Гиперурикемия, подагра и высокий кардиоваскулярный риск – как ими управлять в клинической практике

1. Richette P, Doherty M, Pascual E, еt al. EULAR evidence-based recommendations for the management of gout. Ann Rheum Dis. 2016. doi: 10.1136/annrheumdis-2016-209707
2. Zhu Y, Pandya BJ, Choi HK. 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. doi: 10.1002/art.30520
3. Lin КС, Lin HY, Chou R. 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. 
4. Simkin PA. The pathogenesis of podagra. Ann Intern Med. 1977;86:230-3.
5. Компания «ЭГИС» собрала статистику о распространенности гиперурикемии в сочетании с артериальной гипертензией и сопутствующими заболеваниями среди российских пациентов. Поликлиника. Спецвыпуск. 2017;(4):16. [EGIS collected statistics on the prevalence of hyperuricemia in combination with arterial hypertension and comorbidities  among Russian patients. Polyclinika. Spetsvypusk. 2017;(4):16 (In Russ.)].
6. Mazzali M, Hughes J, Kim YG, Jefferson JA, Kang DH, Gordon KL, Lan HY, Kivlighn S, Johnson RJ. Elevated uric acid increases blood pressure in the rat by a novel crystal-independent mechanism. Hypertension. 2001;38(5):1101-6.
7. Perez-Pozo SE, Schold J, Nakagawa T, Sanchez-Lozada LG, Johnson RJ, Lillo JL. Excessive fructose intake induces the features of metabolic syndrome in healthy adult men: role of uric acid in the hypertensive response. Int J Obes (Lond). 2010;34(3):454-61. 
8. DeBosch BJ, Kluth O, Fujiwara H, Schurmann A, Moley K. Early-onset metabolic syndrome in mice lacking the intestinal uric acid transporter SLC2A9. Nat Commun. 2014;5:4642. doi: 10.1038.ncomms5642
9. Feig DI, Kang DH, Johnson RJ. Uric acid and cardiovascular risk. N Engl J Med. 2008;359(17):1811-21. doi: 10.1056 / NEJMra0800885
10. Richette P, Perez-Ruiz F, Doherty M, Jansen TL, Nuki G, Pascual E, Punzi L, So AK, Bardin T. Improving cardiovascular and renal outcomes in gout: what should we target? Nat Rev Rheumatol. 2014;10(11):654-61. doi: 10.1016/j.jare.2017.04.008
11. Andres M, Quintanilla MA, Sivera F, Sanchez-Paya J, Pascual E, Vela P, Ruiz-Nodar JM. Silent monosodium urate crystal deposits are associated with severe coronary calcification in asymptomatic hyperuricemia: an exploratory study. Arthritis Rheum. 2016;68(6):1531-9. doi: 10.1002/art.39581
12. Saito Y, Nakayama T, Sugimoto K, Fujimoto Y, Kobayashi Y. Relation of lipid content of coronary plaque to level of serum uric acid. Am J Cardiol. 2015;116(9):1346-50. doi: 10.1016/j.amjcard.2015.07.059
13. Ando K, Takahashi H, Watanabe T, Daidoji H, Otaki Y, Nishiyama S, Arimoto T, Shishido T, Miyashita T, Miyamoto 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. doi: 10.5551/jat.33951
14. Park JJ, Roudier MP, Soman D, Mokadam NA, Simkin PA. Prevalence of birefringent crystals in cardiac and prostatic tissues, an observational study. BMJ Open. 2014;4(7):e005308. doi: 10.1136/bmjopen-2014-005308
15. Borghi C, Rosei EA, Bardin T, Dawson J, Dominiczak A, Kielstein JT, Manolis AJ, Perez-Ruiz F, Mancia G. Serum uric acid and the risk of cardiovascular and renal disease. J Hypertens. 2015;33(9):1729-41. doi: 10.1097/HJH.0000000000000701
16. 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. doi: 10.1016/j.atherosclerosis.2013.08.023
17. Nozue T, Yamamoto S, Tohyama S, Fukui K, Umezawa S, Onishi Y, Kunishima T, Hibi K, Terashima M, Michishita I. Correlations between serum uric acid and coronary atherosclerosis before and during statin therapy. Coron Artery Dis. 2014;25(4):343-8. doi: 10.1097/MCA.0000000000000084
18. Tamariz L, Hernandez F, Bush A, Palacio A, Hare JM. Association between serum uric acid and atrial fibrillation: a systematic review and meta-analysis. Heart Rhythm. 2014;11(7):1102-8. doi: 10.1016/j/ hrthm.2014.04.003
19. Kim SY, Guevara JP, Kim KM, Choi HK, Heitjan DF, Albert DA. Hyperuricemia and risk of stroke: a systematic review and meta-analysis. Arthritis Rheum. 2009;61(7):885-92. doi: 10.1002 / art. 24612
20. Harzand A, Tamariz L, Hare JM. Uric acid, heart failure survival, and the impact of xanthine oxidase inhibition. Congest Heart Fail. 2012;18(3):179-82. doi: 10.1111/j.1751-7133.2011.00262.x.
