Hyperuricemia, Gout, and Cardiovascular Disease: An Update

  • Aryeh M. AbelesEmail author
Crystal Arthritis (MH Pillinger and S Krasnokutsky, Section Editors)
Part of the following topical collections:
  1. Topical Collection on Crystal Arthritis


Across the globe, both gout and hyperuricemia have become increasingly common over the last few decades. The burden of gouty disease is made heavier by its association with several comorbid conditions, including hypertension, cardiovascular disease, and chronic kidney disease. Accruing evidence from prospective studies suggests that gout is an independent risk factor for developing cardiovascular disease and for higher cardiovascular mortality. While asymptomatic hyperuricemia does not seem to be an independent risk factor for cardiovascular disease, increasing data implicates hyperuricemia as a risk factor for developing incidental hypertension. Important questions that remain unanswered include whether addressing asymptomatic hyperuricemia forestalls the onset of hypertension, and whether treating gout with urate-lowering agents improves cardiovascular outcomes. This article reviews the most recent data regarding the relationship between hyperuricemia, gout, hypertension, and cardiovascular disease, as well as emerging evidence as to whether treatment of hyperuricemia and gout improves cardiovascular outcomes.


Gout Hyperuricemia Hypertension Cardiovascular disease Allopurinol 


Compliance with Ethics Guidelines

Conflict of Interest

Aryeh M. Abeles declares no conflict of interest.

Human and Animal Rights and Informed Consent

This article does not contain any studies with human or animal subjects performed by the author.


Papers of particular interest, published recently, have been highlighted as: • Of importance

