title: Combination pravastatin and valsartan treatment has additive beneficial effects to simultaneously improve both metabolic and cardiovascular phenotypes beyond that of monotherapy with either drug in patients with primary hypercholesterolemia.
abstract: Statin and angiotensin II type 1 receptor blocker therapy improves endothelial dysfunction using distinct mechanisms. We evaluated simultaneous vascular and metabolic responses to pravastatin and valsartan therapy, alone or in combination, in hypercholesterolemic patients. Forty-eight hypercholesterolemic patients (23 had metabolic syndrome) were given pravastatin 40 mg and placebo, pravastatin 40 mg and valsartan 160 mg, or valsartan 160 mg and placebo daily during each 2-month treatment period in a randomized, single-blind, placebo-controlled, crossover trial with three treatment arms and two washout periods (each 2 months). Brachial artery flow-mediated dilation and C-reactive protein improved to a greater extent with combined therapy compared with either monotherapy. Importantly, we also observed simultaneous improvement in metabolic phenotypes, with all three treatments causing increased plasma adiponectin levels, reduced fasting insulin levels, and increased insulin sensitivity relative to baseline measurements. For the first time in a statin combination trial, pravastatin combined with valsartan therapy increased plasma adiponectin, lowered fasting insulin levels, and improved insulin sensitivity in an additive manner when compared with monotherapy alone. In contrast to other statins, hydrophilic pavastatin may be combined with other drugs to safely reach lipid target levels while simultaneously improving the metabolic and cardiovascular phenotype of patients at high risk.
authors.affiliation: Cardiology, Gachon University Gil Medical Center, Incheon, Korea.
authors.forename: Kwang Kon
authors.initials: KK
authors.lastname: Koh
authors.forename: Soo
authors.initials: S
authors.lastname: Lim
authors.forename: Hanul
authors.initials: H
authors.lastname: Choi
authors.forename: Yonghee
authors.initials: Y
authors.lastname: Lee
authors.forename: Seung Hwan
authors.initials: SH
authors.lastname: Han
authors.forename: Kyounghoon
authors.initials: K
authors.lastname: Lee
authors.forename: Pyung Chun
authors.initials: PC
authors.lastname: Oh
authors.forename: Ichiro
authors.initials: I
authors.lastname: Sakuma
authors.forename: Eak Kyun
authors.initials: EK
authors.lastname: Shin
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Quon
mesh_terms: D047228:Angiotensin II Type 1 Receptor Blockers / Q000008:administration & dosage / Q000627:therapeutic use*; D015992:Body Mass Index; D001916:Brachial Artery; D002097:C-Reactive Protein / Q000378:metabolism; D003324:Coronary Artery Disease / Q000097:blood / Q000188:drug therapy* / Q000503:physiopathology; D018592:Cross-Over Studies; D003924:Diabetes Mellitus, Type 2 / Q000097:blood / Q000188:drug therapy* / Q000503:physiopathology; D003925:Diabetic Angiopathies / Q000097:blood / Q000188:drug therapy* / Q000503:physiopathology*; D004359:Drug Therapy, Combination; D004730:Endothelium, Vascular / Q000187:drug effects; D005260:Female; D006442:Glycated Hemoglobin / Q000378:metabolism; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000008:administration & dosage / Q000627:therapeutic use*; D006937:Hypercholesterolemia / Q000097:blood / Q000188:drug therapy* / Q000503:physiopathology; D007333:Insulin Resistance; D008055:Lipids / Q000097:blood; D008297:Male; D008875:Middle Aged; D010641:Phenotype; D017035:Pravastatin / Q000008:administration & dosage / Q000627:therapeutic use*; D013777:Tetrazoles / Q000008:administration & dosage / Q000627:therapeutic use*; D016896:Treatment Outcome; D014633:Valine / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000627:therapeutic use; D000068756:Valsartan
chemical_list: D047228:Angiotensin II Type 1 Receptor Blockers; D002097:C-Reactive Protein; D006442:Glycated Hemoglobin; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D008055:Lipids; D017035:Pravastatin; D013777:Tetrazoles; D014633:Valine; D000068756:Valsartan; C517652:hemoglobin A1c protein, human