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(Circulation. 2003;107:223.)
© 2003 American Heart Association, Inc.
Brief Rapid Communications |
From the Division of Cardiology (J.A.E., P.W.A.) and the Division of General Internal Medicine (F.A.M.), University of Alberta, Edmonton, Alberta, Canada.
Correspondence to Paul W. Armstrong, MD, 2-51 Medical Sciences Building, University of Alberta, Edmonton, Alberta, Canada T6G 2H7. E-mail paul.armstrong{at}ualberta.ca
| Abstract |
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Methods and Results We analyzed a population-based cohort of patients with new-onset CHF from a database of patients discharged from 138 acute-care hospitals in Alberta, Canada, between April 1993 and March 2001. Logistic regression, Kaplan-Meier survival analyses, and Cox proportional hazards model were used. Among the 12 065 patients with CHF (median age 78 years), 17% had anemia, 58% of whom had anemia of chronic disease. After adjustment for clinical and demographic variables, patients with anemia were more likely to be older (odds ratio [OR] 1.01 per year) and female (OR 1.2 [95% confidence interval 1.1 to 1.3]) and to have a history of chronic renal insufficiency (OR=3.2 [95% confidence interval 2.8 to 3.6]), or hypertension (OR 1.3 [95% confidence interval 1.2 to 1.5]). Hazard ratios for mortality, adjusting for covariates, were 1.34 (1.24 to 1.46) in anemic patients, and 1.36 (1.23 to 1.50) in those patients with anemia of chronic disease.
Conclusions In this large cohort of community-dwelling patients with CHF, anemia is common and an independent prognostic factor for mortality. Further research into the mechanisms of anemia in CHF and randomized controlled trials to test whether correction of anemia improves prognosis in CHF are needed.
Key Words: anemia heart failure epidemiology
| Introduction |
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Although anemia (and its correction) is a well-recognized comorbidity in a variety of conditions, including myocardial ischemia, its role in heart failure has only recently received attention.14 Two studies have examined the prevalence and prognosis of anemia in highly selected CHF populations; prevalence was 4% in clinical trial participants (n=6797) with asymptomatic or mild left ventricular dysfunction (relative risk [RR] for death was 1.03 [95% confidence interval (CI) 1.02 to 1.04] for each 1% drop in hematocrit in this sample),1 whereas 30% of patients (n=1061) followed-up in a specialized clinic for advanced heart failure had anemia (RR 1.13 [95% CI 1.05 to 1.22] for mortality).2 In a small population-based cohort (n=633) of Medicare beneficiaries admitted to hospital for CHF, 14% had an admission hematocrit <30%, and these anemic patients had increased mortality at 1 year (RR 1.60 [95% CI 1.19 to 2.16]) compared with those with a hematocrit
40%.3 Little is known about the prevalence or prognostic importance of anemia in a large unselected population of patients with heart failure.
| Methods |
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We linked the study sample to the Alberta Health Care Insurance Registry, which tracks the vital status of all individuals in the province, and followed-up with all patients from the date of their index hospitalization until the date of their death or September 30, 2001, whichever came first. We determined the prevalence of anemia at the time of initial diagnosis of heart failure (using ICD-9 codes 280 to 289 to capture "all anemia" and 285.9 to capture "anemia of chronic disease") and examined for differences between patients who did and did not have anemia at baseline (Table). Continuous variables were compared using ANOVA adjusted for multiple comparisons by Tukeys test, and ordinal and dichotomous variables were compared using the
2 test. Mortality rates of patients who were anemic when heart failure was diagnosed and those without anemia were compared using the Cox proportional hazards model, controlling for comorbidities and the known prognostic factors in heart failure (listed in the Table). Data for regression analysis is presented as odds or hazard ratio with 95% confidence intervals. In a sensitivity analysis to minimize confounding by unmeasured comorbidities, we examined the associations between anemia and outcomes in the youngest and healthiest subgroup (patients <65 years without documented comorbidities).
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| Results |
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Median follow-up was 573 days (interquartile range 155 to 1224 days), and the 1-year and 5-year mortality rates were 38% and 59% in those with anemia, respectively, compared with 27% and 50% for those without anemia. The survival of patients with anemia was worse even after adjustment for the known prognostic factors and comorbidities in the Table (Figure). Cox proportional hazard ratios for mortality were 1.34 (1.24 to 1.46) in anemic patients, and 1.36 (1.23 to 1.50) in the subset of patients with anemia of chronic disease. As a sensitivity analysis, we restricted this analysis to the youngest and healthiest subgroup (n=654) and found that anemia was even more strongly associated with mortality (OR 2.4 [1.2 to 4.6]).