  1. 1.
    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;63:3136–41.CrossRefPubMedGoogle Scholar
  2. 2.
    Chuang SY, Lee SC, Hsieh YT, Pan WH. Trends in hyperuricemia and gout prevalence: Nutrition and Health Survey in Taiwan from 1993–1996 to 2005–2008. Asia Pac J Clin Nutr. 2011;20(2):301–8.PubMedGoogle Scholar
  3. 3.
    Keenan RT, O’Brien WR, Lee KH, Crittenden DB, Fisher MC, Goldfarb DS, et al. Prevalence of contraindications and prescription of pharmacologic therapies for gout. Am J Med. 2011;124:155–63.CrossRefPubMedGoogle Scholar
  4. 4.
    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. 2014.Google Scholar
  5. 5.
    Mahomed FA. On chronic Bright’s disease, and its essential symptoms. Lancet. 1879;1:399–401.CrossRefGoogle Scholar
  6. 6.
    Breckenridge A. Hypertension and hyperuricaemia. Proc R Soc Med. 1966;59(4):316–9.PubMedCentralPubMedGoogle Scholar
  7. 7.
    Cannon PJ, Stason WB, Demartini FE, Sommers SC, Laragh JH. Hyperuricemia in primary and renal hypertension. N Engl J Med. 1966;275(9):457–64.CrossRefPubMedGoogle Scholar
  8. 8.
    Mazzali M, Hughes J, Kim YG, Jefferson JA, Kang DH, Gordon KL, et al. Elevated uric acid increases blood pressure in the rat by a novel crystal-independent mechanism. Hypertension. 2001;38(5):1101–6.CrossRefPubMedGoogle Scholar
  9. 9.
    Sánchez-Lozada LG, Soto V, Tapia E, Avila-Casado C, Sautin YY, Nakagawa T, et al. Role of oxidative stress in the renal abnormalities induced by experimental hyperuricemia. Am J Physiol Renal Physiol. 2008;295(4):F1134–41.CrossRefPubMedCentralPubMedGoogle Scholar
  10. 10.
    Corry DB, Eslami P, Yamamoto K, Nyby MD, Makino H, Tuck ML. Uric acid stimulates vascular smooth muscle cell proliferation and oxidative stress via the vascular renin-angiotensin system. J Hypertens. 2008;26(2):269–75.CrossRefPubMedGoogle Scholar
  11. 11.
    Mazzali M, Kanellis J, Han L, Feng L, Xia YY, Chen Q, et al. Hyperuricemia induces a primary renal arteriolopathy in rats by a blood pressure-independent mechanism. Am J Physiol Renal Physiol. 2002;282(6):F991–7.CrossRefPubMedGoogle Scholar
  12. 12.
    van der Worp HB, Howells DW, Sena ES, Porritt MJ, Rewell S, O’Collins V, et al. Can animal models of disease reliably inform human studies? PLoS Med. 2010;7(3):e1000245.CrossRefPubMedCentralPubMedGoogle Scholar
  13. 13.
    Watanabe S, Kang DH, Feng L, Nakagawa T, Kanellis J, Lan H. Uric acid, hominoid evolution, and the pathogenesis of salt-sensitivity. Hypertension. 2002;40(3):355–60.CrossRefPubMedGoogle Scholar
  14. 14.
    Feig D, Kang D, Johnson R. Uric acid and cardiovascular risk. N Engl J Med. 2008;359:1811–21.CrossRefPubMedCentralPubMedGoogle Scholar
  15. 15.
    Selby JV, Friedman GD, Quesenberry Jr CP. Precursors of essential hypertension: pulmonary function, heart rate, uric acid, serum cholesterol, and other serum chemistries. Am J Epidemiol. 1990;131(6):1017–27.PubMedGoogle Scholar
  16. 16.
    Nakanishi N, Okamoto M, Yoshida H, Matsuo Y, Suzuki K, Tatara K. Serum uric acid and risk for development of hypertension and impaired fasting glucose or type II diabetes in Japanese male office workers. Eur J Epidemiol. 2003;18:523–30.CrossRefPubMedGoogle Scholar
  17. 17.
    Sundstrom J, Sullivan L, D’Agostino RB, Levy D, Kannel WB, Vasan RS. Relations of serum uric acid to longitudinal blood pressure tracking and hypertension incidence. Hypertension. 2005;45:28–33.CrossRefPubMedGoogle Scholar
  18. 18.
    Yang T, Chu CH, Bai CH, You SL, Chou YC, Hwang LC, et al. Uric acid concentration as a risk marker for blood pressure progression and incident hypertension: a Chinese cohort study. Metabolism. 2012;61(12):1747–55.CrossRefPubMedGoogle Scholar
  19. 19.
    Gaffo AL, Jacobs DR, Sijtsma F, Lewis CE, Mikuls TR, Saag KG. Serum urate association with hypertension in young adults: analysis from the Coronary Artery Risk Development in Young Adults cohort. Ann Rheum Dis. 2013;72:1321–7.CrossRefPubMedGoogle Scholar
  20. 20.
    Forman JP, Choi H, Curhan GC. Plasma uric acid level and risk for incident hypertension among men. J Am Soc Nephrol. 2007;18:287–92.CrossRefPubMedGoogle Scholar
  21. 21.•
    van Durme C, van Echteld IA, Falzon L, Aletaha D, van der Heijde DM, Landewé RB. Cardiovascular risk factors and comorbidities in patients with hyperuricemia and/or gout: a systematic review of the literature. J Rheumatol Suppl. 2014;92:9–14. Exhaustive but concise review of all literature to date regarding hyperuricemia, gout, and cardiovascular disease, focusing on less-biased studies.CrossRefPubMedGoogle Scholar
  22. 22.•
    Wang J, Qin T, Chen J, Li Y, Wang L, Huang H, et al. Hyperuricemia and risk of incident hypertension: a systematic review and meta-analysis of observational studies. PLoS One. 2014;9(12):e114259. This meta-analysis exhaustively reviewed the literature on hyperuricemia and hypertension and concluded that hyperuricemia increases the risk of incidental hypertension in a dose-dependent manner.CrossRefPubMedCentralPubMedGoogle Scholar
