Published Online
on June 7, 2004

A more recent version of this article appeared on August 1, 2004

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Submitted on January 3, 2004
Revised on January 21, 2004

Simvastatin Combined With Ramipril Treatment in Hypercholesterolemic Patients

Kwang Kon Koh^*; Ji Won Son; Jeong Yeal Ahn; Dae Sung Kim; Dong Kyu Jin; Hyung Sik Kim; Seung Hwan Han; Yiel-Hea Seo; Wook-Jin Chung; Woong Chol Kang; and Eak Kyun Shin

From the Departments of Cardiology (K.K.K., J.W.S. D.K.J., S.H.H., W.-J.C., W.C.K., E.K.S.), Clinical Pathology (J.Y.A.,Y.-H.S.), Radiology (H.S.K.), and Preventive Medicine (Biostatistics) (D.S.K.), Gachon Medical School, Incheon, Korea.

^* To whom correspondence should be addressed. E-mail: kwangk{at}ghil.com.

Abstract--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.

Key words: angiotensin-converting enzyme • atherosclerosis • endothelial growth factors • hypercholesterolemia • blood pressure

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