Консенсус по ведению пациентов с гиперурикемией и высоким сердечно-сосудистым риском

Значительное количество эпидемиологических исследований продемонстрировало, что гиперурикемия в высокой степени связана с риском развития сердечно-сосудистых заболеваний, хронической болезни почек и сахарного диабета, в связи с чем необходимо повышенное внимание к мониторингу уровня мочевой кислоты в сыворотке крови у пациентов не только с точки зрения ревматических болезней, но также и в отношении снижения сердечно-сосудистого и почечного риска. Эксперты Европейского общества кардиологов и Российского медицинского общества по артериальной гипертонии включили в рутинные тесты измерение концентрации мочевой кислоты в сыворотке крови у больных артериальной гипертонией. Важным шагом на пути улучшения контроля гиперурикемии в клинической практике являются повышение осведомленности о гиперурикемии как о факторе риска сердечно-сосудистых заболеваний, разработка алгоритма ведения больных с гиперурикемией и высоким сердечно-сосудистым риском, повышение приверженности рекомендациям. Снижение уровня мочевой кислоты в сыворотке крови, достигнутое посредством лечения пациентов уратснижающими препаратами, главным образом ингибитором ксантиноксидазы, связано с улучшением контроля артериального давления и уменьшением частоты нежелательных сердечно-сосудистых событий.

гиперурикемия, мочевая кислота, фактор риска, сердечно-сосудистый риск, артериальная гипертония, ингибитор ксантиноксидазы, аллопуринол

1. Su P, Hong L, Zhao Y et al. Relationship Between Hyperuricemia and Cardiovascular Disease Risk Factors in a Chinese Population: A Cross-Sectional Study. Med Sci Monit 2015; 21: 2707-17.

2. Di Stolfo G, Mastroianno S, Potenza D.R et al. Serum uric acid as a prognostic marker in the setting of advanced vascular disease: a prospective study in the elderly. J Geriatr Cardiol 2015; 12 (5): 515-20.

3. Wu A.H, Gladden J.D, Ahmed M et al. Relation of serum uric acid to cardiovascular disease. Int J Cardiol 2016; 213: 4-7.

4. Williams B, Mancia G, Spiering W et al. 2018 ESC/ESH Guidelines for the management of arterial hypertension. The Task Force for the management of arterial hypertension of the European Society of Cardiology (ESC) and the European Society of Hypertension (ESH). Eur Heart J 2018; 39 (33): 3021-104. DOI: 10.1093/eurheartj/ehy339

5. Чазова И.Е., Жернакова Ю.В. от имени экспертов. Клинические рекомендации. Диагностика и лечение артериальной гипертонии. Системные гипертензии 2019; 16 (1): 6-31. DOI: 10.26442/2075082X.2019.1.190179

6. Haig A. On uric acid and arterial tension. Br Med J 1889; 1 (1467): 288-91. DOI: 10.1136/bmj.1.1467.288

7. Huchard H. Arteriolosclerosis: including its cardiac form. JAMA 1909; 53: 1129.

8. Kuo C.F, Grainge M.J, Zhang W et al. Global epidemiology of gout: prevalence, incidence and risk factors. Nat Rev Rheumatol 2015; 11 (11): 649-62. DOI: 10.1038/nrrheum.2015.91, indexed in PubMed: 26150127.

9. Zhu Y, Pandya B.J, Choi H.K. Comorbidities of gout and hyperuricemia in the US general population: NHANES 2007-2008. Am J Med 2012; 125 (7): 679-87.e1. DOI: 10.1016/j.am-jmed.2011.09.033, indexed in PubMed: 22626509.

10. Zhu Y, Bhavik J, Pandya B.J, Choi H.K. Prevalence of Gout and Hyperuricemia in the US General Population. The National Health and Nutrition Examination Survey 2007-2008. Arthritis Rheum 2011; 63 (10): 3136-41.

11. Chen-Xu M, Yokose C, Rai S.K et al. Contemporary Prevalence of Gout and Hyperuricemia in the United States and Decadal Trends: The National Health and Nutrition Examination Survey, 2007-2016. Arthritis Rheum 2019; 71 (6): 991-9. DOI: 10.1002/art.40807

12. Desideri G, Puig J.G, Richette P. The management of hyperuricemia with urate deposition. Curr Med Res Opin 2015; 31 (Suppl. 2): 27-32.

13. Meneses-Leon J, Denova-Gutiérrez E, Castañón-Robles S et al. Sweetened beverage consumption and the risk of hyperuricemia in Mexican adults: a cross-sectional study. BMC Public Health 2014; 14: 445.

14. Liu B, Wang T, Zhao H.N et al. The prevalence of hyperuricemia in China: a meta-ayalysis. BMC Public Health 2011; 11: 832.

15. Qiu L, Cheng X, Wu J et al. Prevalence of hyperuricemia and its retated risk factors in healthy aduts from Nothern and Northeastern Chinese provinces. BMC Public Health 2013; 13: 664.

16. Шальнова С.А., Деев А.Д., Артамонова Г.В. и др. Гиперурикемия и ее корреляты в российской популяции (результаты эпидемиологического исследования ЭССЕ-РФ). Рациональная фармакотерапия в кардиологии. 2014; 10 (2): 153-9.

17. Conen D, Wietlisbach V, Bovet P et al. Prevalence of hyperuricemia and relation of serum uric acid with cardiovascular risk factors in a developing country. BMC Public Health 2004; 4: 9. DOI: 10.1186/1471-2458-4-9, indexed in PubMed: 15043756.

18. Feig D., Kang D.H, Johnson R.J. Uric acid and cardiovascular risk. N Engl J Med 2008; 359 (17): 1811-21. DOI: 10.1056/NEJMra0800885, indexed in PubMed: 18946066.

19. Johnson R.J, Titte S, Cade J.R et al. Uric acid, evolution and primitive cultures. Semin Nephrol 2005; 25 (1): 3-8, indexed in PubMed: 15660328.

20. Hou L, Zhang M, Han W et al. Influence of Salt Intake on Association of Blood Uric Acid with Hypertension and Related Cardiovascular Risk. PLoS One 2016; 11 (4): e0150451.

21. Leiba A, Vinker S, Dinour D et al. Uric acid levels within the normal range predict increased risk of hypertension: a cohort study. J Am Soc Hypertens 2015; 9 (8): 600-9.

22. Ando K, Takahashi H, Watanabe T 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.

23. Dai X.M, Wei L, Ma L.L et al. Serum uric acid and its relationship with cardiovascular risk profile in Chinese patients with early-onset coronary artery disease. Clin Rheumatol 2015; 34 (9): 1605-11.

