The apolipoprotein epsilon4 allele determines prognosis and the effect on prognosis of simvastatin in survivors of myocardial infarction : a substudy of the Scandinavian simvastatin survival study.
BACKGROUND
Carriers of the epsilon4 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.


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 epsilon4 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 epsilon4 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 epsilon4-carrier status to define 3 groups of patients with different prognoses and benefits from treatment.


CONCLUSIONS
Myocardial infarction survivors with the epsilon4 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.
Gerdes
L U
LU
Departments of Internal Medicine and Cardiology, Aarhus Amtssygehus University Hospital, Aarhus, Denmark. ulrik.gerdes@dadlnet.dk
Gerdes
C
C
Kervinen
K
K
Savolainen
M
M
Klausen
I C
IC
Hansen
P S
PS
Kesäniemi
Y A
YA
Faergeman
O
O
D000328:Adult; D000368:Aged; D000483:Alleles; D053327:Apolipoprotein E4; D001057:Apolipoproteins E / Q000235:genetics*; D005260:Female; D005500:Follow-Up Studies; D005838:Genotype; D006801:Humans; D000960:Hypolipidemic Agents / Q000627:therapeutic use*; D008297:Male; D008875:Middle Aged; D009203:Myocardial Infarction / Q000188:drug therapy* / Q000235:genetics / Q000401:mortality*; D011379:Prognosis; D016016:Proportional Hazards Models; D019821:Simvastatin / Q000627:therapeutic use*
D053327:Apolipoprotein E4; D001057:Apolipoproteins E; D000960:Hypolipidemic Agents; D019821:Simvastatin