The apolipoprotein epsilon 4 allele determines prognosis and the effect on prognosis of simvastatin in survivors of myocardial infarction - A substudy of the Scandinavian Simvastatin Survival Study

Article

关键词: CORONARY-ARTERY DISEASE;    E POLYMORPHISM;    HEART-DISEASE;    RISK FACTOR;    ATHEROSCLEROSIS;    GENE;    METAANALYSIS;    ANGIOPLASTY;    FREQUENCIES;    PROGRESSION;   

DOI  :  10.1161/01.CIR.101.12.1366

来源: SCIE

【 摘 要 】

Background-Carriers of the epsilon 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 epsilon 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 epsilon 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 epsilon 4-carrier status to define 3 groups of patients with different prognoses and benefits from treatment. Conclusions-Myocardial infarction survivors with the epsilon 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.

【 授权许可】

Free