21. Bardin T, Richette Р. Impact of comorbidities on gout and hyperuricemia: an updated on prevalence and treatment options. BMC Med. 2017;15:123. doi: 10.1186/s12916-017-0890-9
22. Lyngdoh T, Vuistiner P, Marques-Vidal P, Rousson V, Waeber G, Vollenweider P, Bochud M. Serum uric acid and adiposity: deciphering causality using a bidirectional Mendelian randomization approach. PLoS One. 2012;7(6):e39321. doi: 10.1371/journal.pone.0039321
23. Nitsch D, Molokhia M, Smeeth L, DeStavola BL, Whittaker JC, Leon DA. Limits to causal inference based on Mendelian randomization: a comparison with randomized controlled trials. Am J Epidemiol. 2006;163(5):397-403. doi: 10.1093/aje/kwj062
24. Doring A, Gieger C, Mehta D, Gohlke H, Prokisch H, Coassin S, Fischer G, Henke K, Klopp N, Kronenberg F, et al. SLC2A9 influences uric acid concentrations with pronounced sex-specific effects. Nat Genet. 2008;40(4):430-6. doi: 10.1038/ng.107
25. Parsa A, Brown E, Weir MR, Fink JC, et al. Genotype-based changes in serum uric acid affect blood pressure. Kidney Int. 2012;81(5):502-7. doi: 10.1038/ki.2011.414
26. Mallamaci F, Testa A, Leonardis D, Tripepi R, Pisano A, Spoto B, Sanguedolce MC, Parlongo RM, Tripepi G, Zoccali C. A polymorphism in the major gene regulating serum uric acid associates with clinic SBP and the white-coat effect in a family-based study. J Hypertens. 2014;32(8):1621-8. doi: 10.1097/HJH.0000000000000224
27. Mallamaci F, Testa A, Leonardis D, Tripepi R, Pisano A, Spoto B, Sanguedolce MC, Parlongo RM, Tripepi G, Zoccali C. A genetic marker of uric acid level, carotid atherosclerosis, and arterial stiffness: a family-based study. Am J Kidney Dis. 2015;65(2):294-302. doi: 10.1038/ ki.2011.414
28. Palmer TM, Nordestgaard BG, Benn M, Tybjaerg-Hansen A, Davey Smith G, Lawlor DA, Timpson NJ. Association of plasma uric acid with ischaemic heart disease and blood pressure: Mendelian randomisation analysis of two large cohorts. BMJ. 2013;347:f4262. doi: 10.1136/bmj.f4262
29. McKeigue PM, Campbell H, Wild S, Vitart V, Hayward C, Rudan I, Wright AF, Wilson JF. Bayesian methods for instrumental variable analysis with genetic instruments (‘Mendelian randomization’): example with urate transporter SLC2A9 as an instrumental variable for effect of urate levels on metabolic syndrome. Int J Epidemiol. 2010;39(3):907-18. doi: 10.1093/ije/dyp397
30. Kleber ME, Delgado G, Grammer TB, Silbernagel G, Huang J, Kramer BK, Ritz E, Marz W. Uric acid and cardiovascular events: a Mendelian randomization study. J Am Soc Nephrol. 2015;26(11):2831-8. doi: 10.1681/ASN.2014070660
31. 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
32. Yang Q, Kottgen A, Dehghan A, Smith AV, Glazer NL, Chen MH, Chasman DI, Aspelund T, Eiriksdottir G, Harris TB, et al. Multiple genetic loci influence serum urate levels and their relationship with gout and cardiovascular disease risk factors. Circ Cardiovasc Genet. 2010;3(6):523-30. doi: 10.1161/CIRCGENETICS.109.934455
33. Keenan T, Zhao W, Rasheed A, Ho WK, Malik R, Felix JF, Young R, Shah N, Samuel M, Sheikh N, et al. Causal assessment of serum urate levels in cardiometabolic diseases through a Mendelian randomization study. J Am Coll Cardiol. 2016;67(4):407-16. doi: 10.1016/j.jacc.2015.10.086
34. Sedaghat S, Pazoki R, Uitterlinden AG, Hofman A, Stricker BH, Ikram MA, Franco OH, Dehghan A. Association of uric acid genetic risk score with blood pressure: the Rotterdam study. Hypertension. 2014;64(5):1061-6. doi: 10.1161/HYPERTENSIONAHA.114.03757Hypertension
35. Higgins P, Dawson J, Lees KR, McArthur K, Quinn TJ, Walters MR. 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
36. Scheepers LE, Wei FF, Stolarz-Skrzypek K, Malyutina S, Tikhonoff V, Thijs L, Salvi E, Barlassina C, Filipovsky J, Casiglia E, et al. Xanthine oxidase gene variants and their association with blood pressure and incident hypertension: a population study. J Hypertens. 2016;34(11):2147-54. doi:10.1097/HJH0000000000001077
37. Scheepers LE, Boonen A, Pijnenburg W, Bierau J, Staessen JA, Stehouwer CD, Thijs C, Arts IC. Associations of plasma uric acid and purine metabolites with blood pressure in children: the KOALA Birth Cohort Study. J Hypertens. 2017;35(5):982-93. doi: 10.1097/ HJH.0000000000001270
38. Schmitz B, Brand SM. Uric acid and essential hypertension: the endothelial connection. J Hypertens. 2016;34(11):2138-9. doi: 10.1097/ HJH.0000000000001109
39. Hootman JM, Helmick CG. Projections of US prevalence of arthritis and associated activity limitations. Arthritis Rheum. 2006;54:226-9. doi: 10.1002/art. 21562
40. Kuo CF, Luo SF. Gout: risk of premature death in gout unchanged for years. Nat Rev Rheumatol. 2017;13(4):200-1. doi: 10.1038/ nrrheum.2017.27
41. 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. doi: 10.7326/0003-4819-131-1-199907060-00003
42. So A, Thorens B. Uric acid transport and disease. J Clin Invest. 2010;120:1791-9. doi: 10.1172/JCI42344
43. Rock KL, Kataoka H, Lai JJ. Uric acid as a danger signal in gout and its comorbidities. Nat Rev Rheumatol. 2013;9:13-23. doi: 10.1038/nrrheum.2012.143
44. Kumar HKVS, Marwaha V. Chronic Tophaceous Gout. Int J Med Health Sci. 2012;1(1):31-2.
45. Liu SC, Xia L, Zhang J, et al. Gout and risk of myocardial infarction: a systematic review and meta-analysis of cohort studies. PLoS ONE. 2015;10:e0134088.
46. Clarson LE, Hider SL, Belcher J, 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. doi: 10.1136/annrheumdis-2014-205252
47. Choi HK, Curhan G. Independent impact of gout on mortality and risk for coronary heart disease. Circulation. 2007;116:894-900. doi: 10.1161/CIRCULATIONAHA.107.703389
48. Егоров И.В., Хитрик Н.М., Цурко В.В. Функциональное состояние нейтрофилов у пожилых больных хроническим подагрическим артритом в стадии обострения. Клиническая геронтология. 2008;(9):70-1 [Egorov IV, Кhitrik NM, Tsurko VV. Functional state of neutrophils in elderly patients with chronic gouty arthritis in the acute stage. Clinical Gerontology. 2008;(9):70-1 (In Russ.)].
49. Perez-Ruiz F, Martinez-Indart L, Carmona L, Herrero-Beites AM, Pijoan JI, Krishnan E. Tophaceous gout and high level of hyperuricaemia are both associated with increased risk of mortality in patients with gout. Ann Rheum Dis. 2014;73(1):177-82. doi: 10.1136/annrheumdis-2012-202421
50. Edwards NL. The role of hyperuricemia and gout in kidney and cardiovascular disease. Clev Clin J Med. 2008;75:13-6. doi:10.3949/ ccjm.75.suppl5.s13
51. Johnson RJ, Kang DH, Feig D, et al. Is there a pathogenetic role for uric acid in hypertension and cardiovascular and renal disease? Hypertension. 2003;41:1183-90. doi: 10.1161/01.HYP.0000069700.62727.C5
52. Briggs AM, Cross MJ, Hoy DG, et al. Musculoskeletal Health Conditions Represent a Global Threat to Healthy Aging: A Report for the 2015 World Health Organization World Report on Ageing and Health. Gerontologist. 2016;56(Suppl 2):S243-255. doi: 10.1093/geront/gnw002 
53. Clauw DJ. Diagnosing and treating chronic musculoskeletal pain based on the underlying mechanism(s). Best Pract Res Clin Rheumatol. 2015;29(1):6-19. doi: 10.1016/j.berh.2015.04.024
54. Цурко В.В., Егоров И.В., Елисеева М.В. Подагра у пожилых пациентов, связь с коморбидностью. Практикующий врач сегодня. 2013;(1):2-8 [Tsurko VV, Egorov IV, Eliseeva MV. Gout in elderly patients, association with comorbidity. Practicing Doctor Today. 2013;(1):2-8 (In Russ.)].
