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Current Pharmaceutical Design


ISSN (Print): 1381-6128
ISSN (Online): 1873-4286

Review Article

Hyperuricemia and Cardiovascular Disease

Author(s): Shuangshuang Zhang, Yong Wang, Jinsong Cheng, Ning Huangfu, Ruochi Zhao, Zhenyu Xu, Fuxing Zhang, Wenyuan Zheng and Dandan Zhang*

Volume 25, Issue 6, 2019

Page: [700 - 709] Pages: 10

DOI: 10.2174/1381612825666190408122557

Price: $65


Purine metabolism in the circulatory system yields uric acid as its final oxidation product, which is believed to be linked to the development of gout and kidney stones. Hyperuricemia is closely correlated with cardiovascular disease, metabolic syndrome, and chronic kidney disease, as attested by the epidemiological and empirical research. In this review, we summarize the recent knowledge about hyperuricemia, with a special focus on its physiology, epidemiology, and correlation with cardiovascular disease. This review also discusses the possible positive effects of treatment to reduce urate levels in patients with cardiovascular disease and hyperuricemia, which may lead to an improved clinical treatment plan.

Keywords: Uric acid, hyperuricaemia, cardiovascular diseases, gout, metabolic syndrome, chronic kidney disease.

Rock KL, Kataoka H, Lai JJ. Uric acid as a danger signal in gout and its comorbidities. Nat Rev Rheumatol 2013; 9(1): 13-23.
Liu G, Chen S, Zhong J, Teng K, Yin Y. Crosstalk between tryptophan metabolism and cardiovascular disease, mechanisms, and therapeutic implications. Oxid Med Cell Longev 2017; 20171602074
Jin M, Yang F, Yang I, et al. Uric acid, hyperuricemia and vascular diseases. Front Biosci 2012; 17: 656-69.
Sharaf El Din UAA, Salem MM, Abdulazim DO. Uric acid in the pathogenesis of metabolic, renal, and cardiovascular diseases: A review. J Adv Res 2017; 8(5): 537-48.
Richette P, Doherty M, Pascual E, et al. 2016 updated EULAR evidence-based recommendations for the management of gout. Ann Rheum Dis 2017; 76(1): 29-42.
Desideri G, Castaldo G, Lombardi A, et al. Is it time to revise the normal range of serum uric acid levels? Eur Rev Med Pharmacol Sci 2014; 18(9): 1295-306.
Kratzer JT, Lanaspa MA, Murphy MN, et al. Evolutionary history and metabolic insights of ancient mammalian uricases. Proc Natl Acad Sci USA 2014; 111(10): 3763-8.
Petreski T, Bevc S, Ekart R, Hojs R. Hyperuricemia and long-term survival in patients with chronic kidney disease undergoing hemodialysis. Clin Nephrol 2017; 88(13): 69-72.
Acevedo A, Benavides J, Chowdhury M, et al. Hyperuricemia and cardiovascular disease in patients with hypertension. Conn Med 2016; 80(2): 85-90.
Terkeltaub R. Update on gout: new therapeutic strategies and options. Nat Rev Rheumatol 2010; 6(1): 30-8.
Li L, Yang C, Zhao Y, Zeng X, Liu F, Fu P. Is hyperuricemia an independent risk factor for new-onset chronic kidney disease?: A systematic review and meta-analysis based on observational cohort studies. BMC Nephrol 2014; 15: 122.
Johnson RJ, Titte S, Cade JR, Rideout BA, Oliver WJ. Uric acid, evolution and primitive cultures. Semin Nephrol 2005; 25(1): 3-8.
Löffler W, Gröbner W, Medina R, Zöllner N. Influence of dietary purines on pool size, turnover, and excretion of uric acid during balance conditions. Isotope studies using 15N-uric acid. Res Exp Med (Berl) 1982; 181(2): 113-23.
Maiuolo J, Oppedisano F, Gratteri S, Muscoli C, Mollace V. Regulation of uric acid metabolism and excretion. Int J Cardiol 2016; 213: 8-14.
Jalal DI, Chonchol M, Chen W, Targher G. Uric acid as a target of therapy in CKD. Am J Kidney Dis 2013; 61(1): 134-46.
