Increased serum uric acid (SUA) levels have been associated with various pathologic processes such as increased oxidative stress, inflammation, and endothelial dysfunction. Thus, it is not surprising that increased SUA is associated with various adverse outcomes including cardiovascular (CV) diseases. Recent epidemiological evidence suggests that increased SUA may be related to acute myocardial infarction (AMI). Accumulating data also showed that elevated UA has pathophysiological role in the development of AMI. However, there are also studies showing that SUA is not related to the risk of AMI. In this narrative review, we summarized the recent literature data regarding SUA and AMI after providing some background information for the association between UA and coronary artery disease. Future studies will show whether decreasing SUA levels is beneficial for outcomes related to AMI and the optimum SUA levels for best outcomes in CV diseases.
MazzaliMKanbayMSegalMS, et al.Uric acid and hypertension: cause or effect?Curr Rheumatol Rep. 2010;12:108–17.
2.
KanbayMJensenTSolakY, et al.Uric acid in metabolic syndrome: From an innocent bystander to a central player. Eur J Intern Med. 2016;29:3–8.
3.
KanbayMSolakYDoganELanaspaMACovicA. Uric acid in hypertension and renal disease: the chicken or the egg?Blood Purif. 2010;30:288–95.
4.
KelkarAKuoAFrishmanWH. Allopurinol as a cardiovascular drug. Cardiol Rev. 2011;19:265–71.
5.
KanbayMSegalMAfsarBKangDHRodriguez-IturbeBJohnsonRJ. The role of uric acid in the pathogenesis of human cardiovascular disease. Heart. 2013;99:759–66.
6.
TurakOOzcanFTokD, et al.Serum uric acid, inflammation, and nondipping circadian pattern in essential hypertension. J Clin Hypertens (Greenwich). 2013;15:7–13.
7.
FeigDIKangDHJohnsonRJ. Uric acid and cardiovascular risk. N Engl J Med. 2008;359:1811–21.
8.
JohnsonRJKangDHFeigD, et al.Is there a pathogenetic role for uric acid in hypertension and cardiovascular and renal disease?Hypertension. 2003;41:1183–90.
9.
HuangHHuangBLiY, et al.Uric acid and risk of heart failure: a systematic review and meta-analysis. Eur J Heart Fail. 2014;16:15–24.
10.
LanaspaMASanchez-LozadaLGChoiYJ, et al.Uric acid induces hepatic steatosis by generation of mitochondrial oxidative stress: potential role in fructose-dependent and -independent fatty liver. J Biol Chem. 2012;287:40732–40744.
11.
AfsarBSagAAOztosunC, et al.The role of uric acid in mineral bone disorders in chronic kidney disease. J Nephrol. 2019;32:709–17.
12.
KanbayMAfsarBCovicA. Uric acid as a cardiometabolic risk factor: to be or not to be. Contrib Nephrol. 2011;171:62–67.
13.
HahnKKanbayMLanaspaMAJohnsonRJEjazAA. Serum uric acid and acute kidney injury: A mini review. J Adv Res. 2017;8:529–36.
14.
JensenTNiwaKHisatomeI, et al.Increased Serum Uric Acid over five years is a Risk Factor for Developing Fatty Liver. Sci Rep. 2018;8:11735.
15.
KanbayMIkizekMSolakY, et al.Uric acid and pentraxin-3 levels are independently associated with coronary artery disease risk in patients with stage 2 and 3 kidney disease. Am J Nephrol. 2011;33:325–31.
16.
KanbayMYilmazMISonmezA, et al.Serum uric acid independently predicts cardiovascular events in advanced nephropathy. Am J Nephrol. 2012;36:324–331.
17.
KatsikiNDimitriadisGDMikhailidisDP. Serum uric acid and diabetes: from pathophysiology to cardiovascular disease. Curr Pharm Des. 2021.
18.
CulletonBFLarsonMGKannelWBLevyD. Serum uric acid and risk for cardiovascular disease and death: the Framingham Heart Study. Ann Intern Med. 1999;131:7–13.
19.
