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Renin-Angiotensin System Genes Polymorphisms and Long-Term Prognosis in Taiwanese Patients with Hypertension and Coronary Artery Disease.

ABSTRACT: OBJECTIVES:The objective of this study was to evaluate the renin-angiotensin system genetic effects and pharmacogenetic interactions for angiotensin-converting enzyme (ACE) inhibitors in hypertensive coronary artery disease (CAD) patients. METHODS:Subjects with hypertension and angiographic CAD were recruited from 1995 to 2003. Baseline characteristics and genetic polymorphisms [ACE gene insertion/deletion (I/D) polymorphism, six polymorphisms of the angiotensinogen (AGT) gene, and A1166C polymorphisms of the angiotensin II type I receptor gene (AGT1R)] were collected. Patients were assigned to 2 groups (ACE inhibitor or No-ACE inhibitor) and followed-for up to 12 years. Kaplan-Meier curves and Cox regression models were used to demonstrate the survival and major cardiovascular events (MACE) event-free survival trends. Pharmacogenetic effects were determined by several Cox regression models. RESULTS:Of the 518 patients in our study, 290 were treated with ACE inhibitors and 228 were not. Prescription of ACE inhibitors was associated with a lower rate of MACE at 4000 days. In addition, ACE I/D gene D was associated with a higher rate of MACE in a multivariate regression analysis [hazard ration (HR): 1.64, 95% confidence interval (CI): 1.27-1.98, p < 0.001]. This effect could be attenuated by the pharmacogenetic interaction of ACE inhibitors and the ACE gene (ACE in hibitors*ACE D gene, HR: 0.68, 95% CI: 0.52-0.84, p = 0.014). CONCLUSIONS:The use of ACE inhibitors was associated with a significant decrease in MACE in hypertensive patients diagnosed with CAD. Genetic variants were also associated with event-free survival, but their effects were modified by the use of ACE inhibitors. KEY WORDS:Angiotensin-converting enzyme inhibitors; Coronary artery disease; Hypertension; Pharmacogenetic.

SUBMITTER: Wu CK

PROVIDER: S-EPMC4804958 | biostudies-literature | 2013 Jan

REPOSITORIES: biostudies-literature

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Renin-Angiotensin System Genes Polymorphisms and Long-Term Prognosis in Taiwanese Patients with Hypertension and Coronary Artery Disease.

Wu Cho-Kai CK Lee Jen-Kuang JK Lin Lian-Yu LY Huang Yin-Tsen YT Hwang Juey-Jen JJ Lin Chunn-Lee CL Tseng Chuen-Den CD Chiang Fu-Tien FT

Acta Cardiologica Sinica 20130101 1

<h4>Objectives</h4>The objective of this study was to evaluate the renin-angiotensin system genetic effects and pharmacogenetic interactions for angiotensin-converting enzyme (ACE) inhibitors in hypertensive coronary artery disease (CAD) patients.<h4>Methods</h4>Subjects with hypertension and angiographic CAD were recruited from 1995 to 2003. Baseline characteristics and genetic polymorphisms [ACE gene insertion/deletion (I/D) polymorphism, six polymorphisms of the angiotensinogen (AGT) gene, an ...[more]

PMID: 27122682

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Project description:The aim of the study was to study the effect of arterial stiffness and multifocal atherosclerosis on the 10-year prognosis of patients after coronary artery bypass grafting.MethodsPatients with coronary artery disease (n = 274) who underwent coronary artery bypass grafting (CABG), in whom cardio-ankle vascular index (CAVI) was assessed using the VaSera VS-1000 device and the presence of peripheral atherosclerosis in Doppler ultrasound. Groups were distinguished with normal CAVI (<9.0, n = 163) and pathological CAVI (≥9.0, n = 111). To assess the prognosis, coronary and non-coronary death, myocardial infarction, acute cerebrovascular accident/transient ischemic attack, repeated CABG, percutaneous coronary intervention, carotid endarterectomy, peripheral arterial surgery, pacemaker implantation were analyzed.ResultsDuring the observation period, mortality was 27.7%. A fatal outcome from all causes was in 37 (22.7%) patients in the group with normal CAVI and in 39 (35.14%) in the group with pathological CAVI (p = 0.023). Death from cardiac causes was more common in the group with CAVI ≥ 9.0-in 25 cases (22.52%) than in the group with CAVI < 9.0-in 19 (11.6%, p = 0.016). The combined endpoint in patients with pathological CAVI was detected in 66 (59.46%) cases, with normal CAVI values-in 76 (46.63%) cases (p = 0.03). The presence of diabetes mellitus, multifocal atherosclerosis (p = 0.004), pathological CAVI (p = 0.063), and male gender were independent predictors of death at 10-year follow-up after CABG. The presence of multifocal atherosclerosis and pathological CAVI during the preoperative examination of patients were independent predictors of the combined endpoint development.FindingsPatients with coronary artery disease with pathological CAVI before CABG were more likely to experience adverse events and death in the long-term follow-up than patients with normal CAVI. Further studies are needed to investigate the possibility of correcting pathological CAVI after CABG after secondary prevention and the possible impact of this correction on prognosis.

Dataset Information

Renin-Angiotensin System Genes Polymorphisms and Long-Term Prognosis in Taiwanese Patients with Hypertension and Coronary Artery Disease.

Publications

Renin-Angiotensin System Genes Polymorphisms and Long-Term Prognosis in Taiwanese Patients with Hypertension and Coronary Artery Disease.

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