55. Kuo CF, Grainge MJ, Mallen C, Zhang W, Doherty M. Comorbidities in patients with gout prior to and following diagnosis: case-control study. Ann Rheum Dis. 2016;75(1):210-7. doi: 10.1136/annrheumdis-2014-206410
56. Choi HK, Ford ES, Li C, Curhan G. Prevalence of the metabolic syndrome in patients with gout: the Third National Health and Nutrition Examination Survey. Arthritis Rheum. 2007;57(1):109-15. doi: 10.1002/art.22466
57. Clarson LE, Hider SL, Belcher J, 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. doi: 10.1136/annrheumdis-2014-205252
58. Елисеев М.С., Новикова А.М. Коморбидность при подагре и гиперурикемии: распространенность, причины, перспективы уратснижающей терапии. Терапевтический архив. 2019;91(5):120-8 [Eliseev MS, Novikova AM. Comorbidity in gout and hyperuricemia: prevalence, causes, prospects of urate lowering therapy. Therapeutic Archive. 2019;91(5):120-8 (In Russ.)]. doi: 10.26442/00403660.2019. 05.000232
59. Krishnan E, Baker JF, Furst DE, Schumacher HR. Gout and the risk of acute myocardial infarction. Arthritis Rheum. 2006;54(8):2688-96. doi: 10.1002/art.22014
60. De Vera MA, Rahman MM, Bhole V, Kopec JA, Choi HK. 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
61. Krishnan E. Gout and the risk for incident heart failure and systolic dysfunction. BMJ Open. 2012;2(1):e000282. doi: 10.1136/bmjopen-2011-000282
62. Richette P, Latourte A, Bardin T. Cardiac and renal protective effects of urate-lowering therapy. Rheumatology (Oxford). 2018;57(suppl 1):i47-i50. doi: 10.1093/rheumatology/kex432
63. Kuo CF, Grainge MJ, Mallen C, Zhang W, Doherty M. Impact of gout on the risk of atrial fibrillation. Rheumatology (Oxford). 2016;55(4):721-8. doi: 10.1093/rheumatology/kev418
64. Chang K, Yokose C, Tenner C, Oh C, Donnino R, Choy-Shan A, Pike VC, Shah BD, Lorin JD, Krasnokutsky S, et al. Association between gout and aortic stenosis. Am J Med. 2017;130(2):230.e1-8. doi: 10.1016/j.amjmed.2016.09.005
65. Stack AG, Hanley A, Casserly LF, Cronin CJ, Abdalla AA, Kiernan TJ, Murthy BV, Hegarty A, Hannigan A, Nguyen HT. Independent and conjoint associations of gout and hyperuricaemia with total and cardiovascular mortality. QJM. 2013;106(7):647-58. doi: 10.1093/qjmed/hct083
66. 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;59:1540-8. doi: 10.1002/art.24209
67. Becker MA, Schumacher HR Jr, Wortmann RL, et al. Febuxostat compared with allopurinol in patients with hyperuricemia and gout. N Engl J Med. 2005;353:2450-61. doi: 10.1056/NEJMoa050373
68. Diaz-Torné C, Perez-Herrero N, Perez-Ruiz F. New medications in development for the treatment of hyperuricemia of gout. Curr Opin Rheumatol. 2015;27:164-9. doi:10.1097/BOR.0000000000000146
69. Edwards NL, So A. Emerging therapies for gout. Rheum Dis Clin North Am. 2014;40:375-87. doi: 10.1016/j.rdc.2014.01.013
70. Terkeltaub RA, Furst DE, Bennett K, et al. High versus low dosing of oral colchicine for early acute gout flare: twenty-four-hour outcome of the first multicenter, randomized, double-blind, placebo-controlled, parallel-group, dose-comparison colchicine study. Arthritis Rheum. 2010;62:1060-8. doi: 10.1002/art.27327
71. Stamp LK, O’Donnell JL, 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;63:412-21. doi: 10.1002/art.30119
72. Stamp LK, Taylor WJ, Jones PB, et al. Starting dose is a risk factor for allopurinol hypersensitivity syndrome: a proposed safe starting dose of allopurinol. Arthritis Rheum. 2012;64:2529-36. doi: 10.1002/art.34488
73. Hung SI, Chung WH, Liou LB, et al. HLA-B*5801 allele as a genetic marker for severe cutaneous adverse reactions caused by allopurinol. Proc Natl Acad Sci USA. 2005;102:4134-9. doi: 10.1073/pnas.0409500102
74. Akkineni R, Tapp S, Tosteson ANA, et al. Treatment of asymptomatic hyperuricemia and prevention of vascular disease: a decision analytic approach. J Rheumatol. 2014;41(4):739-48. doi: 10.3899/irheum.l21231 
75. Abeles AM. Hyperuricemia, gout, and cardiovascular disease: an update. Curr Rheumatol Rep. 2015;17(3):13. doi: 10.1007//sll92601504952
76. Lee JE, Kim YG, Choi YH, et al. Serum uric acid is associated with microalbuminuria in prehypertension. Hypertension. 2006;47(5):962-7. doi: 10.1161/01.HYP.0000210550.97398x2
77. Dalbeth N, Chen P, White M, et al. Impact of bariatric surgery on serum urate targets in people with morbid obesity and diabetes: a prospective longitudinal study. Ann Rheum Dis. 2014;73:797-802. doi: 10.1136/annrheumdis-2013-203970
78. Chen JH, Wen CP, Wu SB, et al. Attenuating the mortality risk of high serum uric acid: the role of physical activity underused. Ann Rheum Dis. 2015;74:2034-42. doi:10.1136/annrheumdis-2014-205312
79. Grimaldi-Bensouda L, Alperovitch A, Aubrun E, Danchin N, Rossignol M, Abenhaim L, Richette P. Impact of allopurinol on risk of myocardial infarction. Ann Rheum Dis. 2015;74(5):836-42. doi: 10.1136/annrheumdis-2012-202972
80. De Abajo FJ, Gil MJ, Rodriguez A, Garcia-Poza P, Alvarez A, Bryant V, Garcia-Rodriguez LA. Allopurinol use and risk of non-fatal acute myocardial infarction. Heart. 2015;101(9):679-85. doi: 10.1136/heartjnl-2014-306670
81. Larsen KS, Pottegard A, Lindegaard HM, Hallas J. Effect of allopurinol on cardiovascular outcomes in hyperuricemic patients: a cohort study. Am J Med. 2016;129(3):299-306. doi: 10.1016/j.amjmed.2015.11.003
