© 2008 European Society of Cardiology
Long-term survival in patients older than 80 years hospitalised for heart failure. A 5-year prospective study
INSERM, ERI 12 Amiens, France and University Hospital Amiens France
* Corresponding author. Department of Cardiology, Avenue René Laënnec, 80054 Amiens Cedex 1, France. Tel.: +33 3 22 45 58 83; fax: +33 3 22 45 56 58. E-mail address: Tribouilloy.Christophe{at}chu-amiens.fr (C. Tribouilloy).
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Abstract |
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 Top Abstract 1. Introduction2. Methods3. Results4. Discussion5. ConclusionAcknowledgmentReferences |
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Background: Although heart failure (HF) is frequent in elderly patients, few studies have focused on patients older than 80 years.
Aims: To evaluate the clinical features, treatment and long-term prognosis of HF in patients older than 80 years.
Methods and results: Consecutive patients hospitalised for a first HF episode in the Somme Department (France) during 2000 were prospectively included. Of the 799 included patients, 305 (38%) were aged over 80 years. The elderly patients were mostly women with a high prevalence of atrial fibrillation, ischaemic and hypertensive heart disease. Ejection fraction (EF) was assessed in 68.5% of elderly patients and 61% had EF 
50%. Angiotensin-converting enzyme inhibitors, beta-blockers, oral anticoagulants and statins were prescribed less frequently in elderly patients. The 5-year survival in elderly patients was 19%, dramatically lower than the survival of age- and sex-matched general population (48%). Cardiovascular causes were recorded in over 60% of deaths. On multivariable analysis, cancer, renal insufficiency, old myocardial infarction, diabetes, hyponatraemia and age were predictors of mortality in elderly patients. Reduced EF was a potent predictor of death (HR 1.72, 95%CI 1.24–2.37, p=0.001) in elderly patients.
Conclusion: Long-term prognosis in HF patients older than 80 years is poor, with a dramatic excess mortality compared to the elderly general population. Life-saving drugs are largely underused in elderly HF patients.
Key Words: Heart failure • Elderly • Prognosis
Received June 29, 2007; Revised September 26, 2007; Accepted November 12, 2007
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1. Introduction |
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TopAbstract1. Introduction2. Methods3. Results4. Discussion5. ConclusionAcknowledgmentReferences |
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Heart failure (HF) represents a growing cause of morbidity and mortality worldwide. The prevalence of HF increases with age, reaching figures as high as 10-12% in patients older than 80 years [1]. HF is one of the leading causes of hospitalisation in elderly patients [2]. The number of hospitalisations for HF is constantly increasing, particularly in the elderly [3]. Aging of the population and the improved outcome of cardiovascular diseases will result in a marked increase in the prevalence of HF in the future. It is estimated that the number of elderly patients with HF will double by the year 2030 [4], resulting in a total HF population of about 3.6 million in France.
Clinical trials conducted in HF have mostly included male patients with a mean age of 60-65 years and systolic dysfunction. Although more than half of all hospitalised patients with HF are older than 75 years, such patients are largely underrepresented in clinical trials [5]. Old patients with HF differ from their younger counterparts in terms of aetiology, left ventricular (LV) function, comorbidities, and treatment tolerability [4,6]. Few reports have focused on HF patients older than 70 years [7-10] and very few data are available on patients older than 80 years. Recent data from the EuroHeart Failure Survey, which focused on short-term outcome, showed that octogenarians with HF have a poor short-term survival and are not managed in accordance with HF practice guidelines [11]. To our knowledge, there are currently few data on the long-term prognosis of octogenarians with HF.
The aims of the present study of consecutive patients hospitalised for a first episode of HF were to: 1) determine the clinical features, long-term prognosis and treatment of patients older than 80 years and 2) compare the long-term prognosis of these patients with their expected survival and with the outcome of younger HF patients.
