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The large body of evidence supporting the cardiovascular implications of gout, clearly suggests the importance of urate-lowering treatment on the progression and clinical outcome of cardiovascular diseases failure has been demonstrated in many different studies either in terms of new onset of the disease or more severe clinical outcome. 23,24 The results of the NHANES III survey have reported a prevalence of congestive heart failure ranging from 9.7% to 11% in patients with gout compared with 1.8% (SE 0.16) of individuals without gout. 9,25 Accordingly, the results from the Framingham offspring study have reported a higher incidence of clinical heart failure and a higher mortality in patients with gout complicating heart failure compared with heart failure without gout. 26 Thanassoulis et al 27 reported an increased risk of death or re-hospitalisation for heart failure (adjusted RR 1.63; 95% CI 1.48–1.80 and 2.06; 95% CI 1.39–3.06, respectively) in a cohort of 25,090 subjects with symptomatic heart failure and a remote history or an acute episode of gout. Gout medications and CVD outcomes The large body of evidence supporting the cardiovascular implications of gout, clearly suggest the importance of urate-lowering treatment (ULT) on the progression and clinical outcome of cardiovascular diseases. According to the results published by Krishnan et al, 28 the ULT can reduce the rate of major CV events with outcome rates comparable to non-gout individuals, whereas patients not on treatment have significantly higher rates of CVD. A significant cardioprotective effects has been described for drugs as xanthine oxidase inhibitors (for example, allopurinol) and colchicine indirectly supporting the association between gout and increased cardiovascular risk. 7 In particular, ULT has been demonstrated to improve both the extent of target organ damage and also the rate of major CV complications even when most of the evidence was collected in patients with hyperuricaemia, with only a small number of studies addressing the problem of gout. Farquharson and colleagues investigated the effect of gout therapies in patients with mild to moderate congestive heart failure treated with increasing doses of allopurinol, (300, 600mg/day) 600mg, or placebo. 29 They demonstrated that both doses of allopurinol dose-dependently improved endothelial function significantly better than placebo. Improvements in endothelial function thus seemed to be a result of a reduction in oxidative stress. 30 Interestingly, Chen et al 31 showed that the use of ULT was associated with a reduction in cardiovascular mortality in patients with gout with a result that was comparable to that observed in patients without gout. The CARES study 32 has clearly demonstrated the comparable safety profile of allopurinol and febuxostat in high CV risk patients with gout complicated by previous cardiovascular disease (mainly CHD), even whether no conclusions can be drawn about the effects of treatment on CV prognosis according to study design (safety end- points, no placebo control). However, an indirect comparison with the results of other studies involving the same population of patients (for example, IMPROVE-IT), seem to suggest a lower rate of major CV disease in treated patients with gout and high cardiovascular risk profile. More information on this issue is expected from the conclusions of ongoing studies (FAST, ALL- HEART, FORWARD; Table 1) as well as from results of the clinical efficacy of newer compounds such as lesinurad, the mechanism of action of which could perfectly integrate with that of the available agents, leading to significant protection against both the articular and cardiac involvement in gout patients. References 1 Egan BM, Zhao Y, Axon RN. US trends in prevalence, awareness, treatment, and control of hypertension,1988–2008. JAMA 2010;303:2043–50. 2 Danaei G et al. Diabetes prevalence and diagnosis in US states: analysis of health surveys. Popul Health Metr 2009;7:16. 3 Flegal KM et al. Prevalence and trends in obesity among US adults, 1999–2008. JAMA 2010;303:235–41. 4 Borghi C et al. Serum uric acid and the risk of cardiovascular and renal disease. J Hypertension 2015;3:1729–41. 