Anemia and associated clinical outcomes in patients with heart failure due to reduced left ventricular systolic function

Peter A. Mccullough, Denise Barnard, Robert Clare, Stephen J. Ellis, Jerome L. Fleg, Gregg C. Fonarow, Barry A. Franklin, Ryan D. Kilpatrick, Dalane W. Kitzman, Christopher M. O'Connor, Ileana L. Pina, Udho Thadani, Vinay Thohan, David J. Whellan

Research output: Contribution to journalArticle

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Abstract

Background Anemia is associated with decreased functional capacity, reduced quality of life, and worsened outcomes among patients with heart failure (HF) due to reduced left ventricular ejection fraction (HFREF). We sought to evaluate the independent effect of anemia on clinical outcomes among those with HFREF. Hypothesis Anemia is associated with cardiovascular events in patients with heart failure. Methods The HF-ACTION trial was a prospective, randomized trial of exercise therapy vs usual care in 2331 patients with HFREF. Patients with New York Heart Association class II to IV HF and left ventricular ejection fractions of ≤35% were recruited. Hemoglobin (Hb) was measured up to 1 year prior to entry and was stratified by quintile. Anemia was defined as baseline Hb <13 g/dL and <12 g/dL in men and women, respectively. Hemoglobin was assessed in 2 models: a global prediction model that had been previously developed, and a modified model including variables associated with anemia and the studied outcomes. Results Hemoglobin was available at baseline in 1763 subjects (76% of total study population); their median age was 59.0 years, 73% were male, and 62% were Caucasian. The prevalence of anemia was 515/1763 (29%). Older age, female sex, African American race, diabetes, hypertension, and lower estimated glomerular filtration rates were all more frequent in lower Hb quintiles. Over a median follow-up of 30 months, the primary outcome of all-cause mortality or all-cause hospitalization occurred in 78% of those with anemia and 64% in those without (P < 0.001). The secondary outcomes of all-cause mortality alone,cardiovascular (CV) mortality or CV hospitalization, and CV mortality or HF hospitalization occurred in 23% vs 15%, 67% vs 54%, and 44 vs 29%, respectively (P < 0.001). Heart failure hospitalizations occurred in 36% vs 22%, and urgent outpatient visits for HF exacerbations occurred in 67% and 55%, respectively (P < 0.001). For the global model, there was an association observed for anemia and all-cause mortality or hospitalization (adjusted hazard ratio [HR]: 1.15, 95% confidence interval [CI]: 1.01-1.32, P = 0.04), but other outcomes were not significant at P < 0.05. In the modified model, the adjusted HR for anemia and the primary outcome of all-cause mortality or all-cause hospitalization was 1.25 (95% CI: 1.10-1.42, P < 0.001). There were independent associations between anemia and all-cause death (HR: 1.11, 95% CI: 0.87-1.42, P = 0.38), CV death or CV hospitalization (HR: 1.16, 95% CI: 1.01-1.33, P = 0.035), and CV death and HF hospitalization (HR: 1.27, 95% CI: 1.06-1.51, P = 0.008). Conclusions Anemia modestly is associated with increased rates of death, hospitalization, and HF exacerbation in patients with chronic HFREF. After adjusting for other important covariates, anemia is independently associated with an excess hazard for all-cause mortality and all-cause hospitalization. Anemia is also associated with combinations of CV death and CV/HF hospitalizations as composite endpoints.

Original languageEnglish (US)
Pages (from-to)611-620
Number of pages10
JournalClinical Cardiology
Volume36
Issue number10
DOIs
StatePublished - 2013

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Left Ventricular Function
Anemia
Heart Failure
Hospitalization
Mortality
Hemoglobins
Confidence Intervals
Stroke Volume
Exercise Therapy
Glomerular Filtration Rate
Proportional Hazards Models
African Americans
Cause of Death
Outpatients
Quality of Life
Hypertension

