Gender Effects on Acute Heart Failure

doi:10.4236/ijcm.2011.23040

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International Journal of Clinical Medicine, 2011, 2, 254-259

doi:10.4236/ijcm.2011.23040 Published Online July 2011 (http://www.SciRP.org/journal/ijcm)

Gender Effects on Acute Heart Failure

Arnon Blum1*, Rizak Sirchan1, Lital Keinan-Boker2,3

1Department of Medicine, Baruch-Padeh Poria Medical Center, Tiberias, Israel; 2Israel Center for Disease Control, Ministry of

Health, Jerusalem, Israel; 3School of Public Health, University of Haifa, Haifa, Israel.

Email: *[email protected]

Received March 10th, 2011; revised April 19th, 2011; accepted May 3rd, 2011.

ABSTRACT

Background: congestive heart failure is the leading cause of hospitalization in the elderly. Little is known about gender

effect on baseline characteristics and in-hospital outcome in patients admitted with acute heart failure. Our purpose

was to study the gender effect on in-hospital mortality in acute heart failure patients. Methods and Results: a prospec-

tive study [143 patients, 67 men (73.9 ± 13.8 years old) and 76 women (77.8 ± 10.1 years old) (p = 0.059)] followed

in-hospital outcome of patients with acute heart failure admitted to the hospital. Clinical parameters included body

mass index (BMI), ankle brachial index (ABI), left ventricular ejection fraction (LVEF), re-admissions within 1 year,

and in-hospital mortality. The gender effects that were studied included height, BMI, smoking, coronary artery disease,

LVEF and mortality: in total, 9 (6.3%) patients died, of them 8 (10.5%) women and 1 (1.5%) man. Women were shorter

(p < 0.001), had a higher BMI (p = 0.053), reported less frequently on current smoking (p < 0.001), had lower preva-

lence of coronary artery disease (p = 0.016), had a better LVEF (p = 0.02), but still, had a higher mortality rate (p =

0.026). The only variables independently affecting in-hospital mortality in women were height and recurrent admissions.

When we tested for the effect of height and recurrent admissions on mortality only among females by a multivariate

analysis height inversely and independently affected in-hospital mortality (p = 0.024), as well as recurrent admissions

(p = 0.031). Conclusions: in-hospital mortality was significantly higher in women compared with men admitted with

acute heart failure. Among females, the only independent variables that affected mortality were low stature and recur-

rent admissions.

Keywords: Gender, Heart Failure, in Hospital Death

1. Introduction

Congestive heart failure (CHF) is the leading cause of

hospitalizations in the elderly. Little is known about

gender differences in baseline characteristics and out-

comes in patients with acute co ng estive h eart failure. Th e

epidemic of cardiovascular disease in women has at-

tained increasing recognition.

The Framingham heart study reported an estimated

prevalence of heart failure of 0.8% in both genders

within the age group of 50 - 59 years. The prevalence

increases notably with advancing age, rising to 6.6% and

7.9% in men and women, respectively, aged 80 - 89

years [1]. A study from Olmsted County, Minnesota, has

evaluated the prevalence of “diastolic” heart failure. In

this survey of the population aged over 45 years, the

overall prevalence of heart failure was 2.2%, 44% of

heart failure cases had preserved systolic function (LVEF

> 50%). The prevalence of diastolic dysfunction was

higher in the older population and in those with a history

of hypertension, diabetes, coronary disease and previous

myocardial infarction. The prevalence of diastolic dys-

function was similar in both genders [2].

According to the Framingham study, the incidence of

heart failure was significantly higher in men compared to

women at all ages, with an age-standardised incidence

ratio of 1.67 [1]. Coronary artery disease was reported as

the etiological factor in 59% of men and 47% of women

for the period 1948- 1988. Va lvular diseas e, hyperten sion,

and diabetes were more common in women than in men

[1].

