© 2008 European Society of Cardiology
Effect of atorvastatin on plasma levels of asymmetric dimethylarginine in patients with non-ischaemic heart failure
a Lipid and Diabetes Research Group, Christchurch Hospital Christchurch, New Zealand
b Clinical Biochemistry Unit, Canterbury Health Laboratories Christchurch, New Zealand
c Department of Medicine, University of Otago Christchurch, New Zealand
* Corresponding author. Lipid & Diabetes Research Group, Christchurch Hospital, Private Bag 4710, Christchurch, New Zealand. Tel.: +64 3 364 1186; fax: +64 3 364 0457. E-mail addresses: joanna.young{at}cdhb.govt.nz (J.M. Young).
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Abstract |
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Background: Elevated plasma levels of asymmetric dimethylarginine (ADMA), an endothelial nitric oxide synthase (eNOS) inhibitor, may contribute to endothelial dysfunction in chronic heart failure (CHF). Since statins upregulate eNOS and ameliorate endothelial dysfunction in non-ischaemic CHF, we hypothesized that this may be in part through modification of ADMA.
Aim: To evaluate the effect of atorvastatin on the relationship between ADMA and endothelial function in non-ischaemic CHF.
Methods: Twenty-four patients with CHF (ejection fraction <40%, New York Heart Association Functional Classes II and III) were randomised to atorvastatin treatment (40 mg) or placebo once daily for 6 weeks in a double-blinded, placebo-controlled crossover study. Plasma ADMA and L-arginine levels were measured by HPLC. Endothelial function was assessed by flow-mediated dilatation and invasive forearm plethysmography.
Results: Post-statin therapy, endothelial function was improved (p<0.05) independent of LDL-cholesterol reductions, but no changes were observed in ADMA levels or the L-arginine to ADMA ratio. There was a trend for ADMA to inversely correlate with endothelial function at baseline.
Conclusions: Short-term atorvastatin treatment in non-ischaemic CHF improves endothelial function but has no effect on ADMA or the L-arginine to ADMA ratio. Our finding suggests that the observed statin-induced improvements in endothelial function are likely mediated via alternative pathways.
Key Words: Asymmetric dimethylarginine • Left ventricular dysfunction • Chronic heart failure • Statin treatment • Endothelial function
Received September 25, 2007; Revised March 13, 2008; Accepted March 26, 2008
1 Current address: Diabetes Team Offices, East Wing, Wansbeck Hospital, Woodhorn Lane, Ashington, Northumberland, NE63 9JJ.