MoriarityJTFolsomARIribarrenCNietoFJRosamondWD. Serum uric acid and risk of coronary heart disease: Atherosclerosis Risk in Communities (ARIC) Study. Ann Epidemiol. 2000;10:136–43.
20.
NiskanenLKLaaksonenDENyyssonenK, 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;164:1546–51.
21.
SilbernagelGHoffmannMMGrammerTBBoehmBOMarzW. Uric acid is predictive of cardiovascular mortality and sudden cardiac death in subjects referred for coronary angiography. Nutr Metab Cardiovas. 2013;23:46–52.
22.
MazidiMKatsikiNMikhailidisDPBanachM, Lipid, Blood Pressure Meta-Analysis Collaboration G. Associations of serum uric acid with total and cause-specific mortality: Findings from individuals and pooling prospective studies. Atherosclerosis. 2020;296:49–58.
23.
KaragiannisAMikhailidisDPTziomalosK, et al.Serum uric acid as an independent predictor of early death after acute stroke. Circ J. 2007;71:1120–27.
24.
KimSYGuevaraJPKimKMChoiHKHeitjanDFAlbertDA. Hyperuricemia and coronary heart disease: a systematic review and meta-analysis. Arthritis Care Res (Hoboken). 2010;62:170–80.
25.
MazidiMKatsikiNMikhailidisDPBartlomiejczykMABanachM. Association of Empirical Dietary Atherogenic Indices with All-Cause and Cause-Specific Mortality in a Multi-Ethnic Adult Population of the United States. Nutrients. 2019;11.
26.
KanbayMAfsarBSiriopolD, et al.Relevance of uric acid and asymmetric dimethylarginine for modeling cardiovascular risk prediction in chronic kidney disease patients. Int Urol Nephrol. 2016;48:1129–36.
27.
KanbayMYilmazMISonmezA, et al.Serum uric acid level and endothelial dysfunction in patients with nondiabetic chronic kidney disease. Am J Nephrol. 2011;33:298–04.
28.
KanbayMSolakYGaipovATakirMWeinerDE. Allopurinol as a kidney-protective, cardioprotective, and antihypertensive agent: hype or reality?Blood Purif. 2014;37:172–78.
29.
ZhangJDiaoBLinXXuJTangF. TLR2 and TLR4 mediate an activation of adipose tissue renin-angiotensin system induced by uric acid. Biochimie. 2019;162:125–33.
30.
McMullanCJBorgiLFisherNCurhanGFormanJ. Effect of Uric Acid Lowering on Renin-Angiotensin-System Activation and Ambulatory BP: A Randomized Controlled Trial. Clin J Am Soc Nephrol. 2017;12:807–16.
31.
SakohTNakayamaMTsuchihashiT, et al.Associations of fibroblast growth factor 23 with urate metabolism in patients with chronic kidney disease. Metabolism. 2016;65:1498–507.
32.
AsiciogluEKahveciAArikanHKocMTuglularSOzenerC. Fibroblast growth factor-23 levels are associated with uric acid but not carotid intima media thickness in renal transplant recipients. Transplant Proc. 2014;46:180–83.
33.
HuXMaXPanX, et al.Fibroblast growth factor 23 is associated with the presence of coronary artery disease and the number of stenotic vessels. Clin Exp Pharmacol Physiol. 2015;42:1152–57.
34.
Perez-GomezMVBartschLACastillo-RodriguezEFernandez-PradoRKanbayMOrtizA. Potential Dangers of Serum Urate-Lowering Therapy. Am J Med. 2019;132:457–67.
35.
BragaTTForesto-NetoOCamaraNOS. The role of uric acid in inflammasome-mediated kidney injury. Curr Opin Nephrol Hypertens. 2020;29:423–31.
36.
BattelliMGBolognesiAPolitoL. Pathophysiology of circulating xanthine oxidoreductase: new emerging roles for a multi-tasking enzyme. Biochim Biophys Acta. 2014;1842:1502–17.
37.
SinghJA. When gout goes to the heart: does gout equal a cardiovascular disease risk factor?Ann Rheum Dis. 2015;74:631–34.
