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.

• Authors: Cho-Kai Wu, Jen-Kuang Lee, Lian-Yu Lin, Yin-Tsen Huang, Juey-Jen Hwang, Chunn-Lee Lin, Chuen-Den Tseng, Fu-Tien Chiang
• Journal: Acta Cardiologica Sinica (Acta Cardiol Sin) Vol. 29 Issue 1 Pg. 28-36 (Jan 2013) ISSN: 1011-6842 [Print] China (Republic : 1949- )
• PMID: 27122682 (Publication Type: Journal Article)