Bobulescu IA, Moe OW. Renal transport of uric acid: evolving concepts and uncertainties. Adv Chronic Kidney Dis 2012; 19(6): 358-71.
Mandal AK, Mount DB. The molecular physiology of uric acid homeostasis. Annu Rev Physiol 2015; 77: 323-45.
Wu AH, Gladden JD, Ahmed M, Ahmed A, Filippatos G. Relation of serum uric acid to cardiovascular disease. Int J Cardiol 2016; 213: 4-7.
Dogan M, Uz O, Aparci M, Atalay M. Confounders of uric acid level for assessing cardiovascular outcomes. J Geriatr Cardiol 2016; 13(2): 197-8.
Culleton BF, Larson MG, Kannel WB, Levy D. Serum uric acid and risk for cardiovascular disease and death: the Framingham Heart Study. Ann Intern Med 1999; 131(1): 7-13.
Jayashankar CA, Andrews HP. Vijayasarathi , et al. Serum uric acid and low-density lipoprotein cholesterol levels are independent predictors of coronary artery disease in Asian Indian patients with type 2 diabetes mellitus. J Nat Sci Biol Med 2016; 7(2): 161-5.
Zhao G, Huang L, Song M, Song Y. Baseline serum uric acid level as a predictor of cardiovascular disease related mortality and all-cause mortality: A meta-analysis of prospective studies. Atherosclerosis 2013; 231(1): 61-8.
De Becker B, Borghi C, Burnier M, van de Borne P. Uric acid and hypertension: A focused review and practical recommendations. J Hypertens 2019; 37(5): 878-83.
Flynn JT, Kaelber DC, Baker-Smith CM, et al. Clinical practice guideline for screening and management of high blood pressure in children and adolescents. Pediatrics 2017; 140(3)e20171904
Rovda Iu I, Kazakova LM, Plaksina EA. Parameters of uric acid metabolism in healthy children and in patients with arterial hypertension. Pediatriia 1990; (8): 19-22.
Wang J, Qin T, Chen J, et al. Hyperuricemia and risk of incident hypertension: A systematic review and meta-analysis of observational studies. PLoS One 2014; 9(12)e114259
Cicero AF, Salvi P, D’Addato S, Rosticci M, Borghi C. Association between serum uric acid, hypertension, vascular stiffness and subclinical atherosclerosis: data from the Brisighella Heart Study. J Hypertens 2014; 32(1): 57-64.
Tutal E, Sayın B, Ertugrul DT, Ibis A, Sezer S, Ozdemir N. Is there a link between hyperuricemia, morning blood pressure surge, and non-dipping blood pressure pattern in metabolic syndrome patients? Int J Nephrol Renovasc Dis 2013; 6: 71-7.
Çağlı K, Turak O, Canpolat U, et al. Association of serum uric acid level with blood pressure variability in newly diagnosed essential hypertension. J Clin Hypertens 2015; 17(12): 929-35.
Li P, Zhang L, Zhang M, Zhou C, Lin N. Uric acid enhances PKC-dependent eNOS phosphorylation and mediates cellular ER stress: A mechanism for uric acid-induced endothelial dysfunction. Int J Mol Med 2016; 37(4): 989-97.
Tassone EJ, Cimellaro A, Perticone M, et al. Uric acid impairs insulin signaling by promoting enpp1 binding to insulin receptor in human umbilical vein endothelial cells. Front Endocrinol (Lausanne) 2018; 9: 98.
Choi YJ, Yoon Y, Lee KY, et al. Uric acid induces endothelial dysfunction by vascular insulin resistance associated with the impairment of nitric oxide synthesis. FASEB J 2014; 28(7): 3197-204.
Chao HH, Liu JC, Lin JW, Chen CH, Wu CH, Cheng TH. Uric acid stimulates endothelin-1 gene expression associated with NADPH oxidase in human aortic smooth muscle cells. Acta Pharmacol Sin 2008; 29(11): 1301-12.
Schwartz IF, Grupper A, Chernichovski T, et al. Hyperuricemia attenuates aortic nitric oxide generation, through inhibition of arginine transport, in rats. J Vasc Res 2011; 48(3): 252-60.
Yu MA, Sánchez-Lozada LG, Johnson RJ, Kang DH. Oxidative stress with an activation of the renin-angiotensin system in human vascular endothelial cells as a novel mechanism of uric acid-induced endothelial dysfunction. J Hypertens 2010; 28(6): 1234-42.
