(Stroke. 1996;27:1755-1759.)
© 1996 American Heart Association, Inc.
Articles |
Apolipoprotein E Polymorphism Is Associated With Segment-Specific Extracranial Carotid Artery Intima-Media Thickening
the Departments of Internal Medicine (J.R.C., J.G.T.), Public Health Sciences (G.H.), and Neurobiology and Anatomy (M.M., M.G.B.), Bowman Gray School of Medicine, Winston-Salem, NC.
Correspondence to John R. Crouse III, MD, Department of Internal Medicine/Section on Endocrinology, Medical Center Blvd, Winston-Salem, NC 27157.
Background and Purpose Apolipoprotein E (apoE) polymorphism affects plasma cholesterol and may influence risk of atherosclerosis. We investigated the association of apoE with carotid artery wall thickening (an index of atherosclerosis) in individuals with and without coronary artery disease (CAD).
Methods ApoE phenotypes were resolved in 260 individuals equally represented by angiographically determined CAD case subjects and disease-free control subjects. Carotid artery intima-media thickening (IMT) was evaluated by B-mode ultrasound. Associations of apoE (E2, E3, or E4) with risk factors and IMT were evaluated in general linear models adjusted for age, sex, and CAD status with and without other traditional risk factors.
Results Total cholesterol (TC) and LDL cholesterol were associated with apoE isoforms. Mean TC and LDL cholesterol were lower in E2 (n=33) carriers than E3 (n=155) and E4 (n=66) carriers (each P<.001). IMT also varied by apoE. E2 carriers had less common carotid IMT than E3 and E4 carriers (P<.01), while internal carotid IMT was less in E2 and E3 carriers than in E4 carriers (P<.02). Bifurcation IMT was not associated with apoE (P=.24). ApoE polymorphism remained associated with common (P<.01) and internal (P<.04) IMT, and the association of apoE with mean IMT of all sites reached significance (P<.04) after adjustment for age, sex, CAD status, TC, LDL cholesterol, HDL cholesterol, triglycerides, diabetes, hypertension, and smoking.
Conclusions ApoE polymorphism is associated with segment-specific carotid IMT. The association of apoE with carotid IMT was statistically independent of apoE-associated variation in LDL cholesterol levels.
Key Words: apolipoproteins • atherosclerosis • carotid arteries • coronary artery disease • ultrasonics
This article has been cited by other articles:
 |
|
 |
|
  D. C. Crawford, A. S. Nord, M. D. Badzioch, J. Ranchalis, L. A. McKinstry, M. Ahearn, C. Bertucci, C. Shephard, M. Wong, M. J. Rieder, et al. A common VLDLR polymorphism interacts with APOE genotype in the prediction of carotid artery disease risk J. Lipid Res., March 1, 2008; 49(3): 588 - 596. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 L. Paternoster, N. A. Martinez Gonzalez, S. Lewis, and C. Sudlow Association Between Apolipoprotein E Genotype and Carotid Intima-Media Thickness May Suggest a Specific Effect on Large Artery Atherothrombotic Stroke Stroke, January 1, 2008; 39(1): 48 - 54. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. M. Bennet, E. Di Angelantonio, Z. Ye, F. Wensley, A. Dahlin, A. Ahlbom, B. Keavney, R. Collins, B. Wiman, U. de Faire, et al. Association of Apolipoprotein E Genotypes With Lipid Levels and Coronary Risk JAMA, September 19, 2007; 298(11): 1300 - 1311. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. Debette, J.-C. Lambert, J. Gariepy, N. Fievet, C. Tzourio, J.-F. Dartigues, K. Ritchie, A.-M. Dupuy, A. Alperovitch, P. Ducimetiere, et al. New Insight Into the Association of Apolipoprotein E Genetic Variants With Carotid Plaques and Intima-Media Thickness Stroke, December 1, 2006; 37(12): 2917 - 2923. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 K. A. Volcik, R. A. Barkley, R. G. Hutchinson, T. H. Mosley, G. Heiss, A. R. Sharrett, C. M. Ballantyne, and E. Boerwinkle Apolipoprotein E Polymorphisms Predict Low Density Lipoprotein Cholesterol Levels and Carotid Artery Wall Thickness but Not Incident Coronary Heart Disease in 12,491 ARIC Study Participants Am. J. Epidemiol., August 15, 2006; 164(4): 342 - 348. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
