Anemia and congestive heart failure.

To the Editor: Anemia has recently become an important issue in patients with heart failure, and in the January 21, 2003 issue of Circulation, 3 studies relating to this subject were published.1–3 In one of these studies, Ezekowitz et al1 showed that anemia is common and is an independent prognostic marker for mortality in community-based patients with congestive heart failure (CHF). To determine the prevalence of anemia, the authors used the International Classification of Diseases, 9th revision (ICD-9). In using this method, however, the authors did not provide a cutoff value for when they considered patients to be anemic. In the recent literature, there is some controversy about the prevalence of anemia in patients with CHF, which not only depends on the severity of CHF, but also on the definition of anemia.4 Therefore, 1 by gest on N ovem er 5, 2017 http://ciajournals.org/ D ow nladed from it would have been important to know which hemoglobin values were used to define anemia. Furthermore, the authors determined the prevalence as follows: ICD-9 codes 280 to 289 to capture “all anemia” and ICD-9 code 285.9 to capture “anemia of chronic disease.” This method also has its limitations, because, for example, serum albumin levels may be decreased in CHF patients, indicating that malnutrition and malabsorption may also result in anemia.5 Also, many CHF patients use anticoagulants, and chronic (microscopic) blood loss may well play a role. Therefore, it would have added significant value if the authors had also evaluated the incidence of iron and vitamin deficiency anemias in their study. Peter van der Meer, MD Wiek H. van Gilst, PhD Dirk J. van Veldhuisen, MD, PhD Department of Cardiology University Hospital Groningen Groningen, the Netherlands [email protected] 1. Ezekowitz JA, McAlister FA, Armstrong PW. Anemia is common in heart failure and is associated with poor outcomes: insights from a cohort of 12 065 patients with new-onset heart failure. Circulation. 2003;107: 223–225. 2. Androne AS, Katz SD, Lund L, et al. Hemodilution is common in patients with advanced heart failure. Circulation. 2003;107:226–229. 3. Mancini DM, Katz SD, Lang CC, et al. Effect of erythropoietin on exercise capacity in patients with moderate to severe chronic heart failure. Circulation. 2003;107:294–299. 4. Cromie N, Lee C, Struthers AD. Anaemia in chronic heart failure: what is its frequency in the UK and its underlying causes? Heart. 2002;87: 377–378. 5. Horwich TB, Fonarow GC, Hamilton MA, et al. Anemia is associated with worse symptoms, greater impairment in functional capacity and a significant increase in mortality in patients with advanced heart failure. J Am Coll Cardiol. 2002;39:1780–1786. Response We appreciate the interest of Drs van der Meer, Fuchs, Steinborn, et al on anemia and congestive heart failure. We agree that the pathogenesis of anemia in congestive heart failure is complex and at least partly related to inflammatory mediators. Additionally, there are likely modulating roles for erythropoietin resistance,1 the renin-angiotensin axis,2 and medications such as angiotensin-converting enzyme inhibitors.3 Although early studies demonstrated a link between neopterin and cardiovascular disease,4 subsequent investigations have failed to confirm this.5 This complex pathway of tryptophan metabolism likely has many avenues that deserve exploration. Interferondirectly inhibits erythroid progenitor cells’ capacity for erythropoiesis; this may be mediated in part by nitric oxide, which blocks heme biosynthesis.1 Regardless of the underlying mechanistic cause(s) for anemia associated with congestive heart failure, treatment of the underlying heart failure with appropriate evidence-based therapies should be the primary goal. Ultimately, elucidation of the putative cellular mechanisms for the associated anemia may lead to more specific clinical strategies. Steinborn and colleagues question the use of administrative data for examining the prevalence of anemia in the community. While they are correct that the recognition of anemia as a significant comorbidity in heart failure is relatively recent for cardiologists, the