Acute and chronic anemia and short- and long-term outcome of patients with peripheral arterial disease and critical limb ischemia

Published:March 22, 2016DOI:


      • Coexistence of anemia was associated with more severe PAD.
      • Patients with more severe PAD had lower rates of endovascular revascularization.
      • Anemia predicts higher rates of in-hospital complications, worse short-term outcome.
      • Anemia denotes higher rates of limb amputation, of short and long-term mortality.
      • Anemia is driver of health-related expenditures, longer hospital stay durations.



      Evident data about the additive effect of “the fifth cardiovascular risk factor” (anemia) and peripheral arterial disease (PAD) focused on morbidity and outcome of patients with PAD are currently still missing.

      Methods and results

      A total of 41,882 PAD patients were included. Of these, 5566 (13.3%) suffered from anemia. Patients with anemia were older (P < 0.001), suffered more often from chronic kidney disease (P < 0.001), coronary artery disease (P < 0.001), and more severe PAD (P < 0.001). However, they received significantly less endovascular revascularizations (P < 0.001), had higher amputation rates (acute anemia: 3.7-fold, P < 0.001; nutritional, aplastic, and anemia in chronic disease: 2.9-fold, P < 0.001), higher in-hospital mortality rates (acute anemia: 6.4-fold, P < 0.001; nutritional, aplastic, and anemia in chronic disease: 4.6-fold; P < 0.001), had significantly higher in-hospital complications (P < 0.001) compared to those without anemia. During a follow-up time up to 4 years (until Dec. 31st, 2012, median 775 days, 25th–75th percentiles 469–1120 days) nutritional, aplastic, and anemia in chronic disease and acute anemia were high significant predictors of long-term mortality and amputation (each P < 0.001). Lengths of hospital stay and reimbursement costs were higher (nutritional, aplastic, and anemia in chronic disease: 2-fold higher (P < 0.001), acute anemia: 3-fold higher (P < 0.001)) than in patients without anemia.


      This study illustrates from a large, comprehensive database the association of acute, nutritional, aplastic, and anemia in chronic disease on morbidity, in-hospital treatment and complications, short- and long term outcome, and costs of patients with PAD.