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine

Cite this

Mccullough, P. A., Barnard, D., Clare, R., Ellis, S. J., Fleg, J. L., Fonarow, G. C., ... Whellan, D. J. (2013). Anemia and associated clinical outcomes in patients with heart failure due to reduced left ventricular systolic function. Clinical Cardiology, 36(10), 611-620. https://doi.org/10.1002/clc.22181

Anemia and associated clinical outcomes in patients with heart failure due to reduced left ventricular systolic function. / Mccullough, Peter A.; Barnard, Denise; Clare, Robert; Ellis, Stephen J.; Fleg, Jerome L.; Fonarow, Gregg C.; Franklin, Barry A.; Kilpatrick, Ryan D.; Kitzman, Dalane W.; O'Connor, Christopher M.; Pina, Ileana L.; Thadani, Udho; Thohan, Vinay; Whellan, David J.

In: Clinical Cardiology, Vol. 36, No. 10, 2013, p. 611-620.

Research output: Contribution to journalArticle

Mccullough, PA, Barnard, D, Clare, R, Ellis, SJ, Fleg, JL, Fonarow, GC, Franklin, BA, Kilpatrick, RD, Kitzman, DW, O'Connor, CM, Pina, IL, Thadani, U, Thohan, V & Whellan, DJ 2013, 'Anemia and associated clinical outcomes in patients with heart failure due to reduced left ventricular systolic function', Clinical Cardiology, vol. 36, no. 10, pp. 611-620. https://doi.org/10.1002/clc.22181
Mccullough, Peter A. ; Barnard, Denise ; Clare, Robert ; Ellis, Stephen J. ; Fleg, Jerome L. ; Fonarow, Gregg C. ; Franklin, Barry A. ; Kilpatrick, Ryan D. ; Kitzman, Dalane W. ; O'Connor, Christopher M. ; Pina, Ileana L. ; Thadani, Udho ; Thohan, Vinay ; Whellan, David J. / Anemia and associated clinical outcomes in patients with heart failure due to reduced left ventricular systolic function. In: Clinical Cardiology. 2013 ; Vol. 36, No. 10. pp. 611-620.
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abstract = "Background Anemia is associated with decreased functional capacity, reduced quality of life, and worsened outcomes among patients with heart failure (HF) due to reduced left ventricular ejection fraction (HFREF). We sought to evaluate the independent effect of anemia on clinical outcomes among those with HFREF. Hypothesis Anemia is associated with cardiovascular events in patients with heart failure. Methods The HF-ACTION trial was a prospective, randomized trial of exercise therapy vs usual care in 2331 patients with HFREF. Patients with New York Heart Association class II to IV HF and left ventricular ejection fractions of ≤35{\%} were recruited. Hemoglobin (Hb) was measured up to 1 year prior to entry and was stratified by quintile. Anemia was defined as baseline Hb <13 g/dL and <12 g/dL in men and women, respectively. Hemoglobin was assessed in 2 models: a global prediction model that had been previously developed, and a modified model including variables associated with anemia and the studied outcomes. Results Hemoglobin was available at baseline in 1763 subjects (76{\%} of total study population); their median age was 59.0 years, 73{\%} were male, and 62{\%} were Caucasian. The prevalence of anemia was 515/1763 (29{\%}). Older age, female sex, African American race, diabetes, hypertension, and lower estimated glomerular filtration rates were all more frequent in lower Hb quintiles. Over a median follow-up of 30 months, the primary outcome of all-cause mortality or all-cause hospitalization occurred in 78{\%} of those with anemia and 64{\%} in those without (P < 0.001). The secondary outcomes of all-cause mortality alone,cardiovascular (CV) mortality or CV hospitalization, and CV mortality or HF hospitalization occurred in 23{\%} vs 15{\%}, 67{\%} vs 54{\%}, and 44 vs 29{\%}, respectively (P < 0.001). Heart failure hospitalizations occurred in 36{\%} vs 22{\%}, and urgent outpatient visits for HF exacerbations occurred in 67{\%} and 55{\%}, respectively (P < 0.001). For the global model, there was an association observed for anemia and all-cause mortality or hospitalization (adjusted hazard ratio [HR]: 1.15, 95{\%} confidence interval [CI]: 1.01-1.32, P = 0.04), but other outcomes were not significant at P < 0.05. In the modified model, the adjusted HR for anemia and the primary outcome of all-cause mortality or all-cause hospitalization was 1.25 (95{\%} CI: 1.10-1.42, P < 0.001). There were independent associations between anemia and all-cause death (HR: 1.11, 95{\%} CI: 0.87-1.42, P = 0.38), CV death or CV hospitalization (HR: 1.16, 95{\%} CI: 1.01-1.33, P = 0.035), and CV death and HF hospitalization (HR: 1.27, 95{\%} CI: 1.06-1.51, P = 0.008). Conclusions Anemia modestly is associated with increased rates of death, hospitalization, and HF exacerbation in patients with chronic HFREF. After adjusting for other important covariates, anemia is independently associated with an excess hazard for all-cause mortality and all-cause hospitalization. Anemia is also associated with combinations of CV death and CV/HF hospitalizations as composite endpoints.",
author = "Mccullough, {Peter A.} and Denise Barnard and Robert Clare and Ellis, {Stephen J.} and Fleg, {Jerome L.} and Fonarow, {Gregg C.} and Franklin, {Barry A.} and Kilpatrick, {Ryan D.} and Kitzman, {Dalane W.} and O'Connor, {Christopher M.} and Pina, {Ileana L.} and Udho Thadani and Vinay Thohan and Whellan, {David J.}",
year = "2013",
doi = "10.1002/clc.22181",
language = "English (US)",
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pages = "611--620",
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TY - JOUR