38.
KanbayMSanchez-LozadaLGFrancoM, et al.Microvascular disease and its role in the brain and cardiovascular system: a potential role for uric acid as a cardiorenal toxin. Nephrol Dial Transplant. 2011;26:430–37.
39.
MalobertiAGiannattasioCBombelliM, et al.Hyperuricemia and Risk of Cardiovascular Outcomes: The Experience of the URRAH (Uric Acid Right for Heart Health) Project. High Blood Press Cardiovasc Prev. 2020;27:121–28.
40.
ChenLLiXLQiaoW, et al.Serum uric acid in patients with acute ST-elevation myocardial infarction. World J Emerg Med. 2012;3:35–39.
41.
MazidiMKatsikiNMikhailidisDPBanachM. Association of ideal cardiovascular health metrics with serum uric acid, inflammation and atherogenic index of plasma: A population-based survey. Atherosclerosis. 2019;284:44–49.
RuggieroCCherubiniABleA, et al.Uric acid and inflammatory markers. Eur Heart J. 2006;27:1174–81.
44.
KonoHChenCJOntiverosFRockKL. Uric acid promotes an acute inflammatory response to sterile cell death in mice. J Clin Invest. 2010;120:1939–49.
45.
DuewellPKonoHRaynerKJ, et al.NLRP3 inflammasomes are required for atherogenesis and activated by cholesterol crystals. Nature. 2010;464:1357–61.
46.
CaiWDuanXMLiuY, et al.Uric Acid Induces Endothelial Dysfunction by Activating the HMGB1/RAGE Signaling Pathway. Biomed Res Int. 2017;2017:4391920.
47.
KhoslaUMZharikovSFinchJL, et al.Hyperuricemia induces endothelial dysfunction. Kidney Int. 2005;67:1739–42.
48.
KanbayMSiriopolDNistorI, et al.Effects of allopurinol on endothelial dysfunction: a meta-analysis. Am J Nephrol. 2014;39:348–356.
49.
KanbayMHuddamBAzakA, et al.A randomized study of allopurinol on endothelial function and estimated glomular filtration rate in asymptomatic hyperuricemic subjects with normal renal function. Clin J Am Soc Nephrol. 2011;6:1887–1894.
50.
LazzeriCValenteSChiostriMSoriABernardoPGensiniGF. Uric acid in the acute phase of ST elevation myocardial infarction submitted to primary PCI: its prognostic role and relation with inflammatory markers: a single center experience. Int J Cardiol. 2010;138:206–09.
51.
LazzeriCValenteSChiostriMPicarielloCGensiniGF. Uric acid in the early risk stratification of ST-elevation myocardial infarction. Intern Emerg Med. 2012;7:33–39.
52.
HajizadehRGhaffariSSalehiRMazaniSAghavaliS. Association of serum uric acid level with mortality and morbidity of patients with acute ST-elevation myocardial infarction. J Cardiovasc Thorac Res. 2016;8:56–60.
53.
LevantesiGMarfisiRMFranzosiMG, et al.Uric acid: a cardiovascular risk factor in patients with recent myocardial infarction. Int J Cardiol. 2013;167:262–69.
54.
von LuederTGGirerdNAtarD, et al.Serum uric acid is associated with mortality and heart failure hospitalizations in patients with complicated myocardial infarction: findings from the High-Risk Myocardial Infarction Database Initiative. Eur J Heart Fail. 2015;17:1144–51.
55.
KayaMGUyarelHAkpekM, et al.Prognostic value of uric acid in patients with ST-elevated myocardial infarction undergoing primary coronary intervention. Am J Cardiol. 2012;109:486–91.
56.
XuQZhangMAbeysekeraIRWangX. High serum uric acid levels may increase mortality and major adverse cardiovascular events in patients with acute myocardial infarction. Saudi Med J. 2017;38:577–85.
57.
LimSSYangYLChenSC, et al.Association of variability in uric acid and future clinical outcomes of patient with coronary artery disease undergoing percutaneous coronary intervention. Atherosclerosis. 2020;297:40–46.