Ejaz AA, Mu W, Kang DH, et al. Could uric acid have a role in acute renal failure? Clin J Am Soc Nephrol 2007; 2(1): 16-21.
Mazzali M, Hughes J, Kim YG, et al. Elevated uric acid increases blood pressure in the rat by a novel crystal-independent mechanism. Hypertension 2001; 38(5): 1101-6.
Abbott RD, Brand FN, Kannel WB, Castelli WP. Gout and coronary heart disease: the Framingham Study. J Clin Epidemiol 1988; 41(3): 237-42.
Zuo T, Liu X, Jiang L, Mao S, Yin X, Guo L. Hyperuricemia and coronary heart disease mortality: A meta-analysis of prospective cohort studies. BMC Cardiovasc Disord 2016; 16(1): 207.
Kim H, Kim SH, Choi AR, et al. Asymptomatic hyperuricemia is independently associated with coronary artery calcification in the absence of overt coronary artery disease: A single-center cross-sectional study. Medicine (Baltimore) 2017; 96(14)e6565
Mutluay R, Deger SM, Bahadir E, Durmaz AO, Citil R, Sindel S. Uric acid is an important predictor for hypertensive early atherosclerosis. Adv Ther 2012; 29(3): 276-86.
Yang G, Lucas R, Caldwell R, Yao L, Romero MJ, Caldwell RW. Novel mechanisms of endothelial dysfunction in diabetes. J Cardiovasc Dis Res 2010; 1(2): 59-63.
Zharikov S, Krotova K, Hu H, et al. Uric acid decreases NO production and increases arginase activity in cultured pulmonary artery endothelial cells. Am J Physiol Cell Physiol 2008; 295(5): C1183-90.
Förstermann U, Münzel T. Endothelial nitric oxide synthase in vascular disease: from marvel to menace. Circulation 2006; 113(13): 1708-14.
Kırça M, Oğuz N, Çetin A, Uzuner F, Yeşilkaya A. Uric acid stimulates proliferative pathways in vascular smooth muscle cells through the activation of p38 MAPK, p44/42 MAPK and PDGFRβ. J Recept Signal Transduct Res 2017; 37(2): 167-73.
Karbach S, Wenzel P, Waisman A, Munzel T, Daiber A. eNOS uncoupling in cardiovascular diseases--the role of oxidative stress and inflammation. Curr Pharm Des 2014; 20(22): 3579-94.
Heijman J, Voigt N, Nattel S, Dobrev D. Cellular and molecular electrophysiology of atrial fibrillation initiation, maintenance, and progression. Circ Res 2014; 114(9): 1483-99.
Canpolat U, Aytemir K, Yorgun H, et al. Usefulness of serum uric acid level to predict atrial fibrillation recurrence after cryoballoon-based catheter ablation. Europace 2014; 16(12): 1731-7.
Kuwabara M, Niwa K, Nishihara S, et al. Hyperuricemia is an independent competing risk factor for atrial fibrillation. Int J Cardiol 2017; 231: 137-42.
Nyrnes A, Toft I, Njølstad I, et al. Uric acid is associated with future atrial fibrillation: An 11-year follow-up of 6308 men and women--the Tromso Study. Europace 2014; 16(3): 320-6.
Letsas KP, Korantzopoulos P, Filippatos GS, et al. Uric acid elevation in atrial fibrillation. Hellenic J Cardiol 2010; 51(3): 209-13.
Tamariz L, Agarwal S, Soliman EZ, et al. Association of serum uric acid with incident atrial fibrillation (from the Atherosclerosis Risk in Communities [ARIC] study). Am J Cardiol 2011; 108(9): 1272-6.
Kim SC, Liu J, Solomon DH. Risk of incident atrial fibrillation in gout: A cohort study. Ann Rheum Dis 2016; 75(8): 1473-8.
Sun GZ, Guo L, Wang J, Ye N, Wang XZ, Sun YX. Association between hyperuricemia and atrial fibrillation in rural China: A cross-sectional study. BMC Cardiovasc Disord 2015; 15: 98.
Zhen H, Gui F. The role of hyperuricemia on vascular endothelium dysfunction. Biomed Rep 2017; 7(4): 325-30.
Du J, Xie J, Zhang Z, et al. TRPM7-mediated Ca2+ signals confer fibrogenesis in human atrial fibrillation. Circ Res 2010; 106(5): 992-1003.
