Effect of atorvastatin on plasma levels of asymmetric dimethylarginine in patients with non-ischaemic heart failure.
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.


OBJECTIVE
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.
Young
Joanna M
JM
Lipid and Diabetes Research Group, Christchurch Hospital, Christchurch, New Zealand. joanna.young@cdhb.govt.nz
Strey
Christopher H
CH
George
Peter M
PM
Florkowski
Christopher M
CM
Sies
Christiaan W
CW
Frampton
Christopher M
CM
Scott
Russell S
RS
D001120:Arginine / Q000031:analogs & derivatives / Q000096:biosynthesis / Q000097:blood; D000069059:Atorvastatin; D018592:Cross-Over Studies; D004311:Double-Blind Method; D004730:Endothelium, Vascular / Q000187:drug effects / Q000378:metabolism; D006333:Heart Failure / Q000097:blood / Q000188:drug therapy / Q000378:metabolism; D006538:Heptanoic Acids / Q000494:pharmacology / Q000627:therapeutic use*; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000494:pharmacology / Q000627:therapeutic use*; D011758:Pyrroles / Q000494:pharmacology / Q000627:therapeutic use*; D018487:Ventricular Dysfunction, Left / Q000188:drug therapy*
D006538:Heptanoic Acids; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D011758:Pyrroles; C018524:N,N-dimethylarginine; D001120:Arginine; D000069059:Atorvastatin