Heart failure is the most common reason for hospitalization among those over the age of 65 in the United States. Despite widespread prevention programs and advances in treatment for coronary disease, heart failure incidence rates continue to increase and the prognosis for patients has not improved.1 This may stem partly from the increasingly acknowledged dissonance between traditional beliefs and actual evidence concerning the demographics of heart failure patients.
The healthcare community has become increasingly aware of gender differences in cardiovascular disease. Several studies have determined substantial distinctions between men and women in terms of symptoms,2 treatment,3 prognosis,4,5 and mortality.6 Although typically thought to predominate in men, more than 3.5 million US women per year are hospitalized with cardiovascular disease, a condition that kills substantially more women than men in this country. Among women, mortality rates for heart disease are higher than the rates for the next 7 causes of death combined, including all forms of cancer,7 yet only a minority of women are aware of this.
Women traditionally are underrepresented in clinical trials of heart failure where only about 20% of patients were women (Table 1).8-10 This is particularly noteworthy when contrasted with the approximately 50% representation by women in health plans, epidemiologic studies, and registries.11-15
Heart failure studies have suggested that within the broad spectrum of the syndrome, important differences exist between women and men both in heart failure etiology and in survival.6,16-18 The Framingham study found better prognosis in women than in men after onset of symptomatic heart failure.19-21 The University of North Carolina Heart Failure Database found better survival in women whose heart failure had nonischemic causes.17 The Flolan International Randomized Survival Trial (FIRST) confirmed that women with advanced heart failure appear to have better survival than men, although their finding was most robust among patients with nonischemic cause for heart failure.6 Patient distribution according to left ventricular ejection fraction (LVEF) and age also varies by gender. In a family practice setting, women had later onset of congestive heart failure and their heart failure was predominantly preserved systolic function, while men had higher incidence of systolic dysfunction at all ages.22 Diller found that preserved LV systolic function carried a better prognosis than systolic dysfunction.
Analysis from the Beta-Blocker Evaluation of Survival Trial (BEST) revealed significant differences in baseline clinical and laboratory characteristics between men and women with heart failure.21 In nonischemic patients, women had a significantly better survival rate than men.6,21 A growing body of basic and clinical evidence also exists, which points to fundamental differences in cardiac physiology and myocardial hypertrophy and adaptation that may explain the survival advantage for women with heart failure.6,23
Because women have been severely underrepresented in heart failure trials, an alternative strategy for determining the clinical characteristics, medical treatment, and outcomes for heart failure patients is needed. ADHERE® (Acute Decompensated Heart Failure National Registry), a Web-based registry of patients hospitalized with a diagnosis of acutely decompensated heart failure, was launched in October 2001.24 ADHERE collects data on the clinical characteristics, management, and outcomes of patients hospitalized for heart failure in acute care facilities across the United States. As of January 2004, there were more than 280 participating hospitals with more than 105,000 patient hospitalizations recorded in the Registry, making ADHERE the largest database of acute heart failure patients available. The goal of this study was to analyze ADHERE Registry data to gain insight into any association between gender and medical history, clinical characteristics, and discharge counseling for patients hospitalized with acute decompensated heart failure.
This preliminary study analyzed the population in the ADHERE Registry as of October 2003. The Registry includes consecutive patients who are at least 18 years old and who are admitted to a participating acute care hospital and later discharged with a diagnosis of heart failure. Registry data end with the patient's discharge, transfer out of the hospital, or in-hospital death. To be included in ADHERE, heart failure must be the focus of treatment during the patient's hospitalization and the medical record must be accessible to the person entering data onsite. For ADHERE, acute heart failure is defined as either new onset heart failure or decompensation of chronic, established heart failure with symptoms sufficient to warrant hospitalization.
Data Collection and Patient Confidentiality
Patient ICD-9 discharge codes (Appendix) for heart failure are obtained retrospectively from hospital billing records. For sites with more than 75 eligible patient discharges each month, a Joint Commission for Accreditation of Healthcare Organizations (JCAHO) approved sampling method could be used. No specific therapeutic agents or treatment regimens were required for eligibility.
Institutional review board approval is required for participation in the ADHERE Registry. However, the data collection system is designed so that informed consent of patients is not necessary. Data are collected by retrospective chart review and are only reported in aggregate format. Direct patient identifiers, such as social security number or hospital record number, are not collected because the Registry accumulates data on individual hospitalizations, not on individual patients. Therefore, individual patients who are rehospitalized may be in the Registry more than once. Hospitalizations of women and hospitalizations of men are referred to simply as women and men throughout the manuscript, acknowledging that any particular woman or man may be represented more than once in the data. However, the treatment and outcomes reported are the result of analysis of each hospitalization.