58.
Mandurino-MirizziACrimiGRaineriC, et al.Elevated serum uric acid affects myocardial reperfusion and infarct size in patients with ST-segment elevation myocardial infarction undergoing primary percutaneous coronary intervention. J Cardiovasc Med (Hagerstown). 2018;19:240–46.
59.
KojimaSSakamotoTIshiharaM, et al.Prognostic usefulness of serum uric acid after acute myocardial infarction (the Japanese Acute Coronary Syndrome Study). Am J Cardiol. 2005;96:489–95.
60.
YanLLiuZZhangC. Uric acid as a predictor of in-hospital mortality in acute myocardial infarction: a meta-analysis. Cell Biochem Biophys. 2014;70:1597–01.
61.
LazarosGTsiachrisDAznaouridisK, et al.Uric acid in-hospital changes predict mortality in patients with acute myocardial infarction. Nutr Metab Cardiovasc Dis. 2013;23:1202–1209.
62.
NdrepepaGBraunSHaaseHU, et al.Prognostic value of uric acid in patients with acute coronary syndromes. Am J Cardiol. 2012;109:1260–1265.
63.
MagnoniMBerteottiMCeriottiF, et al.Serum uric acid on admission predicts in-hospital mortality in patients with acute coronary syndrome. Int J Cardiol. 2017;240:25–29.
64.
NadkarMYJainVI. Serum uric acid in acute myocardial infarction. J Assoc Physicians India. 2008;56:759–62.
65.
TakirMKostekOOzkokA, et al.Lowering Uric Acid With Allopurinol Improves Insulin Resistance and Systemic Inflammation in Asymptomatic Hyperuricemia. J Investig Med. 2015;63:924–29.
66.
KanbayMOzkaraASelcokiY, et al.Effect of treatment of hyperuricemia with allopurinol on blood pressure, creatinine clearence, and proteinuria in patients with normal renal functions. Int Urol Nephrol. 2007;39:1227–33.
67.
AthyrosVGMikhailidisDPLiberopoulosEN, et al.Effect of statin treatment on renal function and serum uric acid levels and their relation to vascular events in patients with coronary heart disease and metabolic syndrome: a subgroup analysis of the GREek Atorvastatin and Coronary heart disease Evaluation (GREACE) Study. Nephrol Dial Transplant. 2007;22:118–27.
68.
HoieggenAAldermanMHKjeldsenSE, et al.The impact of serum uric acid on cardiovascular outcomes in the LIFE study. Kidney Int. 2004;65:1041–49.
69.
AthyrosVGKaragiannisAGanotakisES, et al.Association between the changes in renal function and serum uric acid levels during multifactorial intervention and clinical outcome in patients with metabolic syndrome. A post hoc analysis of the ATTEMPT study. Curr Med Res Opin. 2011;27:1659–68.
70.
AthyrosVGHatzitoliosAIKaragiannisA, et al.IMproving the imPlemEntation of cuRrent guidelines for the mAnagement of major coronary hearT disease rIsk factors by multifactorial interVEntion. The IMPERATIVE renal analysis. Arch Med Sci. 2011;7:984–92.
71.
GoicoecheaMGarcia de VinuesaSVerdallesU, et al.Allopurinol and progression of CKD and cardiovascular events: long-term follow-up of a randomized clinical trial. Am J Kidney Dis. 2015;65:543–49.
72.
CiceroAFGPirroMWattsGFMikhailidisDPBanachMSahebkarA. Effects of Allopurinol on Endothelial Function: A Systematic Review and Meta-Analysis of Randomized Placebo-Controlled Trials. Drugs. 2018;78:99–109.
73.
KokVCHorngJTChangWSHongYFChangTH. Allopurinol therapy in gout patients does not associate with beneficial cardiovascular outcomes: a population-based matched-cohort study. PLoS One. 2014;9: e99102.
74.
KanbayMAfsarBSiriopolD, et al.Effect of Uric Acid-Lowering Agents on Cardiovascular Outcome in Patients With Heart Failure: A Systematic Review and Meta-Analysis of Clinical Studies. Angiology. 2020;71:315–23.
