Comparison of the effect of enalapril and losartan in conjunction with surgical coronary revascularisation versus revascularisation alone on systemic endothelial function.

Abstract

To investigate the effect of enalapril, losartan, and surgical coronary revascularisation on endothelial function, and the role of the angiotensin converting enzyme (ACE) insertion (I)/deletion (D) polymorphism. Randomised, controlled, blinded end point study. University tertiary referral cardiac centre. 49 men awaiting coronary artery bypass grafting (CABG) were randomly assigned to treatment with losartan, enalapril, or control for two months before and three months after surgery. Endothelial function was blindly analysed by brachial artery flow mediated dilatation (FMD) and ACE I/D genotype was determined. FMD was impaired at baseline (1.0-1.7%) and after five months had improved to 5.2% with enalapril (p = 0.015), 5.0% with losartan (p = 0.0004), and 3.0% with CABG alone (p = 0.05). Patients with the II genotype had lower baseline FMD than those with DI or DD (0.1% v 1.7%, p = 0.038) and after enalapril or losartan treatment had greater improvement in FMD (mean (SEM) 7.1 (1.1)%) than patients with DI (3.1 (1.3)%, p = 0.024) or DD genotype (3.1 (1.1)%, p = 0.02). Enalapril and losartan, with surgical coronary revascularisation, significantly improve systemic endothelial function. Revascularisation alone produces a quantitatively smaller, but still significant, improvement. The ACE genotype significantly modulates this response. Patients with the II genotype have a more pronounced impairment in endothelial function at baseline and a greater improvement in response to treatment with these agents.