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        • Spence R.K.
        The economic burden of anemia in heart failure.
        Heart Fail Clin. 2010; 6: 373-383
        • Shah M.
        • Martin A.
        • Myers B.
        • MacSweeney S.
        • Richards T.
        Recognising anaemia and malnutrition in vascular patients with critical limb ischaemia.
        Ann R Coll Surg Engl. 2010; 92: 495-498
        • Vega de Céniga M.
        • Bravo E.
        • Izagirre M.
        • Casco C.
        • Estallo L.
        • Esteban M.
        • et al.
        Anaemia, iron and vitamin deficits in patients with peripheral arterial disease.
        Eur J Vasc Endovasc Surg. 2011; 41: 828-830
        • Weiss G.
        Pathogenesis and treatment of anaemia of chronic disease.
        Blood Rev. 2002; 16: 87-96
        • Tefferi A.
        Anemia in adults: a contemporary approach to diagnosis.
        Mayo Clin Proc. 2003; 78: 1274-1280
        • Roy C.N.
        • Weinstein D.A.
        • Andrews N.C.
        2002 E. Mead Johnson award for research in pediatrics lecture: the molecular biology of the anemia of chronic disease: a hypothesis.
        Pediatr Res. 2003; 53: 507-512
        • Silverberg D.S.
        • Iaina A.
        • Wexler D.
        • Blum M.
        The pathological consequences of anaemia.
        Clin Lab Haematol. 2001; 23: 1-6
        • Jie K.E.
        • Verhaar M.C.
        • Cramer M.J.
        • van der Putten K.
        • Gaillard C.A.
        • Doevendans P.A.
        • et al.
        Erythropoetin and the cardiorenal syndrome: cellular mechanism on the cardiorenal connectors.
        Am J Physiol Renal Physiol. 2006; 291: 932-944
        • Reinecke H.
        • Breithardt G.
        Letter regarding article by McKechnie et al,“Prognostic implication of anemia on in-hospital outcomes after percutaneous coronary intervention”.
        Circulation. 2005; 111: 263-264
        • McCullough P.A.
        • Lepor N.E.
        Piecing together the evidence on anemia: the link between chronic kidney disease and cardiovascular disease.
        Rev Cardiovasc Med. 2005; Suppl. 3: 4-12
        • Anand I.S.
        Anemia and chronic heart failure implications and treatment options.
        J Am Coll Cardiol. 2008; 52: 501-511
        • Reinecke H.
        • Trey T.
        • Wellmann J.
        • Heidrich J.
        • Fobker M.
        • Wichter T.
        • et al.
        Haemoglobin-related mortality in patients undergoing percutaneous coronary interventions.
        Eur Heart J. 2003; 23: 2142-2150
        • McKechnie R.S.
        • Smith D.
        • Montoye C.
        • Kline-Rogers E.
        • O'Donnell M.J.
        • DeFranco A.C.
        • et al.
        Blue Cross Blue Shield of Michigan Cardiovascular Consortium (BMC2). Prognostic implication of anemia on in-hospital outcomes after percutaneous coronary intervention.
        Circulation. 2004; 110: 271-277
        • Kaiafa G.
        • Kanellos I.
        • Savopoulos C.
        • Kakaletsis N.
        • Giannakoulas G.
        • Hatzitolios A.I.
        Is anemia a new cardiovascular risk factor?.
        Int J Cardiol. 2015; 186: 117-124
        • Go A.S.
        • Yang J.
        • Ackerson L.M.
        • Lepper K.
        • Robbins S.
        • Massie B.M.
        • et al.
        Hemoglobin level, chronic kidney disease, and the risks of death and hospitalization in adults with chronic heart failure: the Anemia in Chronic Heart Failure: Outcomes and Resource Utilization (ANCHOR) Study.
        Circulation. 2006; 113: 2713-2723
        • Shander A.
        • Knight K.
        • Thurer R.
        • Adamson J.
        • Spence R.
        Prevalence and outcomes of anemia in surgery: a systematic review of the literature.
        Am J Med. 2004; Suppl. 7A: 58-69
        • Dunne J.R.
        • Malone D.
        • Tracy J.K.
        • Gannon C.
        • Napolitano L.M.
        Perioperative anemia: an independent risk factor for infection, mortality, and resource utilization in surgery.
        J Surg Res. 2002; 102: 237-244
        • Desormais I.
        • Aboyans V.
        • Bura A.
        • Constans J.
        • Cambou J.P.
        • Messas E.
        • et al.
        Anemia, an independent predictive factor for amputation and mortality in patients hospitalized for peripheral artery disease.
        Eur J Vasc Endovasc Surg. 2014; 48: 202-207
        • Reinecke H.
        • Unrath M.
        • Freisinger E.
        • Bunzemeier H.
        • Meyborg M.
        • Lüders F.
        • et al.
        Peripheral arterial disease and critical limb ischaemia: still poor outcomes and lack of guideline adherence.
        Eur Heart J. 2015; 36: 932-938
        • Lüders F.
