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(Circulation. 2003;107:747.)
© 2003 American Heart Association, Inc.

Clinical Investigation and Reports

Blood Pressure, Risk of Ischemic Cerebrovascular and Ischemic Heart Disease, and Longevity in ₁-Antitrypsin Deficiency

The Copenhagen City Heart Study

Morten Dahl, MD; Anne Tybjærg-Hansen, MD, DMSc; Henrik Sillesen, MD, DMSc; Gorm Jensen, MD, DMSc; Rolf Steffensen, MD; Børge G. Nordestgaard, MD, DMSc

From the Department of Clinical Biochemistry, Herlev University Hospital (M.D., B.G.N.), the Department of Clinical Biochemistry, Rigshospitalet, Copenhagen University Hospital (A.T.-H.), the Department of Vascular Surgery, Gentofte University Hospital (H.S.), the Department of Medicine B, Hillerød Hospital (R.S.), and the Copenhagen City Heart Study, Bispebjerg University Hospital (A.T.-H., G.J., B.G.N.), Copenhagen, Denmark.

Correspondence to Dr Nordestgaard, Department of Clinical Biochemistry, Herlev University Hospital, DK-2730 Herlev, Denmark. E-mail brno{at}herlevhosp.kbhamt.dk

Background— Because elastase in ₁-antitrypsin deficiency may attack elastin in the arterial wall, we tested whether ₁-antitrypsin deficiency is associated with reduced blood pressure, risk of ischemic cerebrovascular (ICVD) and ischemic heart disease (IHD), and longevity.

Methods and Results— We genotyped 7963 control subjects from the adult general population of Denmark, 1131 Danish patients with ICVD, and 2221 Danish patients with IHD. Compared with MM/MS individuals, systolic blood pressure was lower by 15 mm Hg in ZZ homozygotes (n=6, P=0.03) and 9 mm Hg in MZ heterozygotes with IHD (n=39, P=0.02). Odds ratios for ICVD and IHD in MZ versus MM/MS individuals were 0.70 (0.51 to 0.96) and 0.77 (0.61 to 0.98). Finally, mean ages of MZ and MM/MS control subjects were 58 and 56 years (Mann-Whitney: P=0.008), and relative ₁-antitrypsin MZ genotype frequencies increased from 20 to 93 years among control subjects (², P=0.002).

Conclusions— ZZ ₁-antitrypsin deficiency and MZ intermediate deficiency in the context of IHD are associated with reduced blood pressure, and MZ is associated with reduced risk of ICVD and IHD. Because MZ heterozygosity was associated with increased age, MZ heterozygosity could be a beneficial condition.

Key Words: blood pressure • ischemia • heart diseases • stroke • genetics

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