Renin-Angiotensin-Aldosterone System Polymorphisms and 5-Year Mortality in Survivors of Acute Myocardial Infarction A Report From the Osaka Acute Coronary Insufficiency Study
Renin-Angiotensin-Aldosterone System Polymorphisms and 5-Year Mortality in Survivors of Acute Myocardial Infarction A Report From the Osaka Acute Coronary Insufficiency Study
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DOI：
10.1536/ihj.13-288
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发表时间：
2014-05-01
影响因子：
1.5
通讯作者：
Komuro, Issei
中科院分区：
文献类型：
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作者：
Hara, Masahiko;Sakata, Yasuhiko;Komuro, Issei
本研究旨在评估肾素-血管紧张素-醛固酮系统（RAAS）的遗传变异是否对经皮冠状动脉介入治疗（PCI）时代急性心肌梗死（AMI）后的长期死亡率产生影响。我们使用多变量 Cox 回归分析，研究了 4 个主要 RAAS 遗传变异、血管紧张素原 (AGT) T1311C、血管紧张素转换酶 (ACE) 插入/缺失 (I/D)、血管紧张素 2 1 型受体 A1166C 和醛固酮合酶 T4660C 的个体和组合对 3149 名 AMI 后患者 5 年死亡率的影响。使用Cox回归分析评估所有可能的RAAS基因组合的预测准确性，并根据最小Akaike信息准则确定影响预后的最佳组合。中位随访时间为 4.9 年，共有 220 人死亡。对任何单一 RAAS 变异的独立分析均未显示出对 5 年死亡率的显着影响。然而，综合分析显示，AGT CC 基因型和 ACE D 等位基因的缺失与较低的 5 年死亡率相关（对数秩 P = 0.005）。与既不具有 AGT CC 也不具有 ACED 等位基因的患者相比，至少具有 AGT CC 或 ACED 等位基因之一的患者死亡率增加，调整后的风险比为 2.07（95% 置信区间 1.18-3.65，P = 0.012）。在检查的 4 个 RAAS 遗传变异中，AGT 和 ACE 多态性的组合与 AMI 后 5 年死亡率相关。
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 ACED 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 ACED allele. Among the 4 RAAS genetic variants examined, a combination of AGT and ACE polymorphisms was associated with 5-year mortality after AMI.