82. Zhang J, Dierckx R, Mohee K, Clark AL, Cleland JG. Xanthine oxidase inhibition for the treatment of cardiovascular disease: an updated systematic review and meta-analysis. ESC Heart Fail. 2017;4(1):40-5. doi: 10.1002/ehf2.12112
83. Kok VC, Horng JT, Chang WS, Hong YF, Chang TH. Allopurinol therapy in gout patients does not associate with beneficial cardiovascular outcomes: a population-based matched-cohort study. PLoS One. 2014;9(6):e99102. doi: 10.1371/journal.pone.0099102
84. Borghi C, Tykarski A, Widecka K, et al. Expert consensus for diagnosis and treatment of patient with hyperuricemia and high cardiovascular risk. Cardiol J. 2018;25(5):545-64. doi: 10.5603/CJ.2018.0116
85. Keenan RT, O’Brien WR, Lee KH, et al. Prevalence of contraindications and prescription of pharmacologic therapies for gout. Am J Med. 2011;124:155-63. doi: 10.1016/j.amjmed.2010.09.012
86. Nidorf SM, Eikelboom JW, Budgeon CA, et al. Low-dose colchicine for secondary prevention of cardiovascular disease. J Am Coll Cardiol. 2013;61:404-10. doi:  10.1016/j.jacc.2012.10.027
87. Deftereos S, Giannopoulos G, Raisakis K, et al. Colchicine treatment for the prevention of bare-metal stent restenosis in diabetic patients. J Am Coll Cardiol. 2013;61:1679-85. doi: 10.1016/j.jacc.2013.01.055
88. Rothenbacher D, Primatesta P, Ferreira A, et al. Frequency and risk factors of gout flares in a large population-based cohort of incident gout. Rheumatology (Oxford). 2011;50:973-81. doi: 10.1093/rheumatology/keq363
89. Yamanaka H. Gout and hyperuricemia in young people. Curr Opin Rheumatol. 2011;23:156-60. doi: 10.1097/BOR.0b013e3283432d35
90. Feig DI, Soletsky B, Johnson RJ. 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
91. Soletsky B, Feig DI. Uric acid reduction rectifies prehypertension in obese adolescents. Hypertension. 2012;60(5):1148-56. doi:  10.1001/ jama.300.8.924
92. McMullan CJ, Borgi L, Fisher N, Curhan G, Forman J. Effect of uric acid lowering on renin-angiotensin-system activation and ambulatory BP: a randomized controlled trial. Clin J Am Soc Nephrol. 2017;12(5):807-16. doi:  10.2215/CJN.10771016
93. Poudel DR, Karmacharya P, Donato A. Risk of acute gout among active smokers: data from nationwide inpatient sample. Clin Rheumatol. 2016;35(12):3015-8. doi: 10.1007/s10067-016-3415-6
94. Gee Teng G, Pan A, Yuan JM, Koh WP. Cigarette smoking and the risk of incident gout in a prospective cohort study. Arthritis Care Res (Hoboken). 2016;68(8):1135-42. doi: 10.1002/acr.22821
95. Wang W, Krishnan E. Cigarette smoking is associated with a reduction in the risk of incident gout: results from the Framingham Heart Study original cohort. Rheumatology (Oxford). 2015;54(1):91-5. doi: 10.1093/rheumatology/keu304
96. Yu TF, Gutman AB. Study of the paradoxical effects of salicylate in low, intermediate and high dosage on the renal mechanisms for excretion of urate in man. J Clin Invest. 1959;38(8):1298-315. doi: 10.1172/JCI103905
97. Zhang Y, Neogi T, Chen C, Chaisson C, Hunter DJ, Choi H. Low-dose aspirin use and recurrent gout attacks. Ann Rheum Dis. 2014;73(2):385-90. doi: 10.1136/annrheumdis-2012-202589
98. Choi HK, Soriano LC, Zhang Y, Rodriguez LA. Antihypertensive drugs and risk of incident gout among patients with hypertension: population based case-control study. BMJ. 2012;344:d8190. doi:  10.1136/bmj.d8190
99. Stamp LK, Barclay ML, O’Donnell JL, Zhang M, Drake J, Frampton C, Chapman PT. Furosemide increases plasma oxypurinol without lowering serum urate – a complex drug interaction: implications for clinical practice. Rheumatology (Oxford). 2012;51(9):1670-6. doi:  10.1093/ rheumatology/kes091
100. Knake C, Stamp L, Bahn A. Molecular mechanism of an adverse drug-drug interaction of allopurinol and furosemide in gout treatment. Biochem Biophys Res Commun. 2014;452(1):157-62. doi: 10.1016/ j.bbrc.2014.08.068
101. Ramsay LE, Shelton JR, Harrison IR. Plasma uric acid and spironolactone response in healthy subjects. Br J Clin Pharmacol. 1977;4(2):247-9.
102. Takahashi S, Moriwaki Y, Yamamoto T, Tsutsumi Z, Ka T, Fukuchi M. Effects of combination treatment using anti-hyperuricaemic agents with fenofibrate and/or losartan on uric acid metabolism. Ann Rheum Dis. 2003;62(6):572-5.
103. Mustard JF, Murphy EA, Ogryzlo MA, Smythe HA. Blood coagulation and platelet economy in subjects with primary gout. Can Med Assoc J. 1963;89:1207-11. PMID: 14084698
104. Yang CY, Chen CH, Deng ST, Huang CS, Lin YJ, Chen YJ, Wu CY, Hung SI, Chung WH. Allopurinol use and risk of fatal hypersensitivity reactions: a nationwide population-based study in Taiwan. JAMA Intern Med. 2015;175(9):1550-7. doi: 10.1001/jamainternmed.2015.3536
105. Perez-Ruiz F, Martínez-Indart L, Carmona L, et al. Tophaceous gout and high level of hyperuricaemia are both associated with increased risk of mortality in patients with gout. Ann Rheum Dis. 2014;73(1):177-82. doi: 10.1136/annrheumdis-2012-202421
106. Bhole V, Krishnan E. Gout and the heart. Rheum Dis Clin North Am. 2014;40:125-43.
107. Agarwal V, Hans N, Messerli FH. Effect of allopurinol on blood pressure: a systematic review and meta-analysis. J Clin Hypertens (Greenwich). 2013;15:435-42. 