Yan M, Chen K, He L, Li S, Huang D, Li J. Uric Acid Induces Cardiomyocyte Apoptosis via Activation of Calpain-1 and Endoplasmic Reticulum Stress. Cell Physiol Biochem 2018; 45(5): 2122-35.
Maharani N, Ting YK, Cheng J, et al. Molecular Mechanisms Underlying Urate-Induced Enhancement of Kv1.5 Channel Expression in HL-1 Atrial Myocytes. Circ J 2015; 79(12): 2659-68.
Dudley SC Jr, Hoch NE, McCann LA, et al. Atrial fibrillation increases production of superoxide by the left atrium and left atrial appendage: role of the NADPH and xanthine oxidases. Circulation 2005; 112(9): 1266-73.
Nattel S, Harada M. Atrial remodeling and atrial fibrillation: recent advances and translational perspectives. J Am Coll Cardiol 2014; 63(22): 2335-45.
Korantzopoulos P, Letsas KP, Liu T. Xanthine oxidase and uric Acid in atrial fibrillation. Front Physiol 2012; 3: 150.
Youn JY, Zhang J, Zhang Y, et al. Oxidative stress in atrial fibrillation: An emerging role of NADPH oxidase. J Mol Cell Cardiol 2013; 62: 72-9.
Choi HK, Atkinson K, Karlson EW, Willett W, Curhan G. Alcohol intake and risk of incident gout in men: A prospective study. Lancet 2004; 363(9417): 1277-81.
Jamnik J, Rehman S, Blanco Mejia S, et al. Fructose intake and risk of gout and hyperuricemia: A systematic review and meta-analysis of prospective cohort studies. BMJ Open 2016; 6(10)e013191
Choi HK, Liu S, Curhan G. Intake of purine-rich foods, protein, and dairy products and relationship to serum levels of uric acid: the Third National Health and Nutrition Examination Survey. Arthritis Rheum 2005; 52(1): 283-9.
Zhang Y, Neogi T, Chen C, Chaisson C, Hunter DJ, Choi HK. Cherry consumption and decreased risk of recurrent gout attacks. Arthritis Rheum 2012; 64(12): 4004-11.
Park KY, Kim HJ, Ahn HS, et al. Effects of coffee consumption on serum uric acid: Systematic review and meta-analysis. Semin Arthritis Rheum 2016; 45(5): 580-6.
Beyl RN Jr, Hughes L, Morgan S. Update on Importance of Diet in Gout. Am J Med 2016; 129(11): 1153-8.
Bredemeier M, Lopes LM, Eisenreich MA, et al. Xanthine oxidase inhibitors for prevention of cardiovascular events: A systematic review and meta-analysis of randomized controlled trials. BMC Cardiovasc Disord 2018; 18(1): 24.
Becker MA, Schumacher HR Jr, Wortmann RL, et al. Febuxostat compared with allopurinol in patients with hyperuricemia and gout. N Engl J Med 2005; 353(23): 2450-61.
Schumacher HR Jr, Becker MA, Wortmann RL, et al. Effects of febuxostat versus allopurinol and placebo in reducing serum urate in subjects with hyperuricemia and gout: A 28-week, phase III, randomized, double-blind, parallel-group trial. Arthritis Rheum 2008; 59(11): 1540-8.
Becker MA, Schumacher HR, Espinoza LR, et al. The urate-lowering efficacy and safety of febuxostat in the treatment of the hyperuricemia of gout: The CONFIRMS trial. Arthritis Res Ther 2010; 12(2): R63.
Bardin T, Keenan RT, Khanna PP, et al. Lesinurad in combination with allopurinol: A randomised, double-blind, placebo-controlled study in patients with gout with inadequate response to standard of care (the multinational CLEAR 2 study). Ann Rheum Dis 2017; 76(5): 811-20.
Saag KG, Fitz-Patrick D, Kopicko J, et al. Lesinurad combined with allopurinol: A randomized, double-blind, placebo-controlled study in gout patients with an inadequate response to standard-of-care allopurinol (a US-based study). Arthritis Rheumatol 2017; 69(1): 203-12.
Shahid H, Singh JA. Investigational drugs for hyperuricemia. Expert Opin Investig Drugs 2015; 24(8): 1013-30.
Malik UZ, Hundley NJ, Romero G, et al. Febuxostat inhibition of endothelial-bound XO: implications for targeting vascular ROS production. Free Radic Biol Med 2011; 51(1): 179-84.