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| Discussion |
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,9 is now thought to be a pathophysiological modulator of heart failure. Hence, we believe it is reasonable to hypothesize that heart failure may cause anemia of chronic disease through cytokine-mediated bone marrow suppression.7 As this is an observational study, some potential limitations deserve discussion. The limitations of administrative databases are well known and described elsewhere.5 However, previous studies have confirmed the accuracy of our data sources and coding for heart failure.5,6 Further, all of our analyses were adjusted for known prognostic factors in heart failure, and we confirmed the robustness of our findings in a sensitivity analysis in the youngest and healthiest subgroup, where unmeasured confounding would presumably be minimized.10
We believe efforts to better detect anemia in heart failure patients, discern the pathophysiology of, and test new therapies for anemia in heart failure should be a future priority. Indeed, small open-label studies have shown improvements in functional capacity and ejection fraction with correction of anemia using erythropoietin with intravenous iron.4,11 There is clearly a need for an appropriately powered randomized trial with meaningful clinical endpoints, such as hospitalizations and mortality, to evaluate the impact of such therapies in anemic heart failure patients.
| Acknowledgments |
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Received October 23, 2002; revision received December 3, 2002; accepted December 4, 2002.
| References |
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I. Anand, J. J.V. McMurray, J. Whitmore, M. Warren, A. Pham, M. A. McCamish, and P. B.J. Burton Anemia and Its Relationship to Clinical Outcome in Heart Failure Circulation, July 13, 2004; 110(2): 149 - 154. [Abstract] [Full Text] [PDF] |
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P. van der Meer, A. A. Voors, E. Lipsic, T. D. J. Smilde, W. H. van Gilst, and D. J. van Veldhuisen Prognostic value of plasma erythropoietin on mortality in patients with chronic heart failure J. Am. Coll. Cardiol., July 7, 2004; 44(1): 63 - 67. [Abstract] [Full Text] [PDF] |
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T. R. Wessel, C. B. Arant, and C. J. Pepine Commentary on "New and Emerging Theories of Cardiovascular Disease" Biol Res Nurs, July 1, 2004; 6(1): 17 - 20. [PDF] |
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R. Sharma, D. P Francis, B. Pitt, P. A Poole-Wilson, A. J.S Coats, and S. D Anker Haemoglobin predicts survival in patients with chronic heart failure: a substudy of the ELITE II trial Eur. Heart J., June 2, 2004; 25(12): 1021 - 1028. [Abstract] [Full Text] [PDF] |
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C. B. Arant, T. R. Wessel, M. B. Olson, C. N. Bairey Merz, G. Sopko, W. J. Rogers, B. L. Sharaf, S. E. Reis, K. M. Smith, B. D. Johnson, et al. Hemoglobin level is an independent predictor for adverse cardiovascular outcomes in women undergoing evaluation for chest pain: Results from the National Heart, Lung, and Blood Institute women's ischemia syndrome evaluation study J. Am. Coll. Cardiol., June 2, 2004; 43(11): 2009 - 2014. [Abstract] [Full Text] [PDF] |
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F. A. McAlister, J. Ezekowitz, M. Tonelli, and P. W. Armstrong Renal Insufficiency and Heart Failure: Prognostic and Therapeutic Implications From a Prospective Cohort Study Circulation, March 2, 2004; 109(8): 1004 - 1009. [Abstract] [Full Text] [PDF] |
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P. van der Meer, A. A. Voors, E. Lipsic, W. H. van Gilst, and D. J. van Veldhuisen Erythropoietin in cardiovascular diseases Eur. Heart J., February 2, 2004; 25(4): 285 - 291. [Abstract] [Full Text] [PDF] |
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H. K. Eltzschig, R. Ehlers, S. K. Shernan, W. Rodriguez, S. M. Silver, D. Schoevaerdts, C. Swine, D. Vanpee, M. Jessup, and S. Brozena Heart Failure N. Engl. J. Med., September 4, 2003; 349(10): 1002 - 1004. [Full Text] [PDF] |
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K. J Smith, A. J Bleyer, W. C Little, and D. C Sane The cardiovascular effects of erythropoietin Cardiovasc Res, September 1, 2003; 59(3): 538 - 548. [Abstract] [Full Text] [PDF] |
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K. Schroecksnadel, B. Wirleitner, D. Fuchs, W. Steinborn, P. Ponikowski, S. Anker, P. van der Meer, W. H. van Gilst, D. J. van Veldhuisen, J. Ezekowitz, et al. Anemia and Congestive Heart Failure * Response Circulation, August 12, 2003; 108 (6): e41 - e42. [Full Text] [PDF] |
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OTHER ARTICLES NOTED (24 Jan 03 to 18 Apr 03) Evid. Based Nurs., July 1, 2003; 6(3): e1 - 12. [Full Text] [PDF] |
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Minerva BMJ, February 8, 2003; 326(7384): 344 - 344. [Full Text] [PDF] |
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