From the Division of Endocrinology, Diabetes and Clinical Nutrition,
Department of Medicine, Oregon Health Sciences University, Portland.
Correspondence to D. Roger Illingworth, MD, PhD, Department of Medicine, L465, Oregon Health Sciences University, 3181 SW Sam Jackson Park Rd, Portland, OR 97201-3098. E-mail bisaccip{at}ohsu.edu
Background—Controversy exists as to
whether the deletion/deletion genotype (DD) of the ACE gene
polymorphism increases the risk of myocardial infarction (MI).
Studies have suggested that the ACE DD genotype is associated
with increased plaque instability. We hypothesized that the ACE DD
genotype may increase the risk of myocardial infarction and
coronary heart disease (CHD) in patients with heterozygous
familial hypercholesterolemia (FH) or familial
defective apolipoprotein B-100 (FDB) who, as a group, are at high risk
of having lipid-rich plaques in their coronary arteries.
Methods and Results—We determined the ACE genotypes and
incidence of MI or surgical intervention for CHD in 213 adult patients
with heterozygous FH or FDB. The incidence of MI in 35 male patients
who carried the ACE DD genotype was 2.5 times that observed in
male patients with the II or DI genotypes, and the incidence of
CHD in male patients with the DD genotype was 2.2 times higher
than in those who had ACE DI+II. The potential effects of ACE
genotype on CHD could not be directly compared in female
patients because of a disparity in the smoking history of the genotypic
groups. From logistic regression analysis, the estimated odds
ratio associated with the ACE DD genotype was 2.57 for MI and
2.21 for CHD adjusted for age, sex, and smoking history.
Conclusions—The ACE DD genotype is associated with an
increased risk of MI and CHD in patients with heterozygous FH or FDB.
Determination of the ACE genotype in asymptomatic
FH and FDB patients provides an additional means to identify those
patients at greatest risk for the premature development of CHD.
© 1998 American Heart Association, Inc.
Clinical Investigation and Reports
Angiotensin-Converting Enzyme DD Genotype and Cardiovascular Disease in Heterozygous Familial Hypercholesterolemia
Key Words: angiotensin • myocardial infarction • hypercholesterolemia • coronary disease
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