Hemoglobin and Change in Hemoglobin Status Predict Mortality, Cardiovascular Events, and Bleeding in Stable Coronary Artery Disease

Published:January 18, 2017DOI:



      Anemia is a predictor of adverse outcomes in acute myocardial infarction. We studied the relationship of hemoglobin, or its change over time, and outcomes in patients with stable coronary artery disease.


      The ProspeCtive observational LongitudinAl RegIstry oF patients with stable coronary arterY disease is a prospective, cohort study of outpatients with stable coronary artery disease (32,901 in 45 countries 2009-2010): 21,829 with baseline hemoglobin levels. They were divided into hemoglobin quintiles and anemia status (anemic or normal at baseline/follow-up: normal/normal; anemic/normal; normal/anemic; anemic/anemic. All-cause mortality, cardiovascular events, and major bleeding at 4-year follow-up were assessed.


      Low baseline hemoglobin was an independent predictor of all-cause, cardiovascular, and noncardiovascular mortality, the composite of cardiovascular death/myocardial infarction or stroke and major bleeds (all P <.001; unadjusted models). Anemia at follow-up was independently associated with all-cause mortality (hazard ratio [HR], 1.90; 95% confidence interval [CI], 1.55-2.33 for anemic/anemic; 1.87; 1.54-2.28 for normal/anemic; both P <.001), noncardiovascular mortality (P <.001), and cardiovascular mortality (P = .001). Patients whose baseline anemia normalized (anemic/normal) were not at increased risk of death (HR, 1.02; 95% CI, 0.77-1.35), although the risk of major bleeding was greater (HR, 2.06; 95% CI, 1.23-3.44; P = .013) than in those with normal hemoglobin throughout. Sensitivity analyses excluding patients with heart failure and chronic kidney disease at baseline yielded qualitatively similar results.


      In this large population with stable coronary artery disease, low hemoglobin was an independent predictor of mortality, cardiovascular events, and major bleeds. Persisting or new-onset anemia is a powerful predictor of cardiovascular and noncardiovascular mortality.


