Blood pressure, risk of ischemic cerebrovascular and ischemic heart disease, and longevity in alpha(1)-antitrypsin deficiency: the Copenhagen City Heart Study.
BACKGROUND
Because elastase in alpha(1)-antitrypsin deficiency may attack elastin in the arterial wall, we tested whether alpha(1)-antitrypsin deficiency is associated with reduced blood pressure, risk of ischemic cerebrovascular (ICVD) and ischemic heart disease (IHD), and longevity.


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 alpha(1)-antitrypsin MZ genotype frequencies increased from 20 to 93 years among control subjects (chi(2), P=0.002).


CONCLUSIONS
ZZ alpha(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.
Dahl
Morten
M
Department of Clinical Biochemistry, Herlev University Hospital, Denmark.
Tybjaerg-Hansen
Anne
A
Sillesen
Henrik
H
Jensen
Gorm
G
Steffensen
Rolf
R
Nordestgaard
Børge G
BG
D000328:Adult; D017677:Age Distribution; D000368:Aged; D000369:Aged, 80 and over; D001794:Blood Pressure / Q000235:genetics*; D002545:Brain Ischemia / Q000453:epidemiology*; D015897:Comorbidity; D003718:Denmark / Q000453:epidemiology; D005260:Female; D005787:Gene Frequency; D005820:Genetic Testing; D005838:Genotype; D006720:Homozygote; D006801:Humans; D016015:Logistic Models; D008297:Male; D008875:Middle Aged; D017202:Myocardial Ischemia / Q000453:epidemiology*; D016017:Odds Ratio; D011110:Polymorphism, Genetic; D012016:Reference Values; D018570:Risk Assessment; D019896:alpha 1-Antitrypsin Deficiency / Q000453:epidemiology* / Q000235:genetics*