) and apoC-III in VLD L+LDL (P=.05), the characteristic constituents of triglyceride-rich li poproteins. In the placebo- and lovastatin-treated groups combined, pr ogressors 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 nonprogr essors. Even after adjustment for treatment group, progressors in the combined placebo- and lovastatin-treated groups had significantly high er levels of LpB(c), LpA-II:B:C:D:E, triglycerides, and apoC-III in VL DL+LDL than nonprogressors. Progressors in the placebo-treated, lovast atin-treated, and combined treatment groups had lower levels of LpA-I but not LpA-I:A-II than nonprogressors, and this difference reached st atistical significance (P=.047) in the combined sample adjusted for tr eatment group. Results of this study show that elevated levels of trig lyceriderich LpB(c) in general and LpA-II:B:C:D:E in particular contri bute significantly to the progression of coronary artery disease. Furt hermore, they provide additional evidence for the potentially protecti ve role of LpA-I particles in the atherogenic process and suggest that apolipoprotein-defined lipoprotein families may be more specific prog nosticators of coronary artery atherosclerosis progression than lipids and apolipoproteins.