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


OBJECTIVE
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.
Department of Cardiovascular Medicine, St. John Providence Health System, Warren, St. John Hospital and Medical Center, Detroit, St. John Hospital Macomb Oakland Center, Madison Heights, Providence Hospitals and Medical Centers, Southfield and Novi, and Providence Park Heart Institute, Novi, Michigan.
Peter A
PA
McCullough
Denise
D
Barnard
Robert
R
Clare
Stephen J
SJ
Ellis
Jerome L
JL
Fleg
Gregg C
GC
Fonarow
Barry A
BA
Franklin
Ryan D
RD
Kilpatrick
Dalane W
DW
Kitzman
Christopher M
CM
O'Connor
Ileana L
IL
Piña
Udho
U
Thadani
Vinay
V
Thohan
David J
DJ
Whellan
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000740:Anemia / Q000097:blood / Q000150:complications* / Q000175:diagnosis / Q000401:mortality / Q000503:physiopathology; D015415:Biomarkers / Q000097:blood; D018450:Disease Progression; D005081:Exercise Therapy; D005260:Female; D006333:Heart Failure / Q000175:diagnosis / Q000209:etiology / Q000401:mortality / Q000503:physiopathology / Q000628:therapy*; D006454:Hemoglobins / Q000378:metabolism; D006760:Hospitalization; D006801:Humans; D053208:Kaplan-Meier Estimate; D016014:Linear Models; D008297:Male; D008875:Middle Aged; D016017:Odds Ratio; D016016:Proportional Hazards Models; D011446:Prospective Studies; D012307:Risk Factors; D013599:Systole; D013997:Time Factors; D016896:Treatment Outcome; D014481:United States; D018487:Ventricular Dysfunction, Left / Q000150:complications / Q000175:diagnosis / Q000401:mortality / Q000503:physiopathology / Q000628:therapy*; D016277:Ventricular Function, Left; D055815:Young Adult
D015415:Biomarkers; D006454:Hemoglobins