Influence of Angiotensin Converting Enzyme Insertion/Deletion Polymorphism on Long-term Total Graft Occlusion after Coronary Artery Bypass Surgery
Background: The renin-angiotensin system has a very important role in coronary thrombosis and restenosis. Plasma angiotensin converting enzyme (ACE) activity is associated with an insertion/deletion polymorphism in the gene coding for ACE. It is known that there is a strong correlation between ACE DD and atherosclerosis. However, little has been documented about its role in venous graft failure. The objective of this study was to investigate the relationships among the ACE gen polymorphism and long-term vein graft occlusion.
Methods: The study population consisted of 87 consecutive white patients with symptomatic coronary artery disease in the previous month, who had had aorto-coronary bypass surgery (ACBS) more than 5 years back and who underwent coronary angiography for diagnostic purposes. On the same day as angiography, 10 mL whole blood was taken for ACE gene insertion/deletion (I/D) polymorphism.
Results: Mean age of the patients was 64.4 ± 8.6 years, and 71 (82%) of the patients were men. The average ACBS time was 7.9 ± 1.9 years. The ACE genotype was II in 15 patients (17.2%), ID in 47 patients (54.0%), and DD in 25 patients (28.7%). Thus, D allele frequency was .82. There was no significant difference between the cases with regard to age, body mass index, blood pressure status, plasma glucose level, plasma lipid profile, smoking status, average of ACBS time or family history of coronary heart disease. In ACE II group 5 patients had total venous graft occlusion, in ACE ID group 27 patients had total occlusion and in ACE DD group 20 patients had at least one graft total occlusion. The frequency of the venous graft occlusion about total venous grafts is 36% in the ACE II group, 49% in the ACE ID group, and 80% in the ACE DD group (P = .01). Conclusion: The ACE I/D gene polymorphism is associated with long-term survival of venous conduit. The ACE DD genotype or D allele influences the angiographic outcome of patients post-ACBS. These data suggest that routine determination of the ACE genotype may help identify patients who are at higher risk of venous graft failure after ACBS.
Campeau L, Enjalbert M, Lesperance J, et al. 1984. The relation of risk factors to the development of atherosclerosis in saphenous vein bypass grafts and the progression of disease in the native circulation: a study 10 years after aortocoronary bypass surgery. N Eng J Med 311:1329-32.nFarber HW, Center DM, Rounds S, et al. 1990. Components of the angiotensin system cause release of a neutrophil chemoattractant from cultured bovine and human endothelial cells. Eur Heart J 11:Suppl 100-7.nO'Donohoe MK, Davies MG, Radic ZS, et al. 1994. Increased concentrations of angiotensin-converting enzyme in the intimal hyperplasia of experimental vein grafts. J Cardiovasc Pharmacol 23:594-601.nSamani NJ, Thompson JR, O'Toole L, et al. 1996. A meta-analysis of the association of the deletion allele of the angiotensin-converting enzyme gene with myocardial infarction. Circulation 94:708-12.nAmant C, Bauters C, Bodart JC, et al. 1997. D allele of the angiotensin I-converting enzyme is a major risk factor for restenosis after coronary stenting. Circulation 96:56-60.nBonithon-Kopp C, Ducimetiere P, Touboul PJ, et al. 1994. Plasma angiotensin-converting enzyme activity and carotid wall thickening. Circulation 89:952-4.nBourassa MG. 1991. Fate of venous grafts: the past, the present, and the future. J Am Coll Cardiol 17:1081-3.nCambien F, Alhenc-Gelas F, Herbeth B, et al. 1988. Familial resemblance of plasma angiotensin-converting enzyme level: the Nancy Study. Am J Hum Genet 43:774-80.nCambien F, Poirier O, Lecerf L, et al. 1992. Deletion polymorphism in the gene for angiotensin converting enzyme is a potent risk factor for myocardial infarction. Nature 359:641-4.nKoch W, Kastrati A, Mehilli J, et al. 2000. Insertion/Deletion of the angiotensin I-converting enzyme gene is not associated with restenosis after coronary stent placement. Circulation 102:197-202.nDelange J, Cambier B, Langlois M, et al. 1997. Haptoglobin polymorphism, a genetic risk factor in coronary artery bypass surgery. Atherosclerosis 132:215-9.nEhlers MR, Riordan JF. 1989. Angiotensin converting enzyme: new concepts concerning its biological role. Biochemistery 28:5311-8.nEvans AE, Poirier O, Kee F, et al. 1994. Polymorphisms of the angiotensin-converting-enzyme gene in subjects who die from coronary heart disease. Q J Med 87:211-4.nRuiz J, Blanche H, Cohen N, et al. 1994. Insertion/deletion polymorphism of the angiotensin converting enzyme gene is strongly associated with coronary heart disease in non-insulin dependent diabetes mellitus. Proc Natl Acad Sci USA 91:3662-5.nMorrow DA, Gersh BJ, Braunwald E. 2005. Chronic coronary artery disease. In: Braunwald E, ed. Heart disease. A textbook of cardiovascular medicine. 7th ed. Philadelphia, PA: WB Saunders; p. 1311-7.nAgerholm-Larsen B, Nordestgaard BG, Steffensen R, et al. 1997. ACE gene polymorphism: ischemic heart disease and longevity in 10150 individuals. A case-referent and retrospective cohort study based on the Copenhagen City Heart Study. Circulation 95:2358-67.nVolzke H, Engel J, Kleine V, et al. 2002. Angiotensin I-converting enzyme insertion/deletion polymorphism and cardiac mortality and morbidity after coronary artery bypass graft surgery. Chest 122:31-6.nFinta KM, Fischer MJ, Lee L, et al. 1993. Ramipril prevents impaired endothelium-dependent relaxation in arteries from rabbits fed on atherogenic diet. Atherosclerosis 100:149-56.nFitzgibbon GM, Kafka HP, Leach AJ, et al. 1996. Coronary bypass graft fate and patient outcome: angiographic follow-up of 5065 grafts related to survival and reoperation in 1388 patients during 25 years. J Am Coll Cardiol 28:616-26.nGardemann A, Weiss T, Schwartz O, et al. 1995. Gene polymorphism but not catalytic activity of angiotensin I-converting enzyme is associated with coronary artery disease and myocardial infarction in low-risk patients. Circulation 92:2796-9.nRibichini F, Steffenino