5 Cicero AF et al. High serum uric acid is associated to poorly controlled blood pressure and higher arterial stiffness in hypertensive subjects, Eur J Intern Med 2017;37:38–42. 6 Pascart T, Lioté F. Gout: state of the art after a decade of developments. Rheumatology (Oxford). 2018;Mar 13 [Epub ahead of print] 7 Bhole V, Krishnan E. Gout and the heart. Rheum Dis Clin North Am 2014;40(1):125–43. 8 Krishnan E et al. Long-term cardiovascular mortality among middle-aged men with gout. Arch Intern Med 2008;168(10):1104. 9 Choi HK, Curhan G. Independent impact of gout on mortality and risk for coronary heart disease. Circulation 2007;116(8):894–900. 10 Pascual E. Persistence of monosodium urate crystals and low-grade inflammation in the synovial fluid of patients with untreated gout. Arthritis Rheum 1991;34:141–5. 11 Richette P et al. 2016 updated EULAR evidence-based recommendations for the management of gout. Ann Rheum Dis 2016;2017;76:29–42. 12 Andrés M et al. Silent monosodium urate crystal deposits are associated with severe coronary calcification in asymptomatic hyperuricemia: an exploratory study. Arthritis Rheumatol 2016;68:1531–9. 13 Andrés M et al. Cardiovascular risk of patients with gout seen at rheumatology clinics following a structured assessment. Ann Rheum Dis 2017;0:1–6. 14 Ando K et al. Impact of serum uric acid levels on coronary plaque stability evaluated using integrated backscatter intravascular ultrasound in patients with coronary artery disease. J Atheroscler Thromb 2016;23(8): 932–9. 15 Chen SY, Chen CL, Shen ML. Severity of gouty arthritis is associated with Q-wave myocardial infarction: a large- scale, cross-sectional study. Clin Rheumatol 2007;26(3):308–13. 16 Abbott RD et al. Gout and coronary heart disease: the Framingham Study. J Clin Epidemiol 1988;41(3):237–42. 17 Takiue Y et al. The effect of female hormones upon urate transport systems in the mouse kidney. Nucleosides Nucleotides Nucleic Acids 2011;30(2):113–19. 18 Stack A et al. Independent and conjoint associations of gout and hyperuricaemia with total and cardiovascular mortality. QJM 2013;106(7):647–58. 19 Clarson LE et al. Increased risk of vascular disease associated with gout: a retrospective, matched cohort study in the UK clinical practice research datalink. Ann Rheum Dis 2015;74:642–7. 20 Teng GG et al. Mortality due to coronary heart disease and kidney disease among middle- aged and elderly men and women with gout in the Singapore Chinese Health Study. Ann Rheum Dis 2012;71(6):924–8. 21 Kuo CF et al. Gout: an independent risk factor for all-cause and cardiovascular mortality. Rheumatology 2010;49(1):141–6. 22 Kok VC et al. Gout and subsequent increased risk of cardiovascular mortality in non- diabetics aged 50 and above: a population-based cohort study in Taiwan. BMC Cardiovasc Disord 2012;12(1):108. 23 Krishnan E. Hyperuricemia and incident heart failure. Circ Heart Fail 2009;2(6):556–62. 24 Anker SD et al. Uric acid and survival in chronic heart failure validation and application in metabolic, functional, and hemodynamic staging. Circulation 2003;107(15):1991–7. 25 Zhu Y, Pandya BJ, Choi HK. Comorbidities of gout and hyperuricemia in the US General Population: NHANES 2007–2008. Am J Med 2012;125(7):679–87.e1. 26 Krishnan E. Gout and the risk for incident heart failure and systolic dysfunction. BMJ Open 2012;2(1):e000282. 27 Thanassoulis G et al. Gout, allopurinol use, and heart failure outcomes. Arch Intern Med 2010;170(15):1358. 28 Krishnan E et al. Hyperuricemia and untreated gout are poor prognostic markers among those with a recent acute myocardial infarction. Arthritis Res Ther 2012;14(1):R10. 29 Farquharson CA et al. Allopurinol improves endothelial dysfunction in chronic heart failure. Circulation 2002;106(2):221–6. 30 George J et al. High-dose allopurinol improves endothelial function by profoundly reducing vascular oxidative stress and not by lowering uric acid. Circulation 2006;114(23):2508–16. 31 Chen JH et al. Effect of urate- lowering therapy on the risk of cardiovascular disease and all-cause mortality in patients with gout: A case-matched cohort study. J Rheumatol 2015;42(9):1694–701. 32 White WB et al; CARES Investigators. Cardiovascular safety of febuxostat or allopurinol in patients with gout. N Engl J Med 2018;378(13):1200–10. hospitalpharmacyeurope.com | 2018 | 19