24. De Oliveira E.P, Burini R.C. High plasma uric acid concentration: causes and consequences. Diabetol Metab Syndr 2012; 4: 12. DOI: 10.1186/1758-5996-4-12, indexed in PubMed: 22475652.

25. Leyva F, Anker S, Swan J.W et al. Serum uric acid as an index of impaired oxidative metabolism in chronic heart failure. Eur Heart J 1997; 18 (5): 858-65.

26. Staub M. Uric acid as a scavenger in oxidative stress. Orv Hetil 1999; 140 (6): 275-9.

27. Ames B.N, Cathcart R, Schwiers E, Hochstein P. Uric acid provides an antioxidant defense in humans against oxidant - and radical-caused aging and cancer: a hypothesis. Proc Natl Acad Sci USA 1981; 78: 6858-62.

28. Tomita М, Mizuno S, Yamanaka H et al. Does hyperuricemia affect mortality? A prospective cohort study of Japanese male workers. J Epidemiol 2000; 10 (6): 403-9.

29. Agudelo C.A, Wise C.M. Gout: diagnosis, pathogenesis, and clinical manifestations. Curr Opin Rheumatol 2001; 13 (3): 234-9.

30. Niskanen L.K, Laaksonen D.E, Nyyssonen K et al. Uric acid level as a risk factor for cardiovascular and all-cause mortality in middle-aged men: a prospective cohort study. Arch Intern Med 2004; 164: 1546.

31. Mazzali M, Kanellis J, Han L et al. Hyperuricemia inducesa primary arteriolopathy in rats by a blood pressure-independent mechanism. Am J Physiol 2002; 282: F991-F997.

32. Choi H, Kim H.C, Song B.M et al. Serum uric acid concentration and metabolic syndrome among elderly Koreans: The Korean Urban Rural Elderly (KURE) study. Arch Gerontol Geriatr 2016; 64: 51-8.

33. Perez-Ruiz F, Calabozo M, Pijoan J.I et al. Effect of urate-lowering therapy on the velocity of size reduction of tophi in chronic gout. Arthritis Rheum 2002; 47 (4): 356-60. doi: 10.1002//art.10511, indexed in PubMed: 12209479.

34. McCarty D.J. A historical note: Leeuwenhoek’s description of crystals from a gouty tophus. Arthritis Rheum 1970; 13 (4): 414-8, indexed in PubMed: 4914047.

35. Lin K.C, Lin H.Y, Chou P. The interaction between uric acid level and other risk factors on the development of gout among asymptomatic hyperuricemic men in a prospective study. J Rheumatol 2000; 27 (6): 1501-5.

36. Hall A.P, Barry P.E, Dawber T.R et al. Epidemiology of gout and hyperuricemia. A long-term population study. Am J Med 1967; 42 (1): 27-37, indexed in PubMed: 6016478.

37. Schlesinger N, Norquist J.M, Watson D.J. Serum urate during acute gout. J Rheumatol 2009; 36 (6): 1287-9. DOI: 10.3899/jrheum.080938, indexed in PubMed: 19369457.

38. Logan J.A, Morrison E, McGill P.E. Serum uric acid in acute gout. Ann Rheum Dis 1997; 56 (11): 696-7, indexed in PubMed: 9462177.

39. Borghi C, Rosei E.A, Bardin T et al. Serum uric acid and the risk of cardiovascular and renal disease. J Hypertens 2015; 33 (9): 1729-41. DOI: 10.1097/HJH.0000000000000701, indexed in PubMed: 26136207.

40. Sivera F, Andrés M, Carmona L et al. Multinational evidence-based recommendations for the diagnosis and management of gout: Integrating systematic literature review and expert opinion of a broad panel of rheumatologists in the 3e initiative. Ann Rheum Dis 2014; 73 (2): 328-35. DOI: 10.1136/annrheumdis-2013-203325

41. Neogi T, Jansen T.L.T.A, Dalbeth N et al. ACR/EULAR CLassification Criteria for Gout. Arthritis Rheum 2015; 67 (10): 2557-68. DOI: 10.1002/art.39254

42. Prasad M, Matteson E.L, Herrmann J et al. Uric acid is associated with inflammation, coronary microvascular dysfunction, and adverse outcomes in postmenopausal women. Hypertension 2017; 69 (2): 236-42. DOI: 10.1161/HYPERTENSIONAHA.116.08436, indexed in PubMed: 27993955.

43. Farquharson C.A et al. Allopurinol improves endothelial dysfunction in chronic heart failure. Circulation 2002; 106 (2): 221-6.

44. Watanabe S, Kang D.H, Feng L et al. Uric acid, hominoid evolution, and the pathogenesis of salt-sensitivity. Hypertension 2002; 40 (3): 355-60, indexed in PubMed: 12215479.

45. Lin C, Zhang Pu, Xue Y et al. Link of renal microcirculatory dysfunction to increased coronary microcirculatory resistance in hypertensive patients. Cardiol J 2017; 24 (6): 623-32. DOI: 10.5603/CJ.a2017.0074, indexed in PubMed: 28653312.

46. Mazzali M, Hughes J, Kim Y.G et al. Elevated uric acid increases blood pressure in the rat by a novel crystal-independent mechanism. Hypertension 2001; 38 (5): 1101-6, indexed in PubMed: 11711505.

47. Kang D.H, Park S.K, Lee I.K et al. Uric acid-induced C-reactive protein expression: implication on cell proliferation and nitric oxide production of human vascular cells. J Am Soc Nephrol 2005; 16 (12): 3553-62. DOI: 10.1681/ASN.2005050572, indexed in PubMed: 16251237.

48. Corry D.B, Eslami P, Yamamoto K et al. Uric acid stimulates vascular smooth muscle cell proliferation and oxidative stress via the vascular renin-angiotensin system. J Hypertens 2008; 26 (2): 269-75. DOI: 10.1097/HJH.0b013e3282f240bf, indexed in PubMed: 18192841.

49. Kang D.H, Han L, Ouyang X et al. Uric acid causes vascular smooth muscle cell proliferation by entering cells via a functional urate transporter. Am J Nephrol 2005; 25 (5): 425-33. DOI: 10.1159/000087713, indexed in PubMed: 16113518.

50. Feig D.I, Nakagawa T, Karumanchi S.A et al. Hypothesis: Uric acid, nephron number, and the pathogenesis of essential hypertension. Kidney Int 2004; 66 (1): 281-7. DOI: 10.1111/j.1523-1755.2004.00729.x, indexed in PubMed: 15200435.

