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31-01-2012 | Cardiology | Article

UDCA could improve endothelial function in heart failure

Abstract

Free abstract

MedWire News: European researchers have unveiled a completely novel approach for improving endothelial function in heart failure (HF).

The "hypothesis-generating study," as it is referred to by editorialists James McCabe (Harvard Medical School, Boston, Massachusetts, USA) and John Teerlink (University of California, San Francisco, USA) in the Journal of the American College of Cardiology, showed that ursodeoxycholic acid (UDCA) produced significant improvements in peak postischemic blood flow in the arm, and a trend toward improvement in peak postischemic blood flow in the leg, but failed to show benefits in exercise capacity and several inflammatory markers.

"Although the study failed on two out of three counts, the observed improvements in post-ischemic arm and leg blood flow make it highly unlikely such findings would have occurred purely by chance," commented Kenneth Dickstein, a spokesperson for the European Society of Cardiology, in a press statement.

"The results are enough to pique real interest and suggest the approach has the potential to offer another string to our bow for improving HF symptoms."

Endothelial function is commonly observed in chronic HF patients, and it contributes to the limitation in exercise capacity that accompanies the condition. Stephan von Haehling (Charité Medical School, Berlin, Germany) and team explain that bacterial lipopolysaccharide may trigger proinflammatory cytokine release and promote further endothelial dysfunction.

They hypothesized that UDCA, a bile acid that is used in the treatment of cholestatic liver disease, has anti-inflammatory and cytoprotective properties, and could help form mixed micelles around lipopolysaccharide.

The crossover study involved 16 clinically stable men with chronic HF (New York Heart Association class I/II, left ventricular ejection fraction <45%). All patients received UDCA 500 mg twice daily for 4 weeks and placebo for another 4 weeks, in random order.

Compared with placebo, UDCA improved peak postischemic blood flow in the arm by a significant 18% (p=0.038) and showed a trend towards improved peak postischemic blood flow in the leg (+17%; p=0.079).

Liver function also improved when compared with placebo; levels of γ-glutamyl transferase, aspartate transaminase, and soluble tumor necrosis factor α receptor 1 were lower with UDCA treatment than after placebo (all p<0.05).

However, there was no significant change in 6-minute walk test results, New York Heart Association functional class, levels of tumor necrosis factor α or interleukin-6 compared with placebo.

Dickstein advised that any future studies undertaken must involve larger cohorts of patients. He added: "One big question for me is whether 4 weeks of treatment is sufficient to produce significant effects. This begs the question of whether higher doses and longer durations of treatment may have produced clearer cut answers."

Of the potential mechanism of UDCA in HF, he commented: "Part of the appeal of the concept is that it's so intuitively attractive. It provides a biologically plausible hypothesis that's really easy for everyone to understand."

McCabe and Teerlink write: "von Haehling et al have demonstrated that UDCA therapy is feasible in a stable HF population, and the provocative finding of improved forearm endothelial function has paved the way for larger studies of safety and efficacy."

MedWire (http://www.medwire-news.md/) is an independent clinical news service provided by Springer Healthcare Limited. © Springer Healthcare Ltd; 2012

By Piriya Mahendra

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