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Hyperuricemia as a prognostic factor after acute coronary syndrome

  • Adriana Lopez-Pineda
    Affiliations
    Cardiology Department, Hospital of San Juan de Alicante, San Juan De Alicante, Spain

    Catedra de Medicina de Familia, Clinical Medicine Department, Miguel Hernandez University, San Juan de Alicante, Spain
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  • Alberto Cordero
    Correspondence
    Corresponding author. Hospital of San Juan de Alicante, Cardiology Department, Ctra. Nnal. 332 s/n, 03550, San Juan de Alicante, Spain.
    Affiliations
    Cardiology Department, Hospital of San Juan de Alicante, San Juan De Alicante, Spain

    Centro de Investigación Biomédica en Red de Enfermedades Cardiovasculares (CIBERCV), Hospital Clínico Universitario de Santiago de Compostela-SERGAS, Instituto de Investigación Sanitaria de Santiago de Compostela (IDIS), Santiago de Compostela, Spain
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  • Concepción Carratala-Munuera
    Affiliations
    Catedra de Medicina de Familia, Clinical Medicine Department, Miguel Hernandez University, San Juan de Alicante, Spain
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  • Domingo Orozco-Beltran
    Affiliations
    Catedra de Medicina de Familia, Clinical Medicine Department, Miguel Hernandez University, San Juan de Alicante, Spain
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  • Jose A. Quesada
    Affiliations
    Catedra de Medicina de Familia, Clinical Medicine Department, Miguel Hernandez University, San Juan de Alicante, Spain
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  • Vicente Bertomeu-Gonzalez
    Affiliations
    Cardiology Department, Hospital of San Juan de Alicante, San Juan De Alicante, Spain

    Clinical Medicine Department, Miguel Hernandez University, San Juan de Alicante, Spain

    Centro de Investigación Biomédica en Red de Enfermedades Cardiovasculares (CIBERCV), Fundación para la Investigacion del Hospital Clínico de la Comunidad Valenciana (Fundación INCLIVA), Valencia, Spain
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  • Vicente F. Gil-Guillen
    Affiliations
    Catedra de Medicina de Familia, Clinical Medicine Department, Miguel Hernandez University, San Juan de Alicante, Spain
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  • Vicente Bertomeu-Martinez
    Affiliations
    Cardiology Department, Hospital of San Juan de Alicante, San Juan De Alicante, Spain
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      Highlights

      • Hyperuricemia is independently associated with poor clinical outcomes after ACS.
      • If GRACE score includes hyperuricemia, risk classification for non-events improves.
      • It is known serum uric acid level is an inexpensive and commonly ordered measure.
      • Uric acid level might help stratify risk for poor outcomes after ACS.

      Abstract

      Background and aims

      Many studies have reported the independent association between uric acid and cardiovascular disease, its role as a risk predictor for outcomes in people with acute coronary syndrome remains controversial. This study aims to assess the association between hyperuricemia and medium/long-term clinical outcomes in people with acute coronary syndrome and determine whether adding hyperuricemia to the GRACE score improves its predictive capability.

      Methods

      This cohort study included patients admitted for acute coronary syndrome between 2008 and 2013. Outcomes were cardiovascular and total mortality, and major cardiovascular events. We used a multivariate model to adjust for potential confounding covariates and presented event rates with Kaplan-Meier curves. After adding hyperuricemia to the GRACE score, we compared scores from the reclassification table and the net reclassification improvement.

      Results

      1119 participants were included and followed-up for a mean of 36 months. Multivariate models showed hyperuricemia was independently associated with higher cardiovascular mortality (HR:1.91; 95% CI:1.32–2.76; p < 0.01), higher all-cause mortality (HR:1.59; 95% CI:1.18–2.15; p < 0.01) and higher major cardiovascular event rates (HR:1.36; 95% CI:1.11–1.67; p < 0.01). The hyperuricemia addition to GRACE score led to reclassifying 26% of the participants, and net reclassification improvement was 34%. However, the area under the curve increase was 0.009 and not statistically significant (p > 0.05).

      Conclusions

      Hyperuricemia is associated with higher medium/long-term mortality and major cardiovascular event rates in patients following acute coronary syndrome. The addition of hyperuricemia to the GRACE score seems to improve risk classification but the discrimination of the new predictive model did not change. Hyperuricemic patients had higher all-cause mortality in medium and high-risk score categories.

