Uric acid associated with acute heart failure presentation in Acute Coronary Syndrome patients

Published:January 17, 2022DOI:


      • Data on the role of Uric Acid (UA) as a determining factor of Heart Failure related issue in Acute Coronary Syndrome (ACS) patients are scanty.
      • UA was confirmed to be significantly associated with Acute Heart Failure, Cardiogenic Shock, Non Invasive Ventilation and Ejection Fraction in ACS patients.
      • Evaluation of UA in ACS patients could help to identify the one with the worst heart failure related outcomes.


      We focused on the role of Uric Acid (UA) as a possible determinant of Heart Failure (HF) related issues in Acute Coronary Syndromes (ACS) patients. Main outcomes were acute HF and cardiogenic shock at admission, secondary outcomes were the use of Non Invasive Ventilation (NIV) and the admission Left Ventricular Ejection Fraction (LVEF). We consecutively enrolled 1269 ACS patients admitted to the cardiological Intensive Care Unit of the Niguarda and San Paolo hospitals (Milan, Italy) from June 2016 to June 2019. Median age was 68 (first-third quartile 59–77) years and males were 970 (76%). All the evaluated outcomes occurred more frequently in the hyperuricemic subjects (UA higher than 6 mg/dL for females and 7 mg/dL for males, n = 292): acute HF 35.8 vs 11.1% (p < 0.0001), cardiogenic shock 10 vs 3.1% (p < 0.0001), NIV 24.1 vs 5.1% (p < 0.0001) and lower admission LVEF (42.9±12.8 vs 49.6±9.9, p < 0.0001). By multivariable analyses, UA was confirmed to be significantly associated with all the outcomes with the following Odds Ratio (OR): acute HF OR = 1.119; 95% CI 1.019;1.229; cardiogenic shock OR = 1.157; 95% CI 1.001;1.337; NIV use OR = 1.208; 95% CI 1.078;1.354; LVEF β = -0.999; 95% CI -1.413;-0.586. We found a significant association between UA and acute HF, cardiogenic shock, NIV use and LVEF. Due to the cross-sectional nature of our study no definite answer on the direction of these relationship can be drawn and further longitudinal study on UA changes over time during an ACS hospitalization are needed.


      To read this article in full you will need to make a payment

      Purchase one-time access:

      Academic & Personal: 24 hour online accessCorporate R&D Professionals: 24 hour online access
      One-time access price info
      • For academic or personal research use, select 'Academic and Personal'
      • For corporate R&D use, select 'Corporate R&D Professionals'


      Subscribe to European Journal of Internal Medicine
      Already a print subscriber? Claim online access
      Already an online subscriber? Sign in
      Institutional Access: Sign in to ScienceDirect