51. Lee J.E, Kim Y.G, Choi Y.H et al. Serum uric acid is associated with microalbuminuria in prehypertension. Hypertension 2006; 47 (5): 962-7. DOI: 10.1161/01.HYP.0000210550.97398.c2, indexed in PubMed: 16520402.

52. Iseki K, Oshiro S, Tozawa M et al. Significance of hyperuricemia on the early detection of renal failure in a cohort of screened subjects. Hypertens Res 2001; 24 (6): 691-7, indexed in PubMed: 11768729.

53. Rosolowsky E.T, Ficociello L.H, Maselli N.J et al. High-normal serum uric acid is associated with impaired glomerular filtration rate in nonproteinuric patients with type 1 diabetes. Clin J Am Soc Nephrol 2008; 3 (3): 706-13. DOI: 10.2215/CJN.04271007, indexed in PubMed: 18272826.

54. Furukawa S, Fujita T, Shimabukuro M et al. Increased oxidative stress in obesity and its impact on metabolic syndrome. J Clin Invest 2004; 114 (12): 1752-61. DOI: 10.1172/JCI21625, indexed in PubMed: 15599400.

55. Fabbrini E, Serafini M, Baric I.C et al. Effect of plasma uric acid on antioxidant capacity, oxidative stress, and insulin sensitivity in obese subjects. Diabetes 2014; 63 (3): 976-81. DOI: 10.2337/db13-1396

56. Grassi D, Desideri G, Di Giacomantonio A et al. Hyperuricemia and cardiovascular risk. High Blood Press Cardiovasc Prev 2014; 21 (4): 235-42. DOI: 10.1007/s40292-014-0046-3

57. Blagojevic-Bucknall M, Mallen C, Muller S et al. The Risk of Gout Among Patients With Sleep Apnea: A Matched Cohort Study. Arthritis Rheum 2019; 71 (1): 154-60. DOI: 10.1002/art.40662

58. Evans P.L, Prior J.A, Belcher J et al. Obesity, hypertension and diuretic use as risk factors for incident gout: A systematic review and meta-analysis of cohort studies. Arthritis Res Ther 2018; 20 (1): 1-15. DOI: 10.1186/s13075-018-1612-1

59. Reginato A.M, Mount D.B, Yang I et al. The genetics of hyperuricaemia and gout. Nat Rev Rheumatol 2012; 8 (10): 610-21. DOI: 10.1038/nrrheum.2012.144, indexed in PubMed: 22945592.

60. Kalousdian S, Fabsitz R, Havlik R et al. Heritability of clinical chemistries in an older twin cohort: the NHLBI Twin Study. Genet Epidemiol. 1987; 4 (1): 1-11. DOI: 10.1002/gepi.1370040102, indexed in PubMed: 3569874.

61. Hediger M.A, Johnson R.J, Miyazaki H.H et al. Molecular Physiology of Urate Transport Physiology 2005; 20: 125-33.

62. Major T.J, Dalbeth N, Stahl E.A et al. An update on the genetics of hyperuricaemia and gout. Nat Rev Rheumatol 2018; 14 (6): 341-53. DOI: 10.1038/s41584-018-0004-x, indexed in PubMed: 29740155.

63. Cannon P.J, Stason W.B, Demartini F.E et al. Hyperuricemia in primary and renal hypertension. N Engl J Med 1966; 275 (9): 457-64. DOI: 10.1056/NEJM196609012750902, indexed in PubMed: 5917940.

64. Ford E.S, Li C, Cook S et al. Serum concentrations of uric acid and the metabolic syndrome among US children and adolescents. Circulation 2007; 115 (19): 2526-32. DOI: 10.1161/CIRCULATIONAHA.106.657627, indexed in PubMed: 17470699.

65. Puig J.G, Martínez M.A. Hyperuricemia, gout and the metabolic syndrome. Curr Opin Rheumatol 2008; 20 (2): 187-91. DOI: 10.1097/BOR.0b013e3282f4b1ed, indexed in PubMed: 18349749.

66. Tuttle K.R, Short R.A, Johnson R.J. Sex differences in uric acid and risk factors for coronary artery disease. Am J Cardiol 2001; 87 (12): 1411-4, indexed in PubMed: 11397367.

67. Dehghan A, van Hoek M, Sijbrands E.J.G et al. High serum uric acid as a novel risk factor for type 2 diabetes. Diabetes Care 2008; 31 (2): 361-2. DOI: 10.2337/dc07-1276, indexed in PubMed: 17977935.

68. Schretlen D.J, Inscore A.B, Vannorsdall T.D et al. Serum uric acid and brain ischemia in normal elderly adults. Neurology 2007; 69 (14): 1418-23. DOI: 10.1212/01.wnl.0000277468.10236.f1, indexed in PubMed: 17909154.

69. Lehto S, Niskanen L, Rönnemaa T et al. Serum uric acid is a strong predictor of stroke in patients with non-insulin-dependent diabetes mellitus. Stroke 1998; 29 (3): 635-9, indexed in PubMed: 9506605.

70. Yu K.H, Kuo C.F, Luo S.F et al. Risk of end-stage renal disease associated with gout: a nationwide population study. Arthritis Res Ther 2012; 14 (2): R83. DOI: 10.1186/ar3806, indexed in PubMed: 22513212.

71. Abbott R.D, Brand F.N, Kannel W.B et al. Gout and coronary heart disease: the Framingham Study. J Clin Epidemiol 1988; 41 (3): 237-42, indexed in PubMed: 3339376.

72. De Vera M.A, Rahman M.M, Bhole V et al. Independent impact of gout on the risk of acute myocardial infarction among elderly women: a population-based study. Ann Rheum Dis 2010; 69 (6): 1162-4. DOI: 10.1136/ard.2009.122770, indexed in PubMed: 20124358.

73. Martillo M.A, Nazzal L, Crittenden D.B. The crystallization of monosodium urate. Curr Rheumatol Rep 2014; 16 (2): 400. DOI: 10.1007/s11926-013-0400-9, indexed in PubMed: 24357445.

74. Choi H.K, Mount D.B, Reginato A.M. Pathogenesis of gout. Ann Intern Med 2005; 143 (7): 499-516, indexed in PubMed: 16204163.

75. Feig D.I, Johnson R.J. Hyperuricemia in childhood primary hypertension. Hypertension 2003; 42 (3): 247-52. DOI: 10.1161/01.HYP.0000085858.66548.59, indexed in PubMed: 12900431.

