Simvastatin combined with ramipril treatment in hypercholesterolemic patients

Mechanisms underlying biological effects of statin and angiotensin-converting enzyme inhibitor therapies differ. Thus, we studied vascular responses to combination therapy in hypercholesterolemic patients. A randomized, double-blind, placebo-controlled, crossover trial was conducted with 50 hypercholesterolemic patients with simvastatin and either placebo or ramipril ( study I) and in 45 hypercholesterolemic diabetic patients with simvastatin or ramipril with placebo or simvastatin combined with ramipril (study II) for 2 months with 2 months washout. In study I simvastatin combined with ramipril significantly reduced blood pressure after 2 months. Simvastatin alone or combined with ramipril significantly changed lipoproteins, improved percent flow-mediated dilator response to hyperemia by 30 +/- 5% and 53 +/- 6%, respectively (P < 0.001), and reduced plasma levels of malondialdehyde by 4 +/- 7% (P = 0.026) and 25 +/- 4% (P < 0.001), respectively. Monocyte chemoattractant protein-1 levels decreased by 3 +/- 3% and 12 +/- 2%, respectively (P = 0.049 and P = 0.001, respectively), C-reactive protein levels changed by 0% and 18%, respectively (P = 0.036 and P < 0.001, respectively), and plasminogen activator inhibitor-1 antigen levels changed by -7 +/- 7% and 17 +/- 5%, respectively (P = 0.828 and P < 0.001, respectively). In study II ramipril alone did not significantly change lipoproteins and C-reactive protein levels, however, simvastatin combined with ramipril significantly changed lipoproteins and C-reactive protein levels more than ramipril alone (P < 0.001 and P = 0.048 by ANOVA, respectively). Ramipril alone or simvastatin combined with ramipril significantly improved the percent flow-mediated dilator response to hyperemia (both P < 0.001), however, simvastatin combined with ramipril showed significantly more improvement than ramipril alone (P < 0.001 by ANOVA). Simvastatin combined with ramipril significantly improved endothelium-dependent vasodilation and fibrinolysis potential and reduced plasma levels of oxidant stress and inflammation markers in hypercholesterolemic patients.