The incidence and prevalence of heart failure is lower

in women than men at all ages. However, due to the

steep increase in incidence with age, and the larger

population of elderly wo men in the d eveloped wor ld, the

total number of men and women living with heart failure

is similar. Heart failure with preserved systolic function

(“diastolic” dysfunction) is more common in women,

perhaps related to gender differences in the myocardial

response to injury, and the lower prevalence of coron ary

Gender Effects on Acute Heart Failure255

artery disease in women at all ages compared with men

[3].

In this prospective study we addressed some of the

questions that were raised about gender and acute heart

failure during in-hospital stay—clinical characteristics

and in hospital outcome. Our purpose was to study the in

hospital outcome of patients that were admitted with

acute heart failure.

2. Methods

This was a prospective, hospital-based study. The study

population included 143 consecutive patients that were

admitted with acute heart failure to the Medicine Ward

in the Baruch-Padeh Poria Medical Center during the

years 2008-2010.

The inclusion criteria included females and male pa-

tients older than 18 years old with no known chronic or

acute infectious, inflammatory or autoimmune disease.

The exclusion criteria included patients younger than 18

years old, patients who also had an active cancer or an

autoimmune, inflammatory or an infectious disease.

All had an exacerbation of a known heart failure and

were treated accordingly by beta blockers, angiotensin

converting enzyme inhibitors, and diuretics as needed.

On admission, all participants had their weight and

height measured and their body mass index (BMI) was

calculated. Their peripheral artery disease was evaluated

by measuring the ankle-brachial index (ABI); the ab-

dominal circumference served as a proxy for central

obesity, and the cardiac function was evaluated by

measuring the ejection fraction (echocardiography).

In addition, information on clinical parameters like

current smoking (self report), alcohol use, prevalence of

Atrial Fibrillation or other arrhythmias, Diabetes Melli-

tus type II, renal function, Hypertension, documented

Coronary Artery Disease (CAD), and Rheumatic Valvu-

lar Heart Disease (documented by echocardiography)

was collected.

Follow up continued during hospitalization.

The primary end point was to study the gender effect

on in-hospital mortality.

3. Statistical Analysis

Gender differences in categorical variables were as-

sessed by using the Chi-square test, and in continuous

variables, by using the independent sample T-test. Uni-

variate analyses, where in-hospital mortality served as

the dependent variable, were used to identify significant

correlates. Multivariate analyses, using logistic regres-

sion models, were stratified by gender and included

variables that significantly affected in-hospital mortality

in univariate analyses. P-value was set at 0.05, and all

analyses were two-tailed. The analyses were carried out

using the Statistical Package for Social Sciences (SPSS),

version 17.

4. Results

One hundred and forty three acute heart failure patients

were admitted to our Medicine Department. There were

67 men (mean age: 73.9 ± 13.8 years old; range: 23 - 99)

and 76 women (mean age: 77.8 ± 10.1 years old; range:

55 - 96) (p = 0.059). Men tended to report on current

smoking more frequently than women (31 men vs. 6

women; p < 0.001), were taller (mean height: 1.69 ± 0.1

meter vs. 1.58 ± 0.1; p < 0.001), and had a lower BMI

(mean BMI: 28.4 ± 5.9 vs. 30.8 ± 8.7; p = 0.053) (Table

1). Coronary artery disease was more prevalent among

men (42 [68%] vs. 36 [47%] in women; p = 0.016), and

their ejection fraction was lower (48.2 ± 15.7 vs. 55.1 ±

13.9 in women; p = 0.020) (Table 1).

No difference was observed between genders in rela-

tion to prevalence of diabetes mellitus, hypertension,

rheumatic valvular heart disease, abdominal circumfer-

ence and ankle brachial index (Table 1), but women had

a trend towards a higher prevalence of recurrent hospi-

talizations (8[11%] vs. 2[3%], p = 0.078), and a lower

prevalence of peripheral artery disease (ABI less than

0.9, 22[33%] among men, 18[24%] among women; p =

0.224) (Table 1).

