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


METHODS
Randomised, controlled, blinded end point study.


METHODS
University tertiary referral cardiac centre.


METHODS
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.


METHODS
Endothelial function was blindly analysed by brachial artery flow mediated dilatation (FMD) and ACE I/D genotype was determined.


RESULTS
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).


CONCLUSIONS
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.
Trevelyan
J
J
Department of Cardiology, University Hospitals of Coventry and Warwickshire, Coventry, UK. dr.trevelyan@virgin.net
Needham
E W A
EW
Morris
A
A
Mattu
R K
RK
D047228:Angiotensin II Type 1 Receptor Blockers / Q000627:therapeutic use*; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000627:therapeutic use*; D003324:Coronary Artery Disease / Q000235:genetics / Q000628:therapy*; D004311:Double-Blind Method; D004656:Enalapril / Q000627:therapeutic use*; D004730:Endothelium, Vascular; D005838:Genotype; D006801:Humans; D019808:Losartan / Q000627:therapeutic use*; D008297:Male; D008875:Middle Aged; D009154:Mutation / Q000235:genetics; D009203:Myocardial Infarction / Q000209:etiology; D009204:Myocardial Revascularization / Q000379:methods*; D018570:Risk Assessment; D012307:Risk Factors
D047228:Angiotensin II Type 1 Receptor Blockers; D000806:Angiotensin-Converting Enzyme Inhibitors; D004656:Enalapril; D019808:Losartan