  23. 23.
    Gois PH, Luchi WM, Seguro AC. Allopurinol on hypertension: insufficient evidence to recommend. J Clin Hypertens (Greenwich). 2013;15(9):700.CrossRefGoogle Scholar
  24. 24.•
    Gois PH, Souza ER. Pharmacotherapy for hyperuricemia in hypertensive patients. Cochrane Database Syst Rev. 2013;1:CD008652. A systematic review on anti-hypertensives for hyperuricemia that underscores the need for prospective clinical trials.PubMedGoogle Scholar
  25. 25.
    Song K, Wang Y, Wang G, Zhang Q, Jiao H, et al. Does decreasing serum uric acid level prevent hypertension?—a nested RCT in cohort study: rationale, methods, and baseline characteristics of study cohort. BMC Public Health. 2013;13:1069.CrossRefPubMedCentralPubMedGoogle Scholar
  26. 26.
    Kim SY, Guevara JP, Kim KM, Choi HK, Heitjan DF, Albert DA. Hyperuricemia and coronary heart disease: a systematic review and meta-analysis. Arthritis Care Res. 2010;62(2):170–80.Google Scholar
  27. 27.
    Baker JF, Schumacher HR, Krishnan E. Serum uric acid level and risk for peripheral arterial disease: analysis of data from the multiple risk factor intervention trial. Angiology. 2007;58:450–7.CrossRefPubMedGoogle Scholar
  28. 28.
    Vinik O, Wechalekar MD, Falzon L, Buchbinder R, van der Heijde DM, Bombardier C. Treatment of asymptomatic hyperuricemia for the prevention of gouty arthritis, renal disease, and cardiovascular events: a systematic literature review. J Rheumatol Suppl. 2014;92:70–4.CrossRefPubMedGoogle Scholar
  29. 29.
    Krishnan E, Baker JF, Furst DE, Schumacher HR. Gout and the risk of acute myocardial infarction. Arthritis Rheum. 2006;54(8):2688–96.CrossRefPubMedGoogle Scholar
  30. 30.
    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.CrossRefPubMedCentralPubMedGoogle Scholar
  31. 31.
    Kuo CF, Yu KH, See LC, Chou IJ, Ko YS, Chang HC, et al. Risk of myocardial infarction among patients with gout: a nationwide population-based study. Rheumatology (Oxford). 2013;52(1):111–7.CrossRefGoogle Scholar
  32. 32.•
    Clarson LE, Hider SL, Belcher J, Heneghan C, Roddy E, Mallen CD. Increased risk of vascular disease associated with gout: a retrospective, matched cohort study in the UK Clinical Practice Research Datalink. Ann Rheum Dis. 2014. doi: 10.1136/annrheumdis-2014-205252. Large and well-performed retrospective cohort study that implicates gout in cardiovascular disease.Google Scholar
  33. 33.
    Seminog OO, Goldacre MJ. Gout as a risk factor for myocardial infarction and stroke in England: evidence from record linkage studies. Rheumatology (Oxford). 2013;52(12):2251–9.CrossRefGoogle Scholar
  34. 34.
    Teng GG, Ang LW, Saag KG, Yu MC, Yuan JM, Koh WP. Mortality due to coronary heart disease and kidney disease among middle-aged and elderly men and women with gout in the Singapore Chinese Health Study. Ann Rheum Dis. 2012;71:924–8.CrossRefPubMedCentralPubMedGoogle Scholar
  35. 35.
    Choi HK, Curhan G. Independent impact of gout on mortality and risk for coronary heart disease. Circulation. 2007;116:894–900.CrossRefPubMedGoogle Scholar
  36. 36.
    Krishnan E, Svendsen K, Neaton JD, Grandits G, Kuller LH, MRFIT Research Group. Long-term cardiovascular mortality among middle-aged men with gout. Arch Intern Med. 2008;168(10):1104–10.CrossRefPubMedGoogle Scholar
  37. 37.
    Go AS, Chertow GM, Fan D, McCulloch CE, Hsu CY. Chronic kidney disease and the risks of death, cardiovascular events, and hospitalization. N Engl J Med. 2004;351(13):1296–305.CrossRefPubMedGoogle Scholar
  38. 38.
    Gansevoort RT, Correa-Rotter R, Hemmelgarn BR, Jafar TH, Heerspink HJ, Mann JF, et al. Chronic kidney disease and cardiovascular risk: epidemiology, mechanisms, and prevention. Lancet. 2013;382:339–52.CrossRefPubMedGoogle Scholar
  39. 39.•
    Grimaldi-Bensouda L, Alpérovitch A, Aubrun E, Danchin N, Rossignol M, Abenhaim L, et al. the PGRx MI Group. Impact of allopurinol on risk of myocardial infarction. Ann Rheum Dis. 2014. doi: 10.1136/annrheumdis-2012-202972. Recent study that concludes that suggests allopurinol use decreases the risk of myocardial infarction in a gout cohort.PubMedGoogle Scholar
  40. 40.
    Crittenden DB, Lehmann RA, Schneck L, Keenan RT, Shah B, Greenberg JD, et al. Colchicine use is associated with decreased prevalence of myocardial infarction in patients with gout. J Rheumatol. 2012;39(7):1458–64.CrossRefPubMedCentralPubMedGoogle Scholar
  41. 41.•
    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. Despite the title of the paper, this study demonstrates that allopurinol therapy decreases the rate of cardiovascular disease, in doses over 100 mg daily.CrossRefPubMedCentralPubMedGoogle Scholar
  42. 42.
    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.CrossRefPubMedCentralPubMedGoogle Scholar

Copyright information

© Springer Science+Business Media New York 2015

Authors and Affiliations

  1. 1.Division of RheumatologyUniversity of Connecticut Health CenterFarmingtonUSA

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