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Arteriosclerosis, Thrombosis, and Vascular Biology. 2006;26:637-642
Published online before print December 22, 2005, doi: 10.1161/01.ATV.0000201038.47949.56
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(Arteriosclerosis, Thrombosis, and Vascular Biology. 2006;26:637.)
© 2006 American Heart Association, Inc.


Atherosclerosis and Lipoproteins

Serum Lipoprotein Lipase Concentration and Risk for Future Coronary Artery Disease

The EPIC-Norfolk Prospective Population Study

Jaap Rip; Melchior C. Nierman; Nicholas J. Wareham; Robert Luben; Sheila A. Bingham; Nicholas E. Day; Joram N.I. van Miert; Barbara A. Hutten; John J.P. Kastelein; Jan Albert Kuivenhoven; Kay-Tee Khaw; S. Matthijs Boekholdt

From the Departments of Vascular Medicine (J.R., M.C.N., J.N.I.M., J.J.P.K., J.A.K.), Cardiology (S.M.B.), and Clinical Epidemiology and Biostatistics (B.A.H.), Academic Medical Center, Amsterdam, The Netherlands; Medical Research Council Epidemiology Unit (N.J.W.), Cambridge, United Kingdom; Medical Research Council Dunn Nutrition Unit (S.A.B.), Cambridge, United Kingdom; and the Department of Public Health and Primary Care (R.L., N.E.D., K.T.K.), Institute of Public Health, University of Cambridge, United Kingdom.

Correspondence to Jan Albert Kuivenhoven, PhD, Academic Medical Center, Department of Vascular Medicine, Room L1-108, Meibergdreef 9, 1105 AZ, Amsterdam. E-mail j.a.kuivenhoven{at}amc.uva.nl

Background— Lipoprotein lipase (LPL) is associated with coronary artery disease (CAD) risk, but prospective population data are lacking. This is mainly because of the need for cumbersome heparin injections, which are necessary for LPL measurements. Recent retrospective studies, however, indicate that LPL concentration can be reliably measured in serum that enabled evaluation of the prospective association between LPL and future CAD.

Methods and Results— LPL concentration was determined in serum samples of men and women in the EPIC-Norfolk population cohort who developed fatal or nonfatal CAD during 7 years of follow-up. For each case (n=1006), 2 controls, matched for age, sex, and enrollment time, were identified. Serum LPL concentration was lower in cases compared with controls (median and interquartile range: 61 [43–85] versus 66 [46–92] ng/mL; P<0.0001). Those in the highest LPL concentration quartile had a 34% lower risk for future CAD compared with those in the lowest quartile (odds ratio [OR] 0.66; confidence interval [CI], 0.53 to 0.83; P<0.0001). This effect remained significant after adjustment for blood pressure, diabetes, smoking, body mass index, and low-density lipoprotein (LDL) cholesterol (OR, 0.77; CI, 0.60–0.99; P=0.02). As expected from LPL biology, additional adjustments for either high-density lipoprotein cholesterol (HDL-C) or triglyceride (TG) levels rendered loss of statistical significance. Of interest, serum LPL concentration was positively linear correlated with HDL and LDL size.

Conclusions— Reduced levels of serum LPL are associated with an increased risk for future CAD. The data suggest that high LPL concentrations may be atheroprotective through decreasing TG levels and increasing HDL-C levels.

Lipoprotein lipase (LPL) is associated with coronary artery disease (CAD) risk, but prospective population data are lacking. This study addresses the prospective association between LPL and future CAD through measuring LPL concentration in serum. The data indicated that reduced levels of serum LPL are associated with an increased risk for future CAD.


Key Words: preheparin lipoprotein lipase • cardiovascular diseases • lipoproteins • lipids • cholesterol




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