Author + information
- Dimitris Tousoulis, MD, PhD⁎ (, )
- Nikolaos Papageorgiou, MD and
- Christodoulos Stefanadis, MD
- ↵⁎Athens University Medical School, Hippokration Hospital, Vasilissis Sofias 114, Athens 115 28, Greece
We read with interest the excellent paper written by von Haehling et al. (1). The authors assessed, in a double-blind, randomized, placebo-controlled, crossover trial, the effects of ursodeoxycholic acid (UDCA) on endothelial function and inflammatory markers in patients with chronic heart failure (HF). They concluded that UDCA improved peak post-ischemic blood flow in the arm and that there was a trend for improved peak post-ischemic blood flow in the leg, while liver function was improved. However, it failed to show benefits in exercise capacity and levels of inflammatory markers, such as tumor necrosis factor α and interleukin-6, compared with placebo.
Previously, it was shown that 6 weeks' UDCA therapy improved endothelium-dependent, nitric oxide–independent vasodilatation, which might maintain arterial flow in patients with HF under conditions of impaired nitric oxide production (2). The present study expanded the previous knowledge in patients with HF. Despite the novelty of the present study, and although it was published many years after the first study of UDCA, there are still aspects requiring attention, such as the drug dose and the study period. Furthermore, the implicated underlying pathways are rather controversial and slightly inexplicable when considering the unequal improvements of peripheral blood flow in the arms and legs.
Similarly, we have highlighted previously the beneficial effects of pharmaceutical agents, different from UDCA, on endothelial function/inflammatory process in patients with HF, and we have shown that short-term treatment with rosuvastatin regulated the inflammatory process in patients with HF by significantly reducing plasma levels of myeloperoxidase compared with allopurinol and placebo (3). Importantly, treatment with rosuvastatin, but not allopurinol, significantly increased the number of circulating endothelial progenitor cells (EPCs) in patients with HF, providing further insight into its role in these individuals. This effect on EPCs was not mediated by changes in inflammatory and oxidative status (4). Considering the previously published data, we conclude that although the results of the study by von Haehling et al. (1) are promising and challenging, these should be considered with care and skepticism. Agents such as statins and others already evaluated in several studies are capable of improving endothelial function and decreasing inflammatory process, and therefore further large-scale randomized studies are required to establish the role of UDCA therapy in patients with HF.
- American College of Cardiology Foundation