108. Noman A, Ang DS, 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;375:2161-7. doi: 10.1016/ SO140-6736(10)60391-1
109. Kelkar A, Kuo A, Frishman WH. Allopurinol as a cardiovascular drug. Cardiol Rev. 2011;19:265-71. 
110. Thanassoulis G, Brophy JM, Richard H, et al. Gout, allopurinol use, and heart failure outcomes. Arch Intern Med. 2010;170:1358-64. doi: 10.1136/bmjopen-2011-000282

________________________________________________

1. Richette P, Doherty M, Pascual E, еt al. EULAR evidence-based recommendations for the management of gout. Ann Rheum Dis. 2016. doi: 10.1136/annrheumdis-2016-209707
2. Zhu Y, Pandya BJ, Choi HK. 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. doi: 10.1002/art.30520
3. Lin КС, Lin HY, Chou R. 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. 
4. Simkin PA. The pathogenesis of podagra. Ann Intern Med. 1977;86:230-3.
5. [EGIS collected statistics on the prevalence of hyperuricemia in combination with arterial hypertension and comorbidities  among Russian patients. Polyclinika. Spetsvypusk. 2017;(4):16 (In Russ.)].
6. Mazzali M, Hughes J, Kim YG, Jefferson JA, Kang DH, Gordon KL, Lan HY, Kivlighn S, Johnson RJ. Elevated uric acid increases blood pressure in the rat by a novel crystal-independent mechanism. Hypertension. 2001;38(5):1101-6.
7. Perez-Pozo SE, Schold J, Nakagawa T, Sanchez-Lozada LG, Johnson RJ, Lillo JL. Excessive fructose intake induces the features of metabolic syndrome in healthy adult men: role of uric acid in the hypertensive response. Int J Obes (Lond). 2010;34(3):454-61. 
8. DeBosch BJ, Kluth O, Fujiwara H, Schurmann A, Moley K. Early-onset metabolic syndrome in mice lacking the intestinal uric acid transporter SLC2A9. Nat Commun. 2014;5:4642. doi: 10.1038.ncomms5642
9. Feig DI, Kang DH, Johnson RJ. Uric acid and cardiovascular risk. N Engl J Med. 2008;359(17):1811-21. doi: 10.1056 / NEJMra0800885
10. Richette P, Perez-Ruiz F, Doherty M, Jansen TL, Nuki G, Pascual E, Punzi L, So AK, Bardin T. Improving cardiovascular and renal outcomes in gout: what should we target? Nat Rev Rheumatol. 2014;10(11):654-61. doi: 10.1016/j.jare.2017.04.008
11. Andres M, Quintanilla MA, Sivera F, Sanchez-Paya J, Pascual E, Vela P, Ruiz-Nodar JM. Silent monosodium urate crystal deposits are associated with severe coronary calcification in asymptomatic hyperuricemia: an exploratory study. Arthritis Rheum. 2016;68(6):1531-9. doi: 10.1002/art.39581
12. Saito Y, Nakayama T, Sugimoto K, Fujimoto Y, Kobayashi Y. Relation of lipid content of coronary plaque to level of serum uric acid. Am J Cardiol. 2015;116(9):1346-50. doi: 10.1016/j.amjcard.2015.07.059
13. Ando K, Takahashi H, Watanabe T, Daidoji H, Otaki Y, Nishiyama S, Arimoto T, Shishido T, Miyashita T, Miyamoto 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. doi: 10.5551/jat.33951
14. Park JJ, Roudier MP, Soman D, Mokadam NA, Simkin PA. Prevalence of birefringent crystals in cardiac and prostatic tissues, an observational study. BMJ Open. 2014;4(7):e005308. doi: 10.1136/bmjopen-2014-005308
15. Borghi C, Rosei EA, Bardin T, Dawson J, Dominiczak A, Kielstein JT, Manolis AJ, Perez-Ruiz F, Mancia G. Serum uric acid and the risk of cardiovascular and renal disease. J Hypertens. 2015;33(9):1729-41. doi: 10.1097/HJH.0000000000000701
16. 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. doi: 10.1016/j.atherosclerosis.2013.08.023
17. Nozue T, Yamamoto S, Tohyama S, Fukui K, Umezawa S, Onishi Y, Kunishima T, Hibi K, Terashima M, Michishita I. Correlations between serum uric acid and coronary atherosclerosis before and during statin therapy. Coron Artery Dis. 2014;25(4):343-8. doi: 10.1097/MCA.0000000000000084
18. Tamariz L, Hernandez F, Bush A, Palacio A, Hare JM. Association between serum uric acid and atrial fibrillation: a systematic review and meta-analysis. Heart Rhythm. 2014;11(7):1102-8. doi: 10.1016/j/ hrthm.2014.04.003
19. Kim SY, Guevara JP, Kim KM, Choi HK, Heitjan DF, Albert DA. Hyperuricemia and risk of stroke: a systematic review and meta-analysis. Arthritis Rheum. 2009;61(7):885-92. doi: 10.1002 / art. 24612
20. Harzand A, Tamariz L, Hare JM. Uric acid, heart failure survival, and the impact of xanthine oxidase inhibition. Congest Heart Fail. 2012;18(3):179-82. doi: 10.1111/j.1751-7133.2011.00262.x.
