doi: 10.1161/hc5001.100795
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
(Circulation. 2001;104:3057.)
© 2001 American Heart Association, Inc.
Clinical Investigation and Reports |
Low Hepatic Lipase Activity Is a Novel Risk Factor for Coronary Artery Disease
From the Department of Internal Medicine I (Endocrinology and Metabolism) (K.A.D., K.B., N.S., B.N., J.G.S., S.M., T.K., C.M., H.K.), Central Laboratory (W.F.), Internal Medicine III (Cardiology) (J.K.), Department of Radiology (M.L.B.), University of Heidelberg, Heidelberg, Germany, and Department of Cardiology (J.R.S.), University of Marburg, Marburg, Germany.
Correspondence to Klaus A. Dugi, MD, Department of Internal Medicine I, Bergheimer Straße 58, 69115 Heidelberg, Germany. E-mail klaus_dugi{at}med.uni-heidelberg.de
Background— The crucial function of hepatic lipase (HL) in lipid metabolism has been well established, but the relationship between HL activity and coronary artery disease (CAD) is disputed.
Methods and Results— We measured HL activity in the postheparin plasma of 200 consecutive men undergoing elective coronary angiography and determined the degree of CAD with the extent score, which has been shown to be better correlated with known risk factors than other measures of CAD extent. We found a significant inverse correlation between HL activity and the extent of CAD (r=-0.19, P<0.01). This association was mainly due to patients with HDL levels >0.96 mmol/L (n=94, r=-0.30, P<0.005). HL activity was lower in 173 patients with CAD than in 40 controls with normal angiograms (286±106 versus 338±108 nmol · mL-1 · min-1, P<0.01). To correct for potential confounding factors, we performed multivariate analyses that confirmed the independent association of HL activity with CAD extent. In addition, the presence of the T allele at position -514 in the HL promoter, which leads to a reduced HL promoter activity, was associated with lower HL activity (r=0.30, P<0.001) and higher CAD extent (42.2±20.8 versus 35.3±23.6 [extent score], P<0.05). In patients with heterozygous familial hypercholesterolemia, calcified lesions in ECG-gated spiral computed tomography were higher in patients with low HL activity (6.3±6.8 versus 1.5±3.1, P=0.01).
Conclusions— Our data show that low HL activity is associated with CAD. Therefore, HL might be useful for CAD risk estimation and might be a target for pharmacological intervention.
Key Words: angiography • atherosclerosis • coronary disease • lipoproteins
This article has been cited by other articles:
 |
|
 |
|
  P. M. Lepper, C. Schumann, K. Triantafilou, F. M. Rasche, T. Schuster, H. Frank, E. M. Schneider, M. Triantafilou, and M. von Eynatten Association of Lipopolysaccharide-Binding Protein and Coronary Artery Disease in Men J. Am. Coll. Cardiol., July 3, 2007; 50(1): 25 - 31. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. von Eynatten, J. G. Schneider, P. M. Humpert, J. Kreuzer, H. Kuecherer, H. A. Katus, P. P. Nawroth, and K. A. Dugi Serum Adiponectin Levels Are an Independent Predictor of the Extent of Coronary Artery Disease in Men J. Am. Coll. Cardiol., May 16, 2006; 47(10): 2124 - 2126. [Full Text] [PDF]
|
|
|
|
 |
|
 S. L. Karackattu, B. Trigatti, and M. Krieger Hepatic Lipase Deficiency Delays Atherosclerosis, Myocardial Infarction, and Cardiac Dysfunction and Extends Lifespan in SR-BI/Apolipoprotein E Double Knockout Mice Arterioscler. Thromb. Vasc. Biol., March 1, 2006; 26(3): 548 - 554. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 N. Stefan, S. Schafer, F. Machicao, J. Machann, F. Schick, C. D. Claussen, M. Stumvoll, H.-U. Haring, and A. Fritsche Liver Fat and Insulin Resistance Are Independently Associated with the -514C>T Polymorphism of the Hepatic Lipase Gene J. Clin. Endocrinol. Metab., July 1, 2005; 90(7): 4238 - 4243. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
