Relationship between serum uric acid levels and the incidence of cardiovascular events after percutaneous coronary intervention

Published:August 31, 2021DOI:https://doi.org/10.1016/j.jjcc.2021.08.005

      Highlights

      • Serum uric acid (SUA) levels were not related with the incidence of major adverse cardiac events in total.
      • Patients with SUA levels of 4.1-5.0 mg/dl had the lowest hazard ratio (HR).
      • Patients with SUA levels of more than 5.0 mg/dl had a higher HR.
      • The HR of patients with SUA levels of less than 4 mg/dl was not lowest.

      Abstract

      Background

      The role of serum uric acid (SUA) as an independent risk factor for coronary artery disease remains unclear. The aim of this study was to investigate whether the SUA levels could affect the incidence of major adverse cardiac events (MACE) after percutaneous coronary intervention (PCI).

      Methods and results

      We retrospectively examined the clinical records of 1,949 patients who underwent successful PCI. First, they were divided into two groups based on an SUA level of 7.0mg/dl. Among the two groups, the incidence of MACE was measured for a maximum of 5 years after PCI. Next, we divided them into 6 groups at SUA intervals of 1.0mg/dl and estimated the hazard ratios of each group. The Kaplan-Meier curve demonstrated that patients with SUA levels of >7.0mg/dl had a higher incidence of MACE than those with 7.0mg/dl or less. However, according to the multivariate analysis, the SUA level was not significantly correlated with the incidence of MACE because other factors could strongly affect it. Meanwhile, the group with SUA levels between 4.1-5.0mg/dl had a lower hazard ratio compared to groups with SUA levels of more than 5.1mg/dl. However, the hazard ratio of the group with SUA levels of 4.0mg or less was not lower than that of the group with SUA levels of 4.1-5.0mg/dl. Even after adjustment for several parameters, nearly the same results before adjustment were obtained for the hazard ratios of each group.

      Conclusion

      The present study demonstrated that the SUA level was one of the most valuable predictors of cardiovascular events after PCI, with elevated SUA levels adversely affecting secondary prevention.

