Human serum albumin in cardiovascular diseases

  • Stephane Arques
    Corresponding author at: Service de Cardiologie, Centre Hospitalier Edmond Garcin, Avenue des Soeurs Gastine, 13400 Aubagne, France.
    Service de Cardiologie, Centre hospitalier Edmond Garcin, Aubagne, France
    Search for articles by this author
Published:April 19, 2018DOI:


      • Cardiovascular diseases are the leading cause of death worldwide.
      • Serum albumin has anti-inflammatory, antioxidant, anticoagulant and antiplatelet aggregation activity.
      • Low serum albumin levels are independently linked to the emergence of several cardiovascular diseases.
      • Hypoalbuminemia is a strong, independent prognosticator in many cardiovascular diseases.
      • Convincing evidence is now that low serum albumin plays as a potentially modifiable risk factor in many cardiovascular diseases.


      Cardiovascular diseases are the leading cause of death worldwide. Endothelial dysfunction, inflammation and oxidative stress are at the forefront in the onset and development of atherosclerosis and many cardiovascular diseases. Epidemiological evidence is that low serum albumin levels are linked to incident ischemic heart disease, heart failure, atrial fibrillation, stroke and venous thromboembolism, independent of risk factors, body mass index and inflammation. Hypoalbuminemia has also emerged as an independent prognosticator in many cardiovascular diseases, such as coronary artery disease, heart failure, congenital heart disease, infective endocarditis and stroke, even after adjusting for usual causal factors and prognostic markers. Given physiological properties of serum albumin that include anti-inflammatory, antioxidant, anticoagulant and antiplatelet aggregation activity as well as colloid osmotic effect, hypoalbuminemia could act as an unrecognized modifiable risk factor. The purpose of this review is to provide an overview of the physiological properties of serum albumin, as well as prevalence, causes, prognostic value and potential contribution to the disease emergence and progression of hypoalbuminemia, and the resulting clinical implications.


      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


        • Hansson G.K.
        Inflammation, atherosclerosis, and coronary artery disease.
        N Engl J Med. 2005 Apr 21; 352: 1685-1695
        • Münzel T.
        • Gori T.
        • Keaney Jr., J.F.
        • Maack C.
        • Daiber A.
        Pathophysiological role of oxidative stress in systolic and diastolic heart failure and its therapeutic implications.
        Eur Heart J. 2015 Oct 7; 36: 2555-2564
        • Redfield M.M.
        Heart failure with preserved ejection fraction.
        N Engl J Med. 2017 Mar 2; 376: 897
        • Korantzopoulos P.
        • Kolettis T.M.
        • Galaris D.
        • Goudevenos J.A.
        The role of oxidative stress in the pathogenesis and perpetuation of atrial fibrillation.
        Int J Cardiol. 2007 Feb 7; 115: 135-143
        • Rodrigo R.
        • Fernández-Gajardo R.
        • Gutiérrez R.
        • et al.
        Oxidative stress and pathophysiology of ischemic stroke: novel therapeutic opportunities.
        CNS Neurol Disord Drug Targets. 2013 Aug; 12: 698-714
        • Kanaan G.N.
        • Harper M.E.
        Cellular redox dysfunction in the development of cardiovascular diseases.
        Biochim Biophys Acta. 2017 Nov; 1861: 2822-2829
        • Goldwasser P.
        • Feldman J.
        Association of serum albumin and mortality risk.
        J Clin Epidemiol. 1997 Jun; 50: 693-703
        • Don B.R.
        • Kaysen G.
        Serum albumin: relationship to inflammation and nutrition.
        Semin Dial. 2004 Nov-Dec; 17: 432-437
        • Arques S.
        • Ambrosi P.
        Human serum albumin in the clinical syndrome of heart failure.
        J Card Fail. 2011 Jun; 17: 451-458
        • Zhang W.J.
        • Frei B.
        Albumin selectively inhibits TNF alpha-induced expression of vascular cell adhesion molecule-1 in human aortic endothelial cells.
        Cardiovasc Res. 2002 Sep; 55: 820-829
        • Wiedermann C.J.
        Anti-inflammatory activity of albumin (letter).
        Crit Care Med. 2007 Mar; 35: 981-982
        • Roche M.
        • Rondeau P.