Bridgeman MB, Chavez B. Febuxostat for the treatment of gout. Expert Opin Pharmacother 2015; 16(3): 395-8.
Paschou E, Gavriilaki E, Papaioannou G, Tsompanakou A, Kalaitzoglou A, Sabanis N. Febuxostat hypersensitivity: Another cause of DRESS syndrome in chronic kidney disease? Eur Ann Allergy Clin Immunol 2016; 48(6): 251-5.
Khanna D, Fitzgerald JD, Khanna PP, et al. 2012 American College of Rheumatology guidelines for management of gout. Part 1: systematic nonpharmacologic and pharmacologic therapeutic approaches to hyperuricemia. Arthritis Care Res (Hoboken) 2012; 64(10): 1431-46.
Davies K, Bukhari MAS. Recent pharmacological advances in the management of gout. Rheumatology (Oxford) 2018; 57(6): 951-8.
Raychaudhuri S, Plenge RM, Rossin EJ, et al. Identifying relationships among genomic disease regions: predicting genes at pathogenic SNP associations and rare deletions. PLoS Genet 2009; 5(6)e1000534
Robbins N, Koch SE, Tranter M, Rubinstein J. The history and future of probenecid. Cardiovasc Toxicol 2012; 12(1): 1-9.
Pui K, Gow PJ, Dalbeth N. Efficacy and tolerability of probenecid as urate-lowering therapy in gout; clinical experience in high-prevalence population. J Rheumatol 2013; 40(6): 872-6.
Reinders MK, van Roon EN, Jansen TL, et al. Efficacy and tolerability of urate-lowering drugs in gout: A randomised controlled trial of benzbromarone versus probenecid after failure of allopurinol. Ann Rheum Dis 2009; 68(1): 51-6.
Ernst ME, Fravel MA. Febuxostat: A selective xanthine-oxidase/xanthine-dehydrogenase inhibitor for the management of hyperuricemia in adults with gout. Clin Ther 2009; 31(11): 2503-18.
Fabbrini E, Serafini M, Colic Baric I, Hazen SL, Klein S. Effect of plasma uric acid on antioxidant capacity, oxidative stress, and insulin sensitivity in obese subjects. Diabetes 2014; 63(3): 976-81.
Kaufmann P, Török M, Hänni A, Roberts P, Gasser R, Krähenbühl S. Mechanisms of benzarone and benzbromarone-induced hepatic toxicity. Hepatology 2005; 41(4): 925-35.
Shen Z, Tieu K, Wilson D, et al. Evaluation of pharmacokinetic interactions between lesinurad, a new selective urate reabsorption inhibitor, and commonly used drugs for gout treatment. Clin Pharmacol Drug Dev 2017; 6(4): 377-87.
Fleischmann R, Kerr B, Yeh LT, et al. Pharmacodynamic, pharmacokinetic and tolerability evaluation of concomitant administration of lesinurad and febuxostat in gout patients with hyperuricaemia. Rheumatology (Oxford) 2014; 53(12): 2167-74.
Perez-Ruiz F, Sundy JS, Miner JN, Cravets M, Storgard C, Group RS. Lesinurad in combination with allopurinol: Results of a phase 2, randomised, double-blind study in patients with gout with an inadequate response to allopurinol. Ann Rheum Dis 2016; 75(6): 1074-80.
Hoy SM. Lesinurad: First Global Approval. Drugs 2016; 76(4): 509-16.
Tausche AK, Alten R, Dalbeth N, et al. Lesinurad monotherapy in gout patients intolerant to a xanthine oxidase inhibitor: A 6 month phase 3 clinical trial and extension study. Rheumatology (Oxford) 2017; 56(12): 2170-8.
Deeks ED. Lesinurad: A Review in Hyperuricaemia of Gout. Drugs Aging 2017; 34(5): 401-10.
Sundy JS, Baraf HS, Yood RA, et al. Efficacy and tolerability of pegloticase for the treatment of chronic gout in patients refractory to conventional treatment: two randomized controlled trials. JAMA 2011; 306(7): 711-20.
Baraf HS, Becker MA, Gutierrez-Urena SR, et al. Tophus burden reduction with pegloticase: results from phase 3 randomized trials and open-label extension in patients with chronic gout refractory to conventional therapy. Arthritis Res Ther 2013; 15(5): R137.
