title: Simvastatin combined with ramipril treatment in hypercholesterolemic patients.
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.
authors.affiliation: Department of Cardiology, Cardiology, Gil Heart Center, Gachon Medical School, 1198 Kuwol-dong, Namdong-gu, Incheon, Korea. kwangk@ghil.com
authors.forename: Kwang Kon
authors.initials: KK
authors.lastname: Koh
authors.forename: Ji Won
authors.initials: JW
authors.lastname: Son
authors.forename: Jeong Yeal
authors.initials: JY
authors.lastname: Ahn
authors.forename: Dae Sung
authors.initials: DS
authors.lastname: Kim
authors.forename: Dong Kyu
authors.initials: DK
authors.lastname: Jin
authors.forename: Hyung Sik
authors.initials: HS
authors.lastname: Kim
authors.forename: Seung Hwan
authors.initials: SH
authors.lastname: Han
authors.forename: Yiel-Hea
authors.initials: YH
authors.lastname: Seo
authors.forename: Wook-Jin
authors.initials: WJ
authors.lastname: Chung
authors.forename: Woong Chol
authors.initials: WC
authors.lastname: Kang
authors.forename: Eak Kyun
authors.initials: EK
authors.lastname: Shin
mesh_terms: D000787:Angina Pectoris / Q000150:complications; D015415:Biomarkers / Q000378:metabolism; D002097:C-Reactive Protein / Q000378:metabolism; D018932:Chemokine CCL2 / Q000378:metabolism; D002784:Cholesterol / Q000097:blood; D008076:Cholesterol, HDL / Q000097:blood; D008078:Cholesterol, LDL / Q000097:blood; D018592:Cross-Over Studies; D048909:Diabetes Complications; D004311:Double-Blind Method; D004359:Drug Therapy, Combination; D004730:Endothelium, Vascular / Q000187:drug effects; D005260:Female; D006801:Humans; D006937:Hypercholesterolemia / Q000150:complications / Q000188:drug therapy*; D006973:Hypertension / Q000150:complications; D008297:Male; D008875:Middle Aged; D009569:Nitric Oxide / Q000378:metabolism; D017395:Plasminogen Activator Inhibitor 1 / Q000378:metabolism; D017257:Ramipril / Q000008:administration & dosage*; D019821:Simvastatin / Q000008:administration & dosage*; D014280:Triglycerides / Q000097:blood; D014664:Vasodilation / Q000187:drug effects
chemical_list: D015415:Biomarkers; C111835:CCL2 protein, human; D018932:Chemokine CCL2; D008076:Cholesterol, HDL; D008078:Cholesterol, LDL; D017395:Plasminogen Activator Inhibitor 1; D014280:Triglycerides; D009569:Nitric Oxide; D002097:C-Reactive Protein; D002784:Cholesterol; D019821:Simvastatin; D017257:Ramipril