Data collected for the Registry included patient demographic and clinical characteristics, medical practices including medications and procedures associated with healthcare outcomes, and practices relating to 4 specific aspects of the JCAHO Hospital Core Measures quality improvement initiative for heart failure.25 These 4 measures include: discharge instructions, left ventricular function assessment, angiotensin converting enzyme inhibitor (ACEI) for left ventricular systolic dysfunction (LVSD), and adult smoking cessation advice/counseling.
One-way ANOVA (for continuous variables) or chi-square test (for categorical variables) was used to analyze between-sex differences.
Of the 85,617 ADHF hospitalizations recorded in the Registry between October 2001 and October 2003, 44,340 (52%) of the admissions were women and 41,276 (48%) of the admissions were men. Hospitalized women were significantly older (mean age 74.6 ± 13.7 years) than hospitalized men (mean age 70.2 ± 13.9 years, P < .0001). While 72% of all ADHERE patients were white, a marginally larger percentage of women than men were African-American (21% vs. 19%). The initial point of care was more often the emergency department for women than for men (80% vs. 75%).
Medical history and exposure to heart disease risk factors differed between women and men. Women were more likely to have a history of hypertension compared with men (75% vs. 69%, P < .0001) and at admission more women than men had a systolic blood pressure >140 mm Hg (56% vs. 44%, P < .0001). History of coronary artery disease was more common in men than in women (64% vs. 51%, P < .0001). Other risk factors for atherosclerosis, including smoking (17% vs. 10%, P < .0001) and hyperlipidemia (37% vs. 32%, P < .0001), were also more common in men.
The mean LVEF in the total ADHERE population was moderately reduced to 37.4% (n = 60,575). Of the 71% of Registry patients for whom ejection fraction was recorded, men had a significantly lower mean LVEF (32.9%, n = 30,831) than women (42.1%, n = 29,744); 51% of women had preserved LV function (EF > 40%) compared to only 28% of men (P < .0001).
At initial evaluation, some signs and symptoms of heart failure differed between men and women (Table 2). For the 80% of patients who reported the duration of their symptoms, men reported having symptoms longer (median 72 hours, IQR 24, 168) than did women (median 48 hours, IQR 24, 144). When admitted, only 3% (3.1% men, 2.5% women) of patients identified a change in diet and 6% reported a nonprescribed change in their medication (6.6% men vs. 5.0% women) as a possible precipitant to worsening heart failure and hospitalization.
At discharge, in those patients for whom data were reported, adherence to 3 of the 4 JCAHO standardized measures of quality of care for heart failure patients was documented more frequently for men than for women (Table 3).
The large number of patient hospitalizations in the ADHERE Registry, combined with the types of data collected, provides an opportunity to examine characteristics and outcomes for patients hospitalized for heart failure across the United States and to make comparisons between groups. Registry data need to be interpreted with caution. Data are collected by medical chart review and are dependent upon the accuracy and completeness of documentation and abstraction. Additionally, in some instances, the large population size results in statistical significance where percentage differences are marginal and clinical significance must be interpreted carefully. Regardless, in a society that is only recently recognizing that heart failure is not exclusively a disease of men, comparing women with men on the Registry parameters available for this preliminary report allows examination of real-world patients. In the ADHERE Registry, there were more hospitalizations of women than men for heart failure. This result is in sharp contrast to the paucity of clinical trial data about heart failure in women.
In the multisite Beta-Blocker Evaluation of Survival Test (BEST) study's examination of gender differences in heart failure patients, women with heart failure were more likely to be African-American.21 Although 72% of patients in the ADHERE Registry were white, the African-American group contained a marginally greater number of women than men (21% vs. 19%). Women in ADHERE are significantly older than men (mean age 74.6 ± 13.7 years vs. mean age 70.2 ± 13.9 years, P < .0001) and are older than the women in the majority of major heart failure trials shown in Table 1. This finding may be explained by the inclusion of patients with preserved left ventricular systolic function in ADHERE but not in BEST; heart failure due to preserved left ventricular systolic function is known to predominate in older women.22,26 Traditionally, most heart failure trials have excluded this population. Nevertheless, this finding is particularly important as we face an increasingly older population. For example, the life expectancy of 75-year-old women in 2001 was 2.2 years longer than that for age-matched men,27 suggesting that an increasing percentage of the aging population will be women, and therefore, an increasing proportion of heart failure patients will be women. In addition, after the age of 45, the incidence of coronary heart disease increases more steeply for women than for men.28 The proportion of female heart failure patients may be changing for reasons other than changes in population demographics or medical management. From 1990 through 1999, the age-adjusted yearly incidence of hospitalization for heart failure increased much faster for women than for men.29 The sex-based disparity in changing incidence may stem from one or more of several factors: recent increases in prevalence of women with risk factors for heart failure such as diabetes mellitus, hypertension, or obesity;30 delayed effect from increased prevalence of female smokers; greater influence of these risk factors on women compared with men;31 or from other factors.
