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Published Online
on June 11, 2007

Circulation. 2007
Published online before print June 11, 2007, doi: 10.1161/CIRCULATIONAHA.106.673442
A more recent version of this article appeared on June 19, 2007
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Submitted on November 1, 2006
Accepted on April 8, 2007

Sex Differences in Clinical Characteristics and Prognosis in a Broad Spectrum of Patients With Heart Failure. Results of the Candesartan in Heart failure: Assessment of Reduction in Mortality and morbidity (CHARM) Program

Eileen O’Meara MD, Tim Clayton MSc, Margaret B. McEntegart MB, ChB, John J.V. McMurray MD*, Ileana L. Piña MD, Christopher B. Granger MD, Jan Östergren MD, PhD, Eric L. Michelson MD, Scott D. Solomon MD, Stuart Pocock PhD, Salim Yusuf DPhil, Karl Swedberg MD, PhD, Marc A. Pfeffer MD, PhD, for the CHARM Investigators

From Western Infirmary (E.O., M.B.M., J.J.V.M.), Glasgow, Scotland, United Kingdom; Montréal Heart Institute (E.O.), Montréal, Canada; London School of Hygiene and Tropical Medicine (T.C., S.P.), London, United Kingdom; Case Western Reserve University (I.P.), Cleveland, Ohio; Duke University Medical Center (C.B.G.), Durham, NC; Karolinska Hospital (J.O.), Stockholm, Sweden; AstraZeneca LP (E.L.M.), Wilmington, Del; Brigham & Women’s Hospital (S.D.S., M.A.P.), Boston, Mass; HGM-McMaster Clinic (S.Y.), Hamilton, Ontario, Canada; and Sahlgrenska University Hospital/Östra (K.S.), Göteborg, Sweden.

* To whom correspondence should be addressed. E-mail: j.mcmurray{at}bio.gla.ac.uk.

Background--We wished to test previous hypotheses that sex-related differences in mortality and morbidity may be due to differences in the cause of heart failure or in left ventricular ejection fraction (LVEF) by comparing fatal and nonfatal outcomes in women and men with heart failure and a broad spectrum of left ventricular ejection fraction.

Methods and Results--We compared outcomes in 2400 women and 5199 men randomized in the Candesartan in Heart failure: Assessment of Reduction in Mortality and morbidity (CHARM) program using multivariable regression analyses. A total of 1188 women (50%) had a low LVEF (≤0.40), and 1212 had a preserved LVEF (>0.40). Among the men, 3388 (65%) had a low LVEF, and 1811 had a preserved LVEF. A total of 1216 women (51%) and 3465 men (67%) had an ischemic cause of their heart failure. All-cause mortality was 21.5% in women and 25.3% in men (adjusted hazard ratio [HR], 0.77; 95% CI, 0.69 to 0.86; P<0.001). Fewer women (30.4%) than men (33.3%) experienced cardiovascular death or heart failure hospitalization (adjusted HR, 0.83; 95% CI, 0.76 to 0.91; P<0.001). The risks of sudden death (HR, 0.70; 95% CI, 0.58 to 0.85) and death due to worsening heart failure (HR, 0.72; 95% CI, 0.58 to 0.89) were reduced to a comparable extent. The adjusted risk of cardiovascular hospitalization was also lower in women (HR, 0.88; 95% CI, 0.82 to 0.95), mainly because of a reduced risk of heart failure hospitalization (HR, 0.87; 95% CI, 0.78 to 0.97). Women had a lower risk of death irrespective of cause of heart failure or LVEF.

Conclusions--Among patients with heart failure, women have lower risks of most fatal and nonfatal outcomes that are not explained, as previously suggested, by LVEF or origin of the heart failure.


Key words: heart failure • sex • etiology • mortality




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