        • Singh N.R.
        • Tarnus E.
        • Bourdon E.
        The antioxidant properties of serum albumin.
        FEBS Lett. 2008 Jun 11; 582: 1783-1787
        • Anraku M.
        • Chuang V.T.
        • Maruyama T.
        • Otagiri M.
        Redox properties of serum albumin.
        Biochim Biophys Acta. 2013 Dec; 1830: 5465-5472
        • Lam F.W.
        • Cruz M.A.
        • Leung H.C.
        • Parikh K.S.
        • Smith C.W.
        • Rumbaut R.E.
        Histone induced platelet aggregation is inhibited by normal albumin.
        Thromb Res. 2013 Jul; 132: 69-76
        • Paar M.
        • Rossmann C.
        • Nusshold C.
        • et al.
        Anticoagulant action of low, physiologic, and high albumin levels in whole blood.
        PLoS One. 2017 Aug 11; 12e0182997
        • Chien S.C.
        • Chen C.Y.
        • Leu H.B.
        • et al.
        Association of low serum albumin concentration and adverse cardiovascular events in stable coronary heart disease.
        Int J Cardiol. 2017 Aug 15; 241: 1-5
        • González-Pacheco H.
        • Amezcua-Guerra L.M.
        • Sandoval J.
        • et al.
        Prognostic implications of serum albumin levels in patients with acute coronary syndromes.
        Am J Cardiol. 2017 Apr 1; 119: 951-958
        • Oduncu V.
        • Erkol A.
        • Karabay C.Y.
        • et al.
        The prognostic value of serum albumin levels on admission in patients with acute ST-segment elevation myocardial infarction undergoing a primary percutaneous coronary intervention.
        Coron Artery Dis. 2013 Mar; 24: 88-94
        • Plakht Y.
        • Gilutz H.
        • Shiyovich A.
        Decreased admission serum albumin level is an independent predictor of long-term mortality in hospital survivors of acute myocardial infarction. Soroka Acute Myocardial Infarction II (SAMI-II) project.
        Int J Cardiol. 2016 Sep 15; 219: 20-24
        • Kempny A.
        • Diller G.P.
        • Alonso-Gonzalez R.
        • et al.
        Hypoalbuminaemia predicts outcome in adult patients with congenital heart disease.
        Heart. 2015 May; 101: 699-705
        • Zhang Q.
        • Lei Y.X.
        • Wang Q.
        • et al.
        Serum albumin level is associated with the recurrence of acute ischemic stroke.
        Am J Emerg Med. 2016 Sep; 34: 1812-1816
        • Hermiller Jr., J.B.
        • Yakubov S.J.
        • Reardon M.J.
        • et al.
        CoreValve United States clinical investigators. Predicting early and late mortality after transcatheter aortic valve replacement.
        J Am Coll Cardiol. 2016 Jul 26; 68: 343-352
        • Wada H.
        • Dohi T.
        • Miyauchi K.
        • et al.
        Impact of serum albumin levels on long-term outcomes in patients undergoing percutaneous coronary intervention.
        Heart Vessels. 2017; 32: 1085-1092
        • Itkin M.
        • Piccoli D.A.
        • Nadolski G.
        • et al.
        Protein-losing enteropathy in patients with congenital heart disease.
        J Am Coll Cardiol. 2017 Jun 20; 69: 2929-2937
        • Nelson J.J.
        • Liao D.
        • Sharrett A.R.
        • et al.
        Serum albumin level as a predictor of incident coronary heart disease: the Atherosclerosis Risk in Communities (ARIC) study.
        Am J Epidemiol. 2000 Mar 1; 151: 468-477
        • Shaper A.G.
        • Wannamethee S.G.
        • Whincup P.H.
        Serum albumin and risk of stroke, coronary heart disease, and mortality: the role of cigarette smoking.
        J Clin Epidemiol. 2004 Feb; 57: 195-202
        • Djoussé L.
        • Rothman K.J.
        • Cupples L.A.
        • Levy D.
        • Ellison R.C.
        Serum albumin and risk of myocardial infarction and all-cause mortality in the Framingham Offspring Study.
        Circulation. 2002 Dec 3; 106: 2919-2924
        • Yang Q.
        • He Y.M.
        • Cai D.P.
        • Yang X.J.
        • Xu H.F.