      Keywords

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      References

        • Mohamed F.A.
        On Bright's disease, and its essential symptoms.
        Lancet. 1879; 1: 399-401
        • Haig A.
        On uric acid and arterial tension.
        BMJ. 1889; 1: 288-291
        • Kanbay M.
        • Segal M.
        • Afsar B.
        • Kang D.H.
        • Rodriguez-Iturbe B.
        • Johnson R.J.
        The role of uric acid in the pathogenesis of human cardiovascular disease.
        Heart. 2013; 99 (): 759-766
        • Braga F.
        • Pasqualetti S.
        • Ferraro S.
        • Panteghini M.
        Hyperuricemia as risk factor for coronary heart disease incidence and mortality in the general population: a systematic review and meta-analysis.
        Clin. Chem. Lab. Med. 2016 Jan; 54: 7-15
        • Yan L.
        • Liu Z.
        • Zhang C.
        Uric acid as a predictor of in-hospital mortality in acute myocardial infarction: a meta-analysis.
        Cell Biochem. Biophys. 2014 Dec; 70: 1597-1601
        • Bickel C.
        • Rupprecht H.J.
        • Blankenberg S.
        • et al.
        Serum uric acid as an independent predictor of mortality in patients with angiographically proven coronary artery disease.
        Am. J. Cardiol. 2002 Jan 1; 89: 12-17
        • 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 Jul 26; 164: 1546-1551
        • Forman J.P.
        • Choi H.
        • Curhan G.C.
        Plasma uric acid level and risk for incident hypertension among men.
        J. Am. Soc. Nephrol. 2007 Jan; 18 (): 287-292
        • Peng T.C.
        • Wang C.C.
        • Kao T.W.
        • et al.
        Relationship between hyperuricemia and lipid profiles in US adults.
        BioMed Res. Int. 2015; 2015: 127596
        • Katsiki N.
        • Papanas N.
        • Fonseca V.A.
        • Maltezos E.
        • Mikhailidis D.P.
        Uric acid and diabetes: is there a link?.
        Curr. Pharmaceut. Des. 2013; 19: 4930-4937
        • Masuo K.
        • Kawaguchi H.
        • Mikami H.
        • Ogihara T.
        • Tuck M.L.
        Serum uric acid and plasma norepinephrine concentrations predict subsequent weight gain and blood pressure elevation.
        Hypertension. 2003 Oct; 42 (): 474-480
        • Soltani Z.
        • Rasheed K.
        • Kapusta D.R.
        • Reisin E.
        Potential role of uric acid in metabolic syndrome, hypertension, kidney injury, and cardiovascular diseases: is it time for reappraisal?.
        Curr. Hypertens. Rep. 2013 Jun; 15: 175-181
        • Shetty S.
        • Rao A.H.
        • Sampath Kumar A.K.
        • Rama Prakasha S.
        Serum uric acid as a prognostic biomarker and its correlation with Killip class in acute myocardial infarction.
        Int. J. Biomed. Res. 2013; 04
        • Feig D.I.
        • Kang D.H.
        • Johnson R.J.
        Uric acid and cardiovascular risk.
        N. Engl. J. Med. 2008 Oct 23; 359: 1811-1821
        • Pascual Izuel J.M.
        Uricemia and metabolic syndrome in patients with arterial hypertension.
        Rev. Clin. Esp. 2012 Oct; 212: 440-441
        • Alderman M.
        • Aiyer K.J.
        Uric acid: role in cardiovascular disease and effects of losartan.
        Curr. Med. Res. Opin. 2004 Mar; 20: 369-379
        • Kim S.Y.
        • Guevara J.P.
        • Kim K.M.
        • Choi H.K.
        • Heitjan D.F.
        • Albert D.A.
        Hyperuricemia and coronary heart disease: a systematic review and meta-analysis.
        Arthritis Care Res. 2010 Feb; 62: 170-180
        • Lazzeri C.
        • Valente S.
        • Chiostri M.
        • Picariello C.
        • Gensini G.F.
        Uric acid in the early risk stratification of ST-elevation myocardial infarction.
        Intern Emerg Med. 2012; 7: 33-39
        • Antman E.M.
        • Hand M.
        • Armstrong P.W.
        • et al.
        2007 focused update of the ACC/AHA 2004 guidelines for the management of patients with ST-elevation myocardial infarction.
        J. Am. Coll. Cardiol. 2008 Jan 15; 51: 210-247
