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 atherosc lerosis. 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 o utcome of the 2-year, randomised, placebo-controlled Lipid Coronary Angiogr aphy Trial (LOCAT), which used gemfibrozil as lipid lowering agent. The RLP -C response to gemfibrozil treatment has not been described before. Gemfibr ozil reduced the median RLP-C concentration by 34%. The on-treatment RLP-C concentration was significantly associated with the progression of the mini mum 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 tri glycerides and the association between on-treatment RLP-C concentration and progression of MLD was not independent of plasma triglycerides. A signific ant relation was seen between RLP-C and the occurrence of new lesions in ve in grafts. Subjects with one new lesion had an <similar to> 25% higher on-t reatment RLP-C concentration and the four patients showing two new lesions had a 100% higher RLP-C concentration than patients without vein graft sten osis. 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 co nclude that the RLP-C concentration, which is likely to reflect the plasma cholesterol contained in postprandially modified VLDL and chylomicron remna nts, is strongly associated with angiographically verified progression of f ocal coronary atherosclerosis, and that lowering of RLPs prevents vein graf t stenosis. (C) 2001 Elsevier Science Ireland Ltd. All rights reserved.