Long-term use of angiotensin-converting enzyme inhibitors to modify endothelial dysfunction: a review of clinical investigations

Objectives: Endothelial dysfunction can be modified by angiotensin-converting enzyme (ACE) inhibitors. The purpose of this paper is to review clinical studies assessing the effect of long-term, oral ACE inhibition on endothelial dysfunction in specific disease syndromes and to identify areas requiring further research. Data sources: A computer search of the entire MEDLINE database and Current Contents complemented by detailed analysis of references in the papers identified. Study selection: Analysis of patients treated on a long-term basis with orally administered ACE inhibitors to modify endothelial function. Data synthesis: Studies were identified of patients with hypertension, diabetes, congestive heart failure, coronary artery disease, dyslipidemias and immunoglobulin A nephropathy (IgAN). These studies used diverse endothelium-mediated end-points, which included dilatory responses in conduit or resistance vessels, measures of coagulant and fibrinolytic factors, soluble adhesion molecules, endothelin-l, systemic and glomerular barrier functions and renal blood flow. Few trials enrolled large numbers of patients or used randomized, double-blind, placebo-controlled designs. However, consistent and positive effects were noted in patients with coronary artery disease, dyslipidemia or IgAN. In hypertensive patients, conduit artery and renal endothelium-mediated responses could be improved earlier and more easily than resistance vessel function, which appears to require prolonged therapy before improvement is seen. Highly disparate results were found in patients with congestive heart failure or diabetes. Conclusions: ACE inhibitors appear to improve endothelial dysfunction in patients with coronary artery disease, dyslipidemia, hypertension and IgAN. Conflicting evidence exists in studies of patients with congestive heart failure and diabetes. Further trials are required to clarify and define the prevalence of endothelial dysfunction and the predictors of response in all these conditions.