(Circulation. 2000;101:1366.)
© 2000 American Heart Association, Inc.
Clinical Investigation and Reports |
The Apolipoprotein 
4 Allele Determines Prognosis and the Effect on Prognosis of Simvastatin in Survivors of Myocardial Infarction
A Substudy of the Scandinavian Simvastatin Survival Study
From the Departments of Internal Medicine and Cardiology, Aarhus Amtssygehus University Hospital, Aarhus, Denmark (L.U.G., C.G., I.C.K., P.S.H., O.F.), and the Department of Internal Medicine and Biocenter Oulu, Oulu University Hospital, Oulu, Finland (K.K., M.S., Y.A.K.).
Correspondence to Dr Lars Ulrik Gerdes, Department of Clinical Biochemistry, Aarhus Amtssygehus University Hospital, DK-8000 Aarhus C, Denmark. E-mail ulrik.gerdes{at}dadlnet.dk
Background—Carriers of the 
4
allele of the apolipoprotein E gene are at a higher risk of
coronary heart disease than individuals with other
genotypes. We examined whether the risk of death or a major
coronary event in survivors of myocardial infarction depended
on apolipoprotein E genotype and whether the benefits of
treatment with simvastatin differed between
genotypes.
Methods and Results—Cox proportional hazards models were
used to analyze 5.5 years of follow-up data from 966 Danish and
Finnish myocardial infarction survivors enrolled in the Scandinavian
Simvastatin Survival Study. A total of 16% of the 166 4
carriers in the placebo group died compared with 9% of the 312
patients without the allele, which corresponds to a mortality risk
ratio of 1.8 (95% confidence interval, 1.1 to 3.1). The risk ratio was
unaffected by considerations of sex, age, concurrent angina, diabetes,
smoking, and serum lipids in multivariate
analyses. Simvastatin treatment reduced the
mortality risk to 0.33 (95% confidence interval, 0.16 to 0.69) in 4
carriers and to 0.66 (95% confidence interval, 0.35 to 1.24) in other
patients (P=0.23 for treatment by genotype
interaction). Apolipoprotein E genotype did not predict the
risk of a major coronary event. Baseline serum levels of
lipoprotein(a) also predicted mortality risk and could be
combined with 4-carrier status to define 3 groups of patients with
different prognoses and benefits from treatment.
Conclusions—Myocardial infarction survivors with the 4
allele have a nearly 2-fold increased risk of dying compared with
other patients, and the excess mortality can be abolished by treatment
with simvastatin.
Key Words: apolipoproteins • genetics • myocardial infarction • prognosis • mortality
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