        • Culleton B.F.
        • Lansom M.G.
        • Kannel W.B.
        • Levy D.
        Serum uric acid and risk for cardiovascular disease and death: the Framingham Heart Study.
        Ann. Intern. Med. 1999 Jul 6; 131: 7-13
        • Niizeki T.
        • Takeishi Y.
        • Arimoto T.
        • et al.
        Hyperuricemia associated with high cardiac event rates in the elderly with chronic heart failure.
        J. Cardiol. 2006 May; 47: 219-228
        • von Lueder T.G.
        • Girerd N.
        • Atar D.
        • et al.
        High-Risk Myocardial Infarction Database Initiative Investigators. 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 Nov; 17: 1144-1151
        • Trkulja V.
        • Car S.
        On-admission serum uric acid predicts outcomes after acute myocardial infarction: systematic review and meta-analysis of prognostic studies.
        Croat. Med. J. 2012 Apr; 53: 162-172
        • Wu A.H.
        • Gladden J.D.
        • Ahmed M.
        • Ahmed A.
        • Filippatos G.
        Relation of serum uric acid to cardiovascular disease.
        Int. J. Cardiol. 2016 Jun 15; 213: 4-7
        • Gazi E.
        • Temiz A.
        • Altun B.
        • et al.
        The association between serum uric acid level and heart failure and mortality in the early period of ST-elevation acute myocardial infarction.
        Turk Kardiyol Dern Ars. 2014 Sep; 42: 501-508
        • Levantesi G.
        • Marfisi R.M.
        • Franzosi M.G.
        • et al.
        Uric acid: a cardiovascular risk factor in patients with recent myocardial infarction.
        Int. J. Cardiol. 2013 Jul 15; 167: 262-269
        • Granger C.B.
        • Goldberg R.J.
        • Dabbous O.
        • et al.
        Predictors of hospital mortality in the global registry of acute coronary events.
        Arch. Intern. Med. 2003; 163: 2345-2353
        • Car S.
        • Trkulja V.
        Higher serum uric acid on admission is associated with higher short-term mortality and poorer long-term survival after myocardial infarction: retrospective prognostic study.
        Croat. Med. J. 2009 Dec; 50: 559-566
        • Cordero A.
        • Bertomeu-Gonzalez V.
        • Moreno-Arribas J.
        • et al.
        Burden of systemic hypertension in patients admitted to cardiology hospitalization units.
        Am. J. Cardiol. 2011; 108: 1570-1575
        • Amsterdam E.A.
        • Wenger N.K.
        • Brindis R.G.
        • et al.
        2014 AHA/ACC guideline for the management of patients with non-ST-elevation acute coronary syndromes: a report of the American college of cardiology/American heart association task force on practice guidelines.
        J. Am. Coll. Cardiol. 2014; 64: 139-228
        • National Kidney Foundation
        K/DOQI clinical practice guidelines for chronic kidney disease: evaluation, classification, and stratification.
        Am. J. Kidney Dis. 2002 Feb; 39 (S1-266)
        • Sachdev M.
        • Sun J.L.
        • Tsiatis A.A.
        • Nelson C.L.
        • Mark D.B.
        • Jollis J.G.
        The prognostic importance of comorbidity for mortality in patients with stable coronary artery disease.
        J. Am. Coll. Cardiol. 2004; 43: 576-582
        • Cook N.R.
        • Ridker P.M.
        Advances in measuring the effect of individual predictors of cardiovascular risk: the role of reclassification measures.
        Ann. Intern. Med. 2009; 150: 795-802
        • Pencina M.J.
        • D'Agostino Sr., R.B.
        • D'Agostino Jr., R.B.
        • Vasan R.S.
        Evaluating the added predictive ability of a new marker: from area under the ROC curve to reclassification and beyond.
        Stat. Med. 2008 Jan 30; 27 (157-72; discussion 207–212)
      1. A. Lopez-Pineda, A. Cordero, C. Carratala-Munuera; D. Orozco-Beltran, JA. Quesada; V. Bertomeu-Gonzalez; VF. Gil-Guillen; V. Bertomeu-Martinez. Association analysis between hyperuricemia and long term mortality after acute coronary syndrome in three subgroups of patients. Data in Brief [submitting].