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2. Methods |
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TopAbstract1. Introduction2. Methods3. Results4. Discussion5. ConclusionAcknowledgmentReferences |
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2.1. Study population and inclusion criteria
The Somme Department is a region of France with a population of 555, 551 inhabitants according to the 1999 census. The Somme Department has a total of 11 healthcare establishments managing patients with HF: 1 university hospital, 7 general hospitals, 2 private clinics and 1 medium and long-stay unit. General practitioners, cardiologists and internal physicians from all of these centres agreed to participate in this study. Consecutive patients aged >20 years, hospitalised for a first episode of HF in these healthcare establishments during 2000 were prospectively enrolled. The diagnosis of HF was made by the physician caring for the patient, based on history, symptoms, physical signs and chest X-ray on admission. During the index hospitalisation, two cardiologists, who were specifically recruited for this purpose, reviewed all medical records in order to validate the diagnosis of HF according to the Framingham criteria amended by the European Society of Cardiology [12]. Twelve patients did not meet these criteria, and were therefore excluded. A total of 799 patients (410 males and 389 females) were finally included. Patients older than 80 years represented 38% of the study population (n=305).
2.2. Data collection
Clinical data including medical history, cardiovascular risk factors and results of other investigations (laboratory tests, ECG, chest X-ray on admission, echocardiography) were recorded on individual case report forms.
Ejection fraction (EF) was determined during hospitalisation by echocardiography (n=648) and/or left ventriculography (n=103). Echocardiograms were recorded according to the guidelines of the American Society of Echocardiography [13]. When more than one method was performed, an average EF was calculated. As usually recommended, an EF value 50% was used to define heart failure with preserved ejection fraction (HFPEF) [14]. An assessment of the EF was available for 83% of the study population. An estimate of the glomerular filtration rate on admission was calculated using the simplified MDRD formula including age, race, sex and serum creatinine [15]. Hyponatraemia was defined as a sodium level <135 mEq/l.
Ischaemic aetiology was assumed in patients with a history of ischaemic heart disease, recent documented history of myocardial infarction (MI) or angina pectoris, or coronary artery disease confirmed by coronary angiography [6]. A patient was considered to have hypertension in the presence of any of the following criteria: high blood pressure during hospitalisation (>160/95 mm Hg), previous diagnosis of hypertension or normal blood pressure with ongoing antihypertensive therapy [16]. HF due to valvular heart disease was identified on the basis of clinical history, physical examination and echocardiography. Dilated cardiomyopathy, restrictive and hypertrophic cardiomyopathy, constrictive pericarditis and other rare aetiologies of HF were diagnosed in a minority of cases.
Medical treatment records were completed at discharge and 1, 3 and 5 years after discharge. Prescription of the main therapeutic classes in HF was recorded.
2.3. Prognosis
Total mortality and cardiovascular mortality were determined at 1, 3 and 5 years. Sudden death was classified as cardiovascular death. The vital status at 1, 3 and 5 years was obtained either by a consultation with the general practitioner or the referring cardiologist or by consulting the civil registry. Cause of death was ascertained from hospital records, death certificates, and autopsy records or by contacting the patients' physicians. Five patients younger than 80 years were lost to follow-up at 5 years.
2.4. Statistical analysis
Continuous variables were expressed as mean±standard deviation and were compared between groups using Student's t-test. Categorical variables were summarized by frequency percents and analyzed by a Chi-square test. Univariate and multivariable analyses of mortality were made using Cox proportional hazards models. Covariates considered to be of potential prognostic impact (age, sex, history of MI, hypertensive aetiology, diabetes mellitus, stroke, cancer, creatinine clearance on admission) and factors associated with 5-year mortality on univariate analysis (p value<0.15) were entered in the multivariable models in a backward stepwise regression analysis to identify independent predictive factors for total mortality in elderly patients. A second multivariable model was run in elderly patients who had an assessment of EF (n=209) and included EF as covariate. In elderly patients surviving the index hospitalisation (n=267) the multivariable model was adjusted to the treatment at discharge. Age was entered in the models as a continuous variable while all other covariates were entered as dichotomous variables. The criterion for statistical significance was p<0.05. Survival curves for the two groups (patients older and younger than 80 years) were estimated by the Kaplan-Meier method. Differences in time-to-death between groups were analyzed using a two-sided log-rank test.
