The effect of aggressive and moderate lowering of LDL-cholesterol and low dose anticoagulation on plasma lipids, apolipoproteins and lipoprotein families in post coronary artery bypass graft trial.
The reported results (The Post Coronary Artery Bypass Graft Trial Investigators. The effect of aggressive lowering of low-density lipoprotein cholesterol levels and low-dose anticoagulation on obstructive changes in saphenous-vein coronary-artery bypass grafts. New Engl J Med 1997;336:153-162) of the Post Coronary Artery Bypass Graft (Post CABG) trial have shown that aggressive lowering was more effective than moderate lowering of low density lipoprotein (LDL) cholesterol in reducing the progression of atherosclerosis in saphenous-vein grafts (27 vs. 39%; P < 0.001); low dose warfarin had no effect on the progression of atherosclerosis. The present report describes the effect of long-term (an average of 4.3 years) aggressive treatment with high (40-80 mg/day) and moderate treatment with low (2.5-5 mg/day) doses of lovastatin on lipids, apolipoproteins (apo) and apoA- and apoB-containing lipoprotein families. To achieve the target LDL-cholesterol levels (60-85 mg/dl for aggressive group and 134-140 mg/dl for moderate group), cholestyramine (8 g/day) was given to 25% of subjects on aggressive and 5% of subjects on moderate treatment. Although with both treatment strategies there were significant decreases (P<0.001) in the levels of total cholesterol, LDL-cholesterol, apoB, LDL-apoB and cholesterol-rich Lp-B family, percent changes in the levels of these variables were greater in the aggressive- than in the moderate-treatment groups. These treatments had only marginal effects in increasing the levels of high density lipoprotein cholesterol, apoA-I and Lp-A-I and Lp-A-I:A-II families. The long-term aggressive treatment exerted no effect on the concentrations of triglycerides, apoC-IlI, apoC-III in VLDL + LDL and triglyceride-rich Lp-Bc families. Neither treatment affected the levels of Lp(a). The potentially modifying influence of warfarin and apoE phenotypes on lovastatin-induced changes in lipoprotein variables was found to be of little significance. It is likely that the beneficial effect of lovastatin in reducing the progression of atherosclerosis in grafts is mediated through its specific lowering effect on cholesterol-rich Lp-B particles.
Alaupovic
P
P
Lipid and Lipoprotein Laboratory, Oklahoma Medical Research Foundation, Oklahoma City, USA.
Fesmire
J D
JD
Hunnighake
D
D
Domanski
M
M
Forman
S
S
Knatterud
G L
GL
Forrester
J
J
Herd
J A
JA
Hoogwerf
B
B
Campeau
L
L
Gobel
F L
FL
D000924:Anticholesteremic Agents / Q000627:therapeutic use*; D000925:Anticoagulants / Q000627:therapeutic use*; D001053:Apolipoproteins / Q000097:blood*; D001057:Apolipoproteins E / Q000097:blood / Q000235:genetics; D001161:Arteriosclerosis / Q000097:blood / Q000150:complications / Q000628:therapy*; D008076:Cholesterol, HDL / Q000097:blood; D008078:Cholesterol, LDL / Q000097:blood*; D001026:Coronary Artery Bypass; D003327:Coronary Disease / Q000601:surgery*; D018450:Disease Progression; D004311:Double-Blind Method; D005260:Female; D006083:Graft Occlusion, Vascular / Q000097:blood / Q000209:etiology / Q000517:prevention & control*; D006801:Humans; D008055:Lipids / Q000097:blood*; D008079:Lipoproteins, VLDL / Q000097:blood; D008297:Male; D008875:Middle Aged; D012501:Saphenous Vein / Q000637:transplantation; D016896:Treatment Outcome; D014280:Triglycerides / Q000097:blood
D000924:Anticholesteremic Agents; D000925:Anticoagulants; D001053:Apolipoproteins; D001057:Apolipoproteins E; D008076:Cholesterol, HDL; D008078:Cholesterol, LDL; D008055:Lipids; D008079:Lipoproteins, VLDL; D014280:Triglycerides