        • L B.
        • W T.
        • Z H.N.
        • et al.
        The prevalence of hyperuricemia in China: a meta-analysis.
        BMC Publ. Health. 2011 Oct 27; 11: 832
        • Timóteo A.T.
        • Lousinha A.
        • Labandeiro J.
        • et al.
        Serum uric acid: a forgotten prognostic marker in acute coronary syndromes?.
        Eur Heart J Acute Cardiovasc Care. 2013 Mar; 2: 44-52
        • Campion E.W.
        • Glynn R.J.
        • DeLabry L.O.
        Asymptomatic hyperuricemia. Risks and consequences in the normative aging study.
        Am. J. Med. 1987 Mar; 82: 421-426
        • Abdurhman S.A.-A.
        Hyperuricemia in Saudi Arabia.
        Rheumatol. Int. 2001; : 61-64
        • Ndrepepa G.
        • Braun S.
        • Haase H.U.
        • et al.
        Prognostic value of uric acid in patients with acute coronary syndromes.
        Am. J. Cardiol. 2012 May 1; 109: 1260-1265
        • Shacham Y.
        • Gal-Oz A.
        • Flint N.
        • Keren G.
        • Arbel Y.
        Serum Uric Acid Levels and Renal Impairment Among ST-segment elevation myocardial infarction patients undergoing primary percutaneous intervention.
        Cardiorenal Med. 2016 May; 6: 191-197
        • Jordan K.M.
        • Cameron J.S.
        • Snaith M.
        • et al.
        British society for rheumatology and British health professionals in rheumatology guideline for the management of gout.
        Rheumatology. 2007; 46: 1372-1374
        • Liese A.D.
        • Liese A.D.
        • Hense H.W.
        • et al.
        Association of serum uric acid with all-cause and cardiovascular disease mortality and incident myocardial infarction in the MONICA Augsburg cohort. world health Organization Monitoring trends and determinants in cardiovascular diseases.
        Epidemiology. 1999 Jul; 10: 391-397
        • Kaya M.G.
        • Uyarel H.
        • Akpek M.
        • et al.
        Prognostic value of uric acid in patients with ST-elevated myocardial infarction undergoing primary coronary intervention.
        Am. J. Cardiol. 2012; 109: 486-491
        • Panero F.
        • Gruden G.
        • Perotto M.
        • et al.
        Uric acid is not an independent predictor of cardiovascular mortality in type 2 diabetes: a population-based study.
        Atherosclerosis. 2012 Mar; 221: 183-188
        • Zoppini G.
        • Targher G.
        • Negri C.
        • et al.
        Elevated serum uric acid concentrations independently predict cardiovascular mortality in type 2 diabetic patients.
        Diabetes Care. 2009; 32: 1716-1720
        • Lazzeri C.
        • Valente S.
        • Chiostri M.
        • Spini V.
        • Angelotti P.
        • Gensini G.F.
        Uric acid and mild renal impairment in patients with ST-elevation myocardial infarction.
        Scand. Cardiovasc. J. 2015 Feb; 49: 14-19
        • Kowalczyk J.
        • Francuz P.
        • Swoboda R.
        • et al.
        Prognostic significance of hyperuricemia in patients with different types of renal dysfunction and acute myocardial infarction treated with percutaneous coronary intervention.
        Nephron Clin. Pract. 2010; 116: 114-122
        • Alderman M.H.
        • Cohen H.
        • Madhavan S.
        • Kivlighn S.
        Serum uric acid and cardiovascular events in successfully treated hypertensive patients.
        Hypertension. 1999; 34 (): 144-150
        • Barrabes J.A.
        • Bardaji A.
        • Jimenez-Candil J.
        • et al.
        Prognosis and management of acute coronary syndrome in Spain in 2012: the DIOCLES Study.
        Rev. Esp. Cardiol. 2015 Feb; 68: 98-106

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