Gender Differences in the Acute HEArt Database Registry

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Abstract

Acute heart failure (AHF) is a major and growing cause of in-hospital mortality in developed countries. Differences between males and females hospitalized for AHF were observed in all registries and clinical studies. In this article, we compare data from European registries—the Acute HEArt Database (AHEAD), the EuroHeart Failure Survey program II (EHFS II), and the Dispensibility Improvement And Remodeling in Diastolic Heart Failure (DIAMOND) study—and US registries—the Acute Decompensated Heart Failure National Registry (ADHERE) and the Organized Program to Initiate Life-saving Treatment in Hospitalized Patients with Heart Failure (OPTIMIZE-HF). Women are older than men when admitted with HF in all registries: the mean age of women is 73–75 years and the mean age of men is 68–70 years. Women have higher systolic blood pressure—the mean systolic blood pressure is about 140mmHg for women and 130mmHg for men—while diastolic blood pressure is about 80mmHg for both sexes. HF with preserved left ventricular function predominates in women: the mean ejection fraction is about 43% in women and approximately 38% in men. Men have obstructive lung disease more often, while women more frequently have anemia. Despite these differences, length of stay and in-hospital mortality rates are similar but, if adjusted for age, male gender is associated with an increased risk for death.

Disclosure
Jindrich Spinar, MD, PhD, is a consultant for Abbott, sanofi-aventis, and KRKA. Lenka Spinarová, MD, PhD, is a consultant for Abbott and Astellas. The AHEAD registry is supported by a Czech Republic Ministry of Health grant 1A - 8606-5.
Correspondence
Jindrich Spinar, MD, PhD, Internal Cardiology Department, University Hospital Brno, Jihlavska 20, 625 00 Brno, Czech Republic. E: jspinar@fnbrno.cz
Received date
16 June 2009
Accepted date
05 October 2009

Acute heart failure (AHF) is a major and growing cause of in-hospital mortality in developed countries. The prevalence of HF in an unselected population >45 years of age is estimated to be 2% and in a population >65 years of age is estimated to be 8.8%.1,2 The combination of aging of the population in many countries and improved survival after acute myocardial infarction has created rapid growth in the number of patients currently living with chronic heart failure, with a concomitant increase in the number of hospitalizations for decompensated HF.3–5 Coronary heart disease is the etiology of AHF in 60–70% of patients, particularly in the elderly population.6,7 AHF is defined as the rapid onset of symptoms and signs secondary to abnormal cardiac function.3 It may occur with or without previous cardiac disease. Little is known about sex differences in baseline characteristics and outcomes in patients with AHF.

The Acute HEArt failure Database (AHEAD) program consists of the AHEAD MAIN, AHEAD CORE (single-center extended registry), and AHEAD NETWORK (including hospitals without catheterization laboratory studies). AHEAD MAIN included patients hospitalized from July 2006 to December 31, 2008 in five university hospitals, all of which had a 24-hour catheterization laboratory service. All data were prospectively collected using an Internet program (www.ahead.registry.cz). Two thousand, two hundred and forty-five patients were included: 903 females (40.2%) and 1,342 males (59.8%). Mean age, body mass index, blood pressure, and ejection fraction at admission are shown in Table 1. The duration of hospitalization was nine days in women and 9.1 days in men (p=NS). In-hospital mortality was 11.1% in women and 12% in men (p=NS). Baseline characteristics according to etiology of HF and mortality data are shown in Table 2 (all data are NS for gender differences). Biochemistry parameters at baseline are shown in Table 3.

The most important gender differences in the AHEAD registry are that women hospitalized for AHF are significantly older and slightly more frequently have de novo HF with elevated systolic blood pressure and higher ejection fraction than males. Females frequently have more anemia, and less frequently have renal insufficiency. In-hospital mortality is similar, but if adjusted for age the prognosis of female patients is clearly better.

Patients enrolled in clinical trials are usually younger, are more frequently men, have fewer comorbidities, are properly treated, and have better prognosis than real-life patients. Therefore, data from international and/or national registries more accurately reflect reality and can provide important information about the subject.

The EuroHeart Failure Survey program II (EHFS II) was performed in 30 European countries and 133 participating hospitals. University hospitals accounted for 47% of the hospitals, 49% were community or district hospitals, and 4% were private clinics.6,8 Of the 3,580 patients included in EHFS II, 1,384 (39%) were women, whose mean age was 73 years. Two thousand, one hundred and ninety-six (61%) were men, whose mean age was 68 years. Female patients had a higher systolic blood pressure, a higher rate of hypertension (67.4 versus 59.4%), diabetes (35 versus 31.4%), anemia (18.5 versus 12.4%), and thyroid disease (11.1 versus 4.4%), and less coronary artery disease (44.1 versus 59.4%). Male patients were more frequently smokers (19.8 versus 6.9%; p<0.001) and more frequently had chronic obstructive pulmonary disease (22.1 versus 15%; p<0.001). There were no differences in the proportion of acute coronary syndrome (29.3 versus 30.7%), and women had slightly more supraventricular arrhythmias (32 versus 27.7%). New-onset AHF was significantly more common in female patients (41%) than in male subjects (35%). Woman had higher systolic blood pressure (140 versus 130mmHg; p<0.001), while diastolic blood pressure was the same (80mmHg for both sexes). Echocardiography results were available in the majority of patients enrolled in EHFS II. Median left ventricular end-diastolic diameter was smaller (53 versus 60mm) and ejection fraction was significantly higher (43.7 versus 35.1%) in women. The baseline data from EHFS II confirm all the significant findings from the AHEAD registry.