        • Virdis A
        • Masi S
        • Casiglia E
        • Tikhonoff V
        • Cicero AFG
        • Ungar A
        • Rivasi G
        • Salvetti M
        • Barbagallo CM
        • Bombelli M
        • From the Working Group on Uric Acid and Cardiovascular Risk of the Italian Society of Hypertension
        • et al.
        Identification of the uric acid thresholds predicting an increased total and cardiovascular mortality over 20 years.
        Hypertension. 2020; 75: 302-308
        • Tscharre M
        • Herman R
        • Rohla M
        • Hauser C
        • Farhan S
        • Freynhofer MK
        • Huber K
        • Weiss TW.
        Uric acid is associated with long-term adverse cardiovascular outcomes in patients with acute coronary syndrome undergoing percutaneous coronary intervention.
        Atherosclerosis. 2018; 270: 173-179
        • Tamariz L
        • Harzand A
        • Palacio A
        • Verma S
        • Jones J
        • Hare J.
        Uric acid as a predictor of all-cause mortality in heart failure: a meta-analysis.
        Congestive Heart Fail. 2011; 17: 25-30
        • Coiro S
        • Carluccio E
        • Biagioli P
        • Alunni G
        • Murrone A
        • D'Antonio A
        • Zuchi C
        • Mengoni A
        • Girerd N
        • Borghi C
        • et al.
        Elevated serum uric acid concentration at discharge confers additive prognostic value in elderly patients with acute heart failure.
        Nutr Metab Cardiovasc Dis. 2018; 28: 361-368
        • Muiesan ML
        • Salvetti M
        • Virdis A
        • Masi S
        • Casiglia E
        • Tikhonoff V
        • Barbagallo CM
        • Bombelli M
        • Cicero AFG
        • Cirillo M
        • From the Working Group on Uric Acid, Cardiovascular Risk of the Italian Society of Hypertension
        • et al.
        Serum uric acid, predicts heart failure in a large Italian cohort: search for a cut-off value the URic acid Right for heArt Health study.
        J Hypertens. 2021; 39: 62-69
        • Krishnan E
        • Hariri A
        • Dabbous O
        • Pandya BJ.
        Hyperuricemia and the echocardiographic measures of myocardial dysfunction.
        Congestive Heart Fail. 2012; 18: 138-143
        • Bagai J
        • Brilakis ES.
        Update in the management of acute coronary syndrome patients with cardiogenic shock.
        Curr Cardiol Rep. 2019; 21: 17
        • Kaya MG
        • Uyarel H
        • Akpek M
        • Kalay N
        • Ergelen M
        • Ayhan E
        • Isik T
        • Cicek G
        • Elcik D
        • Sahin O
        • 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
        • Basar N
        • Sen N
        • Ozcan F
        • Erden G
        • Kanat S
        • Sokmen E
        • Isleyen A
        • Yuzgecer H
        • Ozlu MF
        • Yildirimkaya M
        • et al.
        Elevated serum uric acid predicts angiographic impaired reperfusion and 1-year mortality in ST-segment elevation myocardial infarction patients undergoing percutaneous coronary intervention.
        J Investig Med. 2011; 59: 931-937
        • von Lueder TG
        • Girerd N
        • Atar D
        • Agewall S
        • Lamiral Z
        • Kanbay M
        • Pitt B
        • Dickstein K
        • Zannad F
        • Rossignol P
        • 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; 17: 1144-1151
        • Centola M
        • Maloberti A
        • Castini D
        • Persampieri S
        • Sabatelli L
        • Ferrante G
        • Lucreziotti S
        • Morici N
        • Sacco A
        • Oliva F
        • et al.
        Of admission serum acid uric levels on in-hospital outcomes in patients with acute coronary syndrome.
        Eur J Intern Med. 2020; (Epub ahead of print)
        • Thygesen K
        • Alpert JS
        • Jaffe AS
        • Chaitman BR
        • Bax JJ
        • Morrow DA
        • White HD
        Executive Group on behalf of the Joint European Society of Cardiology (ESC)/American College of Cardiology (ACC)/American Heart Association (AHA)/World Heart Federation (WHF) Task Force for the Universal Definition of Myocardial Infarction. Fourth universal definition of myocardial infarction (2018).
        J Am Coll Cardiol. 2018; 72: 2231-2264
        • Collet JP
        • Thiele H
        • Barbato E
        • Barthélémy O
        • Bauersachs J
        • Bhatt DL
        • Dendale P
        • Dorobantu M
        • Edvardsen T
        • Folliguet T
        • ESC Scientific Document Group
        • et al.
        2020 ESC Guidelines for the management of acute coronary syndromes in patients presenting without persistent ST-segment elevation.
        Eur Heart J. 2020; (Epub ahead of print)
        • Lazzeri C
        • Valente S
        • Chiostri M
        • Sori A
        • Bernardo P
        • Gensini GF.
        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: 206-209
        • Tedeschi A
        • Agostoni P
        • Pezzuto B
        • Corra' U
        • Scrutinio D
        • La Gioia R
        • Raimondo R
        • Passantino A
        • Piepoli MF
        Role of comorbidities in heart failure prognosis Part 2: Chronic kidney disease, elevated serum uric acid.
        Eur J Prev Cardiol. 2020; 27: 35-45
        • Egas-Izquierdo M
        • Wong-Achi X
        • Alvarado-Villa G
        • Mautong H.
        Relation between serum uric acid levels with the degree of coronary artery disease: A prospective study from Ecuador.
        Clin Investig Arterioscler. 2019; 31: 8-14
        • Mandurino-Mirizzi A
        • Crimi G
        • Raineri C
        • Pica S
        • Ruffinazzi M
        • Gianni U
        • Repetto A
        • Ferlini M
        • Marinoni B
        • Leonardi S
        • 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: 240-246
        • Akpek M
        • Kaya MG
        • Uyarel H
        • Yarlioglues M
        • Kalay N
        • Gunebakmaz O
        • Dogdu O
        • Ardic I
        • Elcik D
        • Sahin O
        • et al.
        The association of serum uric acid levels on coronary flow in patients with STEMI undergoing primary PCI.
        Atherosclerosis. 2011; 219: 334-341
