Cholesterol reduction rapidly improves endothelial function after acute coronary syndromes. The RECIFE (reduction of cholesterol in ischemia and function of the endothelium) trial.
BACKGROUND
Cholesterol lowering reduces coronary events. One mechanism could be improvement of endothelial function. In line with this hypothesis, this study investigates whether cholesterol reduction can result in rapid improvement of endothelial function after acute coronary syndromes.


RESULTS
Patients with acute myocardial infarction or unstable angina and total cholesterol levels at admission >/=5.2 mmol/L or LDL >/=3.4 mmol/L were randomized to placebo (n=30) or pravastatin 40 mg daily (n=30) for 6 weeks. Brachial ultrasound was used to measure endothelium-dependent flow-mediated dilatation (FMD) and response to endothelium-independent nitroglycerin. Changes in the levels of markers of platelet activation, coagulation factors, and plasma endothelin levels were also assessed. Total and LDL cholesterol levels were similar at admission and before randomization in both groups. With pravastatin, but not with placebo, they decreased by 23% (P<0.05) and 33% (P<0.01), respectively. FMD was unchanged with placebo, 5.43+/-0.74% (mean+/-SEM) to 5.84+/-0.81%, but increased with pravastatin, 4.93+/-0.81% to 7.0+/-0.79% (P=0.02), representing a 42% relative increase. Responses to nitroglycerin were similar during the time course of the study in the 2 groups. Markers of platelet activity, coagulation factors, and endothelin levels were not affected by pravastatin.


CONCLUSIONS
Cholesterol reduction with pravastatin initiated early after acute coronary syndromes rapidly improves endothelial function after 6 weeks of therapy.
Dupuis
J
J
Department of Medicine and Research Centre, Montreal Heart Institute, Montreal, Quebec, Canada. dupuisj@icm.umontrea.ca
Tardif
J C
JC
Cernacek
P
P
Théroux
P
P
D000924:Anticholesteremic Agents / Q000627:therapeutic use*; D001794:Blood Pressure / Q000187:drug effects; D001916:Brachial Artery / Q000000981:diagnostic imaging / Q000187:drug effects; D002784:Cholesterol / Q000097:blood*; D015986:Confounding Factors, Epidemiologic; D003327:Coronary Disease / Q000097:blood / Q000000981:diagnostic imaging / Q000209:etiology* / Q000503:physiopathology*; D004311:Double-Blind Method; D016232:Endothelins / Q000097:blood; D004730:Endothelium, Vascular / Q000187:drug effects*; D005260:Female; D006339:Heart Rate / Q000187:drug effects; D006801:Humans; D006937:Hypercholesterolemia / Q000097:blood / Q000150:complications* / Q000000981:diagnostic imaging / Q000503:physiopathology*; D008055:Lipids / Q000097:blood; D008297:Male; D008875:Middle Aged; D017035:Pravastatin / Q000627:therapeutic use*; D013318:Stroke Volume / Q000187:drug effects; D013577:Syndrome; D014463:Ultrasonography; D014664:Vasodilation / Q000187:drug effects
D000924:Anticholesteremic Agents; D016232:Endothelins; D008055:Lipids; D002784:Cholesterol; D017035:Pravastatin