        Risk burdens of modifiable risk factors incorporating lipoprotein (a) and low serum albumin concentrations for first incident acute myocardial infarction.
        Sci Rep. 2016 Oct 17; 635463
        • Gopal D.M.
        • Kalogeropoulos A.P.
        • Georgiopoulou V.V.
        • et al.
        Health ABC study. Serum albumin concentration and heart failure risk the health, aging, and body composition study.
        Am Heart J. 2010 Aug; 160: 279-285
        • Filippatos G.S.
        • Desai R.V.
        • Ahmed M.I.
        • et al.
        Hypoalbuminaemia and incident heart failure in older adults.
        Eur J Heart Fail. 2011 Oct; 13: 1078-1086
        • Mukamal K.J.
        • Tolstrup J.S.
        • Friberg J.
        • Grønbaek M.
        • Jensen G.
        Fibrinogen and albumin levels and risk of atrial fibrillation in men and women (the Copenhagen City Heart Study).
        Am J Cardiol. 2006 Jul 1; 98: 75-81
        • Xu W.H.
        • Dong C.
        • Rundek T.
        • Elkind M.S.
        • Sacco R.L.
        Serum albumin levels are associated with cardioembolic and cryptogenic ischemic strokes: northern Manhattan study.
        Stroke. 2014 Apr; 45: 973-978
        • Folsom A.R.
        • Lutsey P.L.
        • Heckbert S.R.
        • Cushman M.
        Serum albumin and risk of venous thromboembolism.
        Thromb Haemost. 2010 Jul; 104: 100-104
        • Königsbrügge O.
        • Posch F.
        • Riedl J.
        • et al.
        Association between decreased serum albumin with risk of venous thromboembolism and mortality in cancer patients.
        Oncologist. 2016 Feb; 21: 252-257
        • Kunutsor S.K.
        • Seidu S.
        • Katechia D.T.
        • Laukkanen J.A.
        Inverse association between serum albumin and future risk of venous thromboembolism: interrelationship with high sensitivity C-reactive protein.
        Ann Med. 2018 May; 50: 240-248
        • Danesh J.
        • Collins R.
        • Appleby P.
        • Peto R.
        Association of fibrinogen, C-reactive protein, albumin, or leukocyte count with coronary heart disease: meta-analyses of prospective studies.
        JAMA. 1998 May 13; 279: 1477-1482
        • Kurtul A.
        • Murat S.N.
        • Yarlioglues M.
        • et al.
        Usefulness of serum albumin concentration to predict high coronary SYNTAX score and in-hospital mortality in patients with acute coronary syndrome.
        Angiology. 2016 Jan; 67: 34-40
        • Celik I.E.
        • Yarlioglues M.
        • Kurtul A.
        • et al.
        Preprocedural albumin levels and risk of in-stent restenosis after coronary stenting with bare-metal stent.
        Angiology. 2016 May; 67: 478-483
        • Akboga M.K.
        • Yayla C.
        • Balci K.G.
        • et al.
        Relationship between serum albumin level and monocyte-to-high-density lipoprotein cholesterol ratio with saphenous vein graft disease in coronary bypass.
        Thorac Cardiovasc Surg. 2017 Jun; 65: 315-321
        • Arques S.
        • Roux E.
        • Stolidi P.
        • Gelisse R.
        • Ambrosi P.
        Usefulness of serum albumin and serum total cholesterol in the prediction of hospital death in older patients with severe, acute heart failure.
        Arch Cardiovasc Dis. 2011 Oct; 104: 502-508
        • Su W.
        • An T.
        • Zhou Q.
        • et al.
        Serum albumin is a useful prognostic indicator and adds important information to NT-proBNP in a Chinese cohort of heart failure.
        Clin Biochem. 2012 May; 45: 561-565
        • Ambrosy A.P.
        • Vaduganathan M.
        • Huffman M.D.
        • et al.
        EVEREST trial investigators. Clinical course and predictive value of liver function tests in patients hospitalized for worsening heart failure with reduced ejection fraction: an analysis of the EVEREST trial.
        Eur J Heart Fail. 2012 Mar; 14: 302-311
        • Liu M.
        • Chan C.P.
        • Yan B.P.
        • et al.
        Albumin levels predict survival in patients with heart failure and preserved ejection fraction.