There were no gender-related differences in the use of continuous positive airway pressure mask or mechanical ventilation; however, inotropic agents and levosimendan were less often prescribed to female patients than to male patients.9 In-hospital mortality was 6.6% in all patients without any significant difference between the genders. Mean length of stay in hospital was nine days for both genders (female patients 10.1 days, male patients 9.7 days). There was no gender difference in the proportion of re-hospitalizations for HF after follow-up at three months. The length of stay in hospital is similar in the AHEAD and EHFS II registries, and in-hospital mortality is significantly higher in the AHEAD registry, probably due to the concentration of acute coronary syndromes in the specialized university departments with catheterization laboratories. Acute coronary syndromes and/or pulmonary embolism with HF were associated with high mortality in the AHEAD registry.

Ritter performed a prospective observational study evaluating gender differences among 217 AHF patients (124 men and 93 women).10 Women were older (78±13 versus 72±10 years) and had less pulmonary comorbidity but more noticeable jugular venous distension, as well as lower systolic and diastolic blood pressure and higher ejection fraction (44±14 versus 38±17%). Among contributing causes of acute CHF, myocardial ischemia, and anemia were more frequent in women. The initial outcome, including 30-day mortality, time to discharge, and total treatment cost, was not different between women and men. Important differences were noted during long-term follow-up. Mean cumulative survival was 619 days in women compared with 669 days in men (p=0.0663); however, after multivariate adjustment female gender was not an independent predictor of long-term mortality. Conversely, in the Dispensibility Improvement And Remodeling in Diastolic Heart Failure study (DIAMOND) study from Denmark, female sex was associated with better long-term survival in patients hospitalized with congestive HF.11 Survival analysis included 5,491 consecutive patients admitted with congestive HF to 34 Danish hospitals between 1993 and 1996; follow-up time was five to eight years. Women were older (75 versus 72 years), had less evidence of ischemic heart disease (53 versus 59%), and their ventricular systolic function was preserved to a greater extent than in males (wall-motion index 1.6 versus 1.2; p<0.01). One thousand, five hundred and sixty-nine of the women (72%) and 2,386 of the men (72%) died during the follow-up period. When the age difference between men and women was adjusted for, male gender was associated with an increased risk of death (relative risk [RR] 1.25, 1.17–1.34).

In the US, the Organized Program to Initiate Life-saving Treatment in Hospitalized Patients with Heart Failure (OPTIMIZE-HF) registry included 48,312 patients with AHF. Mean age was 73.1 years, 52% were women, 74% were Caucasian, and 46% had ischemic etiology;12 in-hospital mortality occurred in 1,834 (3.8%). Multivariable predictors of mortality included advanced age, high heart rate, low systolic blood pressure, low sodium, and high creatinine. The US national registry, Acute Decompensated Heart Failure National Registry (ADHERE), reported data from the first 105,388 patients in 2006.13 Women accounted for 52% of these admissions and were older than men (74.5 versus 70.1 years) and more commonly had preserved left ventricular function (51 versus 28%). Based on history, women were less likely to have coronary artery disease (51 versus 64%) and its risk factors, but more commonly had hypertension (76 versus 70%).

Both genders received similar intravenous diuretic regiments, but fewer women received vasoactive therapy (24 versus 31%). Mean length of stay (women 5.9 days, men 5.8 days) and the risk-adjusted in-hospital mortality was similar in both genders. Of 2002, we followed for five years all patients hospitalized at the Internal Cardiology Department of the University Hospital St Ann in Brno.14 From 2,346 hospitalized patients, 320 (13.6%) suffered from chronic HF and 28 (1.2%) died during hospitalization. The in-hospital mortality rate was similar to that not suffering from chronic HF (p=0.3). Women with HF were older and had higher systolic blood pressure and ejection fraction. Of 292 patients who were discharged, 162 (55%) died during the next five years. The pre-determined parameters of pure prognosis were low diastolic blood pressure (p=0.008), low cholesterol (p=0.012), and high creatinin (p=0.009), and there were no gender differences.

Conclusion

More men than women (60:40) are hospitalized with AHF. Only the US registries—ADHERE and OPTIMIZE-HF—had slightly more female patients (52% in both trials). Women are five to six years older than men when admitted with HF: the mean age of women is 73–75 years while that of men is 68–70 years. Women have higher systolic blood pressure—mean systolic blood pressure is 140mmHg for women and 130mmHg for men— while diastolic blood pressure is about 80mmHg for both sexes. HF with preserved left ventricular function predominates in women: mean ejection fraction is slightly over 40% in women and slightly less than 40% in men. Men more frequently have obstructive lung disease, while women more frequently have anemia. Although women are treated less aggressively, treatment gaps exists in both sexes. Despite these differences, length of stay and in-hospital mortality rates are similar, but if adjusted for age, male gender is associated with an increased risk for death.

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