ACE Inhibition and Endothelial Function: Main Findings of PERFECT, a Sub-Study of the EUROPA Trial

Background: ACE inhibition results in secondary prevention of coronary artery disease (CAD) through different mechanisms including improvement of endothelial dysfunction. The Perindopril-Function of the Endothelium in Coronary artery disease Trial (PERFECT) evaluated whether long-term administration of perindopril improves endothelial dysfunction. Methods: PERFECT is a 3-year double blind randomised placebo controlled trial to determine the effect of perindopril 8 mg once daily on brachial artery endothelial function in patients with stable CAD without clinical heart failure. Endothelial function in response to ischaemia was assessed using ultrasound. Primary endpoint was difference in flow-mediated vasodilatation (FMD) assessed at 36 months. Results: In 20 centers, 333 patients randomly received perindopril or matching placebo. Ischemia-induced FMD was 2.7% (SD 2.6). In the perindopril group FMD went from 2.6% at baseline to 3.3% at 36 months and in the placebo group from 2.8 to 3.0%. Change in FMD after 36 month treatment was 0.55% (95% confidence interval −0.36, 1.47; p = 0.23) higher in perindopril than in placebo group. The rate of change in FMD per 6 months was 0.14% (SE 0.05, p = 0.02) in perindopril and 0.02% (SE 0.05, p = 0.74) in placebo group (0.12% difference in rate of change p = 0.07). Conclusion: Perindopril resulted in a modest, albeit not statistically significant, improvement in FMD

Primary and secondary prevention in cardiovascular disease: an old-fashioned concept?

Objective. Is the concept of primary and secondary cardiovascular prevention an old-fashioned concept that needs to be re-defined? Design. Discussion paper. Results. Cardiovascular prevention means reduction of absolute risk for cardiovascular disease (CVD), irrespective of clinical stage. Conclusion. For the calculation of an individual probability to develop CVD all factors that contribute to the risk must be taken into account, including previous CVD events

Aggressive lipid lowering does not improve endothelial function in type 2 diabetes - The Diabetes Atorvastatin Lipid Intervention (DALI) study:A randomized, double-blind, placebo-controlled trial

OBJECTIVE - Endothelial dysfunction is considered an important early marker of atherosclerosis and cardiovascular risk and is currently used as a surrogate end point for cardiovascular at risk in clinical trials. Type 2 diabetic patients show a characteristic dyslipidemia. Aggressive lipid lowering might he an effective method to improve endothelial function in these patients. RESEARCH DESIGN AND METHODS - A randomized, double-blind, placebo-controlled trial was completed to study the effect of 30 weeks' administration of atorvastatin 10 rug and 80 rug on endothelial function, as assessed by B-mode ultrasound of the brachial artery, in 133 patients with type 2 diabetes without a history of cardiovascular disease. RESULTS- patients with diabetes and diabetic dyslipidemia had considerable endothelium-dependent and endothelium-independent dysfunction; mean flow-mediated vasodilation (SD) was 3.16% (3.56), and mean response on sublingual nitroglycerin was 6.58% (6.04). Despite su stantia owering of all atherogenic lipid parameters, no improvement of endotheliumdependent vasodilatation was found (P > 0.8). CONCLUSIONS - We observed considerable baseline endothelium-dependent and endothelium-independent dysfunction in patients with diabetes and diabetic dyslipidemia without a history of cardiovascular disease. Aggressive lipid lowering by administration of atorvastatin, resulting in substantial improvement of the lipid profile, did not reverse endothelial dysfunction