title: Improving cardiovascular and renal outcomes in gout: what should we target?
abstract: Epidemiological and experimental studies have shown that hyperuricaemia and gout are intricately linked with hypertension, metabolic syndrome, chronic kidney disease and cardiovascular disease. A number of studies suggest that hyperuricaemia and gout are independent risk factors for the development of these conditions and that these conditions account, in part, for the increased mortality rate of patients with gout. In this Review, we first discuss the links between hyperuricaemia, gout and these comorbidities, and present the mechanisms by which uric acid production and gout might favour the development of cardiovascular and renal diseases. We then emphasize the potential benefit of urate-lowering therapies on cardiovascular and renal outcomes in patients with hyperuricaemia. The mechanisms that link elevated serum uric acid levels and gout with these comorbidities seem to be multifactorial, implicating low-grade systemic inflammation and xanthine oxidase (XO) activity, as well as the deleterious effects of hyperuricaemia itself. Patients with asymptomatic hyperuricaemia should be treated by nonpharmacological means to lower their SUA levels. In patients with gout, long-term pharmacological inhibition of XO is a treatment strategy that might also reduce cardiovascular and renal comorbidities, because of its dual effect of lowering SUA levels as well as reducing free-radical production during uric acid formation.
authors.affiliation: Hôpital Lariboisière, Fédération de Rhumatologie, Centre Viggo Petersen 2, rue Ambroise Parè 75475 Cedex 10, Paris, France.
authors.forename: Pascal
authors.initials: P
authors.lastname: Richette
authors.affiliation: Servicio de Reumatología and BioCruces Health Research Institute, Cruces University Hospital, Plaza Cruces S/N, 48903 Barakaldo, Spain.
authors.forename: Fernando
authors.initials: F
authors.lastname: Perez-Ruiz
authors.affiliation: Division of Academic Rheumatology, University of Nottingham, Clinical Sciences Building, City Hospital Nottingham, Hucknall Road, Nottingham NG5 1PB, UK.
authors.forename: Michael
authors.initials: M
authors.lastname: Doherty
authors.affiliation: Department of Rheumatology, Radboud University Medical Center, Geert Grooteplein Zuid 8, 6525 GA Nijmegen, Netherlands.
authors.forename: Tim L
authors.initials: TL
authors.lastname: Jansen
authors.affiliation: Department of Rheumatology, University of Edinburgh, Western General Hospital, Crewe Road South, Edinburgh EH4 2XU, UK.
authors.forename: George
authors.initials: G
authors.lastname: Nuki
authors.affiliation: Department of Medicine, Rheumatology Section, Alicante University and General Hospital, University Miguel Hernández, Av. Pintor Baeza 12, Alicante 03010, Spain.
authors.forename: Eliseo
authors.initials: E
authors.lastname: Pascual
authors.affiliation: Department of Rheumatology, Rheumatology Unit, University of Padova, Via Giustiniani 2, 35128 Padova, Italy.
authors.forename: Leonardo
authors.initials: L
authors.lastname: Punzi
authors.affiliation: Service of Rheumatology, Centre Hospitalier Universitaire Vaudois, Avenue Pierre Decker 4, 1011 Lausanne, Switzerland.
authors.forename: Alexander K
authors.initials: AK
authors.lastname: So
authors.affiliation: Hôpital Lariboisière, Fédération de Rhumatologie, Centre Viggo Petersen 2, rue Ambroise Parè 75475 Cedex 10, Paris, France.
authors.forename: Thomas
authors.initials: T
authors.lastname: Bardin
mesh_terms: D000493:Allopurinol / Q000627:therapeutic use; D002318:Cardiovascular Diseases / Q000150:complications / Q000517:prevention & control*; D003078:Colchicine / Q000627:therapeutic use; D003924:Diabetes Mellitus, Type 2 / Q000150:complications; D019468:Disease Management; D006073:Gout / Q000150:complications / Q000188:drug therapy*; D006074:Gout Suppressants / Q000627:therapeutic use*; D006801:Humans; D033461:Hyperuricemia / Q000150:complications / Q000188:drug therapy*; D007249:Inflammation; D024821:Metabolic Syndrome / Q000150:complications; D011339:Probenecid / Q000627:therapeutic use; D051436:Renal Insufficiency, Chronic / Q000150:complications / Q000517:prevention & control*; D016896:Treatment Outcome; D014528:Uricosuric Agents / Q000627:therapeutic use*; D014969:Xanthine Oxidase / Q000037:antagonists & inhibitors*
chemical_list: D006074:Gout Suppressants; D014528:Uricosuric Agents; D000493:Allopurinol; D014969:Xanthine Oxidase; D011339:Probenecid; D003078:Colchicine