Remnant-like lipoprotein particle cholesterol concentration and progression of coronary and vein-graft atherosclerosis in response to gemfibrozil treatment.
Remnant lipoproteins such as chylomicron and very low density lipoprotein (VLDL) remnants have been implicated in the progression of coronary atherosclerosis. Recently, a novel method for the determination of the remnant-like lipoprotein particle cholesterol (RLP-C) concentration was developed based on immunoaffinity-separation of plasma. The compositional characteristics of RLP are strikingly similar to those of postprandially modified VLDL. In addition, the method also detects chylomicron remnants. We investigated the relationship between the plasma RLP-C concentration and the angiographic outcome of the 2-year, randomised, placebo-controlled Lipid Coronary Angiography Trial (LOCAT), which used gemfibrozil as lipid lowering agent. The RLP-C response to gemfibrozil treatment has not been described before. Gemfibrozil reduced the median RLP-C concentration by 34%. The on-treatment RLP-C concentration was significantly associated with the progression of the minimum lumen diameter (MLD) (P<0.004). The plasma levels of RLP-C as well as the change in response to treatment was closely associated with plasma triglycerides and the association between on-treatment RLP-C concentration and progression of MLD was not independent of plasma triglycerides. A significant relation was seen between RLP-C and the occurrence of new lesions in vein grafts. Subjects with one new lesion had an approximately 25% higher on-treatment RLP-C concentration and the four patients showing two new lesions had a 100% higher RLP-C concentration than patients without vein graft stenosis. A total of 19 out of 23 subjects having one new lesion, and all four patients showing two new lesions, were assigned to the placebo group. We conclude that the RLP-C concentration, which is likely to reflect the plasma cholesterol contained in postprandially modified VLDL and chylomicron remnants, is strongly associated with angiographically verified progression of focal coronary atherosclerosis, and that lowering of RLPs prevents vein graft stenosis.
Karpe
F
F
Oxford Lipid Metabolism Group, Centre for Diabetes, Endocrinology and Metabolism, Radcliffe Infirmary, University of Oxford, Oxford OX2 6HE, UK. fredrik.karpe@oxlip.ox.ac.uk
Taskinen
M R
MR
Nieminen
M S
MS
Frick
M H
MH
Kesäniemi
Y A
YA
Pasternack
A
A
Hamsten
A
A
Syvänne
M
M
D001053:Apolipoproteins / Q000097:blood; D002784:Cholesterol / Q000097:blood; D003251:Constriction, Pathologic / Q000097:blood / Q000188:drug therapy*; D003324:Coronary Artery Disease / Q000097:blood / Q000188:drug therapy*; D004311:Double-Blind Method; D015248:Gemfibrozil / Q000008:administration & dosage*; D006801:Humans; D000960:Hypolipidemic Agents / Q000008:administration & dosage*; D008074:Lipoproteins / Q000097:blood; D014280:Triglycerides / Q000097:blood; D014680:Veins / Q000473:pathology
D001053:Apolipoproteins; D000960:Hypolipidemic Agents; D008074:Lipoproteins; D014280:Triglycerides; C112017:remnant-like particle cholesterol; D002784:Cholesterol; D015248:Gemfibrozil