G, Dellavalle A, et al. 1998. Plasma activity and insertion/deletion polymorphism of angiotensin I converting enzyme: a major risk factor and a marker of risk for coronary stent restenosis. Circulation 97:147-54.nRigat B, Hubert C, Alhenc-Gelas F, et al. 1990. An insertion/deletion polymorphism in the angiotensin I-converting enzyme gene accounting for half the variance of serum enzyme levels. J Clin Invest 86:1343-6.nMattu RK, Needham EW, Galton DJ, et al. A DNA variant at the angiotensin-converting enzyme locus associates with coronary artery disease in the Caerphilly Heart Study. Circulation 91:270-4.nMotwani JG, Topol EJ. 1998. Aortocoronary saphenous vein graft disease: pathogenesis, predisposition, and prevention. Circulation 97:916-31.nOike Y, Hata A, Ogata Y, et al. 1995. Angiotensin converting enzyme as a genetic risk factor for coronary artery spasm. Implication in the pathogenesis of myocardial infarction. J Clin Invest 96:2975-9.n
How to Cite
Author Disclosure & Copyright Transfer Agreement
In order to publish the original work of another person(s), The Heart Surgery Forum® must receive an acknowledgment of the Author Agreement and Copyright Transfer Statement transferring to Forum Multimedia Publishing, L.L.C., a subsidiary of Carden Jennings Publishing Co., Ltd. the exclusive rights to print and distribute the author(s) work in all media forms. Failure to check Copyright Transfer agreement box below will delay publication of the manuscript.
A current form follows:
The author(s) hereby transfer(s), assign(s), or otherwise convey(s) all copyright ownership of the manuscript submitted to Forum Multimedia Publishing, LLC (Publisher). The copyright transfer covers the exclusive rights to reproduce and distribute the article and the material contained therein throughout the world in all languages and in all media of expression now known or later developed, including but not limited to reprints, photographic reproduction, microfilm, electronic data processing (including programming, storage, and transmission to other electronic data record(s), or any other reproductions of similar nature), and translations.
However, Publisher grants back to the author(s) the following:
- The right to make and distribute copies of all or part of this work for use of the author(s) in teaching;
- The right to use, after publication in The Heart Surgery Forum, all or part of the material from this work in a book by the author(s), or in a collection of work by the author(s);
- The royalty-free right to make copies of this work for internal distribution within the institution/company that employs the author(s) subject to the provisions below for a work-made-for-hire;
- The right to use figures and tables from this work, and up to 250 words of text, for any purpose;
- The right to make oral presentations of material from this work.
Publisher reserves the right to grant or refuse permission to third parties to republish all or part of the article or translations thereof. To republish, such third parties must obtain written permission from the Publisher. (This is in accordance with the Copyright Statute, United States Code, Title 17. Exception: If all authors were bona fide officers or employees of the U.S. Government at the time the paper was prepared, the work is a “work of the US Government” (prepared by an officer or employee of the US Government as part of official duties), and therefore is not subject to US copyright; such exception should be indicated on signature lines. If this work was prepared under US Government contract or grant, the US Government may reproduce, royalty-free, all or portions of this work and may authorize others to do so, for official US Government purposes only, if the US Government contract or grant so requires.
I have participated in the conception and design of this work and in the writing of the manuscript and take public responsibility for it. Neither this manuscript nor one with substantially similar content under my authorship has been published, has been submitted for publication elsewhere, or will be submitted for publication elsewhere while under consideration by The Heart Surgery Forum, except as described in an attachment. I have reviewed this manuscript (original version) and approve its submission. If I am listed above as corresponding author, I will provide all authors with information regarding this manuscript and will obtain their approval before submitting any revision. I attest to the validity, accuracy, and legitimacy of the content of the manuscript and understand that Publisher assumes no responsibility for the validity, accuracy, and legitimacy of its content. I warrant that this manuscript is original with me and that I have full power to make this Agreement. I warrant that it contains no matter that is libelous or otherwise unlawful or that invades individual privacy or infringes any copyright or other proprietary right. I agree to indemnify and hold Publisher harmless of and from any claim made against Publisher that relates to or arises out of the publication of the manuscript and agree that this indemnification shall include payment of all costs and expenses relating to the defense of any such claim, including all reasonable attorney’s fees.
I warrant that I have no financial interest in the drugs, devices, or procedures described in the manuscript (except as disclosed in the attached statement).
I state that the institutional Human Subjects Committee and/or the Ethics Committee approved the clinical protocol reported in this manuscript for the use of experimental techniques, drugs, or devices in human subjects and appropriate informed consent documents were utilized.
Furthermore, I state that any and all animals used for experimental purposes received humane care in USDA registered facilities in compliance with the “Principles of Laboratory Animal Care” formulated by the National Society for Medical Research and the “Guide for the Care and Use of Laboratory Animals” prepared by the Institute of Laboratory Animal Resources and published by the National Institutes of Health (NIH Publication No. 85-23, revised 1985).