21. Bardin T, Richette Р. Impact of comorbidities on gout and hyperuricemia: an updated on prevalence and treatment options. BMC Med. 2017;15:123. doi: 10.1186/s12916-017-0890-9
22. Lyngdoh T, Vuistiner P, Marques-Vidal P, Rousson V, Waeber G, Vollenweider P, Bochud M. Serum uric acid and adiposity: deciphering causality using a bidirectional Mendelian randomization approach. PLoS One. 2012;7(6):e39321. doi: 10.1371/journal.pone.0039321
23. Nitsch D, Molokhia M, Smeeth L, DeStavola BL, Whittaker JC, Leon DA. Limits to causal inference based on Mendelian randomization: a comparison with randomized controlled trials. Am J Epidemiol. 2006;163(5):397-403. doi: 10.1093/aje/kwj062
24. Doring A, Gieger C, Mehta D, Gohlke H, Prokisch H, Coassin S, Fischer G, Henke K, Klopp N, Kronenberg F, et al. SLC2A9 influences uric acid concentrations with pronounced sex-specific effects. Nat Genet. 2008;40(4):430-6. doi: 10.1038/ng.107
25. Parsa A, Brown E, Weir MR, Fink JC, et al. Genotype-based changes in serum uric acid affect blood pressure. Kidney Int. 2012;81(5):502-7. doi: 10.1038/ki.2011.414
26. Mallamaci F, Testa A, Leonardis D, Tripepi R, Pisano A, Spoto B, Sanguedolce MC, Parlongo RM, Tripepi G, Zoccali C. A polymorphism in the major gene regulating serum uric acid associates with clinic SBP and the white-coat effect in a family-based study. J Hypertens. 2014;32(8):1621-8. doi: 10.1097/HJH.0000000000000224
27. Mallamaci F, Testa A, Leonardis D, Tripepi R, Pisano A, Spoto B, Sanguedolce MC, Parlongo RM, Tripepi G, Zoccali C. A genetic marker of uric acid level, carotid atherosclerosis, and arterial stiffness: a family-based study. Am J Kidney Dis. 2015;65(2):294-302. doi: 10.1038/ ki.2011.414
28. Palmer TM, Nordestgaard BG, Benn M, Tybjaerg-Hansen A, Davey Smith G, Lawlor DA, Timpson NJ. Association of plasma uric acid with ischaemic heart disease and blood pressure: Mendelian randomisation analysis of two large cohorts. BMJ. 2013;347:f4262. doi: 10.1136/bmj.f4262
29. McKeigue PM, Campbell H, Wild S, Vitart V, Hayward C, Rudan I, Wright AF, Wilson JF. Bayesian methods for instrumental variable analysis with genetic instruments (‘Mendelian randomization’): example with urate transporter SLC2A9 as an instrumental variable for effect of urate levels on metabolic syndrome. Int J Epidemiol. 2010;39(3):907-18. doi: 10.1093/ije/dyp397
30. Kleber ME, Delgado G, Grammer TB, Silbernagel G, Huang J, Kramer BK, Ritz E, Marz W. Uric acid and cardiovascular events: a Mendelian randomization study. J Am Soc Nephrol. 2015;26(11):2831-8. doi: 10.1681/ASN.2014070660
31. 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
32. Yang Q, Kottgen A, Dehghan A, Smith AV, Glazer NL, Chen MH, Chasman DI, Aspelund T, Eiriksdottir G, Harris TB, et al. Multiple genetic loci influence serum urate levels and their relationship with gout and cardiovascular disease risk factors. Circ Cardiovasc Genet. 2010;3(6):523-30. doi: 10.1161/CIRCGENETICS.109.934455
33. Keenan T, Zhao W, Rasheed A, Ho WK, Malik R, Felix JF, Young R, Shah N, Samuel M, Sheikh N, et al. Causal assessment of serum urate levels in cardiometabolic diseases through a Mendelian randomization study. J Am Coll Cardiol. 2016;67(4):407-16. doi: 10.1016/j.jacc.2015.10.086
34. Sedaghat S, Pazoki R, Uitterlinden AG, Hofman A, Stricker BH, Ikram MA, Franco OH, Dehghan A. Association of uric acid genetic risk score with blood pressure: the Rotterdam study. Hypertension. 2014;64(5):1061-6. doi: 10.1161/HYPERTENSIONAHA.114.03757Hypertension
35. Higgins P, Dawson J, Lees KR, McArthur K, Quinn TJ, Walters MR. 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
36. Scheepers LE, Wei FF, Stolarz-Skrzypek K, Malyutina S, Tikhonoff V, Thijs L, Salvi E, Barlassina C, Filipovsky J, Casiglia E, et al. Xanthine oxidase gene variants and their association with blood pressure and incident hypertension: a population study. J Hypertens. 2016;34(11):2147-54. doi:10.1097/HJH0000000000001077
37. Scheepers LE, Boonen A, Pijnenburg W, Bierau J, Staessen JA, Stehouwer CD, Thijs C, Arts IC. Associations of plasma uric acid and purine metabolites with blood pressure in children: the KOALA Birth Cohort Study. J Hypertens. 2017;35(5):982-93. doi: 10.1097/ HJH.0000000000001270
38. Schmitz B, Brand SM. Uric acid and essential hypertension: the endothelial connection. J Hypertens. 2016;34(11):2138-9. doi: 10.1097/ HJH.0000000000001109
39. Hootman JM, Helmick CG. Projections of US prevalence of arthritis and associated activity limitations. Arthritis Rheum. 2006;54:226-9. doi: 10.1002/art. 21562
40. Kuo CF, Luo SF. Gout: risk of premature death in gout unchanged for years. Nat Rev Rheumatol. 2017;13(4):200-1. doi: 10.1038/ nrrheum.2017.27
41. 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. doi: 10.7326/0003-4819-131-1-199907060-00003
42. So A, Thorens B. Uric acid transport and disease. J Clin Invest. 2010;120:1791-9. doi: 10.1172/JCI42344
43. Rock KL, Kataoka H, Lai JJ. Uric acid as a danger signal in gout and its comorbidities. Nat Rev Rheumatol. 2013;9:13-23. doi: 10.1038/nrrheum.2012.143
44. Kumar HKVS, Marwaha V. Chronic Tophaceous Gout. Int J Med Health Sci. 2012;1(1):31-2.
45. Liu SC, Xia L, Zhang J, et al. Gout and risk of myocardial infarction: a systematic review and meta-analysis of cohort studies. PLoS ONE. 2015;10:e0134088.
46. Clarson LE, Hider SL, Belcher J, 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. doi: 10.1136/annrheumdis-2014-205252
47. Choi HK, Curhan G. Independent impact of gout on mortality and risk for coronary heart disease. Circulation. 2007;116:894-900. doi: 10.1161/CIRCULATIONAHA.107.703389
48. [Egorov IV, Кhitrik NM, Tsurko VV. Functional state of neutrophils in elderly patients with chronic gouty arthritis in the acute stage. Clinical Gerontology. 2008;(9):70-1 (In Russ.)].
49. Perez-Ruiz F, Martinez-Indart L, Carmona L, Herrero-Beites AM, Pijoan JI, Krishnan E. Tophaceous gout and high level of hyperuricaemia are both associated with increased risk of mortality in patients with gout. Ann Rheum Dis. 2014;73(1):177-82. doi: 10.1136/annrheumdis-2012-202421
50. Edwards NL. The role of hyperuricemia and gout in kidney and cardiovascular disease. Clev Clin J Med. 2008;75:13-6. doi:10.3949/ ccjm.75.suppl5.s13
51. Johnson RJ, Kang DH, Feig D, et al. Is there a pathogenetic role for uric acid in hypertension and cardiovascular and renal disease? Hypertension. 2003;41:1183-90. doi: 10.1161/01.HYP.0000069700.62727.C5
52. Briggs AM, Cross MJ, Hoy DG, et al. Musculoskeletal Health Conditions Represent a Global Threat to Healthy Aging: A Report for the 2015 World Health Organization World Report on Ageing and Health. Gerontologist. 2016;56(Suppl 2):S243-255. doi: 10.1093/geront/gnw002 
53. Clauw DJ. Diagnosing and treating chronic musculoskeletal pain based on the underlying mechanism(s). Best Pract Res Clin Rheumatol. 2015;29(1):6-19. doi: 10.1016/j.berh.2015.04.024
54. [Tsurko VV, Egorov IV, Eliseeva MV. Gout in elderly patients, association with comorbidity. Practicing Doctor Today. 2013;(1):2-8 (In Russ.)].