        Eur J Heart Fail. 2012 Jan; 14: 39-44
        • Bavishi C.
        • Ather S.
        • Bozkurt B.
        • Deswal A.
        Prognostic significance of hypoalbuminemia among ambulatory heart failure patients with reduced and preserved ejection fraction (abstract).
        Circulation. 2013; 128: A16960
        • Bonilla-Palomas J.L.
        • Gámez-López A.L.
        • Moreno-Conde M.
        • et al.
        Hypoalbuminemia in acute heart failure patients: causes and its impact on hospital and long-term mortality.
        J Card Fail. 2014 May; 20: 350-358
        • Cleland J.G.
        • Chiswell K.
        • Teerlink J.R.
        • et al.
        Predictors of postdischarge outcomes from information acquired shortly after admission for acute heart failure: a report from the placebo-controlled randomized study of the selective A1 adenosine receptor antagonist Rolofylline for patients hospitalized with acute decompensated heart failure and volume overload to assess treatment effect on congestion and renal function (PROTECT) study.
        Circ Heart Fail. 2014 Jan; 7: 76-87
        • Metra M.
        • Cotter G.
        • El-Khorazaty J.
        • et al.
        Acute heart failure in the elderly: differences in clinical characteristics, outcomes, and prognostic factors in the VERITAS Study.
        J Card Fail. 2015 Mar; 21: 179-188
        • Alshawabkeh L.I.
        • Hu N.
        • Carter K.D.
        • et al.
        Wait-list outcomes for adults with congenital heart disease listed for heart transplantation in the U.S.
        J Am Coll Cardiol. 2016 Aug 30; 68: 908-917
        • Ancion A.
        • Allepaerts S.
        • Oury C.
        • Gori A.S.
        • Piérard L.A.
        • Lancellotti P.
        Serum albumin level and hospital mortality in acute non-ischemic heart failure.
        ESC Heart Fail. 2017 May; 4: 138-145
        • Cowger J.
        • Sundareswaran K.
        • Rogers J.G.
        • et al.
        Predicting survival in patients receiving continuous flow left ventricular assist devices: the HeartMate II risk score.
        J Am Coll Cardiol. 2013 Jan 22; 61: 313-321
        • Uchikawa T.
        • Shimano M.
        • Inden Y.
        • Murohara T.
        Serum albumin levels predict clinical outcomes in chronic kidney disease (CKD) patients undergoing cardiac resynchronization therapy.
        Intern Med. 2014; 53: 555-561
        • Kato T.S.
        • Cheema F.H.
        • Yang J.
        • et al.
        Preoperative serum albumin levels predict 1-year postoperative survival of patients undergoing heart transplantation.
        Circ Heart Fail. 2013 Jul; 6: 785-791
        • Jabbour R.
        • Ling H.Z.
        • Norrington K.
        • et al.
        Serum albumin changes and multivariate dynamic risk modelling in chronic heart failure.
        Int J Cardiol. 2014 Sep 20; 176: 437-443
        • Dziedzic T.
        • Slowik A.
        • Szczudlik A.
        Serum albumin level as a predictor of ischemic stroke outcome.
        Stroke. 2004 Jun; 35: e156-8
        • Idicula T.T.
        • Waje-Andreassen U.
        • Brogger J.
        • Naess H.
        • Thomassen L.
        Serum albumin in ischemic stroke patients: the higher the better. The Bergen Stroke Study.
        Cerebrovasc Dis. 2009; 28: 13-17
        • Famakin B.
        • Weiss P.
        • Hertzberg V.
        • et al.
        Hypoalbuminemia predicts acute stroke mortality: Paul Coverdell Georgia Stroke Registry.
        J Stroke Cerebrovasc Dis. 2010 Jan; 19: 17-22
        • Wallace S.M.
        • Walton B.I.
        • Kharbanda R.K.
        • Hardy R.
        • Wilson A.P.
        • Swanton R.H.
        Mortality from infective endocarditis: clinical predictors of outcome.
        Heart. 2002; 88: 53-60
        • Marks D.J.
        • Hyams C.
        • Koo C.Y.
        • et al.
        Clinical features, microbiology and surgical outcomes of infective endocarditis: a 13-year study from a UK tertiary cardiothoracic referral centre.