T1 - Anemia and associated clinical outcomes in patients with heart failure due to reduced left ventricular systolic function

AU - Mccullough, Peter A.

AU - Barnard, Denise

AU - Clare, Robert

AU - Ellis, Stephen J.

AU - Fleg, Jerome L.

AU - Fonarow, Gregg C.

AU - Franklin, Barry A.

AU - Kilpatrick, Ryan D.

AU - Kitzman, Dalane W.

AU - O'Connor, Christopher M.

AU - Pina, Ileana L.

AU - Thadani, Udho

AU - Thohan, Vinay

AU - Whellan, David J.

PY - 2013

Y1 - 2013

N2 - Background Anemia is associated with decreased functional capacity, reduced quality of life, and worsened outcomes among patients with heart failure (HF) due to reduced left ventricular ejection fraction (HFREF). We sought to evaluate the independent effect of anemia on clinical outcomes among those with HFREF. Hypothesis Anemia is associated with cardiovascular events in patients with heart failure. Methods The HF-ACTION trial was a prospective, randomized trial of exercise therapy vs usual care in 2331 patients with HFREF. Patients with New York Heart Association class II to IV HF and left ventricular ejection fractions of ≤35% were recruited. Hemoglobin (Hb) was measured up to 1 year prior to entry and was stratified by quintile. Anemia was defined as baseline Hb <13 g/dL and <12 g/dL in men and women, respectively. Hemoglobin was assessed in 2 models: a global prediction model that had been previously developed, and a modified model including variables associated with anemia and the studied outcomes. Results Hemoglobin was available at baseline in 1763 subjects (76% of total study population); their median age was 59.0 years, 73% were male, and 62% were Caucasian. The prevalence of anemia was 515/1763 (29%). Older age, female sex, African American race, diabetes, hypertension, and lower estimated glomerular filtration rates were all more frequent in lower Hb quintiles. Over a median follow-up of 30 months, the primary outcome of all-cause mortality or all-cause hospitalization occurred in 78% of those with anemia and 64% in those without (P < 0.001). The secondary outcomes of all-cause mortality alone,cardiovascular (CV) mortality or CV hospitalization, and CV mortality or HF hospitalization occurred in 23% vs 15%, 67% vs 54%, and 44 vs 29%, respectively (P < 0.001). Heart failure hospitalizations occurred in 36% vs 22%, and urgent outpatient visits for HF exacerbations occurred in 67% and 55%, respectively (P < 0.001). For the global model, there was an association observed for anemia and all-cause mortality or hospitalization (adjusted hazard ratio [HR]: 1.15, 95% confidence interval [CI]: 1.01-1.32, P = 0.04), but other outcomes were not significant at P < 0.05. In the modified model, the adjusted HR for anemia and the primary outcome of all-cause mortality or all-cause hospitalization was 1.25 (95% CI: 1.10-1.42, P < 0.001). There were independent associations between anemia and all-cause death (HR: 1.11, 95% CI: 0.87-1.42, P = 0.38), CV death or CV hospitalization (HR: 1.16, 95% CI: 1.01-1.33, P = 0.035), and CV death and HF hospitalization (HR: 1.27, 95% CI: 1.06-1.51, P = 0.008). Conclusions Anemia modestly is associated with increased rates of death, hospitalization, and HF exacerbation in patients with chronic HFREF. After adjusting for other important covariates, anemia is independently associated with an excess hazard for all-cause mortality and all-cause hospitalization. Anemia is also associated with combinations of CV death and CV/HF hospitalizations as composite endpoints.