There were 8 in-hospital deaths among women and

only 1 in-hospital death among men (p = 0.026) (Table

1). Variables that were significantly associated with

in-hospital mortality included gender (female), recurrent

hospitalizations, height (lower) and weight (lower) (Ta-

ble 2). Age, current smoking, BMI, LVEF, and preva-

lence of comorbidites (atrial fibrillation, diabetes melli-

tus, hypertension, coronary artery disease and valvular

rheumatic heart disease) did not seem to significantly

Table 1. Clinical characteristic s of the study population.

Total Males Femal es

-value

Gender 143 (100%) 67 (47%) 76 (53%)

Age 76.1 ± 12.0 73.9 ± 13.8 77.8 ± 10.1 0.059

Weight (Kg) 78.6 ± 20.1 80.9 ± 17.7 76.5 ± 21.8 0.187

Height (M) 1.63 ± 0.1 1.69 ± 0.1 1.58 ± 0.1 <0.001

BMI 29.6 ± 7.6 28.4 ± 5.9 30.8 ± 8.7 0.053

Abd Circ (cm) 108.4 ± 20.9108.3 ± 19.7 108.5 ± 22.00.951

ABI 0.97 ± 0.29 0.98 ± 0.33 0.97 ± 0.24 0.764

Smokers 37 (27%) 31 (50%) 6 (8%) <0. 001

DM type II 77 (56%) 35 (56%) 42 (55%) 0. 889

HTN 119 (86%) 51 (82%) 68 (89%) 0.221

CAD 78 (56%) 42 (68%) 36 (47%) 0.016

RHD 54 (39%) 21 (34%) 33 (43%) 0.253

A. Fibrillation 57 (42%) 24 (39%) 33 (43%) 0.630

LVEF (%) 51.9 ± 15.1 48.2 ± 15.7 55.1 ± 13.9 0.020

Recurrent

Admissions 10 (7%) 2 (3%) 8 (11%) 0.078

In-Hospital Death 9 (6%) 1 (2%) 8 ( 11%) 0.026

Gender Effects on Acute Heart Failure

256

Table 2. Correlates of in-hospital mortality—univariate

analyses.

Variable Mortality+ Mortality–

-value

Gender (n = 143)

Males 1 (1.5%) 66 (98.5%) 0.026

Females 8 (10.5%) 68 (89.5%)

Recurrent Hospitalizations (n = 143)

Yes 4 (40%) 6 (60%) <0.001

No 5 (3.8%) 128 (96.2%)

Continuous Variables

Height (M) (n=141) 1.50 ± 0.07 1.63 ± 0.08 <0.001

Weight (Kg) (n=140) 63.00 ± 24.55 79.41 ± 19.61 0.035

affect the outcome.

When stratified by gender, the only significant factor

in men was recurrent hospitalizations (p < 0.001). In

women, significant correlates affecting in-hospital mor-

tality included recurrent hospitalizations (p = 0.009),

low ABI < 0.9 (p = 0.006), and being shorter (p =

0.006).

We used a logistic regression model to assess the in-

dependent effect of each of these variables on in-hospital

mortality in women. Only height (OR = 0.000, 95% CI

0.000 - 0.116, p = 0.024) and recurrent admissions (OR

= 9.290, 95% CI 1.229 - 70.220, p = 0.031) remained

statistically significant (Table 3). The model was not

applied for men since only one man died.

5. Discussion

Of all the cardiovascular diseases, the prevalence of

heart failure is the only one that continues to increase in

the United States [4]. Heart failure affects mainly the

elderl y, the preval ence and incid ence of heart failur e are

expected to increase over the next several decades.

Gender differences in the syndrome of heart failure oc-

cur in etiology and pathophysiology and lead to differ-

ences in the clinical presentation and course of the syn-

drome. Hypertension and diabetes play a major role as

causes of heart failure in women [5]. Major risk factors

for heart failure have been evaluated in the past 50 years

in the Framingham heart study program. Hypertension

carried the largest population-attributable risk factor for

heart failure, underlying 59% of heart failure cases in

women and 39% in men with a hazard ratio of 3.35 in

women and 2.07 in men [6]. A particularly steep in-

crease in the prevalence of hypertension with increasing

Table 3. Logistic regression model to assess the independe nt

effect of each of these variables on in-hospital mortality in

women.