Data on survival of the two groups were compared with the expected survival of subjects of the same age and sex in the Somme Department (France). Control data were obtained from French life tables for the Somme Department for 1999 provided by the French Institute of Statistics (INSEE) and represent the survival of the Somme general population. Relative survival was computed as the ratio of observed to expected survival (observed number of deaths/expected number of deaths in the general population). Data were entered into a SPSS 13.0 statistical software file on a PC (SPSS Inc., Chicago, IL, USA).
2.5. Ethics
The study conforms to the principles outlined in the Declaration of Helsinki and was approved by local institutional review boards. Informed consent was obtained from the patients before entering data into the electronic database. The database was approved by the CNIL (French computers and privacy commission).
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3. Results |
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TopAbstract1. Introduction2. Methods3. Results4. Discussion5. ConclusionAcknowledgmentReferences |
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3.1. Baseline characteristics and treatment
Seven hundred and ninety nine patients were included (mean age 75±12 years). Forty-nine percent of patients were women. Three hundred and five patients (38.2%) were older than 80 years. Table 1 presents the baseline characteristics of octogenarians compared to their younger counterparts. Elderly patients comprised a large proportion of women with a high prevalence of ischaemic and hypertensive heart disease. Older patients exhibited more atrial fibrillation on admission. Co-morbidities such as stroke, peripheral artery disease, chronic obstructive pulmonary disease (COPD) and cancer, had a similar prevalence in old and young patients. Diabetes was more prevalent in younger patients.
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Elderly patients received less intensive medical care in terms of diagnostic procedures and therapy and had longer hospitalisations (12.2±7.9 vs. 9.9±6.2, p<0.001). Only 68.5% of elderly patients had an assessment of EF, compared to 92% of patients in the younger group. The mean EF was 52.2%±16 in elderly patients compared to 49.6%±16 in the younger group. Sixty-one percent of elderly patients had HFPEF. Fewer old patients were admitted to cardiology departments and intensive care units. As expected, patients older than 80 years had significantly more hospitalisations in geriatric departments. ACE-inhibitors were prescribed significantly more frequently in younger patients at discharge (Table 1) and at 1 and 3 years of follow-up. Beta-blockers, statins and oral anticoagulants were administered more often in younger patients at discharge as well as during follow-up. Older patients more often received aspirin and nitrates (Table 1).
3.2. Prognosis
During the 5-year follow-up, 247 patients older than 80 years died (81%). Survival rates at 1, 3 and 5 years after admission in octogenarians were 56%, 33% and 19%, respectively, compared to 80%, 64% and 52% in younger patients (p<0.001), respectively (Fig. 1A). Compared to the expected survival of an age- and sex-matched general population (Fig. 1B), the 1, 3 and 5-year survival rates in HF patients older than 80 years were dramatically lower (56% vs. 88%, 33% vs. 66%, and 19% vs. 48%, respectively). Younger HF patients also had a poorer survival than the matched general population, but the difference was less impressive. One-year, 3 and 5-year relative survival rates of octogenarians were lower than those of the younger group (64% vs. 82%; 49% vs. 71% and 40% vs. 62%, respectively; Fig. 2).
