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ACE Gene Polymorphism as a Risk Factor for Ischemic Cerebrovascular Disease

Birgit Agerholm-Larsen, MS; Anne Tybjaerg-Hansen, MD, DMSc; Ruth Frikke-Schmidt, MD; Marie-Louise M. Gronholdt, MD; Gorm Jensen, MD, DMSc; and Borge G. Nordestgaard, MD, DMSc
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From the Herlev University Hospital, Herlev, Denmark; and National University Hospital and University of Copenhagen, Copenhagen, Denmark. Acknowledgments: The authors thank Poul Westermann and Mette Refstrup for technical assistance and Merete Appleyard for advice on the Copenhagen City Heart Study database. Grant Support: By the Danish Heart Foundation, the Danish Research Academy, Copenhagen County, and Chief Physician Johan Boserup's and Lise Boserup's Fund. Requests for Reprints: Borge G. Nordestgaard, MD, DMSc, Department of Clinical Biochemistry, Herlev University Hospital, DK-2730 Herlev, Denmark. Current Author Addresses: Ms. Agerholm-Larsen and Drs. Tybjaerg-Hansen Frikke-Schmidt, and Nordestgaard: Department of Clinical Biochemistry, Herlev University Hospital, DK-2730 Herlev, Denmark.

Copyright ©2004 by the American College of Physicians

Ann Intern Med. 1997;127(5):346-355. doi:10.7326/0003-4819-127-5-199709010-00002
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Background: Researchers have suggested that the deletional allele of the ACE (angiotensin-converting enzyme) gene insertion-deletion polymorphism is a potent risk factor for myocardial infarction. This association could not be confirmed in the Copenhagen City Heart Study, in which 10 150 persons were studied. The ACE gene polymorphism has also recently been suggested as a potent risk factor for ischemic cerebrovascular disease.

Objective: To investigate the association between ACE gene polymorphism and ischemic cerebrovascular disease.

Design: Two case-referent studies and a cross-sectional study.

Setting: University hospital in Copenhagen, Denmark.

Participants: Case-referent study 1: 35 women and 38 men who developed ischemic cerebrovascular disease before 50 years of age compared with 1454 women and 1737 men from a general population sample. Case-referent study 2: 82 women and 137 men with ischemic cerebrovascular disease and carotid stenosis greater than 40% compared with 4273 women and 3091 men from the general population sample. Cross-sectional study of the general population sample: 67 women and 93 men with ischemic cerebrovascular disease compared with 4077 women and 3156 men without such disease.

Measurements: Genotype; age; body mass index; smoking habits; levels of lipids, lipoproteins, apolipoproteins, and fibrinogen; and diagnosis of hypertension, diabetes mellitus, and ischemic cerebrovascular disease.

Results: Odds ratios for ischemic cerebrovascular disease by ACE genotype classes were not significantly different from 1.0 in women or men in any of the three studies, separately or combined. In a logistic regression analysis that controlled for age and conventional cardiovascular risk factors, odds ratios in either sex still did not significantly differ from 1.0 in any study, separately or combined.

Conclusion: In two case-referent studies, a cross-sectional study, and the three studies combined, no statistically significant difference was found in the development of ischemic cerebrovascular disease between genotype classes of the ACE gene polymorphism in women or men.


Grahic Jump Location
Figure 1.
Study designs.

Arrows indicate groups compared in the three studies.

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