Circulating estradiol and mortality in men with systolic chronic heart failure.
BACKGROUND
Androgen deficiency is common in men with chronic heart failure (HF) and is associated with increased morbidity and mortality. Estrogens are formed by the aromatization of androgens; therefore, abnormal estrogen metabolism would be anticipated in HF.


OBJECTIVE
To examine the relationship between serum concentration of estradiol and mortality in men with chronic HF and reduced left ventricular ejection fraction (LVEF).


METHODS
A prospective observational study at 2 tertiary cardiology centers (Wroclaw and Zabrze, Poland) of 501 men (mean [SD] age, 58 [12] years) with chronic HF, LVEF of 28% (SD, 8%), and New York Heart Association [NYHA] classes 1, 2, 3, and 4 of 52, 231, 181, and 37, respectively, who were recruited between January 1, 2002, and May 31, 2006. Cohort was divided into quintiles of serum estradiol (quintile 1, < 12.90 pg/mL; quintile 2, 12.90-21.79 pg/mL; quintile 3, 21.80-30.11 pg/mL; quintile 4, 30.12-37.39 pg/mL; and quintile 5, > or = 37.40 pg/mL). Quintile 3 was considered prospectively as the reference group.


METHODS
Serum concentrations of estradiol and androgens (total testosterone and dehydroepiandrosterone sulfate [DHEA-S]) were measured using immunoassays.


RESULTS
Among 501 men with chronic HF, 171 deaths (34%) occurred during the 3-year follow-up. Compared with quintile 3, men in the lowest and highest estradiol quintiles had increased mortality (adjusted hazard ratio [HR], 4.17; 95% confidence interval [CI], 2.33-7.45 and HR, 2.33; 95% CI, 1.30-4.18; respectively; P < .001). These 2 quintiles had different clinical characteristics (quintile 1: increased serum total testosterone, decreased serum DHEA-S, advanced NYHA class, impaired renal function, and decreased total fat tissue mass; and quintile 5: increased serum bilirubin and liver enzymes, and decreased serum sodium; all P < .05 vs quintile 3). For increasing estradiol quintiles, 3-year survival rates adjusted for clinical variables and androgens were 44.6% (95% CI, 24.4%-63.0%), 65.8% (95% CI, 47.3%-79.2%), 82.4% (95% CI, 69.4%-90.2%), 79.0% (95% CI, 65.5%-87.6%), and 63.6% (95% CI, 46.6%-76.5%); respectively (P < .001).


CONCLUSIONS
Among men with chronic HF and reduced LVEF, high and low concentrations of estradiol compared with the middle quintile of estradiol are related to an increased mortality.
Center for Heart Disease, Cardiology Department, Military Hospital, ul Weigla 5, 50-981 Wroclaw, Poland. ewa.jankowska@antro.pan.wroc.pl
Ewa A
EA
Jankowska
Piotr
P
Rozentryt
Beata
B
Ponikowska
Oliver
O
Hartmann
Dorota
D
Kustrzycka-Kratochwil
Krzysztof
K
Reczuch
Jolanta
J
Nowak
Ludmila
L
Borodulin-Nadzieja
Lech
L
Polonski
Waldemar
W
Banasiak
Philip A
PA
Poole-Wilson
Stefan D
SD
Anker
Piotr
P
Ponikowski
D000368:Aged; D002908:Chronic Disease; D019314:Dehydroepiandrosterone Sulfate / Q000097:blood; D004958:Estradiol / Q000097:blood*; D054143:Heart Failure, Systolic / Q000097:blood* / Q000401:mortality*; D006801:Humans; D008297:Male; D008875:Middle Aged; D011379:Prognosis; D011446:Prospective Studies; D013318:Stroke Volume; D015996:Survival Rate; D013739:Testosterone / Q000097:blood
D013739:Testosterone; D004958:Estradiol; D019314:Dehydroepiandrosterone Sulfate