Objec tives: The ob jec tive of this study was to eval u ate the renin-an gio ten sin sys tem ge netic ef fects and pharmacogenetic in ter ac tions for an gio ten sin-con vert ing en zyme (ACE) in hib i tors in hy per ten sive cor o nary ar tery disease (CAD) patients.
Methods: Sub jects with hy per ten sion and angiographic CAD were re cruited from 1995 to 2003. Base line char ac ter is tics and ge netic polymorphisms [ACE gene in ser tion/de le tion (I/D) poly mor phism, six polymorphisms of the angiotensinogen (AGT) gene, and A1166C polymorphisms of the an gio ten sin II type I re cep tor gene (AGT1R)] were col lected. Pa tients were as signed to 2 groups (ACE in hib i tor or No-ACE in hib i tor) and fol lowed-for up to 12 years. Kaplan-Meier curves and Cox re gres sion mod els were used to dem on strate the sur vival and ma jor car dio vas cu lar events (MACE) event-free sur vival trends. Pharmacogenetic ef fects were determined by several Cox regression models.
Results: Of the 518 pa tients in our study, 290 were treated with ACE in hib i tors and 228 were not. Pre scrip tion of ACE in hib i tors was as so ci ated with a lower rate of MACE at 4000 days. In ad di tion, ACE I/D gene D was as so ci ated with a higher rate of MACE in a multivariate re gres sion anal y sis [hazard ration (HR): 1.64, 95% confidence interval (CI): 1.27-1.98, p < 0.001]. This ef fect could be at ten u ated by the pharmacogenetic in ter ac tion of ACE in hib i tors and the ACE gene (ACE in hib i tors*ACE D gene, HR: 0.68, 95% CI: 0.52-0.84, p = 0.014).
Concluasions: The use of ACE in hib i tors was as so ci ated with a sig nif i cant de crease in MACE in hy per ten sive pa tients di ag nosed with CAD. Ge netic vari ants were also as so ci ated with event-free sur vival, but their ef fects were mod i fied by the use of ACE inhibitors.