76. Nakagawa T, Tuttle K.R, Short R.A et al. Hypothesis: fructose-induced hyperuricemia as a causal mechanism for the epidemic of the metabolic syndrome. Nat Clin Pract Nephrol 2005; 1 (2): 80-6. DOI: 10.1038/ncpneph0019, indexed in PubMed: 16932373.

77. Niskanen L.K, Laaksonen D.E, Nyyssönen K et al. Uric acid level as a risk factor for cardiovascular and all-cause mortality in middle-aged men: a prospective cohort study. Arch Intern Med 2004; 164 (14): 1546-51. DOI: 10.1001/archinte.164.14.1546, indexed in PubMed: 15277287.

78. Yan D, Wang J, Jiang F et al. A causal relationship between uric acid and diabetic macrovascular disease in Chinese type 2 diabetes patients: A Mendelian randomization analysis. Int J Cardiol 2016; 214: 194-9. DOI: 10.1016/j.ijcard.2016.03.206, indexed in PubMed: 27064641.

79. Kuwabara M, Borghi C, Cicero A.F.G et al. Elevated serum uric acid increases risks for developing high LDL cholesterol and hypertriglyceridemia: A five-year cohort study in Japan. Int J Cardiol 2018; 261: 183-8. DOI: 10.1016/j.ijcard.2018.03.045, indexed in PubMed: 29551256.

80. Borghi C, Desideri G. Urate-Lowering drugs and prevention of cardiovascular disease: the emerging role of xanthine oxidase inhibition. Hypertension 2016; 67 (3): 496-8. DOI: 10.1161/HYPERTENSIONAHA.115.06531, indexed in PubMed: 26865197.

81. Bove M, Cicero A.F, Veronesi M et al. An evidence-based review on urate-lowering treatments: implications for optimal treatment of chronic hyperuricemia. Vasc Health Risk Manag 2017; 13: 23-8.

82. Lurbe E, Torro M.I, Alvarez-Pitti J et al. Uric acid is linked to cardiometabolic risk factors in overweight and obese youths. J Hypertens 2018; 36 (9): 1840-6. DOI: 10.1097/HJH.0000000000001814, indexed in PubMed: 29916994.

83. Jalal D.I, Chonchol M, Chen W et al. Uric acid as a target of therapy in CKD. Am J Kidney Dis 2013; 61 (1): 134-46. DOI: 10.1053/j.ajkd.2012.07.021, indexed in PubMed: 23058478.

84. Shadick N.A, Kim R, Weiss S et al. Effect of low level lead exposure on hyperuricemia and gout among middle aged and elderly men: the normative aging study. J Rheumatol 2000; 27 (7): 1708-12, indexed in PubMed: 10914856.

85. Yü TF, Berger L, Dorph D.J et al. Renal function in gout. V. Factors influencing the renal hemodynamics. Am J Med 1979; 67 (5): 766-71, indexed in PubMed: 507087.

86. Tykarski A. Evaluation of renal handling of uric acid in essential hypertension: hyperuricemia related to decreased urate secretion. Nephron 1991; 59 (3): 364-8. DOI: 10.1159/000186593, indexed in PubMed: 1758523.

87. Messerli F.H, Frohlich E.D, Dreslinski G.R et al. Serum uric acid in essential hypertension: an indicator of renal vascular involvement. Ann Intern Med 1980; 93 (6): 817-21, indexed in PubMed: 7447188.

88. Alper A.B, Chen W, Yau L et al. Childhood uric acid predicts adult blood pressure: the Bogalusa Heart Study. Hypertension 2005; 45 (1): 34-8. DOI: 10.1161/01.HYP.0000150783.79172.bb, indexed in PubMed: 15569853.

89. Dyer A.R, Liu K, Walsh M et al. Ten-year incidence of elevated blood pressure and its predictors: the CARDIA study. Coronary Artery Risk Development in (Young) Adults. J Hum Hypertens 1999; 13 (1): 13-21, indexed in PubMed: 9928747.

90. Forman J.P, Choi H, Curhan G.C. Plasma uric acid level and risk for incident hypertension among men. J Am Soc Nephrol 2007; 18 (1): 287-92. DOI: 10.1681/ASN.2006080865, indexed in PubMed: 17167112.

91. Hunt S.C, Stephenson S.H, Hopkins P.N et al. Predictors of an increased risk of future hypertension in Utah. A screening analysis. Hypertension 1991; 17 (6_pt_2): 969-76. DOI: 10.1161/01.hyp.17.6.969

92. Imazu M, Yamamoto H, Toyofuku M et al. Hyperinsulinemia for the development of hypertension: data from the Hawaii-Los Angeles-Hiroshima Study. Hypertens Res 2001; 24 (5): 531-6, indexed in PubMed: 11675947.

93. Jossa F, Farinaro E, Panico S et al. Serum uric acid and hypertension: the Olivetti heart study. J Hum Hypertens 1994; 8 (9): 677-81, indexed in PubMed: 7807497.

94. Krishnan E, Kwoh C.K, Schumacher H.R et al. Hyperuricemia and incidence of hypertension among men without metabolic syndrome. Hypertension 2007; 49 (2): 298-303. DOI: 10.1161/01.HYP.0000254480.64564.b6, indexed in PubMed: 17190877.

95. Masuo K, Kawaguchi H, Mikami H et al. Serum uric acid and plasma norepinephrine concentrations predict subsequent weight gain and blood pressure elevation. Hypertension 2003; 42 (4): 474-80. DOI: 10.1161/01.HYP.0000091371.53502.D3, indexed in PubMed: 12953019.

96. Mellen P, Bleyer A, Erlinger T et al. Serum Uric Acid Predicts Incident Hypertension in a Biethnic Cohort. Hypertension 2006; 48 (6): 1037-42. DOI: 10.1161/01.hyp.0000249768.26560.66

97. Nagahama K, Inoue T, Iseki K et al. Hyperuricemia as a predictor of hypertension in a screened cohort in Okinawa, Japan. Hypertension Res 2004; 27 (11): 835-41. DOI: 10.1291//hypres.27.835

98. Taniguchi Y, Hayashi T, Tsumura K et al. Serum uric acid and the risk for hypertension and Type 2 diabetes in Japanese men: The Osaka Health Survey. J Hypertens 2001; 19 (7): 1209-15, indexed in PubMed: 11446710.