L. E. Viiri, O. T. Raitakari, H. Huhtala, M. Kahonen, R. Rontu, M. Juonala, N. Hutri-Kahonen, J. Marniemi, J. S. A. Viikari, P. J. Karhunen, et al. Relations of APOE promoter polymorphisms to LDL cholesterol and markers of subclinical atherosclerosis in young adults J. Lipid Res., June 1, 2006; 47(6): 1298 - 1306. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. BEDNARSKA-MAKARUK, M. RODO, C. MARKUSZEWSKI, A. ROZENFELD, M. SWIDERSKA, B. HABRAT, and H. WEHR POLYMORPHISMS OF APOLIPOPROTEIN E AND ANGIOTENSIN-CONVERTING ENZYME GENES AND CAROTID ATHEROSCLEROSIS IN HEAVY DRINKERS Alcohol Alcohol., July 1, 2005; 40(4): 274 - 282. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. Hamsten, A. Silveira, S. Boquist, R. Tang, M. G. Bond, U. de Faire, and J. Bjorkegren The apolipoprotein CI content of triglyceride-rich lipoproteins independently predicts early atherosclerosis in healthy middle-aged men J. Am. Coll. Cardiol., April 5, 2005; 45(7): 1013 - 1017. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
R. Elosua, J. M. Ordovas, L. A. Cupples, C. S. Fox, J. F. Polak, P. A. Wolf, R. A. D'Agostino Sr., and C. J. O'Donnell Association of APOE genotype with carotid atherosclerosis in men and women: the Framingham Heart Study J. Lipid Res., October 1, 2004; 45(10): 1868 - 1875. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 T. A. Manolio, E. Boerwinkle, C. J. O'Donnell, and A. F. Wilson Genetics of Ultrasonographic Carotid Atherosclerosis Arterioscler Thromb Vasc Biol, September 1, 2004; 24(9): 1567 - 1577. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 Y. Song, M. J. Stampfer, and S. Liu Meta-Analysis: Apolipoprotein E Genotypes and Risk for Coronary Heart Disease Ann Intern Med, July 20, 2004; 141(2): 137 - 147. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. P. Beilby, C. C.J. Hunt, L. J. Palmer, C. M.L. Chapman, J. P. Burley, B. M. McQuillan, P. L. Thompson, and J. Hung Apolipoprotein E Gene Polymorphisms Are Associated With Carotid Plaque Formation but Not With Intima-Media Wall Thickening: Results From the Perth Carotid Ultrasound Disease Assessment Study (CUDAS) Stroke, April 1, 2003; 34(4): 869 - 874. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. G. Terry, R. Tang, M. A. Espeland, D. H. Davis, J. L.C. Vieira, M. F. Mercuri, and J. R. Crouse III Carotid Arterial Structure in Patients With Documented Coronary Artery Disease and Disease-Free Control Subjects Circulation, March 4, 2003; 107(8): 1146 - 1151. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. R. Crouse III, R. Tang, M. A. Espeland, J. G. Terry, T. Morgan, and M. Mercuri Associations of Extracranial Carotid Atherosclerosis Progression With Coronary Status and Risk Factors in Patients With and Without Coronary Artery Disease Circulation, October 15, 2002; 106(16): 2061 - 2066. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 T. Lehtimaki, P. Dastidar, H. Jokela, T. Koivula, S. Lehtinen, C. Ehnholm, and R. Punnonen Effect of Long-Term Hormone Replacement Therapy on Atherosclerosis Progression in Postmenopausal Women Relates to Functional Apolipoprotein E Genotype J. Clin. Endocrinol. Metab., September 1, 2002; 87(9): 4147 - 4153. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
