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Effects of statin treatment on endothelial function, oxidative stress and inflammation in patients with arterial hypertension and normal cholesterol levels

Schneider, Markus P.a,b; Schmidt, Bernhard M.c; John, Stefana; Schmieder, Roland E.a

doi: 10.1097/HJH.0b013e32834a509a
Original papers: Oxidative stress

Objective: Patients with arterial hypertension are characterized by impaired endothelial function and increased cardiovascular risk. Statins have been proposed as a potential treatment option in hypertension, even in those with normal low-density lipoprotein (LDL)-cholesterol levels. We tested whether fluvastatin reduces oxidative stress and inflammation, and improves endothelial function in patients with arterial hypertension and normal LDL-cholesterol.

Methods: In a cross-over designed, double-blind randomized trial, 26 patients with arterial hypertension and LDL-cholesterol below 160 mg/dl were treated for 2 weeks with either placebo or fluvastatin 80 mg/day. Endothelium-dependent vasodilation (EDV) was assessed as the forearm blood flow (FBF) response to intra-arterial infusion of acetylcholine (ACH, 12 and 48 μg/min), and endothelium-independent vasodilation (EIV) as the FBF response to nitroprusside (3.2 and 12.8 μg/min). Furthermore, we measured reduced to oxidized glutathione (GSH/GSSG) ratio in red blood cells, total antioxidant capacity in plasma (TAC) and high-sensitivity C-reactive protein (hs-CRP) levels.

Results: Fluvastatin lowered LDL-cholesterol from 118 ± 16 to 90 ± 25 mg/dl (P < 0.0001), but had no effect on blood pressure, high-density lipoprotein (HDL)-cholesterol or triglycerides. EDV and EIV were unaffected by fluvastatin treatment (e.g. increase of FBF 48 μg/min: 339 ± 285% during placebo versus 268 ± 194% during fluvastatin, n.s.). Finally, GSH/GSSG ratio, TAC and hs-CRP levels were similar between fluvastatin and placebo treatment.

Conclusion: Fluvastatin treatment did not improve endothelial function, oxidative stress or inflammation in patients with arterial hypertension and normal LDL-cholesterol levels. These data argue against the usefulness of statins in patients with arterial hypertension in the absence of hypercholesterolemia or other additional risk factors.

aDepartment of Nephrology and Hypertension, University of Erlangen-Nuremberg, Erlangen, Germany

bBHF Glasgow Cardiovascular Research Centre, University of Glasgow, Glasgow,Scotland, UK

cDepartment of Nephrology and Hypertension, University of Hannover, Hannover, Germany

Correspondence to Dr Markus P. Schneider, BHF Glasgow Cardiovascular Research Centre, Institute of Cardiovascular & Medical Sciences, University of Glasgow, 126 University Place, Glasgow G12 8TA, UKTel: +44 141 330 5941; fax: +44 141 330 1689; e-mail: Markus.Schneider@glasgow.ac.uk

Abbreviations: ACH, acetylcholine; BP, blood pressure; EDV, endotheliumdependent vasodilation; EIV, endothelium-independent vasodilation; FBF, forearm blood flow; GSH, reduced glutathione; GSH/GSSG ratio, reduced to oxidized glutathione ratio; GSSG, oxidized glutathione; hs-CRP, highsensitivity C-reactive protein; L-NMMA, NG-monomethyl-L-arginine; ROS, reactive oxygen species; TAC, total antioxidant capacity; VITC, vitamin C

Received 15 February, 2011

Revised 14 June, 2011

Accepted 27 June, 2011

© 2011 Lippincott Williams & Wilkins, Inc.