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Correspondence to:
John J. P. Kastelein
Lipoprotein lipase (LPL) is crucial in the hydrolysis of triglycerides (TG) in TG-rich lipoproteins in the formation of HDL particles. As both these lipoproteins play an important role in the pathogenesis of atherosclerotic vascular 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 were drawn from the REGRESS study, totaled 730 in number and were evaluated against 75 healthy, normolipidemic male controls. Fasting mean PH-LPL activity in the CAD subjects was 108 (46) mU/ml, compared to 138 (44) mU/ml in controls (P < 0.0001). When these patients were divided into activity quartiles, those in the lowest versus the highest quartile had higher levels of TG (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 mutations in the LPL gene associated with partial LPL deficiency (N291S and D9N carriers) in the lowest quartile for LPL activity was more than double the frequency in the highest quartile (12.0% vs. 5.0%; P = 0.006). By contrast, 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 of 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 LPL PH-LPL activities; and that PH-LPL activity is strongly associated with changes in lipids and lipoproteins.—Henderson, H. E., J. J. P. Kastelein, A. H. Zwinderman, E. Gagne, J. W. Jukema, P. W. A. Reymer, B. E. Groenemeyer, K. I. Lie, A. V. G. Bruschke, M. R. Hayden, and H. Jansen. Lipoprotein lipase activity is decreased in a large cohort of patients with coronary artery disease and is associated with changes in lipids and lipoproteins. J. Lipid Res. 1999. 40: 735–743.
Supplementary key words:
REGRESS study, VLDL, LDL, HDL, cholesterol, triglyceride
Copyright © 1999 by Lipid Research, Inc.
Original Article
Lipoprotein lipase activity is decreased in a large cohort of patients with coronary artery disease and is associated with changes in lipids and lipoproteins
Howard E. Hendersona,b,
John J. P. Kasteleina,c,
Aeilko H. Zwindermand,
Eric Gagnéa,
J. Wouter Jukemae,
Paul W. A. Reymere,
Björn E. Groenemeyerg,
Kong I. Lief,
Albert V. G. Bruschkee,
Michael R. Haydena, and
Hans Jansenh
a Department of Medical Genetics, University of British Columbia, Vancouver, Canada
b Department of Chemical Pathology, University of Cape Town, Cape Town, South Africa
c Lipid Research Group, Department of Vascular Medicine, University of Amsterdam, Amsterdam, The Netherlands
d Department of Medical Statistics, University of Leiden, Leiden, The Netherlands
e Department of Cardiology, University Hospital, Leiden, The Netherlands
f Department of Cardiology, University of Amsterdam, Amsterdam, The Netherlands
g Interuniversity Cardiology Institute of the Netherlands (ICIN), Utrecht, The Netherlands
h Department of Biochemistry, Erasmus University, Rotterdam, The Netherlands
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