55. Kuo CF, Grainge MJ, Mallen C, Zhang W, Doherty M. Comorbidities in patients with gout prior to and following diagnosis: case-control study. Ann Rheum Dis. 2016;75(1):210-7. doi: 10.1136/annrheumdis-2014-206410
56. Choi HK, Ford ES, Li C, Curhan G. Prevalence of the metabolic syndrome in patients with gout: the Third National Health and Nutrition Examination Survey. Arthritis Rheum. 2007;57(1):109-15. doi: 10.1002/art.22466
57. Clarson LE, Hider SL, Belcher J, 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. doi: 10.1136/annrheumdis-2014-205252
58. [Eliseev MS, Novikova AM. Comorbidity in gout and hyperuricemia: prevalence, causes, prospects of urate lowering therapy. Therapeutic Archive. 2019;91(5):120-8 (In Russ.)]. doi: 10.26442/00403660.2019. 05.000232
59. Krishnan E, Baker JF, Furst DE, Schumacher HR. Gout and the risk of acute myocardial infarction. Arthritis Rheum. 2006;54(8):2688-96. doi: 10.1002/art.22014
60. De Vera MA, Rahman MM, Bhole V, Kopec JA, Choi HK. 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
61. Krishnan E. Gout and the risk for incident heart failure and systolic dysfunction. BMJ Open. 2012;2(1):e000282. doi: 10.1136/bmjopen-2011-000282
62. Richette P, Latourte A, Bardin T. Cardiac and renal protective effects of urate-lowering therapy. Rheumatology (Oxford). 2018;57(suppl 1):i47-i50. doi: 10.1093/rheumatology/kex432
63. Kuo CF, Grainge MJ, Mallen C, Zhang W, Doherty M. Impact of gout on the risk of atrial fibrillation. Rheumatology (Oxford). 2016;55(4):721-8. doi: 10.1093/rheumatology/kev418
64. Chang K, Yokose C, Tenner C, Oh C, Donnino R, Choy-Shan A, Pike VC, Shah BD, Lorin JD, Krasnokutsky S, et al. Association between gout and aortic stenosis. Am J Med. 2017;130(2):230.e1-8. doi: 10.1016/j.amjmed.2016.09.005
65. Stack AG, Hanley A, Casserly LF, Cronin CJ, Abdalla AA, Kiernan TJ, Murthy BV, Hegarty A, Hannigan A, Nguyen HT. Independent and conjoint associations of gout and hyperuricaemia with total and cardiovascular mortality. QJM. 2013;106(7):647-58. doi: 10.1093/qjmed/hct083
66. 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;59:1540-8. doi: 10.1002/art.24209
67. Becker MA, Schumacher HR Jr, Wortmann RL, et al. Febuxostat compared with allopurinol in patients with hyperuricemia and gout. N Engl J Med. 2005;353:2450-61. doi: 10.1056/NEJMoa050373
68. Diaz-Torné C, Perez-Herrero N, Perez-Ruiz F. New medications in development for the treatment of hyperuricemia of gout. Curr Opin Rheumatol. 2015;27:164-9. doi:10.1097/BOR.0000000000000146
69. Edwards NL, So A. Emerging therapies for gout. Rheum Dis Clin North Am. 2014;40:375-87. doi: 10.1016/j.rdc.2014.01.013
70. Terkeltaub RA, Furst DE, Bennett K, et al. High versus low dosing of oral colchicine for early acute gout flare: twenty-four-hour outcome of the first multicenter, randomized, double-blind, placebo-controlled, parallel-group, dose-comparison colchicine study. Arthritis Rheum. 2010;62:1060-8. doi: 10.1002/art.27327
71. Stamp LK, O’Donnell JL, 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;63:412-21. doi: 10.1002/art.30119
72. Stamp LK, Taylor WJ, Jones PB, et al. Starting dose is a risk factor for allopurinol hypersensitivity syndrome: a proposed safe starting dose of allopurinol. Arthritis Rheum. 2012;64:2529-36. doi: 10.1002/art.34488
73. Hung SI, Chung WH, Liou LB, et al. HLA-B*5801 allele as a genetic marker for severe cutaneous adverse reactions caused by allopurinol. Proc Natl Acad Sci USA. 2005;102:4134-9. doi: 10.1073/pnas.0409500102
74. Akkineni R, Tapp S, Tosteson ANA, et al. Treatment of asymptomatic hyperuricemia and prevention of vascular disease: a decision analytic approach. J Rheumatol. 2014;41(4):739-48. doi: 10.3899/irheum.l21231 
75. Abeles AM. Hyperuricemia, gout, and cardiovascular disease: an update. Curr Rheumatol Rep. 2015;17(3):13. doi: 10.1007//sll92601504952
76. Lee JE, Kim YG, Choi YH, et al. Serum uric acid is associated with microalbuminuria in prehypertension. Hypertension. 2006;47(5):962-7. doi: 10.1161/01.HYP.0000210550.97398x2
77. Dalbeth N, Chen P, White M, et al. Impact of bariatric surgery on serum urate targets in people with morbid obesity and diabetes: a prospective longitudinal study. Ann Rheum Dis. 2014;73:797-802. doi: 10.1136/annrheumdis-2013-203970
78. Chen JH, Wen CP, Wu SB, et al. Attenuating the mortality risk of high serum uric acid: the role of physical activity underused. Ann Rheum Dis. 2015;74:2034-42. doi:10.1136/annrheumdis-2014-205312
79. Grimaldi-Bensouda L, Alperovitch A, Aubrun E, Danchin N, Rossignol M, Abenhaim L, Richette P. Impact of allopurinol on risk of myocardial infarction. Ann Rheum Dis. 2015;74(5):836-42. doi: 10.1136/annrheumdis-2012-202972
80. De Abajo FJ, Gil MJ, Rodriguez A, Garcia-Poza P, Alvarez A, Bryant V, Garcia-Rodriguez LA. Allopurinol use and risk of non-fatal acute myocardial infarction. Heart. 2015;101(9):679-85. doi: 10.1136/heartjnl-2014-306670
81. Larsen KS, Pottegard A, Lindegaard HM, Hallas J. Effect of allopurinol on cardiovascular outcomes in hyperuricemic patients: a cohort study. Am J Med. 2016;129(3):299-306. doi: 10.1016/j.amjmed.2015.11.003
82. Zhang J, Dierckx R, Mohee K, Clark AL, Cleland JG. Xanthine oxidase inhibition for the treatment of cardiovascular disease: an updated systematic review and meta-analysis. ESC Heart Fail. 2017;4(1):40-5. doi: 10.1002/ehf2.12112
83. Kok VC, Horng JT, Chang WS, Hong YF, Chang TH. Allopurinol therapy in gout patients does not associate with beneficial cardiovascular outcomes: a population-based matched-cohort study. PLoS One. 2014;9(6):e99102. doi: 10.1371/journal.pone.0099102