Our analysis demonstrated that the signs and symptoms of women with acutely decompensated heart failure differed somewhat from those of men. Women, marginally more often than men, presented with dyspnea, pulmonary edema, congestion on chest x-ray films, rales, or some combination of these, whereas men presented with peripheral edema slightly often than women. These results support conclusions from other studies and reviews.32,33 Because clinical tests and algorithms presently used to diagnose heart failure were developed on the basis of systolic heart failure alone as seen predominantly in men, and because many of these algorithms begin with a healthcare professional's clinical impression of heart failure as a possible diagnosis, sex-based disparities in signs and symptoms of heart failure may lead to missed or delayed diagnoses in women.
Slightly more men than women reported a change of diet and/or a nonprescribed change in their medication immediately prior to hospitalization, changes that could be considered noncompliance with prescribed cardiovascular regimens. These results must be viewed with caution, however, because compliance data were self-reported and were reported by a small percentage of the ADHERE Registry population. Substantial data exist that attribute noncompliance as a much more common underlying cause for heart failure hospitalizations than was found with this registry group.34,35
In the ADHERE population, women received somewhat less intensive counseling efforts aimed at improving their prognosis than did men; less counseling could lead to increased rates of rehospitalization and mortality. Management of heart failure patients posthospitalization depends, in part, on educating both patients and their families. The JCAHO established specific discharge instructions for hospitals to ensure that all patients receive the necessary education and counseling. In this analysis, JCAHO Hospital Core Measures indicators for quality of care for heart failure patients were not consistently performed for patients of either sex.
The second JCAHO quality of care indicator requires that left ventricular function be measured before or during hospitalization or that a postdischarge appointment for this test be scheduled by discharge. Measurement of left ventricular function is essential to distinguish between LVSD and left ventricular preserved systolic function. Treatment may vary depending on this measurement. In our analysis, no record of left ventricular function assessment (or scheduled appointment for assessment) existed for about 18% of women and 14% of men. Treatment with an ACEI, the third JCAHO core measure, reduces morbidity and mortality in heart failure patients with LVSD.36 While about one-fourth of both men and women with LVSD did not have a documented prescription for this therapy at discharge, this was true for slightly but still significantly fewer women than men.
Although there is no significant difference between the genders with regard to smoking cessation counseling at discharge, it is striking that only 41% of current smokers among both men and women received this counseling or a prescription for a nicotine patch or other smoking cessation aid. Studies have shown that smokers who receive even brief sessions of smoking cessation advice from their physicians are more likely to stop smoking than those who do not receive any counseling on this issue.37
In gender analysis of discharge counseling, readmission rates could be a factor if they differed between the sexes. This does not appear to be the case. The recently reported EPOCH study of congestive heart failure patients concluded that overall readmission rates and readmission rates specifically for CHF were high, but were not associated with gender. This held true even after adjusting for potential confounders.38 Additional studies have reported equal frequency for readmissions for male and female heart failure patients.39,40
Improvement in compliance with the JCAHO Hospital Core Measures for heart failure provides an opportunity for cardiovascular nurses to improve the quality of care for heart failure patients of either sex. Nurses can educate patients about self-management, compliance, diet, weight management, and smoking cessation tools; can confirm that left ventricular function testing has been done or is scheduled by discharge; and can confirm that appropriate postdischarge medications have been prescribed. In addition, it has been reported that women with heart failure have a lower perceived quality of life than do men with heart failure.34 Because women with heart failure may be at higher risk of depression or other psychosocial distress, they may benefit particularly from support services.41 Although women of all ages respond well to cardiac rehabilitation programs42 and older female patients respond as well as do age-matched male patients, physicians are less likely to refer female heart failure patients to these programs.43 Healthcare professionals would do female heart failure patients a great service by providing them with counseling and information as well as with contacts for support groups and other programs.34,41
Until more specific evidence- and gender-based diagnostic, treatment, and prevention guidelines can be established, high-quality care and self-management education are crucial for all patients with heart failure. Patient-education materials, such as handouts on heart failure, cardiovascular medications, and diet and weight will help patients manage their disease. Using checklists to ensure performance of JCAHO quality of measures for every heart failure patient will help ensure high-quality care. In addition, nationwide education programs, such as the "Go Red for Women" campaign launched by the American Heart Association and programs developed by the Heart Failure Society of America and the American Association of Heart Failure Nurses will help to reshape the public perception of the typical heart failure patient. Expert-based tools and pathways, such as the ADHERE Heart Failure Management Toolkit, are available to provide such resources as treatment algorithms, wall charts, patient cards, and dosing cards.44-46
In the ADHERE Registry for patients hospitalized with ADHF, women accounted for more hospital admissions than men. Women were significantly older, more likely to have a history of hypertension, and more likely to present with heart failure in the setting of preserved LV function than men. Men presented with a greater history of coronary artery disease and its associated risk factors and had a significantly lower mean LVEF than women. Three of the 4 JCAHO standardized measures of quality of care for discharge of heart failure patients were documented more frequently for men than for women.