        QJM. 2015; 108: 219-229
        • Yang F.
        • Zhang B.
        • Yu J.
        • et al.
        Epidemiology and the prognosis of healthcare-associated infective endocarditis in China: the significance of non-nosocomial acquisition.
        Emerg Microbes Infect. 2015; 4e38
        • Kates R.E.
        • Yee Y.G.
        • Hill I.
        Effect of albumin on the electrophysiologic stability of isolated perfused rabbit hearts.
        J Cardiovasc Pharmacol. 1989 Jan; 13: 168-172
        • Aykal G.
        • Güven R.
        • Yeğin A.
        • Ellidağ H.Y.
        • Bayindir A.
        • Yilmaz N.
        The diagnostic value of oxidative/antioxidative balance parameters in venous thromboembolism.
        Clin Lab. 2015; 61: 769-775
        • Garcia-Dorado D.
        • Oliveras J.
        Myocardial oedema: a preventable cause of reperfusion injury?.
        Cardiovasc Res. 1993 Sep; 27: 1555-1563
        • Jeserich M.
        • Föll D.
        • Olschewski M.
        • et al.
        Evidence of myocardial edema in patients with nonischemic dilated cardiomyopathy.
        Clin Cardiol. 2012 Jun; 35: 371-376
        • Verbrugge F.H.
        • Bertrand P.B.
        • Willems E.
        • et al.
        Global myocardial oedema in advanced decompensated heart failure.
        Eur Heart J Cardiovasc Imaging. 2017 Jul 1; 18: 787-794
        • Bleske B.E.
        • Clark M.M.
        • Wu A.H.
        • Dorsch M.P.
        The effect of continuous infusion loop diuretics in patients with acute decompensated heart failure with hypoalbuminemia.
        J Cardiovasc Pharmacol Ther. 2013 Jul; 18: 334-337
        • Blindauer C.A.
        • Khazaipoul S.
        • Yu R.
        • Stewart A.J.
        Fatty acid-mediated inhibition of metal binding to the multi-metal site on serum albumin: implications for cardiovascular disease.
        Cur Top Med Chem. 2016; 16: 3021-3032
        • Faure P.
        • Wiernsperger N.
        • Polge C.
        • Favier A.
        • Halimi S.
        Impairment of the antioxidant properties of serum albumin in patients with diabetes: protective effects of metformin.
        Clin Sci (Lond). 2008 Feb; 114: 251-256
        • Dhindsa S.
        • Ghanim H.
        • Dandona P.
        Nonesterified fatty acids, albumin, and platelet aggregation.
        Diabetes. 2015 Mar; 64: 703-705
        • Wu Y.
        • Fan W.
        • Huang D.
        • Sun X.
        Possible intermediary role of autophagy in serum albumin decrease-associated cardiovascular events among patients with coronary heart disease (letter).
        Int J Cardiol. 2018; 250: 64
        • Kremer H.
        • Baron-Menguy C.
        • Tesse A.
        • et al.
        Human serum albumin improves endothelial dysfunction and survival during experimental endotoxemia: concentration-dependent properties.
        Crit Care Med. 2011; 39: 1414-1422
        • Bonilla-Palomas J.L.
        • Gámez-López A.L.
        • Castillo Dominguez J.C.
        • et al.
        Nutritional intervention in malnourished hospitalized patients with heart failure.
        Arch Med Res. 2016; 47: 535-540
        • Bonilla-Palomas J.L.
        • Gámez-López A.L.
        • Castillo Dominguez J.C.
        • Moreno-Conde M.
        • López-Ibáñez M.C.
        • Anguita Sánchez M.
        Does nutritional interventions maintain their prognostic benefit in the long term for malnourished patients hospitalized for heart failure?.
        Rev Clin Esp. 2018 March; 218: 58-60
        • Kato T.S.
        • Kitada S.
        • Yang J.
        • et al.
        Relation of preoperative serum albumin levels to survival in patients undergoing left ventricular assist device implantation.
        Am J Cardiol. 2013 Nov 1; 112: 1484-1488
        • Gopal D.J.
        • Hanff T.C.
        • Mazurek J.A.
        • et al.
        Prognostic implications of changes in albumin following left ventricular assist device implantation in patients with severe heart failure.
        Am J Cardiol. 2017; 120: 2003-2007