84. Borghi C, Tykarski A, Widecka K, et al. Expert consensus for diagnosis and treatment of patient with hyperuricemia and high cardiovascular risk. Cardiol J. 2018;25(5):545-64. doi: 10.5603/CJ.2018.0116
85. Keenan RT, O’Brien WR, Lee KH, et al. Prevalence of contraindications and prescription of pharmacologic therapies for gout. Am J Med. 2011;124:155-63. doi: 10.1016/j.amjmed.2010.09.012
86. Nidorf SM, Eikelboom JW, Budgeon CA, et al. Low-dose colchicine for secondary prevention of cardiovascular disease. J Am Coll Cardiol. 2013;61:404-10. doi:  10.1016/j.jacc.2012.10.027
87. Deftereos S, Giannopoulos G, Raisakis K, et al. Colchicine treatment for the prevention of bare-metal stent restenosis in diabetic patients. J Am Coll Cardiol. 2013;61:1679-85. doi: 10.1016/j.jacc.2013.01.055
88. Rothenbacher D, Primatesta P, Ferreira A, et al. Frequency and risk factors of gout flares in a large population-based cohort of incident gout. Rheumatology (Oxford). 2011;50:973-81. doi: 10.1093/rheumatology/keq363
89. Yamanaka H. Gout and hyperuricemia in young people. Curr Opin Rheumatol. 2011;23:156-60. doi: 10.1097/BOR.0b013e3283432d35
90. Feig DI, Soletsky B, Johnson RJ. 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
91. Soletsky B, Feig DI. Uric acid reduction rectifies prehypertension in obese adolescents. Hypertension. 2012;60(5):1148-56. doi:  10.1001/ jama.300.8.924
92. McMullan CJ, Borgi L, Fisher N, Curhan G, Forman J. Effect of uric acid lowering on renin-angiotensin-system activation and ambulatory BP: a randomized controlled trial. Clin J Am Soc Nephrol. 2017;12(5):807-16. doi:  10.2215/CJN.10771016
93. Poudel DR, Karmacharya P, Donato A. Risk of acute gout among active smokers: data from nationwide inpatient sample. Clin Rheumatol. 2016;35(12):3015-8. doi: 10.1007/s10067-016-3415-6
94. Gee Teng G, Pan A, Yuan JM, Koh WP. Cigarette smoking and the risk of incident gout in a prospective cohort study. Arthritis Care Res (Hoboken). 2016;68(8):1135-42. doi: 10.1002/acr.22821
95. Wang W, Krishnan E. Cigarette smoking is associated with a reduction in the risk of incident gout: results from the Framingham Heart Study original cohort. Rheumatology (Oxford). 2015;54(1):91-5. doi: 10.1093/rheumatology/keu304
96. Yu TF, Gutman AB. Study of the paradoxical effects of salicylate in low, intermediate and high dosage on the renal mechanisms for excretion of urate in man. J Clin Invest. 1959;38(8):1298-315. doi: 10.1172/JCI103905
97. Zhang Y, Neogi T, Chen C, Chaisson C, Hunter DJ, Choi H. Low-dose aspirin use and recurrent gout attacks. Ann Rheum Dis. 2014;73(2):385-90. doi: 10.1136/annrheumdis-2012-202589
98. Choi HK, Soriano LC, Zhang Y, Rodriguez LA. Antihypertensive drugs and risk of incident gout among patients with hypertension: population based case-control study. BMJ. 2012;344:d8190. doi:  10.1136/bmj.d8190
99. Stamp LK, Barclay ML, O’Donnell JL, Zhang M, Drake J, Frampton C, Chapman PT. Furosemide increases plasma oxypurinol without lowering serum urate – a complex drug interaction: implications for clinical practice. Rheumatology (Oxford). 2012;51(9):1670-6. doi:  10.1093/ rheumatology/kes091
100. Knake C, Stamp L, Bahn A. Molecular mechanism of an adverse drug-drug interaction of allopurinol and furosemide in gout treatment. Biochem Biophys Res Commun. 2014;452(1):157-62. doi: 10.1016/ j.bbrc.2014.08.068
101. Ramsay LE, Shelton JR, Harrison IR. Plasma uric acid and spironolactone response in healthy subjects. Br J Clin Pharmacol. 1977;4(2):247-9.
102. Takahashi S, Moriwaki Y, Yamamoto T, Tsutsumi Z, Ka T, Fukuchi M. Effects of combination treatment using anti-hyperuricaemic agents with fenofibrate and/or losartan on uric acid metabolism. Ann Rheum Dis. 2003;62(6):572-5.
103. Mustard JF, Murphy EA, Ogryzlo MA, Smythe HA. Blood coagulation and platelet economy in subjects with primary gout. Can Med Assoc J. 1963;89:1207-11. PMID: 14084698
104. Yang CY, Chen CH, Deng ST, Huang CS, Lin YJ, Chen YJ, Wu CY, Hung SI, Chung WH. Allopurinol use and risk of fatal hypersensitivity reactions: a nationwide population-based study in Taiwan. JAMA Intern Med. 2015;175(9):1550-7. doi: 10.1001/jamainternmed.2015.3536
105. Perez-Ruiz F, Martínez-Indart L, Carmona L, et al. Tophaceous gout and high level of hyperuricaemia are both associated with increased risk of mortality in patients with gout. Ann Rheum Dis. 2014;73(1):177-82. doi: 10.1136/annrheumdis-2012-202421
106. Bhole V, Krishnan E. Gout and the heart. Rheum Dis Clin North Am. 2014;40:125-43.
107. Agarwal V, Hans N, Messerli FH. Effect of allopurinol on blood pressure: a systematic review and meta-analysis. J Clin Hypertens (Greenwich). 2013;15:435-42. 
108. Noman A, Ang DS, 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;375:2161-7. doi: 10.1016/ SO140-6736(10)60391-1
109. Kelkar A, Kuo A, Frishman WH. Allopurinol as a cardiovascular drug. Cardiol Rev. 2011;19:265-71. 
110. Thanassoulis G, Brophy JM, Richard H, et al. Gout, allopurinol use, and heart failure outcomes. Arch Intern Med. 2010;170:1358-64. doi: 10.1136/bmjopen-2011-000282

В.В. Фомин 1, Т.Е. Морозова 1, В.В. Цурко 1,2

1 ФГАОУ ВО «Первый Московский государственный медицинский университет им. И.М. Сеченова» Минздрава России (Сеченовский Университет), Москва, Россия;
2 ФГБОУ ВО «Российский национальный исследовательский медицинский университет им. Н.И. Пирогова» Минздрава России, Москва, Россия

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 V.V. Fomin 1, T.E. Morosova 1, V.V. Tsurko 1,2 

1 Sechenov First Moscow State Medical University (Sechenov University), Moscow, Russia;
2 Pirogov Russian National Research Medical University, Moscow, Russia