99. Kang D.H, Nakagawa T, Feng L et al. A role for uric acid in the progression of renal disease. J Am Soc Nephrol 2002; 13 (12): 2888-97, indexed in PubMed: 12444207.

100. Syamala S, Li J, Shankar A. Association between serum uric acid and prehypertension among US adults. J Hypertens 2007; 25 (8): 1583-9. DOI: 10.1097/HJH.0b013e32813aeb6c, indexed in PubMed: 17620953.

101. Grayson P.C, Kim S.Y, LaValley M et al. Hyperuricemia and incident hypertension: a systematic review and meta-analysis. Arthritis Care Res (Hoboken) 2011; 63 (1): 102-10. DOI: 10.1002//acr.20344, indexed in PubMed: 20824805.

102. Bombelli M, Ronchi I, Volpe M et al. Prognostic value of serum uric acid: new-onset in and out-of-office hypertension and long-term mortality. J Hypertens 2014; 32 (6): 1237-44. DOI: 10.1097/HJH.0000000000000161, indexed in PubMed: 24675682.

103. Perlstein T.S, Gumieniak O, Williams GH et al. Uric acid and the development of hypertension: the normative aging study. Hypertension 2006; 48 (6): 1031-6. DOI: 10.1161/01.HYP.0000248752.08807.4c, indexed in PubMed: 17060508.

104. Forman J.P, Choi H, Curhan G.C. Uric acid and insulin sensitivity and risk of incident hypertension. Arch Intern Med 2009; 169 (2): 155-62. DOI: 10.1001/archinternmed.2008.521, indexed in PubMed: 19171812.

105. Zhang W, Sun K, Yang Y et al. Plasma uric acid and hypertension in a Chinese community: prospective study and metaanalysis. Clin Chem 2009; 55 (11): 2026-34. DOI: 10.1373//clinchem.2009.124891, indexed in PubMed: 19729471.

106. Shankar A, Klein R, Klein BEK et al. The association between serum uric acid level and long-term incidence of hypertension: Population-based cohort study. J Hum Hypertens 2006; 20 (12): 937-45. DOI: 10.1038/sj.jhh.1002095, indexed in PubMed: 17024135.

107. Sundström J, Sullivan L, D’Agostino RB et al. Relations of serum uric acid to longitudinal blood pressure tracking and hypertension incidence. Hypertension 2005; 45 (1): 28-33. DOI: 10.1161/01

108. Juraschek S.P, Kovell L.C, Miller E.R et al. Association of kidney disease with prevalent gout in the United States in 1988-1994 and 2007-2010. Semin Arthritis Rheum 2013; 42 (6): 551-61. DOI: 10.1016/j.semarthrit.2012.09.009, indexed in PubMed: 23312548.

109. Jing J, Kielstein JT, Schultheiss U.T et al. Prevalence and correlates of gout in a large cohort of patients with chronic kidney disease: the German Chronic Kidney Disease (GCKD) study. Nephrol Dial Transplant 2015; 30 (4): 613-21. DOI: 10.1093/ndt/gfu352, indexed in PubMed: 25395390.

110. Johnson R.J, Nakagawa T, Jalal D et al. Uric acid and chronic kidney disease: which is chasing which? Nephrol Dial Transplant 2013; 28 (9): 2221-8. DOI: 10.1093/ndt/gft029, indexed in PubMed: 23543594.

111. Hsu Cy, Iribarren C, McCulloch C.E et al. Risk factors for end-stage renal disease: 25-year follow-up. Arch Intern Med 2009; 169 (4): 342-50. DOI: 10.1001/archinternmed.2008.605, indexed in PubMed: 19237717.

112. Myllymäki J, Honkanen T, Syrjänen J et al. Uric acid correlates with the severity of histopathological parameters in IgA nephropathy. Nephrol Dial Transplant 2005; 20 (1): 89-95. DOI: 10.1093//ndt/gfh584, indexed in PubMed: 15572382.

113. Liu P, Chen Y, Wang B et al. Allopurinol treatment improves renal function in patients with type 2 diabetes and asymptomatic hyperuricemia: 3-year randomized parallel-controlled study. Clin Endocrinol (Oxf) 2015; 83 (4): 475-82. DOI: 10.1111/cen.12673, indexed in PubMed: 25400252.

114. Hart A, Jackson S, Kasiske B.L et al. Uric acid and allograft loss from interstitial fibrosis/tubular atrophy: post hoc analysis from the angiotensin II blockade in chronic allograft nephropathy trial. Transplantation 2014; 97 (10): 1066-71. DOI: 10.1097/01.TP.0000440952.29757.66, indexed in PubMed: 24503762.

115. Bellomo G, Venanzi S, Verdura C et al. Association of uric acid with change in kidney function in healthy normotensive individuals. Am J Kidney Dis 2010; 56 (2): 264-72. DOI: 10.1053/j.ajkd.2010.01.019, indexed in PubMed: 20385436.

116. Obermayr R.P, Temml C, Knechtelsdorfer M et al. Predictors of new-onset decline in kidney function in a general middle-european population. Nephrol Dial Transplant 2008; 23 (4): 1265-73. DOI: 10.1093/ndt/gfm790, indexed in PubMed: 18039642.

117. Krishnan E, Pandya B.J, Lingala B 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. DOI: 10.1186/ar3684, indexed in PubMed: 22251426.

118. Bos M.J, Koudstaal P.J, Hofman A et al. Uric acid is a risk factor for myocardial infarction and stroke: the Rotterdam study. Stroke 2006; 37 (6): 1503-7. DOI: 10.1161/01.STR.0000221716.55088.d4, indexed in PubMed: 16675740.

119. Tscharre M, Herman R, Rohla M et al. Uric acid is associated with long-term adverse cardiovascular outcomes in patients with acute coronary syndrome undergoing percutaneous coronary intervention. Atherosclerosis 2018; 270: 173-9. DOI: 10.1016/j.atherosclerosis.2018.02.003, indexed in PubMed: 29432935.

120. Andrés M, Quintanilla M.A, Sivera F et al. Silent monosodium urate crystal deposits are associated with severe coronary calcification in asymptomatic hyperuricemia: an exploratory study. Arthritis Rheumatol 2016; 68 (6): 1531-9. DOI: 10.1002//art.39581, indexed in PubMed: 26748935.

121. Holme I, Aastveit A.H, Hammar N et al. Uric acid and risk of myocardial infarction, stroke and congestive heart failure in 417,734 men and women in the Apolipoprotein MOrtality RISk study (AMORIS). J Intern Med 2009; 266 (6): 558-70. DOI: 10.1111/j.1365-2796.2009.02133.x, indexed in PubMed: 19563390.