AB - Background Anemia is associated with decreased functional capacity, reduced quality of life, and worsened outcomes among patients with heart failure (HF) due to reduced left ventricular ejection fraction (HFREF). We sought to evaluate the independent effect of anemia on clinical outcomes among those with HFREF. Hypothesis Anemia is associated with cardiovascular events in patients with heart failure. Methods The HF-ACTION trial was a prospective, randomized trial of exercise therapy vs usual care in 2331 patients with HFREF. Patients with New York Heart Association class II to IV HF and left ventricular ejection fractions of ≤35% were recruited. Hemoglobin (Hb) was measured up to 1 year prior to entry and was stratified by quintile. Anemia was defined as baseline Hb <13 g/dL and <12 g/dL in men and women, respectively. Hemoglobin was assessed in 2 models: a global prediction model that had been previously developed, and a modified model including variables associated with anemia and the studied outcomes. Results Hemoglobin was available at baseline in 1763 subjects (76% of total study population); their median age was 59.0 years, 73% were male, and 62% were Caucasian. The prevalence of anemia was 515/1763 (29%). Older age, female sex, African American race, diabetes, hypertension, and lower estimated glomerular filtration rates were all more frequent in lower Hb quintiles. Over a median follow-up of 30 months, the primary outcome of all-cause mortality or all-cause hospitalization occurred in 78% of those with anemia and 64% in those without (P < 0.001). The secondary outcomes of all-cause mortality alone,cardiovascular (CV) mortality or CV hospitalization, and CV mortality or HF hospitalization occurred in 23% vs 15%, 67% vs 54%, and 44 vs 29%, respectively (P < 0.001). Heart failure hospitalizations occurred in 36% vs 22%, and urgent outpatient visits for HF exacerbations occurred in 67% and 55%, respectively (P < 0.001). For the global model, there was an association observed for anemia and all-cause mortality or hospitalization (adjusted hazard ratio [HR]: 1.15, 95% confidence interval [CI]: 1.01-1.32, P = 0.04), but other outcomes were not significant at P < 0.05. In the modified model, the adjusted HR for anemia and the primary outcome of all-cause mortality or all-cause hospitalization was 1.25 (95% CI: 1.10-1.42, P < 0.001). There were independent associations between anemia and all-cause death (HR: 1.11, 95% CI: 0.87-1.42, P = 0.38), CV death or CV hospitalization (HR: 1.16, 95% CI: 1.01-1.33, P = 0.035), and CV death and HF hospitalization (HR: 1.27, 95% CI: 1.06-1.51, P = 0.008). Conclusions Anemia modestly is associated with increased rates of death, hospitalization, and HF exacerbation in patients with chronic HFREF. After adjusting for other important covariates, anemia is independently associated with an excess hazard for all-cause mortality and all-cause hospitalization. Anemia is also associated with combinations of CV death and CV/HF hospitalizations as composite endpoints.

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