Y.-M. Fan, P. Dastidar, H. Jokela, R. Punnonen, and T. Lehtimaki Hepatic Lipase C-480T Genotype-Dependent Benefit from Long-Term Hormone Replacement Therapy for Atherosclerosis Progression in Postmenopausal Women J. Clin. Endocrinol. Metab., June 1, 2005; 90(6): 3786 - 3792. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 H. Gonzalez-Navarro, Z. Nong, M. J. A. Amar, R. D. Shamburek, J. Najib-Fruchart, B. J. Paigen, H. B. Brewer Jr., and S. Santamarina-Fojo The Ligand-binding Function of Hepatic Lipase Modulates the Development of Atherosclerosis in Transgenic Mice J. Biol. Chem., October 29, 2004; 279(44): 45312 - 45321. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. Santamarina-Fojo, H. Gonzalez-Navarro, L. Freeman, E. Wagner, and Z. Nong Hepatic Lipase, Lipoprotein Metabolism, and Atherogenesis Arterioscler. Thromb. Vasc. Biol., October 1, 2004; 24(10): 1750 - 1754. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. Isaacs, F. A. Sayed-Tabatabaei, O. T. Njajou, J. C. M. Witteman, and C. M. van Duijn The -514 C->T Hepatic Lipase Promoter Region Polymorphism and Plasma Lipids: A Meta-Analysis J. Clin. Endocrinol. Metab., August 1, 2004; 89(8): 3858 - 3863. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 Y M Fan, J T Salonen, T A Koivu, T-P Tuomainen, K Nyyssonen, T A Lakka, R Salonen, K Seppanen, S T Nikkari, E Tahvanainen, et al. Hepatic lipase C-480T polymorphism modifies the effect of HDL cholesterol on the risk of acute myocardial infarction in men: a prospective population based study J. Med. Genet., March 1, 2004; 41(3): e28 - 28. [Full Text] [PDF]
|
|
|
|
 |
|
 J. E. Hokanson, M. I. Kamboh, S. Scarboro, R. H. Eckel, and R. F. Hamman Effects of the Hepatic Lipase Gene and Physical Activity on Coronary Heart Disease Risk Am. J. Epidemiol., November 1, 2003; 158(9): 836 - 843. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 E S. Tai, D. Corella, M. Deurenberg-Yap, J. Cutter, S. K. Chew, C. E. Tan, and J. M. Ordovas Dietary Fat Interacts with the -514C>T Polymorphism in the Hepatic Lipase Gene Promoter on Plasma Lipid Profiles in a Multiethnic Asian Population: The 1998 Singapore National Health Survey J. Nutr., November 1, 2003; 133(11): 3399 - 3408. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. L. Anderson and J. F. Carlquist Genetic polymorphisms of hepatic lipase and cholesteryl ester transfer protein, intermediate phenotypes, and coronary risk: Do they add up yet? J. Am. Coll. Cardiol., June 4, 2003; 41(11): 1990 - 1993. [Full Text] [PDF]
|
|
|
|
 |
|
 J. L. Anderson, J. F. Carlquist, B. D. Home, and J. B. Muhlestein Cardiovascular Pharmacogenomics: Current Status, Future Prospects Journal of Cardiovascular Pharmacology and Therapeutics, March 1, 2003; 8(1): 71 - 83. [Abstract] [PDF]
|
|
|
|
 |
|
 J. M. Ordovas, D. Corella, S. Demissie, L. A. Cupples, P. Couture, O. Coltell, P. W.F. Wilson, E. J. Schaefer, and K. L. Tucker Dietary Fat Intake Determines the Effect of a Common Polymorphism in the Hepatic Lipase Gene Promoter on High-Density Lipoprotein Metabolism: Evidence of a Strong Dose Effect in This Gene-Nutrient Interaction in the Framingham Study Circulation, October 29, 2002; 106(18): 2315 - 2321. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 H. Jansen, A. J. M. Verhoeven, and E. J. G. Sijbrands Hepatic lipase: a pro- or anti-atherogenic protein? J. Lipid Res., September 1, 2002; 43(9): 1352 - 1362. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. Q. Zhang, B. Smith, M. M. Langdon, H. L. Messimer, G. Y. Sun, R. H. Cox, M. James-Kracke, and T. R. Thomas Changes in LPLa and reverse cholesterol transport variables during 24-h postexercise period Am J Physiol Endocrinol Metab, August 1, 2002; 283(2): E267 - E274. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. E. Hokanson, S. Cheng, J. K. Snell-Bergeon, B. A. Fijal, M. A. Grow, C. Hung, H. A. Erlich, J. Ehrlich, R. H. Eckel, and M. Rewers A Common Promoter Polymorphism in the Hepatic Lipase Gene (LIPC-480C>T) Is Associated With an Increase in Coronary Calcification in Type 1 Diabetes Diabetes, April 1, 2002; 51(4): 1208 - 1213. [Abstract] [Full Text] [PDF]
|
|