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On multivariable analysis, after adjustment for predictors of mortality identified by univariate analysis, age greater than 80 years emerged as a potent independent predictor of overall mortality (HR=1.97, 95%CI 1.62 to 2.41, p<0.001). In patients older than 80 years, on univariate analysis, older age (HR=1.06; 95%CI 1.04 to 1.09; p<0.001), history of MI (HR=1.64; 95%CI 1.17 to 2.31; p=0.004), ischaemic aetiology of HF (HR=1.33; 95%CI 1.04 to 1.71; p=0.026), cancer (HR=1.59; 95%CI 1.11 to 2.28; p=0.012), reduced EF (HR=1.61; 95%CI 1.17 to 2.20; p=0.003), renal insufficiency (HR=1.57; 95%CI 1.19 to 2.07; p=0.001) and hyponatraemia (HR=1.38; 95%CI=1.03 to 1.84; p=0.031) were factors associated with poorer outcome. On multivariable analysis, cancer, renal insufficiency, history of MI, diabetes mellitus, hyponatraemia and older age were identified as independent predictors of overall mortality in elderly patients (Table 2). The same independent predictors of 5-year overall mortality were identified in octogenarians surviving the index hospitalisation (Table 2). In the group with an assessment of the EF, on multivariable analysis, reduced EF was a potent predictor of a poorer 5-year outcome (Table 2). In elderly patients, cardiovascular causes were responsible for more than 60% of deaths. Cardiovascular mortality rates in elderly patients were significantly higher than in the younger group (31% vs. 14% at 1 year, 44% vs. 22% at 3 years and 50% vs. 29% at 5 years; p<0.001).
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4. Discussion |
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TopAbstract1. Introduction2. Methods3. Results4. Discussion5. ConclusionAcknowledgmentReferences |
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Significant clinical and prognostic features were identified in HF patients older than 80 years. The major finding of the present study is the very poor long-term prognosis of octogenarians with HF and the impressive excess mortality compared to an age- and sex-matched general population. Marked differences from the expected survival were observed in elderly HF patients (twofold increase in mortality at 3 years and approximately threefold increase in mortality at 5 years). As expected, the prognosis in elderly HF patients was found to be dramatically poorer than that of younger HF patients. Cancer, renal failure, history of MI, diabetes mellitus, hyponatraemia, older age and reduced EF were identified as factors associated with a poorer outcome in HF patients older than 80 years. Cardiovascular causes of death were predominant in elderly patients. ACE-inhibitors, beta-blockers, statins and oral anticoagulants were prescribed less often in this group of patients.
4.1. Prevalence, characteristics and treatment of HF in elderly patients
The patients in the present series were old, with an average age of 75 years and more than one third of the study population was older than 80 years. These figures clearly reflect the modern demography of HF patients. Of the 7,788 patients included in the Digitalis Investigation Group Study, 32% were older than 70 years [17]. The EuroHeart Failure Survey reported that 51% of women and 31% of men admitted for HF were over 75 years of age [18]. A community-based retrospective study conducted in the Olmsted County also showed a high proportion of octogenarians among HF patients [6].
It is now well recognized that the prevalence of HF increases with age [19]. Significant differences between old and young patients with HF were noted in the present study. Elderly patients had a higher prevalence of hypertension and ischaemic heart disease. The prevalence of hypertension was 67% among elderly patients, which is in accordance with figures reported in large studies, such as the National Heart Failure Project (62%) and the Cardiovascular Heart Study (55%) [20]. Renal failure was more prevalent among elderly patients. Atrial fibrillation was recorded in over 35% of elderly patients, mainly due to ischaemic and hypertensive heart disease. Interestingly, the prevalence of diabetes among younger patients was almost twice that observed in elderly patients.
Females were over-represented among octogenarians with HF. Elderly individuals had a high prevalence of HFPEF (61%). This high proportion of preserved EF in the elderly and in women has also been observed in other studies [6,18,19,21].
Overviews of trials with ACE-inhibitors and beta-blockers have demonstrated that the benefits on mortality apply to both young and old patients. However, in our study, patients older than 80 years were significantly less likely to receive ACE-inhibitors and beta-blockers compared to younger individuals. Our findings are consistent with data from a recent study in outpatients with HF showing that ACE-inhibitors and beta-blockers were prescribed significantly more frequently in patients under the age of 70 years [22]. Inherent difficulties in therapy management and perhaps a higher prevalence of renal insufficiency at advanced ages may account for the lower prescription rates of ACE-inhibitors in elderly HF patients. Beta-blocker treatment was recently reported to be well tolerated and not associated with an increased risk of adverse events in elderly HF patients [23].
