title: Renin-angiotensin-aldosterone system polymorphisms and 5-year mortality in survivors of acute myocardial infarction: a report from the Osaka Acute Coronary Insufficiency Study.
abstract: This study sought to evaluate whether genetic variants in the renin-angiotensin-aldosterone system (RAAS) have an impact on long-term mortality after acute myocardial infarction (AMI) in the percutaneous coronary intervention (PCI) era. We investigated the impacts of individual and combinations of 4 major RAAS genetic variants, angiotensinogen (AGT) T1311C, angiotensin-converting enzyme (ACE) insertion/deletion (I/D), angiotensin 2 type 1 receptor A1166C, and aldosterone synthase T4660C on 5-year mortality in 3149 post-AMI patients using multivariate Cox regression analysis. The predictive accuracy of all possible RAAS genetic combinations was evaluated using Cox regression analysis, and the best combination that affected prognosis was determined based on the minimal Akaike Information Criterion. There were 220 deaths during a median follow-up of 4.9 years. Independent analyses of any single RAAS variant did not show significant impacts on 5-year mortality. However, analyses in combination revealed that absence of both AGT CC genotype and ACE D allele was associated with lower 5-year mortality (log-rank P = 0.005). Patients with at least either of the AGT CC or ACE D allele had increased mortality with adjusted hazard ratios of 2.07 (95% confidence interval 1.18-3.65, P = 0.012), compared with those with neither the AGT CC nor ACE D allele. Among the 4 RAAS genetic variants examined, a combination of AGT and ACE polymorphisms was associated with 5-year mortality after AMI.
authors.affiliation: Department of Cardiovascular Medicine, Osaka University Graduate School of Medicine.
authors.forename: Masahiko
authors.initials: M
authors.lastname: Hara
authors.forename: Yasuhiko
authors.initials: Y
authors.lastname: Sakata
authors.forename: Daisaku
authors.initials: D
authors.lastname: Nakatani
authors.forename: Shinichiro
authors.initials: S
authors.lastname: Suna
authors.forename: Masaya
authors.initials: M
authors.lastname: Usami
authors.forename: Sen
authors.initials: S
authors.lastname: Matsumoto
authors.forename: Toshifumi
authors.initials: T
authors.lastname: Sugitani
authors.forename: Kouichi
authors.initials: K
authors.lastname: Ozaki
authors.forename: Masami
authors.initials: M
authors.lastname: Nishino
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Sato
authors.forename: Tetsuhisa
authors.initials: T
authors.lastname: Kitamura
authors.forename: Shinsuke
authors.initials: S
authors.lastname: Nanto
authors.forename: Toshimitsu
authors.initials: T
authors.lastname: Hamasaki
authors.forename: Toshihiro
authors.initials: T
authors.lastname: Tanaka
authors.forename: Masatsugu
authors.initials: M
authors.lastname: Hori
authors.forename: Issei
authors.initials: I
authors.lastname: Komuro
mesh_terms: D000368:Aged; D000808:Angiotensinogen / Q000235:genetics; D005260:Female; D005500:Follow-Up Studies; D005787:Gene Frequency; D005838:Genotype; D006801:Humans; D007564:Japan / Q000453:epidemiology; D008297:Male; D008875:Middle Aged; D009203:Myocardial Infarction / Q000235:genetics* / Q000378:metabolism / Q000401:mortality*; D007703:Peptidyl-Dipeptidase A / Q000235:genetics; D011110:Polymorphism, Genetic; D044140:Receptor, Angiotensin, Type 1 / Q000235:genetics; D012084:Renin-Angiotensin System / Q000235:genetics*; D012189:Retrospective Studies; D012307:Risk Factors; D015996:Survival Rate / Q000639:trends; D017741:Survivors; D013997:Time Factors
chemical_list: D044140:Receptor, Angiotensin, Type 1; D000808:Angiotensinogen; D007703:Peptidyl-Dipeptidase A