122. Crosta F, Occhiuzzi U, Passalacqua G et al. Association Between the Serum Uric Acid Levels and Lacunar Infarcts in the Elderly. J Mol Neurosci 2018; 65 (3): 385-90. DOI: 10.1007/s12031-018-1096-0, indexed in PubMed: 29974380.

123. Stack A.G, Hanley A, Casserly L.F et al. Independent and conjoint associations of gout and hyperuricaemia with total and cardiovascular mortality. QJM 2013; 106 (7): 647-58. DOI: 10.1093/qjmed//hct083, indexed in PubMed: 23564632.

124. Ioachimescu A.G, Brennan D.M, Hoar B.M et al. Serum uric acid is an independent predictor of all-cause mortality in patients at high risk of cardiovascular disease: a preventive cardiology information system (PreCIS) database cohort study. Arthritis Rheum 2008; 58 (2): 623-30. DOI: 10.1002/art.23121, indexed in PubMed: 18240236.

125. Choi H.K, Curhan G. Independent impact of gout on mortality and risk for coronary heart disease. Circulation 2007; 116 (8): 894-900. DOI: 10.1161/CIRCULATIONAHA.107.703389, indexed in PubMed: 17698728.

126. Kuo C.F, See L.C, Yu K.H et al. Significance of serum uric acid levels on the risk of all-cause and cardiovascular mortality. Rheumatology (Oxford) 2013; 52 (1): 127-34. DOI: 10.1093/rheuma-tology/kes223, indexed in PubMed: 22923756.

127. Tamariz L, Harzand A, Palacio A et al. Uric acid as a predictor of all-cause mortality in heart failure: a meta-analysis. Congest Heart Fail 2011; 17 (1): 25-30. DOI: 10.1111/j.1751-7133.2011.00200.x, indexed in PubMed: 21272224.

128. Thanassoulis G, Brophy J.M, Richard H et al. Gout, allopurinol use, and heart failure outcomes. Arch Intern Med 2010; 170 (15): 1358-64. DOI: 10.1001/archinternmed.2010.198, indexed in PubMed: 20696962.

129. 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. DOI: 10.1136/annrheumdis-2016-209707, indexed in PubMed: 27457514.

130. Khanna D, Fitzgerald J.D, Khanna P.P 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. DOI: 10.1002/acr.21772, indexed in PubMed: 23024028.

131. Hui M, Carr A, Cameron S et al. The British Society for Rheumatology Guideline for the Management of Gout. Rheumatology 2017; 56 (7): 1246. DOI: 10.1093/rheumatology/kex250

132. Fotherby M.D, Potter J.F. Metabolic and orthostatic blood pressure responses to a low-sodium diet in elderly hypertensives. J Hum Hypertens 1997; 11 (6): 361-6, indexed in PubMed: 9249230.

133. Singh J.A, Reddy S.G, Kundukulam J. Risk factors for gout and prevention: a systematic review of the literature. Curr Opin Rheumatol 2011; 23 (2): 192-202. DOI: 10.1097/BOR.0b013e3283438e13, indexed in PubMed: 21285714.

134. Matsumura K, Arima H, Tominaga M et al. Effect of losartan on serum uric acid in hypertension treated with a diuretic: the COMFORT study. Clin Exp Hypertens 2015; 37 (3): 192-6. DOI: 10.3109/10641963.2014.933968, indexed in PubMed: 25051056.

135. Jacob R.A, Spinozzi G.M, Simon V.A et al. Consumption of cherries lowers plasma urate in healthy women. J Nutr 2003; 133 (6): 1826-9. DOI: 10.1093/jn/133.6.1826, indexed in PubMed: 12771324.

136. Schlesinger N. Dietary factors and hyperuricaemia. Curr Pharm Des 2005; 11 (32): 4133-8, indexed in PubMed: 16375734.

137. Richette P, Poitou C, Manivet P et al. Weight Loss, Xanthine Oxidase, and Serum Urate Levels: A Prospective Longitudinal Study of Obese Patients. Arthritis Care Res (Hoboken) 2016; 68 (7): 1036-42. DOI: 10.1002/acr.22798, indexed in PubMed: 26844534.

138. Chen J.H, Wen C.P, Wu S.B et al. Attenuating the mortality risk of high serum uric acid: the role of physical activity underused. Ann Rheum Dis 2015; 74 (11): 2034-42. DOI: 10.1136/annrheumdis-2014-205312, indexed in PubMed: 25053714.

139. Borghi C, Perez-Ruiz F. Urate lowering therapies in the treatment of gout: a systematic review and meta-analysis. Eur Rev Med Pharmacol Sci 2016; 20 (5): 983-92, indexed in PubMed: 27010159.

140. Neogi T et al. Renal dosing of allopurinol results in suboptimal gout care. Ann Rheum Dis 2017; 76 (1): e1.

141. Stamp L.K, O’Donnell J.L, Zhang M et al. Using allopurinol above the dose based on creatinine clearance is effective and safe in patients with chronic gout, including those with renal impairment. Arthritis Rheum 2011; 63 (2): 412-21. DOI: 10.1002/art.30119, indexed in PubMed: 21279998.

142. Rees F, Jenkins W, Doherty M. Patients with gout adhere to curative treatment if informed appropriately: proof-of-concept observational study. Ann Rheum Dis 2013; 72 (6): 826-30. DOI: 10.1136/annrheumdis-2012-201676, indexed in PubMed: 22679303.

143. Ramasamy S, Korb-Wells C, Kannangara D et al. Allopurinol Hypersensitivity: A Systematic Review of All Published Cases, 1950-2012. Drug Safety 2013; 36 (10): 953-80. DOI: 10.1007//s40264-013-0084-0

144. Hershfield M.S, Callaghan J.T, Tassaneeyakul W et al. Clinical Pharmacogenetics Implementation Consortium guidelines for human leukocyte antigen-B genotype and allopurinol dosing. Clin Pharmacol Ther 2013; 93 (2): 153-8. DOI: 10.1038//clpt.2012.209, indexed in PubMed: 23232549.

145. Hande K.R, Noone R.M, Stone W.J. Severe allopurinol toxicity. Description and guidelines for prevention in patients with renal insufficiency. Am J Med 1984; 76 (1): 47-56.

146. Beattie C.J, Fulton R.L, Higgins P et al. Allopurinol initiation and change in blood pressure in older adults with hypertension. Hypertension 2014; 64 (5): 1102-7. DOI: 10.1161/HYPERTEN-SIONAHA.114.03953, indexed in PubMed: 25135183.