75.
de AbajoFJGilMJRodriguezA, et al.Allopurinol use and risk of non-fatal acute myocardial infarction. Heart. 2015;101:679–85.
76.
Grimaldi-BensoudaLAlperovitchAAubrunE, et al.Impact of allopurinol on risk of myocardial infarction. Ann Rheum Dis. 2015;74:836–42.
77.
SinghJARamachandaranRYuSCurtisJR. Allopurinol use and the risk of acute cardiovascular events in patients with gout and diabetes. BMC Cardiovasc Disord. 2017;17:76.
78.
SinghJAYuS. Allopurinol reduces the risk of myocardial infarction (MI) in the elderly: a study of Medicare claims. Arthritis Res Ther. 2016;18:209.
79.
LukAJLevinGPMooreEEZhouXHKestenbaumBRChoiHK. Allopurinol and mortality in hyperuricaemic patients. Rheumatology (Oxford). 2009;48:804–06.
80.
WeiLMackenzieISChenYStruthersADMacDonaldTM. Impact of allopurinol use on urate concentration and cardiovascular outcome. Br J Clin Pharmacol. 2011;71:600–07.
81.
WhiteWBSaagKGBeckerMA, et al.Cardiovascular Safety of Febuxostat or Allopurinol in Patients with Gout. N Engl J Med. 2018;378:1200–10.
82.
ChoiHNeogiTStampLDalbethNTerkeltaubR. New Perspectives in Rheumatology: Implications of the Cardiovascular Safety of Febuxostat and Allopurinol in Patients With Gout and Cardiovascular Morbidities Trial and the Associated Food and Drug Administration Public Safety Alert. Arthritis Rheumatol. 2018;70:1702–19.
83.
KatsikiNBorghiC. The future of febuxostat after the Cardiovascular Safety of Febuxostat and Allopurinol in Patients with Gout and Cardiovascular Morbidities (CARES) trial: who CARES?Expert Opin Pharmacother. 2018;19:1853–56.
84.
MackenzieISFordINukiG, et al.Long-term cardiovascular safety of febuxostat compared with allopurinol in patients with gout (FAST): a multicentre, prospective, randomised, open-label, non-inferiority trial. Lancet. 2020;396:1745–57.
85.
MellinVIsabelleMOudotA, et al.Transient reduction in myocardial free oxygen radical levels is involved in the improved cardiac function and structure after long-term allopurinol treatment initiated in established chronic heart failure. Eur Heart J. 2005;26:1544–50.
86.
AlemMM. Allopurinol and endothelial function: A systematic review with meta-analysis of randomized controlled trials. Cardiovasc Ther. 2018;36: e12432.
87.
NomanAAngDSOgstonSLangCCStruthersAD. Effect of high-dose allopurinol on exercise in patients with chronic stable angina: a randomised, placebo controlled crossover trial. Lancet. 2010;375:2161–67.
88.
DesideriGCastaldoGLombardiA, et al.Is it time to revise the normal range of serum uric acid levels?Eur Rev Med Pharmacol Sci. 2014;18:1295–306.
89.
KuwabaraMHisatomeINiwaK, et al.The Optimal Range of Serum Uric Acid for Cardiometabolic Diseases: A 5-Year Japanese Cohort Study. J Clin Med. 2020;9.
90.
YerlikayaADagelTKingC, et al.Dietary and commercialized fructose: Sweet or sour?Int Urol Nephrol. 2017;49:1611–20.
91.
TsengWCChenYTOuSMShihCJTarngDC, Taiwan Geriatric Kidney Disease Research G. U-Shaped Association Between Serum Uric Acid Levels With Cardiovascular and All-Cause Mortality in the Elderly: The Role of Malnourishment. J Am Heart Assoc. 2018;7.
92.
PinedaCSoto-FajardoCMendozaJGutierrezJSandovalH. Hypouricemia: what the practicing rheumatologist should know about this condition. Clin Rheumatol. 2020;39:135–47.