Variable OR 95% CI P-value

Recurrent patient (ref: no) 9.290 1. 22 9 - 70 .2 20 0.031

Height in cm (continuous) 0.000 0.000 - 0.116 0.024

age in women compared with men has also been ob-

served in a European WHO-MONICA cohort [7]. Myo-

cardial cell death, apoptosis, and cellular hypertrophy of

the remaining cells are more pronounced in the male

than in the female myocardium [8,9]. Female patients

with aortic stenosis exhibit relatively less ventricular

dilatation and less myocardial hypertrophy and have

better preserved left ventricular function at a comparable

degree of stenosis than male patients [9].

Adipose tissue produces inflammatory mediators that

increase the risk for cardiovascular disease and diabetes

[10]. Adipocytokines (interleukin-1 β, interleukin 6,

leptin, tumor necrosis factor α) and adiponectin levels

exhibit large sexual dimorphisms. Fat tissue expresses

aromatase, and conversion of testosterone to estrogen by

aromatase is one of the main sources for estrogen in

postmenopausal women [5].

The primary end point of our study was the gender

effect on in-hospital mortality, and the secondary end

points were to study the gender effect on recurrent hos-

pitalizations and peripheral artery disease (measured by

ABI of less than 0.9).

In our study there were much more in-hospital deaths

among women. Variables that were significantly associ-

ated with in-hospital mortality included gender (female

patients), recurrent ho spitalizations, height (lower height

—more deaths), and weight (lower weights—more

deaths). The on ly significant factor in men was recurrent

hospitalizations, while in women increased death rates

were affected by recurrent hospitalizations, peripheral

artery disease (ABI lower than 0.9) and a low stature.

After using a logistic regression analysis only height

remained statistically significant.

A prospective study evaluated gender differences

among 217 patients presenting with acute heart failure to

the emergency department in Switzerland. The primary

end point was all—cause mortality. Women were older

and had less pulmonary co-morbidity, more jugular ve-

nous pressure and higher diastolic blood pressure and

troponin level at presentation; however, the trend toward

lower survival in women seemed primarily related to

higher age rather than gender itself. Female sex was not

found as an independent predictor of long-term mortality

in acute heart failure [11]. Another study (a retrospective

one) did not find any significant gender differences in

the initial presentation, disposition, and diagnostic test-

ing of patients with acute heart failure admitted through

the emergency department [12].

The impact of gender was assessed in the beta blocker

evaluation of survival trial (BEST) which randomized 2

708 patients with NYHA class III/IV and LVEF less

than 35% to bucindolol versus placebo. Significant dif-

ferences in baseline clinical and laboratory characteris-

Gender Effects on Acute Heart Failure257

tics were found. Compared to men, women were

younger, more likely to be black, had a higher preva-

lence of non-ischemic etiology, had higher right and left

ventricular ejection fraction, higher heart rate, greater

cardiothoracic ratio, higher prevalence of left bundle

branch block, lower prevalence of atrial fibrillation, and

lower plasma nor-epinephrine level. Coronary artery

disease and LVEF appeared to be stronger predictors of

prognosis in women; however, in the non-ischemic pa-

tients, women had a significantly better survival rate

compared with men [13].

Obesity could be a factor in prognosis in heart failure

patients; however, studies have shown a better survival

in heart failure patients with decreased LVEF and a

higher BMI compared to those with a lower BMI

[14-19]. Another study has demonstrated an increased

mortality in patients with heart failure and preserved

systolic function and low BMI; however, with a BMI >

45 mortality increased, raising the possibility of a U

shaped relationship between BMI and survival [20]. A

meta-analysis of 9 retrospective studies (mean follow-up

of 2.7 years) found that compared to individuals without

elevated BMI, both overweight and obese patients had a

lower all-cause mortality and also lower cardiovascular

mortality. In a risk-adjusted sensitivity analysis, both

obesity and overweight remained protective against

mortality [21].

