6533b837fe1ef96bd12a288b

RESEARCH PRODUCT

Anti-gout drugs as potential therapy for atrial fibrillation.

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description

Atrial fibrillation (AF) is an important cardiovascular disease in theelderly [1]. Noticeably, it has been increasingly demonstrated thatserum uric acid (UA) is associated with AF [2–9]. In a recent meta-analysis performed by Tamariz and coworkers, the authors concludedthat high levels of UA and AF are clearly associated [10]. Interestingly,serum UA has been linked to AF in obstructive sleep apnea patients[11], whereas it has been also associated with thromboembolic risk inpatients with nonvalvular AF [12].The treatment of gout, a metabolic disorder caused by chronic hyper-uricemia, is based on administration of colchicine, xanthine oxidase (XO)competitive inhibitors such as allopurinol, and most recently, fubuxostat[13].IntheColchicineforPreventionofthePostpericardiotomySyndromeand Postoperative Atrial Fibrillation (COPPS) randomized clinical trial,Imazio et al. reported that colchicine prevents both postpericardiotomysyndromeandpostoperativeAFwhencolchicinewasgiven48to72hbe-fore cardiac surgery [14]. Singhal et al. also reported that colchicine mayreverse atrial remodeling and suppress AF in failing heart [15]. Interest-ingly,allopurinolhasrecentlybeenassociatedwithareducedriskofmyo-cardialinfarction(MI),whilenodecreasedriskofMIhasbeenfoundwithcolchicine administration [16].Although increasing evidence suggests that purine metabolism isimplicated in the pathophysiology of AF, mechanistic explanationshavenotbeendescribedsofar.Theexactmechanismofactionofcolchi-cine is not completely understood, even for the treatment of gout,whereas the high rate of adverse effects is regarded as an importanthurdle foritsprescription.Onthe other hand, higherUAreflectsupreg-ulatedXOactivity,animportantsourceofreactiveoxygenspecies(ROS)which may trigger cardiac tissue injury. It is well-known that allopuri-nol improves endothelial function, reduces blood pressure in essentialhypertensionandalsoexertssignificantanti-ischemiceffectsinpatientswith stable angina. These effects are probably attributable to decreasesROS levels. Finally, there are no data on the cardiovascular effects ofthe newly released non-purine XO inhibitor febuxostat.It is likely that the metabolism of purines is involved in the patho-physiologyofAF,andtherefore,anti-gouttherapyrepresentsapotentialstrategytopreventthistypeofarrhythmia.Atthispointintime,howev-er, the lack of knowledge about precise molecular mechanisms bywhich it operates greatly limits its applicability in the cardiologyarena. Further studies that clarify these mechanisms are needed toallow further progresses in this field.Conflicts of interestsThe authors declare that no conflict of interest exists.References