        • Doehner W
        • Jankowska EA
        • Springer J
        • Lainscak M
        • Anker SD.
        Uric acid and xanthine oxidase in heart failure - emerging data and therapeutic implications.
        Int. J. Cardiol. 2016; 213: 15-19
        • Okazaki H
        • Shirakabe A
        • Matsushita M
        • Shi-bata Y
        • Sawatani T
        • Uchiyama S
        • et al.
        Plasma xanthine oxidoreductase activity in patients with decompensated acute heart failure re-quiring intensive care.
        ESC Heart Fail. 2019; 6: 336-343
        • Maloberti A
        • Bombelli M
        • Facchetti R
        • Barbagallo CM
        • Bernardino B
        • Rosei EA
        • Casiglia E
        • Giuseppe Cicero AF
        • Cirillo M
        • Cirillo P
        • Working Group on Uric Acid, Cardiovascular Risk of the Italian Society of Hypertension (SIIA)
        • et al.
        Relationships between diuretic-related hyperuricemia and cardiovascular events: data from the URic acid Right for heArt Health study.
        J Hypertens. 2020; (Epub ahead of print)
        • Hare JM
        • Mangal B
        • Brown J
        • Fisher Jr, C
        • Freudenberger R
        • Colucci WS
        • et al.
        Impact of oxypurinol in patients with symptomatic heart failure: Results of the OPT-CHF study.
        J Am Coll Cardiol. 2008; 51: 2301-2309
        • Givertz MM
        • Anstrom KJ
        • Redfield MM
        • Deswal A
        • Haddad H
        • Butler J
        • et al.
        Effects of xanthine oxidase inhibition in hyperuricemic heart failure patients: the xanthine oxidase inhibition for hyperuricemic heart failure patients (EXACT-HF) study.
        Circulation. 2015; 131: 1763-1771
        • Pavlusova M
        • Jarkovsky J
        • Benesova K
        • Vitovec J
        • Linhart A
        • Widimsky P
        • Spinarova L
        • Zeman K
        • Belohlavek J
        • et al.
        Hyperuricemia treatment in acute heart failure patients does not improve their long-term prognosis: a propensity score matched analysis from the AHEAD registry.
        Clin Cardiol. 2019; 42: 720-727
        • Yamamoto H
        • Nagatomo Y
        • Mahara K
        • Yoshikawa T.
        In-hospital serum uric acid change predicts adverse outcome in patients with heart failure.
        J Card Fail. 2020; 26: 968-976
        • Zhou HB
        • Xu TY
        • Liu SR
        • Bai YJ
        • Huang XF
        • Zhan Q
        • Zeng QC
        • Xu DL.
        Association of serum uric acid change with mortality, renal function and diuretic dose administered in treatment of acute heart failure.
        Nutr Metab Cardiovasc Dis. 2019; 29: 351-359
        • Nambu H
        • Takada S
        • Maekawa S
        • Matsumoto J
        • Kakutani N
        • Furihata T
        • Shirakawa R
        • Katayama T
        • Nakajima T
        • Yamanashi K
        • et al.
        Inhibition of xanthine oxidase in the acute phase of myocardial infarction prevents skeletal muscle abnormalities and exercise intolerance.
        Cardiovasc Res. 2020; (Epub ahead of print)
        • Krishnan E
        • Hariri A
        • Dabbous O
        • Pandya BJ.
        Hyperuricemia and the echocardiographic measures of myocardial dysfunction.
        Congest Heart Fail. 2012; 18: 138-143
        • Oki Y
        • Kawai M
        • Minai K
        • Ogawa K
        • Inoue Y
        • Morimoto S
        • Tanaka T
        • Nagoshi T
        • Ogawa T
        • Yoshimura M.
        High serum uric acid is highly associated with a reduced left ventricular ejection fraction rather than increased plasma b-type natriuretic peptide in patients with cardiovascular diseases.
        Sci Rep. 2019; 9: 682
        • Christensen EF
        • Jacobsen J
        • Anker-Møller E
        • Schultz P
        • Spangsberg N.
        Increased urinary loss of uric acid in adults with acute respiratory failure requiring mechanical ventilation.
        Chest. 1992; 102: 556-559
        • Maloberti A
        • Biolcati M
        • Ruzzenenti G
        • Giani V
        • Leidi F
        • Monticelli M
        • Algeri M
        • Scarpellini S
        • Nava S
        • Soriano F
        • et al.
        The role of uric acid in acute and chronic coronary syndromes.
        J Clin Med. 2021; 10
        • Mackenzie IS
        • Ford I
        • Walker A
        • Hawkey C
        • Begg A
        • Avery A
        • et al.
        ALL-HEART study group. Multicentre, prospective, randomised, open-label, blinded end point trial of the efficacy of allopurinol therapy in improving cardiovascular outcomes in patients with ischaemic heart disease: protocol of the ALL-HEART study.
        BMJ Open. 2016; 6e013774
        • Kojima S
        • Sakamoto T
        • Ishihara M
        • Kimura K
        • Miyazaki S
        • Yamagishi M
        • Tei C
        • Hiraoka H
        • Sonoda M
        • Tsuchihashi K
        • Japanese Acute Coronary Syndrome Study (JACSS) Investigators
        • et al.
        Prognostic usefulness of serum uric acid after acute myocardial infarction (the Japanese Acute Coronary Syndrome Study).
        Am J Cardiol. 2005; 96: 489-495

      Linked Article

      • Uric acid and cardiovascular risk stratification in the acute coronary syndromes: a friend we should mind
        European Journal of Internal MedicineVol. 99
        • Preview
          Uric acid (UA) is the end product of purine metabolism. Whilst being primarily known as the leading risk factor for the onset of gout [1], UA has also been acknowledged as a significant CV risk factor [2]. However, international guidelines report as pathological threshold only the saturation point of UA (6.0 mg/dL in women and ≥7.0 mg/dL in men) [3], yet failing to identify a specific CV prevention cut-off [4]. This somewhat neglects UA predictive role in CV disease [5]. In a large (n=22,714) Italian-population based observation cohort study, we have described how UA markedly impact all-cause and CV mortality starting from lower serum levels (respectively, 4.7 and 5.6 mg/dL) [2].
        • Full-Text
        • PDF