In our study a gender effect was observed on BMI;

women had a higher BMI compared with men (30.0 ±

8.7 vs. 28.4 ± 5.9, p = 0.053)—but such an effect should

have been a protective factor according to recent studies

on BMI and weight in patients with heart failure [20, 21],

but in our study obesity and overweight did not serve as

a protective factor against in-hospital mortality and had

no advan tag e for wo men.

Another interesting finding was the gender effect on

height; women were significantly shorter than men with

acute heart failure (1.58 ± 0.1 m vs. 1.69 ± 0.1 m, p <

0.001).

An autopsy Finish study evaluated coronary athero-

sclerosis among 599 females that died a sudden death

and found that 50% of women over 41 years old had

coronary lesions, 32% in women from 31 to 40 years,

17% in women from 21 to 30, and 6% in women under

20 years. Coronary atherosclerosis was correlated with

short stature as well as with BMI and abdominal fat [22].

A retrospective meta-analysis assessed the relationship

between short stature and coronary heart disease from 52

studies (3,012,747 individuals). The short ones were

below 160.5 cm and the tall ones over 173.9 cm on av-

erage. Among the shortest height category, the relative

risks were 1.35 for all-cause mortality, 1.55 for all car-

diovascular disease mortality, 1.49 for coronary heart

disease, and 1.52 for myocardial infarction when com-

pared with those within the highest height category.

Short stature was associated with increased cardiovas-

cular morbidity and mortality in both genders. No gen-

der effect was observed in this study. Only height was

the independent parameter that affected death [23]. On

the other hand, a prospective study of women hospital-

ized with acute coronary event (292 Swedish women,

aged 65 years or younger, follow-up 4.8 years) found

that independent of the confounding effects of other risk

factors of clinical importance for CHD the shortest 25%

of women (<160 cm) had a 2.1-fold increased rate of

developing adverse cardiac events compared with the

tallest 25% (>165 cm) [24].

To examine the influence of race and gender on hos-

pital outcome for patients with congestive heart failure a

retrospective study examined records on all 1995 New

York State hospital discharges assigned ICD-9-CM

codes indicative of this diagnosis. It was found that

45,894 patients (black women, 4750; black men, 3370;

white women, 21,165; white men, 16,609) had were

admitted with congestive heart failure. Blacks under-

went noninvasive cardiac procedures more often than

whites; procedure and specialty use rates were lower

among women than among men. After adjusting for

other patient characteristics and hospital type and loca-

tion, we found race to be an important determinant of

length of stay in the hospital (black, 10.4 days; white,

9.3 days; p = 0.0001), hospital charges (black, $13,711;

white, $11,074; p = 0.0001), mortality (black-to-white

odds ratio = 0.832; p = 0.003), and readmission

(black-to-white odds ratio = 1.301; p = 0.0001). Gender

was an important determinant of length of stay (women,

9.8 days; men, 9.2 days; p = 0.0001), hospital charges

(women, $11,690; men, $11,348; p = 0.02), and mortal-

ity (women-to-men odds ratio = 0.878; p = 0.0008). The

conclusion of that study was that race and gender affect

care process and hospital-based case outcomes for pa-

tients with CHF [25].

6. Conclusions

Our study has demonstrated a gender effect on in-hospi-

tal mortality among acute heart failure patients. The only

epidemiological data that could help explain our results

are studies that have demonstrated a link between short

stature and cardiovascular morbidity and mortality. Our

female population was about 10 cm shorter compared

with men, and this significant difference may explain our

results.

The novelty of our study was that it was a prospective

study that evaluated gender effect on in-hospital mortal-

ity in patients admitted with acute heart failure—unlike

any other study that examined these specific parameters

Gender Effects on Acute Heart Failure

258

in patients admitted with acute heart failure.

7. Study Limitation

The small sample size is limiting our ability to have

definite conclusions. We believe that by enlarging the

population of heart failure patients we will be able to

have more solid conclusions. Our plan is to continue

with this study and to recruit many more patients with

acute heart failure.

8. Conflict of Interest Disclosures

NONE for all authors.

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