Robinson PC, Dalbeth N. Lesinurad for the treatment of hyperuricaemia in people with gout. Expert Opin Pharmacother 2017; 18(17): 1875-81.
Sherman MR, Saifer MG, Perez-Ruiz F. PEG-uricase in the management of treatment-resistant gout and hyperuricemia. Adv Drug Deliv Rev 2008; 60(1): 59-68.
Li Q, Li X, Kwong JS, et al. Diagnosis and treatment for hyperuricaemia and gout: A protocol for a systematic review of clinical practice guidelines and consensus statements. BMJ Open 2017; 7(6)e014928
Becker MA, Baraf HS, Yood RA, et al. Long-term safety of pegloticase in chronic gout refractory to conventional treatment. Ann Rheum Dis 2013; 72(9): 1469-74.
Zhang T, Pope JE. Cardiovascular effects of urate-lowering therapies in patients with chronic gout: A systematic review and meta-analysis. Rheumatology (Oxford) 2017; 56(7): 1144-53.
Cicero AF, Rosticci M, Cagnati M, et al. Serum uric acid and markers of low-density lipoprotein oxidation in nonsmoking healthy subjects: data from the Brisighella Heart Study. Pol Arch Med Wewn 2014; 124(12): 661-8.
Soletsky B, Feig DI. Uric acid reduction rectifies prehypertension in obese adolescents. Hypertension 2012; 60(5): 1148-56.
Saddekni MB, Saag KG, Dudenbostel T, et al. The effects of urate lowering therapy on inflammation, endothelial function, and blood pressure (SURPHER) study design and rationale. Contemp Clin Trials 2016; 50: 238-44.
Li S, Yang H, Guo Y, et al. Comparative efficacy and safety of urate-lowering therapy for the treatment of hyperuricemia: A systematic review and network meta-analysis. Sci Rep 2016; 6: 33082.
Beattie CJ, Fulton RL, Higgins P, et al. Allopurinol initiation and change in blood pressure in older adults with hypertension. Hypertension 2014; 64(5): 1102-7.
Borghi C, Rosei EA, Bardin T, et al. Serum uric acid and the risk of cardiovascular and renal disease. J Hypertens 2015; 33: 1729-41.
McGillicuddy FC, de la Llera Moya M, Hinkle CC, et al. Inflammation impairs reverse cholesterol transport in vivo. Circulation 2009; 119(8): 1135-45.
Thanassoulis G, Brophy JM, Richard H, Pilote L. Gout, allopurinol use, and heart failure outcomes. Arch Intern Med 2010; 170(15): 1358-64.
Grimaldi-Bensouda L, Alpérovitch A, Aubrun E, et al. Impact of allopurinol on risk of myocardial infarction. Ann Rheum Dis 2015; 74(5): 836-42.
Kato M, Hisatome I, Tomikura Y, et al. Status of endothelial dependent vasodilation in patients with hyperuricemia. Am J Cardiol 2005; 96(11): 1576-8.
Ogino K, Kato M, Furuse Y, et al. Uric acid-lowering treatment with benzbromarone in patients with heart failure: A double-blind placebo-controlled crossover preliminary study. Circ Heart Fail 2010; 3(1): 73-81.
Chen X, Wu G, Schwarzschild MA. Urate in Parkinson’s disease: more than a biomarker? Curr Neurol Neurosci Rep 2012; 12(4): 367-75.
Hershfield MS, Roberts LJ II, Ganson NJ, et al. Treating gout with pegloticase, a PEGylated urate oxidase, provides insight into the importance of uric acid as an antioxidant in vivo. Proc Natl Acad Sci USA 2010; 107(32): 14351-6.
Kuo CF, See LC, Yu KH, Chou IJ, Chiou MJ, Luo SF. Significance of serum uric acid levels on the risk of all-cause and cardiovascular mortality. Rheumatology (Oxford) 2013; 52(1): 127-34.
Khanna D, Khanna PP, Fitzgerald JD, et al. 2012 American College of Rheumatology guidelines for management of gout. Part 2: therapy and antiinflammatory prophylaxis of acute gouty arthritis. Arthritis Care Res (Hoboken) 2012; 64(10): 1447-61.
Yamanaka H, Metabolism TG. Essence of the revised guideline for the management of hyperuricemia and gout. Japan Med Assoc J 2012; 55(4): 324-9.

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