Lipoprotein lipase activity is decreased in a large cohort of patients with coronary artery disease and is associated with changes in lipids and lipoproteins

Lipoprotein lipase (LPL) is crucial in the hydrolysis of triglycerides (TG) in TG-rich lipoproteins in the formation of HDL particles. As both these l ipoproteins play an important role in the pathogenesis of atherosclerotic v ascular disease, we sought to assess the relationship between post-heparin LPL (PH-LPL) activity and lipids and lipoproteins in a large, well-defined cohort of Dutch males with coronary artery disease (CAD), These subjects we re: drawn from the REGRESS study, totaled 730 in number and were evaluated against 75 healthy, normolipidemic male controls. Easting mean PH-LPL activ ity in the CAD subjects was 108 (46) mU/ml, compared to 138 (44) mU/ml in c ontrols (P < 0.0001). When these patients were divided into activity quarti les, those in the lowest versus the highest quartile had higher levels of T G (P < 0.001), VLDLc and VLDL-TG (P = 0.001). Conversely, levels of TC, LDL , and HDLc were lower in these patients (P = 0.001, P = 0.02, and P = 0.001 , respectively). Also, in this cohort PH-LPL relationships with lipids and lipoproteins were not altered by apoE genotypes, The frequency of common mu tations in the LPL gene associated with partial LPL deficiency (N291S and D 9N carriers) in the lowest quartile for LPL activity was more than double t he frequency in the highest quartile (12.0% vs. 5.0%; P = 0.006). By contra st, the frequency of the S447X LPL variant rose from 11.5% in the lowest to 18.3% (P = 0.006) in the highest quartile. This study, in a large cohort o f CAD patients, has shown that PH-LPL activity is decreased (22%; P = 0.001 ) when compared to controls; that the D9N and N291S, and S447X LPL variants are genetic determinants, respectively, in CAD patients of low and high LP L PH-LPL activities; and that PH-LPL activity is strongly associated with c hanges in lipids and lipoproteins.