147. Feig D.I, Soletsky B, Johnson R.J. Effect of allopurinol on blood pressure of adolescents with newly diagnosed essential hypertension: a randomized trial. JAMA 2008; 300 (8): 924-32. DOI: 10.1001/jama.300.8.924, indexed in PubMed: 18728266.

148. Agarwal V, Hans N, Messerli F.H. Effect of allopurinol on blood pressure: a systematic review and meta-analysis. J Clin Hypertens (Greenwich) 2013; 15 (6): 435-42. DOI: 10.1111/j.1751-7176.2012.00701.x, indexed in PubMed: 23730993.

149. Kostka-Jeziorny K, Uruski P, Tykarski A. Effect of allopurinol on blood pressure and aortic compliance in hypertensive patients. Blood Press 2011; 20 (2): 104-10. DOI: 10.3109/08037051.2010.532323, indexed in PubMed: 21405957.

150. Khan F, George J, Wong K et al. Allopurinol treatment reduces arterial wave reflection in stroke survivors. Cardiovasc Ther 2008; 26 (4): 247-52. DOI: 10.1111/j.1755-5922.2008.00057.x, indexed in PubMed: 19035875.

151. Soletsky B, Feig D.I. Uric acid reduction rectifies prehypertension in obese adolescents. Hypertension 2012; 60 (5): 1148-56. DOI: 10.1161/HYPERTENSIONAHA.112.196980, indexed in PubMed: 23006736.

152. Borghi C, Omboni S, Reggiardo G et al. Effects of the concomitant administration of xanthine oxidase inhibitors with zofenopril or other ACE-inhibitors in post-myocardial infarction patients: a meta-analysis of individual data of four randomized, double-blind, prospective studies. BMC Cardiovasc Dis 2018; 18 (1): 112. DOI: 10.1186/s12872-018-0800-x, indexed in PubMed: 29866077.

153. Luk A.J, Levin G.P, Moore E.E et al. Allopurinol and mortality in hyperuricaemic patients. Rheumatology (Oxford) 2009; 48 (7): 804-6. DOI: 10.1093/rheumatology/kep069, indexed in PubMed: 19447769.

154. MacIsaac R.L, Salatzki J, Higgins P et al. Allopurinol and cardiovascular outcomes in adults with hypertension. Hypertension 2016; 67 (3): 535-40. DOI: 10.1161/HYPERTENSIONA-HA.115.06344, indexed in PubMed: 26865199.

155. Wei Li, Mackenzie I.S, Chen Y et al. Impact of allopurinol use on urate concentration and cardiovascular outcome. Br J Clin Pharmacol 2011; 71 (4): 600-7. DOI: 10.1111/j.1365-2125.2010.03887.x, indexed in PubMed: 21395653.

156. Noman A, Ang D.S.C, Ogston S et al. Effect of high-dose allopurinol on exercise in patients with chronic stable angina: a randomised, placebo controlled crossover trial. Lancet 2010; 375 (9732): 2161-7. DOI: 10.1016/S0140-6736 (10)60391-1, indexed in PubMed: 20542554.

157. Rekhraj S, Gandy S.J, Szwejkowski B.R et al. High-dose allopurinol reduces left ventricular mass in patients with ischemic heart disease. J Am Coll Cardiol 2013; 61 (9): 926-32. DOI: 10.1016/j.jacc.2012.09.066, indexed in PubMed: 23449426.

158. Higgins P, Dawson J, Lees KR et al. Xanthine oxidase inhibition for the treatment of cardiovascular disease: a systematic review and meta-analysis. Cardiovasc Ther 2012; 30 (4): 217-26. DOI: 10.1111/j.1755-5922.2011.00277.x, indexed in PubMed: 22099531.

159. George J, Carr E, Davies 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. DOI: 10.1161/CIRCULATIONAHA.106.651117, indexed in PubMed: 17130343.

160. Givertz M.M, Anstrom K.J, Redfield M.M et al. Effects of Xanthine Oxidase Inhibition in Hyperuricemic Heart Failure Patients: The Xanthine Oxidase Inhibition for Hyperuricemic Heart Failure Patients (EXACT-HF) Study. Circulation 2015; 131 (20): 1763-71. DOI: 10.1161/CIRCULATIONAHA.114.014536, indexed in PubMed: 25986447.

161. Cleland J.G.F, Coletta A.P, Clark A.L. Clinical trials update from the Heart Failure Society of America meeting: FIX-CHF-4, selective cardiac myosin activator and OPT-CHF. Eur J Heart Fail 2006; 8 (7): 764-6. DOI: 10.1016/j.ejheart.2006.10.001, indexed in PubMed: 17049305.

162. Freudenberger R.S, Schwarz R.P, Brown J et al. Rationale, design and organisation of an efficacy and safety study of oxypurinol added to standard therapy in patients with NYHA class III-IV congestive heart failure. Expert Opin Investig Drugs 2004; 13 (11): 1509-16. DOI: 10.1517/13543784.13.11.1509, indexed in PubMed: 15500398.

163. George J, Struthers A. The OPT-CHF (Oxypurinol Therapy for Congestive Heart Failure) trial: a question of dose. J Am Coll Cardiol 2009; 53 (25): 2405. DOI: 10.1016/j.jacc.2008.07.076, indexed in PubMed: 19539154.

164. Hare J.M, Mangal B, Brown J et al. Impact of oxypurinol in patients with symptomatic heart failure. Results of the OPT-CHF study. J Am Coll Cardiol 2008; 51 (24): 2301-9. DOI: 10.1016/j.jacc.2008.01.068, indexed in PubMed: 18549913.

165. Goicoechea M, de Vinuesa S.G, Verdalles U et al. Effect of allopurinol in chronic kidney disease progression and cardiovascular risk. Clin J Am Soc Nephrol 2010; 5 (8): 1388-93. DOI: 10.2215//CJN.01580210, indexed in PubMed: 20538833.

166. Su X, Xu B, Yan B et al. Effects of uric acid-lowering therapy in patients with chronic kidney disease: A meta-analysis. PLoS One 2017; 12 (11): e0187550. DOI: 10.1371/journal.pone.0187550, indexed in PubMed: 29095953.

167. Siu Y.P, Leung K.T, Tong M.K.H et al. Use of allopurinol in slowing the progression of renal disease through its ability to lower serum uric acid level. Am J Kidney Dis 2006; 47 (1): 51-9. DOI: 10.1053/j.ajkd.2005.10.006, indexed in PubMed: 16377385.