4.2. Survival and predictors of outcome
Despite a high prevalence of HF at advanced ages, elderly patients are generally excluded from clinical trials. Moreover, most HF trials use a low EF as an inclusion criterion, thereby excluding at least half of all elderly patients with clinical HF. Therefore, trials may not reflect the real prognosis and response to treatment of older individuals. Several hospital- and community-based studies have included patients about a decade older than patients in clinical trials. A Danish community-based study that included patients with a first diagnosis of HF between 1993 and 1998 reported 3- and 5-year mortality rates of 55% and 65%, respectively, in patients older than 76 years [24]. In a selected cohort of elderly patients with prior MI (mean age 82 years), Aronow et al. observed 1-year mortality rates ranging from 19% to 41% depending on the EF, but nevertheless higher than the 20% mortality rate observed in younger patients [8]. In a recent report from the large EuroHeart Failure Survey I database, octogenarians with HF had a poor short-term outcome, with a 25% mortality rate over the 12-week follow-up [11].
In our study, the 3- and 5-year overall mortality rates in elderly patients after a first admission for HF were 67% and 81%, respectively.
As expected, age represented an independent predictor of outcome in our elderly patients, in accordance with previous reports [9,22]. Interestingly, reduced EF was identified as an independent predictor of poorer outcome in octogenarians although there is growing evidence in favour of similar outcomes for HFPEF and HF with reduced EF [25]. However, this issue has not yet been addressed in very elderly patients.
Our findings underline the extremely poor prognosis of HF in very old patients. The goals of HF therapy in elderly populations are often different and quality of life may be more relevant for the attending physician than prolongation of life. Nevertheless, since all evidence-based therapies also reduce symptoms and improve quality of life, a better use of guideline-oriented therapies is preferred to "comfort care measures". Moreover, managing HF in the elderly can be particularly difficult because of a higher prevalence of cognitive impairment and depression. As these are factors that lower treatment adherence, complex programmes are needed in elderly populations with HF. In our cohort, medical treatment was less intensive in elderly patients during follow-up. Our findings emphasize the need for effective multidisciplinary strategies to improve the survival of this population.
4.3. Limitations
Our study was exclusively hospital-based, with the advantage of allowing prospective recruitment of all individuals hospitalised for a first episode of HF. Therefore, patients with HF treated exclusively on an outpatient basis or in a long-term care facility were not included. Our patients were enrolled from all establishments managing patients with HF: community hospitals, private clinics and one university hospital. This should reduce referral bias of hospital-based studies performed exclusively in tertiary centres. Echocardiography was not systematically performed during the first few hours after hospital admission, as in most epidemiologic studies of this type. However, LV function was evaluated in 83% of patients, an acceptable figure compared to most studies [6,25]. Age-related conditions of potential clinical and prognostic importance, such as disability, depression, dementia, gait, and visual and auditory impairments, were not available in our population. Therefore, comorbidity rate was probably underestimated.
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5. Conclusion |
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TopAbstract1. Introduction2. Methods3. Results4. Discussion5. ConclusionAcknowledgmentReferences |
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This prospective, hospital-based study confirms the high proportion of patients older than 80 years among the HF population. The prognosis of these elderly patients is very poor after a first hospitalisation for HF, with a 5-year overall mortality rate as high as 81%, a high prevalence of cardiovascular mortality and an impressive excess mortality compared to an age- and sex-matched general population. The benefit of classical treatment is less clearly established in this growing population. Further studies are needed to clearly define reliable treatment guidelines in this particular category of HF patients.
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Acknowledgment |
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TopAbstract1. Introduction2. Methods3. Results4. Discussion5. ConclusionAcknowledgmentReferences |
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This study was funded by a grant from the French Ministry of Health.
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