L. Djousse, R. H. Myers, M. A. Province, S. C. Hunt, J. H. Eckfeldt, G. Evans, J. M. Peacock, and R. C. Ellison Influence of Apolipoprotein E, Smoking, and Alcohol Intake on Carotid Atherosclerosis: National Heart, Lung, and Blood Institute Family Heart Study Stroke, May 1, 2002; 33(5): 1357 - 1361. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A.J.C. Slooter, M. L. Bots, L. M. Havekes, A. I. del Sol, M. Cruts, D. E. Grobbee, A. Hofman, C. Van Broeckhoven, J.C.M. Witteman, and C. M. van Duijn Apolipoprotein E and Carotid Artery Atherosclerosis: The Rotterdam Study Stroke, September 1, 2001; 32(9): 1947 - 1952. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. M. HAGBERG, K. R. WILUND, and R. E. FERRELL APO E gene and gene-environment effects on plasma lipoprotein-lipid levels Physiol Genomics, December 18, 2000; 4(2): 101 - 108. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
R. B. Weinberg, B. W. Geissinger, K. Kasala, K. J. Hockey, J. G. Terry, L. Easter, and J. R. Crouse Effect of apolipoprotein A-IV genotype and dietary fat on cholesterol absorption in humans J. Lipid Res., December 1, 2000; 41(12): 2035 - 2041. [Abstract] [Full Text]
|
|
|
|
 |
|
 A. Hassan and H. S. Markus Genetics and ischaemic stroke Brain, September 1, 2000; 123(9): 1784 - 1812. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 K. Yaffe, M. Haan, A. Byers, C. Tangen, and L. Kuller Estrogen use, APOE, and cognitive decline: Evidence of gene-environment interaction Neurology, May 23, 2000; 54(10): 1949 - 1954. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 T Pohjasvaara, R Mantyla, H J Aronen, M Leskela, O Salonen, M Kaste, and T Erkinjuntti Clinical and radiological determinants of prestroke cognitive decline in a stroke cohort J. Neurol. Neurosurg. Psychiatry, December 1, 1999; 67(6): 742 - 748. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C. Skoglund-Andersson, R. Tang, M. G. Bond, U. de Faire, A. Hamsten, and F. Karpe LDL Particle Size Distribution Is Associated With Carotid Intima-Media Thickness in Healthy 50-Year-Old Men Arterioscler Thromb Vasc Biol, October 1, 1999; 19(10): 2422 - 2430. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. Boquist, G. Ruotolo, R. Tang, J. Bjorkegren, M. G. Bond, U. de Faire, F. Karpe, and A. Hamsten Alimentary Lipemia, Postprandial Triglyceride-Rich Lipoproteins, and Common Carotid Intima-Media Thickness in Healthy, Middle-Aged Men Circulation, August 17, 1999; 100(7): 723 - 728. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. A. Espeland, R. Tang, J. G. Terry, D. H. Davis, M. Mercuri, and J. R. Crouse III Associations of Risk Factors With Segment-Specific Intimal-Medial Thickness of the Extracranial Carotid Artery Stroke, May 1, 1999; 30(5): 1047 - 1055. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
H Hénon, F Pasquier, I Durieu, J P Pruvo, and D Leys Medial temporal lobe atrophy in stroke patients: relation to pre-existing dementia J. Neurol. Neurosurg. Psychiatry, November 1, 1998; 65(5): 641 - 647. [Abstract] [Full Text]
|
|
|
|
|
|
H. Henon, F. Pasquier, H. Henon, F. Pasquier, F. Durieu, O. Godefroy, C. Lucas, F Lebert, and D. Leys Preexisting Dementia in Stroke Patients : Baseline Frequency, Associated Factors, and Outcome Stroke, December 1, 1997; 28(12): 2429 - 2436. [Abstract] [Full Text]
|
|
|
|
|
|
C. Kessler, C. Spitzer, D. Stauske, S. Mende, J. Stadlmuller, R. Walther, and R. Rettig The Apolipoprotein E and ß-Fibrinogen G/A-455 Gene Polymorphisms Are Associated With Ischemic Stroke Involving Large-Vessel Disease Arterioscler Thromb Vasc Biol, November 1, 1997; 17(11): 2880 - 2884. [Abstract] [Full Text]
|
|