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        • Sarnak M.J.
        • Tighiouart H.
        • Manjunath G.
        • et al.
        Anemia as a risk factor for cardiovascular disease in The Atherosclerosis Risk in Communities (ARIC) study.
        J Am Coll Cardiol. 2002; 40: 27-33
        • Ang D.S.
        • Kao M.P.
        • Noman A.
        • et al.
        The prognostic significance of early and late anaemia in acute coronary syndrome.
        QJM. 2012; 105: 445-454
        • Lawler P.R.
        • Filion K.B.
        • Dourian T.
        • et al.
        Anemia and mortality in acute coronary syndromes: a systematic review and meta-analysis.
        Am Heart J. 2013; 165: 143-153e5
        • Kunadian V.
        • Mehran R.
        • Lincoff A.M.
        • et al.
        Effect of anemia on frequency of short- and long-term clinical events in acute coronary syndromes (from the Acute Catheterization and Urgent Intervention Triage Strategy Trial).
        Am J Cardiol. 2014; 114: 1823-1829
        • Pilgrim T.
        • Rothenbuhler M.
        • Kalesan B.
        • et al.
        Additive effect of anemia and renal impairment on long-term outcome after percutaneous coronary intervention.
        PLoS One. 2014; 9: e114846
        • van Straten A.H.
        • Hamad M.A.
        • van Zundert A.J.
        • et al.
        Preoperative hemoglobin level as a predictor of survival after coronary artery bypass grafting: a comparison with the matched general population.
        Circulation. 2009; 120: 118-125
        • Weiss G.
        • Goodnough L.T.
        Anemia of chronic disease.
        N Engl J Med. 2005; 352: 1011-1023
        • Libby P.
        • Hansson G.K.
        Inflammation and immunity in diseases of the arterial tree: players and layers.
        Circ Res. 2015; 116: 307-311
        • McCullough P.A.
        • Barnard D.
        • Clare R.
        • et al.
        Anemia and associated clinical outcomes in patients with heart failure due to reduced left ventricular systolic function.
        Clin Cardiol. 2013; 36: 611-620
        • He S.W.
        • Wang L.X.
        The impact of anemia on the prognosis of chronic heart failure: a meta-analysis and systemic review.
        Congest Heart Fail. 2009; 15: 123-130
        • Kalra P.R.
        • Garcia-Moll X.
        • Zamorano J.
        • et al.
        Impact of chronic kidney disease on use of evidence-based therapy in stable coronary artery disease: a prospective analysis of 22,272 patients.
        PLoS One. 2014; 9: e102335
        • Steg P.G.
        • Greenlaw N.
        • Tardif J.C.
        • et al.
        Women and men with stable coronary artery disease have similar clinical outcomes: insights from the international prospective CLARIFY registry.
        Eur Heart J. 2012; 33: 2831-2840
        • Ferrari R.
        • Abergel H.
        • Ford I.
        • et al.
        Gender- and age-related differences in clinical presentation and management of outpatients with stable coronary artery disease.
        Int J Cardiol. 2013; 167: 2938-2943
        • Fauchier L.
        • Greenlaw N.
        • Ferrari R.
        • et al.
        Use of anticoagulants and antiplatelet agents in stable outpatients with coronary artery disease and atrial fibrillation. International CLARIFY Registry.
        PLoS One. 2015; 10: e0125164
        • World Health Organization (WHO)
        Haemoglobin concentrations for the diagnosis of anaemia and assessment of severity.
        (Available at:) (Accessed October 6, 2016)
        • Levey A.S.
        • Stevens L.A.
        • Schmid C.H.
        • et al.
        A new equation to estimate glomerular filtration rate.
        Ann Intern Med. 2009; 150: 604-612
        • Ennezat P.V.
        • Marechaux S.
        • Pincon C.
        • et al.
        Anaemia to predict outcome in patients with acute coronary syndromes.
        Arch Cardiovasc Dis. 2013; 106: 357-365
        • Rathod K.S.
        • Jones D.A.
        • Rathod V.S.
        • et al.
        Prognostic impact of anaemia on patients with ST-elevation myocardial infarction treated by primary PCI.
        Coron Artery Dis. 2014; 25: 52-59
        • Landes U.
        • Kornowski R.
        • Assali A.
        • et al.
        Predictors of long term outcomes in 11,441 consecutive patients following percutaneous coronary interventions.
        Am J Cardiol. 2015; 115: 855-859
        • Muzzarelli S.
        • Pfisterer M.
        • TIME Investigators
        Anemia as independent predictor of major events in elderly patients with chronic angina.
        Am Heart J. 2006; 152: 991-996
        • Lipsic E.
        • Asselbergs F.W.
        • van der Meer P.
        • et al.
        Anaemia predicts cardiovascular events in patients with stable coronary artery disease.
        Neth Heart J. 2005; 13: 254-258
        • Groenveld H.F.
        • Januzzi J.L.
        • Damman K.
        • et al.
        Anemia and mortality in heart failure patients a systematic review and meta-analysis.
        J Am Coll Cardiol. 2008; 52: 818-827
        • Leshem-Rubinow E.
        • Steinvil A.
        • Rogowski O.
        • et al.
        Hemoglobin nonrecovery following acute myocardial infarction is a biomarker of poor outcome: a retrospective database study.
        Int J Cardiol. 2013; 169: 349-353
        • Wilhelm S.M.
        • Rjater R.G.
        • Kale-Pradhan P.B.
        Perils and pitfalls of long-term effects of proton pump inhibitors.
        Expert Rev Clin Pharmacol. 2013; 6: 443-451
        • Shikata T.
        • Sasaki N.
        • Ueda M.
        • et al.
        Use of proton pump inhibitors is associated with anemia in cardiovascular outpatients.
        Circ J. 2015; 79: 193-200
        • Tonelli M.
        • Sacks F.
        • Arnold M.
        • et al.
        Relation between red blood cell distribution width and cardiovascular event rate in people with coronary disease.
        Circulation. 2008; 117: 163-168