168. Sampson A.L, Singer R.F, Walters G.D. Uric acid lowering therapies for preventing or delaying the progression of chronic kidney disease. Cochrane Database Syst Rev 2017; 10: CD009460. DOI: 10.1002/14651858.CD009460.pub2, indexed in PubMed: 29084343.

169. Levy G.D, Rashid N, Niu F et al. Effect of urate-lowering therapies on renal disease progression in patients with hyperuricemia. J Rheumatol 2014; 41 (5): 955-62. DOI: 10.3899/jrheum.131159, indexed in PubMed: 24692523.

170. Richette P, Perez-Ruiz F, Doherty M et al. Improving cardiovascular and renal outcomes in gout: what should we target? Nat Rev Rheumatol 2014; 10 (11): 654-61. DOI: 10.1038/nr-rheum.2014.124, indexed in PubMed: 25136785.

171. Okafor O.N, Farrington K, Gorog D.A. Allopurinol as a therapeutic option in cardiovascular disease. Pharmacol Ther 2017; 172: 139-50. DOI: 10.1016/j.pharmthera.2016.12.004, indexed in PubMed: 27916655.

172. Pacher P, Nivorozhkin A, Szabó C. Therapeutic effects of xanthine oxidase inhibitors: renaissance half a century after the discovery of allopurinol. Pharmacol Rev 2006; 58 (1): 87-114. DOI: 10.1124/pr.58.1.6, indexed in PubMed: 16507884.

173. Wei Li, Mackenzie I.S, Chen Y et al. Impact of allopurinol use on urate concentration and cardiovascular outcome. Br J Clin Pharmacol 2011; 71 (4): 600-7. DOI: 10.1111/j.1365-2125.2010.03887.x, indexed in PubMed: 21395653.

174. Wei L, Fahey T, Struthers A.D et al. Association between allopurinol and mortality in heart failure patients: a long-term follow-up study. Int J Clin Pract 2009; 63 (9): 1327-33. DOI: 10.1111/j.1742-1241.2009.02118.x, indexed in PubMed: 19691616.

175. Dubreuil M, Zhu Y, Zhang Y et al. Allopurinol initiation and all-cause mortality in the general population. Ann Rheum Dis 2015; 74 (7): 1368-72. DOI: 10.1136/annrheumdis-2014-205269, indexed in PubMed: 24665118.

176. Becker M.A, Schumacher H.R, 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. doi: 10.1186/ar2978, indexed in PubMed: 20370912.

177. Becker M.A, Schumacher H.R, Wortmann RL et al. Febuxostat compared with allopurinol in patients with hyperuricemia and gout. N Engl J Med 2005; 353 (23): 2450-61. doi: 10.1056/NEJMoa050373, indexed in PubMed: 16339094.

178. White W.B, Saag K.G, Becker M.A et al. CARES Investigators. Cardiovascular safety of febuxostat or allopurinol in patients with gout. N Engl J Med 2018; 378 (13): 1200-10. DOI: 10.1056//NEJMoa1710895, indexed in PubMed: 29527974.

179. Zhang T, Pope J.E. Cardiovascular effects of urate-lowering therapies in patients with chronic gout: a systematic review and meta-analysis. Rheumatology (Oxford) 2017; 56 (7): 1144-53. DOI: 10.1093/rheumatology/kex065, indexed in PubMed: 28379501.

180. Whelton A, MacDonald P.A, Chefo S et al. Preservation of renal function during gout treatment with febuxostat: a quantitative study. Postgrad Med 2013; 125 (1): 106-14. DOI: 10.3810/pgm.2013.01.2626, indexed in PubMed: 23391676.

181. Kimura K, Hosoya T, Uchida S et al. Febuxostat Therapy for Patients With Stage 3 CKD and Asymptomatic Hyperuricemia: A Randomized Trial. Am J Kidney Dis 2018 [Epub ahead of print]. DOI: 10.1053/j.ajkd.2018.06.028, indexed in PubMed: 30177485.

182. Jansen TLTA, Janssen M. Gout lessons from 2018: CARES, a direct comparison of febuxostat vs allopurinol, and CANTOS, IL1 blocker for cardiovascular risk minimisation. Clin Rheumatol 2019; 38 (1): 263-5. DOI: 10.1007/s10067-018-4396-4

183. Pillinger M.H, Fields T, Yeo A.E, Lipsky P.E. Dissociation Between Clinical Benefit and Persistent Urate Lowering in Patients with Chronic Refractory Gout Treated with Pegloticase. J Rheumatol 2019. DOI: 10.3899/jrheum.190161

184. Richette P, Brière C, Hoenen-Clavert V et al. Rasburicase for tophaceous gout not treatable with allopurinol: an exploratory study. J Rheumatol 2007; 34 (10): 2093. LP - 2098. http://www.jrheum.org/content/34/10/2093.abstract

185. Solomon D.H, Liu C-C, Kuo I-H et al. The Effects of Colchicine on Risk of Cardiovascular Events and Mortality Among Patients with Gout: A Cohort Study Using Electronic Medical Records Linked with Medicare Claims. Ann Rheum Dis 2016; 75 (9): 1674-9. DOI: 110.1016/j.bbi.2017.04.008

186. Solomon D.H, Glynn R.J, MacFadyen J.G et al. Relationship of Interleukin-1b Blockade With Incident Gout and Serum Uric Acid Levels: Exploratory Analysis of a Randomized Controlled Trial. Ann Intern Med 2018; 169 (8): 535-42. DOI: 10.7326/M18-1167

187. Tran A.P, Edelman J. Interleukin-1 inhibition by anakinra in refractory chronic tophaceous gout. Int J Rheum Dis 2011; 14 (3): 33-7. DOI: 10.1111/j.1756-185X.2011.01629.x

188. Ruoff G, Edwards NL. Overview of serum uric acid treatment targets in gout: why less than 6 mg/dL? Postgrad Med 2016; 128 (7): 706-15. DOI: 10.1080/00325481.2016.1221732, indexed in PubMed: 27558643.

189. FitzGerald J.D, Mikuls T.R, Neogi T et al. Development of the American College of Rheumatology Electronic Clinical Quality Measures for Gout. Arthritis Care Res (Hoboken) 2018; 70 (5): 659-71. DOI: 10.1002/acr.23500, indexed in PubMed: 29649348.

190. Khanna D, Fitzgerald J.D, Khanna P.P 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. DOI: 10.1002/acr.21772, indexed in PubMed: 23024028.