      Graphical abstract

      Keywords

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      References

        • Fang J
        • Alderman MH.
        Serum uric acid and cardiovascular mortality the NHANES I epidemiologic follow-up study, 1971–1992. National Healthand Nutrition Examination Survey.
        JAMA. 2000; 283: 2404-2410
        • Niskanen LK
        • Laaksonen DE
        • Nyyssonen K
        • Alftan S
        • Lakka HM
        • Lakka TM
        • et al.
        Uric acidlevel as a risk factor for cardiovascular and all-cause mortalityin middle-aged men: a prospective cohort study.
        Arch Intern Med. 2004; 164: 1546-1551
        • Zhao G
        • Huan L
        • Song M
        • Song Y
        Baseline serum uric acid level as a predictor of prospective studies.
        Atherosclerosis. 2013; 231: 61-68
        • Zuo T
        • Liu X
        • Jiang L
        • Mao S
        • Yin X
        • Guo L.
        Hyperuricemia and coronary heart disease mortality: a meta-analysis of prospective cohort studies.
        BMC Cardiovasc. Disord. 2016; 16: 207
        • Kim SY
        • Guevara JP
        • Kim KM
        • Choi HK
        • Heitjan DF
        • DA Albert
        Hyperuricemia and coronary heart disease: a systematic review and meta-analysis.
        Arthritis Care Res (Hoboken). 2010; 62: 170-180
        • Okura T
        • Higaki J
        • Kurata M
        • Irita J
        • Miyoshi K
        • Yamazaki T
        • et al.
        Elevated serum uric acid is an independent predictor for cardiovascular events in patients with severe coronary artery stenosis - subanalysis of the japanese coronary artery disease (JCAD) Study.
        Circ J. 2009; 73: 885-891
        • Williams B
        • Mancia G
        • Spiering W
        • Rosei EA
        • Azizi M
        • Burnier M
        • et al.
        2018 ESC/ESH guidelines for the management of arterial hypertension.
        Eur Heart J. 2018; 39: 3021-3104
        • Vaccarino V
        • Krumholz HM.
        Risk factors for cardiovascular disease: one down, many more to evaluate.
        Ann Intern Med. 1999; 131: 62-63
        • Alderman MH.
        Serum uric acid as a cardiovascular risk factor for heart disease.
        Curr Hypertens Rep. Jun 2001; 3: 184-189
        • Choi HK
        • Ford ES.
        Prevalence of the metabolic syndrome in individuals with hyperuricemia.
        Am J Med. May 2007; 120: 442-447
        • Takae K
        • Nagata M
        • Hata J
        • Mukai N
        • Hirakawa Y
        • Yoshida D
        • et al.
        Serum Uric Acid as a Risk Factor for Chronic Kidney Disease in a Japanese Community – The Hisayama Study.
        Circ J. 2016; 80: 1857-1862
        • Wheeler JG
        • Juzwishin KD
        • Eiriksdottir G
        • Gudnason V
        • Danesh J.
        Serum uric acid and coronary heart disease in 9,458 incident cases and 155,084 controls: prospective study and meta-analysis.
        PLoS Med. 2005; 2: e76
        • Cappuccio FP
        • Strazzullo P
        • Farinaro E
        • Trevisan M.
        Uric acid metabolism and tubular sodium handling: results from a population-based study.
        JAMA. 1993; 270: 354-359
        • Galvan AQ
        • Natali A
        • Baldi S
        • Frascerra S
        • Sanna G
        • Ciociaro D
        • et al.
        Effect of insulin on uric acid excretion in humans.
        Am J Physiol. 1995; 268: E1-E5
        • 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: 7-13
        • De Leeuw PW
        • Thijs L
        • Birkenhager WH
        • Voyaki SM
        • Efstratopoulos AD
        • Fagard RH
        • et al.
        Prognostic significance of renal function in elderly patients with isolated systolic hypertension: Results from the Syst-Eur trial.
        J Am Soc Nephrol. 2002; 13: 2213-2222
        • Spoon DB
        • Lerman A
        • Rule AD
        • Prasad A
        • Lennon RJ
        • Holmes DR
        • et al.
        The association of serum uric acid levels with outcomes following percutaneous coronary intervention.
        J Interv Cardiol. Jun 2010; 23: 277-283
        • Okuya Y
        • Saito Y
        • Takahashi T
        • Kishi K.
        Impact of Elevated Serum Uric Acid Level on Target Lesion Revascularization After Percutaneous Coronary Intervention for Chronic Total Occlusion.
        Am J Cardiol. 15 Dec 2019; 124: 1827-1832
      1. Hisatome I, Ichida K, Mineo I, Ohtahara A, Ogino K, et al Japanese society of gout and nucleic acid 2019 guideline for management of hyperuricemia and gout third edition. Gout Uric Nucleic Acids 2020; Vol. 44 Supplement

