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

Abstract

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 b 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 b 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 Larginine to ADMA ratio. Our finding suggests that the observed statin-induced improvements in endothelial function are likely mediated via alternative pathways.

Statins as Regulators of Redox State in the Vascular Endothelium: Beyond Lipid Lowering

“…However, the results of human studies have been contradictory. Some randomized trials have demonstrated that shortterm statin treatment lowers circulating ADMA levels in humans (61, 76, 112), while other studies have failed to find such an effect (36,74,85,109,121). These discordant results could possibly be attributed to differences in the characteristics of the populations examined.…”

The Role of Asymmetric Dimethylarginine (ADMA) in Endothelial Dysfunction and Cardiovascular Disease

“…In the majority of the studies, no impact on the ADMA levels was observed with statin therapy [89][90][91][92]. However rosuvastatin appeared to reduce ADMA levels in one study [93].…”

A systematic review and meta-analysis on the effect of statins on plasma asymmetric dimethylarginine concentrations

“…Duration of trials ranged between 6 weeks and 24 months. Six trials were designed as parallel-group studies 22,25,27,[29][30][31] and 2 trials as cross-over studies 23,28 . One study 26 was a prospective follow-up trial conducted in 3 stages.…”

“…The number of participants in these trials ranged from 53 to 650. The included studies were published between 2003 and 2012, and were conducted in Norway, Taiwan, the Netherlands, Bulgaria, Italy Turkey, New Zealand, China and Finland [22][23][24][25][26][27][28][29][30] . Statins (pravastatin, rosuvastatin, simvastatin, fluvastatin, and atorvastatin) were administered at doses from 10 to 80 mg/day.…”