Endothelium-dependent responses in patients with hypercholesterolemic coronary artery disease under the effects of simvastatin and enalapril, either separately or combined.

BACKGROUND: Endothelial dysfunction is an early event in atherosclerotic disease that precedes clinical manifestations and complications. The noninvasive assessment of endothelial function in patients with risk factors undergoing clinical treatment is an important medical advance. In this setting, altered endothelial function in patients with coronary hypercholesterolemia and its modifications by treatment with enalapril and simvastatin, either separately or in combination, was assessed in the brachial artery in a randomized, double-blind, 2-period crossover study. METHODS: Thirty-eight patients were separated in 2 groups. Group 1 (18 patients, 3 female, mean age 63 +/- 6.0 years) received simvastatin 10 mg/d for 8 weeks and simvastatin plus enalapril 5 mg/d for another 8 weeks. Group 2 (20 patients, 3 female, mean age 64 +/- 5.8 years) received enalapril 5 mg/d for 8 weeks and enalapril plus simvastatin 10 mg/d for another 8 weeks. All subjects underwent measurements of brachial artery diameter before and after postischemic hyperemia with high-resolution ultrasound at basal conditions (control) and under the effects of the drugs at the end of 8 and 16 weeks. RESULTS: Cholesterol and LDL cholesterol levels significantly decreased with simvastatin treatment alone or with enalapril. Mean baseline arterial diameter was 5.24 +/- 1.25 mm in group 1 and 4.83 +/- 0.99 mm in group 2 (not significant). In group 1 after the first 8 weeks, endothelium-dependent vasodilation significantly increased with simvastatin treatment (control, 4.4%; 8 weeks, 7.6%; P <.001). After 16 weeks with the addition of enalapril, a further increase in vasodilation was seen (8.6%, P <.05 vs 8 weeks). In group 2, with enalapril treatment an increase in vasodilation versus control was seen (control, 4.3%; 8 weeks, 5.8%; P <.01). After 16 weeks, with the addition of simvastatin an additional increase in vasodilation was observed (9.1%, P <.001 vs 8 weeks). After nitroglycerin, vasodilation in group 1 at control, 8, and 16 weeks was 17%, 17.5%, and 18%, respectively. In group 2, nitroglycerin vasodilation at control, 8, and 16 weeks was 21%, 21%, and 22%, respectively. CONCLUSIONS: Simvastatin significantly increased the postischemic vasodilator response in patients with coronary hypercholesterolemia, either as single treatment or added to enalapril. Similarly, the response was increased by enalapril, either alone or while simvastatin was being administered. Both drugs improve vasodilation and additive effects appear to be present.

Impaired endothelial function in patients with rapidly stabilized unstable angina: assessment by noninvasive brachial artery ultrasonography.

BACKGROUND: Endothelial dysfunction may contribute to symptoms of instability in patients with acute coronary syndromes. High-resolution external ultrasound assessment of the brachial artery responses allows noninvasive determination of endothelial function. HYPOTHESIS: This study was conducted to assess endothelial function in patients with unstable angina using a noninvasive technique. METHODS: We studied 189 patients who were subdivided into three groups. Group 1: 60 apparently healthy subjects with no cardiovascular risk factors or symptoms of coronary artery disease; Group 2: 105 subjects with cardiovascular risk factors--arterial hypertension, hypercholesterolemia, cigarette smoking, diabetes, and obesity, but no evidence of coronary artery disease; and Group 3: 24 patients with unstable angina (chest pain at rest within the 24 h preceding study entry). All patients underwent pre- and postischemic brachial artery test evaluation with measurements of internal arterial diameters and blood flow. RESULTS: Results are expressed as percentage change from basal values. Subjects in Groups 1 and 2 showed a diameter increase of 19.1 and 11.9%, respectively, whereas patients in Group 3 showed a diameter change of 1.2% (p < 0.002 and < 0.0001, respectively). Calculated blood flow did not differ significantly in Groups 1 or 2 (74.4 and 56.4%), but was notably lower in Group 3 (18.4%, p < 0.005 vs. Groups 1 and 2). In nine patients of Group 3, the brachial studies were repeated 4 weeks after symptom stabilization and showed values comparable with those in Group 2. CONCLUSIONS: Patients with unstable angina showed endothelial dysfunction compared with control individuals. It is of interest that in patients whose symptoms were stabilized by medical therapy, endothelial function was restored 4 weeks after hospital discharge.