        • Yu MA
        • Sánchez-Lozada LG
        • Johnson RJ
        • Kang DH
        Oxidative stress with an activation of the renin-angiotensin system in human vascular endothelial cells as a novel mechanism of uric acid-induced endothelial dysfunction.
        J Hypertens. 2010; 28: 1234-1242
        • Kang DH
        • Park SK
        • Lee IK
        • Johnson RJ.
        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: 3553-3562
        • Joe M
        • McCord JM.
        Oxygen-derived free radicals in postischemic tissue injury.
        N Engl J Med. 1985; 312: 159-163
        • Harrison R.
        Structure and function of xanthine oxidoreductase: where are we now?.
        Free Radic Biol Med. Sep 2002; 33: 774-797
        • Spiekermann S
        • Landmesser U
        • Dikalov S
        • Bredt M
        • Games G
        • Tatge H
        • et al.
        Electron spin resonance characterization of vascular xanthine and NAD(P)H oxidase activity in patients with coronary artery disease: relation to endothelium-dependent vasodilation.
        Circulation. Mar 2003; 107: 1383-1389
        • Valeska O
        • Soumyalekshmi N
        • Omar E
        • Aguayo C
        • Salomon C
        • Zuniga FA
        • et al.
        Association between insulin resistance and the development of cardiovascular disease.
        Cardiovasc Diabetol. 2018; 17: 122
        • Tae WY
        • Ki C S
        • Hun SS
        • Byung JK
        • Bum SK
        • Jin HK
        • et al.
        Relationship between serum uric acid concentration and insulin resistance and metabolic syndrome.
        Circ J. 2005; 69: 928-933
        • Kang DH
        • Nakagawa T
        • Feng L
        • Watanabe S
        • Han L
        • Mazzali M
        • et al.
        A role for uric acid in the progression of renal disease.
        J Am Soc Nephrol. 2002; 13: 2888-2897
        • Mazzali M
        • Hughes J
        • Kim YG
        • Jefferson JA
        • Gordon KL
        • Lan HY
        • et al.
        Elevated uric acid increases blood pressure in the rat by a novel crystal-independent mechanism.
        Hypertension. 2001; 38: 1101-1106
        • Ron TG
        • Ricardo CR
        • Brenda RH
        • Tazeen HJ
        • Heerspink HJL
        • Mann JF
        • et al.
        Chronic kidney disease and cardiovascular risk: epidemiology, mechanisms, and prevention.
        Lancet. Jul 2013; 382: 339-352
        • Cho SK
        • Chang Y
        • Kim I
        Ryu S. U-shaped association between serum uric acid level and risk of mortality: a cohort study.
        Arthritis Rheumatol. 2018; 70: 1122-1132
        • Zhang W
        • Iso H
        • Murakami Y
        • Miura K
        • Nagai M
        • Sugiyama D
        • et al.
        Serum uric acid and mortality from cardiovascular disease: EPOCH-JAPAN study.
        J Atheroscler Thromb. 2016; 23: 692-703
        • Kuo CF
        • See LC
        • Yu KH
        • Chou IJ
        • Chiou MJ
        • Luo SF.
        Significance of serum uric acid levels on the risk of all-cause and cardiovascular mortality.
        Rheumatology (Oxford). 2013; 52: 127-134
        • Sugihara S
        • Hisatome I
        • Kuwabara M
        • Niwa K
        • Maharani N
        • Kato M
        • et al.
        Depletion of uric acid due to SLC22A12 (URAT1) loss-of-function mutation causes endothelial dysfunction in hypouricemia.
        Circ J. 2015; 79: 1125-1132
        • Waring WS
        • Webb DJ
        Maxwell SR systemic uric acid administration increases serum antioxidant capacity in healthy volunteers.
        J Cardiovasc Pharmacol. 2001; 38: 365-371
        • Thanassoulis G
        • Brophy JM
        • Richard H
        • Pilote L
        Gout, allopurinol use, and heart failure outcomes.
        ArchIntern Med. 2010; l70: 1358−64
        • Ulf Landmesser
        • Spiekermann S
        • Dikalov S
        • Tatge H
        • Wilke R
        • et al.
        Vascular oxidative stress and endothelial dysfunction in patients with chronic heart failure.
        Circulation. 2002; 106: 3073-3078
        • Mishima M
        • Hamada T
        • Maharani N
        • Ikeda N
        • Onohara T
        • et al.
        Effects of uric acid on the NO production of HUVECs and its restoration by Urate lowering agents.
        Drug Res (Stuttg). May 2016; 66: 270-274
        • Franse LV
        • Pahor M
        • Bari MD
        • Shorr RI
        • Wan JY
        • Somes GW
        • et al.
        Serum uric acid, diuretic treatment and risk of cardiovascular events in the Systolic Hypertension in the Elderly Program (SHEP).
        J Hypertens. 2000; 18: 1149-1154