        • Bunzemeier H.
        • Engelbertz Ch.
        • Malyar N.
        • Meyborg M.
        • Roeder H.
        • et al.
        CKD and acute and long-term outcome of patients with peripheral artery disease and critical limb ischemia.
        Clin J Am Soc Nephrol. 2015 Dec 14; ([pii: CJN.05600515])
        • Nikolsky E.
        • Aymong E.D.
        • Halkin A.
        • Grines C.L.
        • Cox D.A.
        • Garcia E.
        • et al.
        Impact of anaemia in patients with acute myocardial infarction undergoing primary percutaneous coronary intervention: analysis from the Controlled Abciximab and Device Investigation to Lower Late Angioplasty Complications (CADILLAC) trial.
        J Am Coll Cardiol. 2004; 44: 547-553
        • Jeremias A.
        • Gruberg L.
        • Patel J.
        • Connors G.
        • Brown D.L.
        Effect of peripheral arterial disease on in-hospital outcomes after primary percutaneous coronary intervention for acute myocardial infarction.
        Am J Cardiol. 2010; 105: 1268-1271
        • Karkouti K.
        • Wijeysundera D.N.
        • Beattie W.S.
        Reducing Bleeding in Cardiac Surgery (RBC) Investigators. Risk associated with preoperative anemia in cardiac surgery: a multicenter cohort study.
        Circulation. 2008; 117: 478-484
        • Shahian D.M.
        • O'Brien S.M.
        • Sheng S.
        • Grover F.L.
        • Mayer J.E.
        • Jacobs J.P.
        • et al.
        Predictors of long-term survival after coronary artery bypass grafting surgery: results from the Society of Thoracic Surgeons Adult Cardiac Surgery Database (the ASCERT study).
        Circulation. 2012; 125: 1491-1500
        • Anand I.S.
        • Kuskowski M.A.
        • Rector T.S.
        • Florea V.G.
        • Glazer R.D.
        • Hester A.
        • et al.
        Anemia and change in hemoglobin over time related to mortality and morbidity in patients with chronic heart failure: results from Val-HeFT.
        Circulation. 2005; 112: 1121-1127
        • Inglis S.C.
        • Hermis A.
        • Shehab S.
        • Newton P.J.
        • Lal S.
        • Davidson P.M.
        Peripheral arterial disease and chronic heart failure: a dangerous mix.
        Heart Fail Rev. 2013; 18: 457-464
        • Macdougall I.C.
        Steering Committee of the CREATE trial, CREATE Study Group. CREATE: new strategies for early anaemia management in renal insufficiency.
        Nephrol Dial Transplant. 2003; Suppl. 2: 13-16
        • Resnick H.E.
        • Lindsay R.S.
        • McDermott M.M.
        • Devereux R.B.
        • Jones K.L.
        • Fabsitz R.R.
        • et al.
        Relationship of high and low ankle brachial index to all-cause and cardiovascular disease mortality: the Strong Heart Study.
        Circulation. 2004; 109: 733-739
        • O'Hare A.M.
        • Katz R.
        • Shlipak M.G.
        • Cushman M.
        • Newman A.B.
        Mortality and cardiovascular risk across the ankle-arm index spectrum: results from the Cardiovascular Health Study.
        Circulation. 2006; 113: 388-393
        • Sulaiman K.
        • Prashanth P.
        • Al-Zakwani I.
        • Al-Mahmeed W.
        • Al-Motarreb A.
        • Al Suwaidi J.
        • et al.
        Impact of anemia on in-hospital, one-month and one-year mortality in patients with acute coronary syndrome from the Middle East.
        Clin Med Res. 2012; 10: 65-71
        • Que B.
        • Ma C.S.
        • Nie S.P.
        • Dong J.Z.
        • Wu X.S.
        • Liu X.H.
        • et al.
        Impact of chronic anemia on in-hospital clinical outcome of revascularization in patients with coronary artery disease.
        Zhongguo Wei Zhong Bing Ji Jiu Yi Xue. 2007; 19: 641-643
        • Felker G.M.
        • Stough W.G.
        • Shaw L.K.
        • O'Connor C.M.
        Anaemia and coronary artery disease severity in patients with heart failure.
        Eur J Heart Fail. 2006; 8: 54-57
        • Komajda M.
        • Anker S.D.
        • Charlesworth A.
        • Okonko D.
        • Metra M.
        • Di Lenarda A.
        • et al.
        The impact of new onset anaemia on morbidity and mortality in chronic heart failure: results from COMET.
        Eur Heart J. 2006; 27: 1440-1446
        • Tang Y.D.
        • Katz S.D.
        The prevalence of anemia in chronic heart failure and its impact on clinical outcomes.
        Heart Fail Rev. 2008; 13: 387-392
        • Al-Ahmad A.
        • Rand W.M.
        • Manjunath G.
        • Konstam M.A.
        • Salem D.N.
        • Levey A.S.
        • et al.
        Reduced kidney function and anemia as risk factors for mortality in patients with left ventricular dysfunction.
        J Am Coll Cardiol. 2001; 38: 955-962