coding for anemia is (and has) been consistently done by trained health records abstractors in our locale throughout the entire study time period, and does not rely solely on recognition by the physician of record (see References 5 and 6 of the original paper6). We did not analyze polycythemia in this cohort. The term “new-onset heart failure” relates to a 1-year “washout” to identify patients with recent onset of heart failure. Hence, patients admitted to hospital for heart failure within the preceding year were excluded; when we applied a 1-, 2-, or 5-year washout, the prevalence of anemia (and its prognostic significance) was unchanged. Finally, the discrepancy in numbers between the 2 analyses relates to 3 factors, which were applied to create a more homogeneous dataset and permit examination between anemia and heart failure with minimum confounding (to obviate concerns that the heart failure diagnosis was secondary to the anemia, making any observed prognostic relationships spurious). First, we restricted our analysis to only those patients with incident heart failure (thus excluding anyone with a pre-existing diagnosis). Second, we analyzed only those patients with a most responsible diagnosis of heart failure, thus excluding any patients with a non–heart failure primary diagnosis and in whom heart failure was a secondary or complicating diagnosis. Third, we excluded patients transferred between hospitals because of concerns of double counting based on recoding pursuant to subsequent in-hospital events. Of note, the prevalence of anemia and its association with worsened outcome was similar in the heterogeneous cohort data previously presented7 and in the more homogeneous cohort data published in Circulation. This strengthens our belief that the relationship between anemia and prognosis in heart failure is real and, pending the results of ongoing trials, likely causal. Justin Ezekowitz, MBBCh Finlay McAlister, MD Paul W. Armstrong, MD Division of Cardiology Department of Medicine University of Alberta Edmonton, Alberta, Canada 1. Weiss G. Pathogenesis and treatment of anaemia of chronic disease. Blood Rev. 2002;16:87–96. 2. Cole J, Ertoy D, Lin H, et al. Lack of angiotensin II-facilitated erythropoiesis causes anemia in angiotensin-converting enzyme-deficient mice. J Clin Invest. 2000;106:1391–1398. 3. Macdougall IC. ACE inhibitors and erythropoietin responsiveness. Am J Kidney Dis. 2001;38:649–651. 4. Rudzite V, Skards JI, Fuchs D, et al. Serum kynurenine and neopterin concentrations in patients with cardiomyopathy. Immunol Lett. 1992;32: 125–129. 5. Caforio AL, Goldman JH, Baig MK, et al. Elevated serum levels of soluble interleukin-2 receptor, neopterin and -2-microglobulin in idiopathic dilated cardiomyopathy: relation to disease severity and autoimmune pathogenesis. Eur J Heart Fail. 2001;3:155–163. 6. Ezekowitz JA, McAlister FA, Armstrong PW. Anemia is common in heart failure and is associated with poor outcomes: insights from a cohort of 12 065 patients with new-onset heart failure. Circulation. 2003;107: 223–225. 7. Ezekowitz JA, Franijic N, Chang WC, et al. What is the relationship between anemia and survival in patients with CHF? A population-based analysis of 29302 patients. Circulation. 2002;106 (suppl II):II-472. 2 Correspondence by gest on N ovem er 5, 2017 http://ciajournals.org/ D ow nladed from Katharina Schroecksnadel, Barbara Wirleitner and Dietmar Fuchs Anemia and Congestive Heart Failure Print ISSN: 0009-7322. Online ISSN: 1524-4539 Copyright © 2003 American Heart Association, Inc. All rights reserved. is published by the American Heart Association, 7272 Greenville Avenue, Dallas, TX 75231 Circulation doi: 10.1161/01.CIR.0000084394.37044.E2 2003;108:e41-e42 Circulation. http://circ.ahajournals.org/content/108/6/e41 World Wide Web at: The online version of this article, along with updated information and services, is located on the http://circ.ahajournals.org//subscriptions/ is online at: Circulation Information about subscribing to Subscriptions: http://www.lww.com/reprints Information about reprints can be found online at: Reprints: document. 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