Lipoprotein lipase gene mutations, plasma lipid levels, progression regression of coronary atherosclerosis, response to therapy, and future clinical events - Lipoproteins and Coronary Atherosclerosis Study

Mutations in human lipoprotein lipase (LPL) gene are potential risk factors for susceptibility to coronary artery disease (CAD). The objectives of thi s study were to determine the influence LPL mutations Asn(291)Ser and Ser(4 47)Ter on plasma lipid levels, regression and progression of CAD, clinical events rate, and response to fluvastatin therapy in the Lipoprotein and Cor onary Atherosclerosis Study (LCAS) population. LCAS is a double blind, rand omized, placebo-controlled study designed to test the influence of fluvasta tin on progression or regression of CAD. The Asn(291)Ser and Ser(447)Ter ge notypes were determined by polymerase chain reaction (PCR) and restriction enzyme digestion. Fasting plasma lipid profiles were measured and quantitat ive coronary angiography was performed at baseline and 2.5 years following randomization. Fatal and non-fatal cardiovascular events during the follow- up period were recorded. A total of 4% (14/363) and 18% (62/352) of the sub jects had the Asn291Ser and Ser(447)Ter mutations, respectively. Overall, t here was no statistically association between the Asn(291)Ser and Ser(447)T er mutations and the baseline or final mean plasma levels of lipids, number of coronary lesions, total occlusions, the mean minimal lumen diameter (ML D) stenoses and the clinical events rate. However, patients with the Ser(44 7)Ter variant had a slightly higher baseline high density lipoprotein-chole sterol (HDL-C) level (46.2 +/- 12 vs 43.2 +/- 11, P = 0.057), less increase in plasma HDL levels in response to fluvastatin therapy (3 vs 11%, P = 0.0 56) and a higher cardiovascular events rate (23 vs 13%, P = 0.056). Thus, t he Ser(447)Ter variant had a modest influence on plasma HDL levels and the rate of cardiovascular events. These changes were of borderline statistical significance. Neither the Ser(447)Ter nor the Asn(291)Ser mutation had a m ajor impact on susceptibility to CAD, progression or regression of CAD, cli nical events rate or response to fluvastatin therapy in LCAS population. (C ) 1999 Elsevier Science Ireland Ltd. All rights reserved.