Analysis of the ADHERE Registry real-world data about patients hospitalized with heart failure may lead to better recognition of the signs and symptoms of heart failure in women, increasing the proportion of women who are diagnosed correctly. A focus on counseling and prevention, coupled with earlier disease recognition and better diagnostic tests and treatments, may ultimately increase the life expectancy of women with heart failure and perhaps even delay or defer the development of systolic dysfunction or heart failure with preserved LV systolic function. Cardiovascular research trials must increase the number of female participants to expand the knowledge base of the diagnosis, pathophysiology, and treatment of heart disease in women. Registries such as ADHERE will continue to collect data to inform the healthcare industry and help to support gender-specific considerations in heart failure guidelines.
The ADHERE Registry Scientific Advisory Committee
William T. Abraham, MD, FACP, FACC, The Ohio State University Heart Center, Columbus, OH
Kirkwood F. Adams, Jr, MD, University of North Carolina, Chapel Hill, NC
Robert L. Berkowitz, MD, PhD, Hackensack University Hospital, Hackensack, NJ
Maria Rosa Costanzo, MD, Midwest Heart Specialists, Naperville, IL
Teresa De Marco, MD, University of California, San Francisco, CA
Charles L. Emerman, MD, FACEP, Cleveland Clinic Foundation, Cleveland, OH
Gregg C. Fonarow, MD, Ahmanson-UCLA Cardiomyopathy Center, Los Angeles, CA
Marie Galvao, MSN, ANP-C, Montefiore Medical Center, Bronx, NY
J. Thomas Heywood, MD, FACC, Loma Linda University Medical Center, Loma Linda, CA
Thierry H. LeJemtel, MD, Albert Einstein Hospital, Bronx, NY
Lynne Warner Stevenson, MD, Brigham and Women's Hospital, Boston, MA
Clyde W. Yancy, MD, FACC, University of Texas, Southwestern Medical Center Medical Center, Dallas, TX
The ADHERE Registry Study Group
Sharon Tellyer, DVM, ELS, Department of Clinical Registries, Scios Inc., Fremont, CA
Janet Wynne, MS, Department of Biostatistics, Scios Inc., Fremont, CA
The authors gratefully acknowledge Dr. Jalal Ghali for his insight and contributions that led to the development of Table 1. The contribution of Clara Davilman, RN to the registry is greatly appreciated.
ADHERE is funded by Scios Inc., Fremont, CA.
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ICD-9 Codes of Heart Failure Patients Enrolled in the ADHERE® Registry
- Hypertensive heart disease malignant with heart failure 402.01
- Hypertensive heart disease benign with heart failure 402.11
- Hypertensive heart disease unspecified with heart failure 402.91
- Hypertensive heart and renal disease malignant with heart failure 404.01
- Hypertensive heart and renal disease malignant with heart failure and renal failure 404.03
- Hypertensive heart and renal disease benign with heart failure 404.11
- Hypertensive heart and renal disease benign with heart failure and renal failure 404.13
- Hypertensive heart and renal disease unspecified with heart failure 404.91
- Hypertensive heart and renal disease unspecified with heart failure and renal failure 404.93
- Congestive heart failure, unspecified 428.00
- Heart failure; left heart failure 428.10
- Heart failure unspecified 428.90
- Unspecified systolic heart failure 428.20
- Acute systolic heart failure 428.21
- Chronic systolic heart failure 428.22
- Acute on chronic systolic heart failure 428.23
- Unspecified diastolic heart failure 428.30
- Acute diastolic heart failure 428.31
- Chronic diastolic heart failure 428.32
- Acute on chronic diastolic heart failure 428.33
- Unspecified combined systolic and diastolic heart failure 428.40
- Acute combined systolic and diastolic heart failure 428.41
- Chronic combined systolic and diastolic heart failure 428.42
- Acute on chronic combined systolic and diastolic heart failure 428.43