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European Journal of Heart Failure 2008 10(10):1040-1047; doi:10.1016/j.ejheart.2008.07.003
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© 2008 European Society of Cardiology

Global perceived health and ten-year cardiovascular mortality in elderly primary care patients with possible heart failure

Peter Johanssona,b,*, Anders Broströmb,c, Ulf Dahlströma,b and Urban Alehagena,b

a Department of Cardiology, Linköping University Hospital S-58185 Linköping, Sweden
b Department of Medicine and Care, Faculty of Health Sciences Linköping University S-58185 Linköping, Sweden
c Division of Clinical Neurophysiology, Linköping University Hospital S-58185 Linköping, Sweden

* Corresponding author. Department of Cardiology, University Hospital, S-581 85 Linköping, Sweden. Tel.: +46 13 222223; fax: +46 13 222224. E-mail address: peter.johansson{at}aries.vokby.se (P. Johansson).


   Abstract
Top
 Abstract
1. Introduction
 2. Method
 3. Results
 4. Discussion
 References
 
Introduction: Although multi-item health-related quality of life (HRQoL) instruments provide prognostic information, they are rarely used in routine clinical practice.

Aim: To examine whether a single question about global perceived health (GPH) was a prognostic indicator of cardiovascular (CV) mortality over 10 years of follow-up in elderly patients with possible heart failure (HF) in primary care.

Method: GPH was measured using the first question on the Short-Form-36 concerning current health status. Of the 510 patients who underwent baseline evaluation, 448 patients were included.

Results: Cox proportional regression hazard analysis controlled for age, sex, NYHA class, diabetes, ischaemic heart disease, left ventricular ejection fraction and B-type natriuretic peptide plasma concentrations, showed that patients with GPH rated as "poor" or "good" were at four (HR 4.1 CI 95% 1.8–9.4) and three times (HR 3.4 CI 95% 1.4–7.8) the risk of CV mortality, respectively.

Conclusion: GPH is an independent predictor of CV mortality in elderly patients with possible HF. As a complement to clinical factors when evaluating severity of HF, GPH could be an important tool for identifying patients at risk of adverse CV events and in need of improved treatment.

Key Words: Health status indicator • Mortality • Aging • Chronic heart failure

Received January 22, 2008; Revised May 24, 2008; Accepted July 1, 2008


   1. Introduction
Top
 Abstract
 1. Introduction
2. Method
 3. Results
 4. Discussion
 References
 
Health-related quality of life (HRQoL) provides important information about the impact of chronic heart failure (CHF) on certain aspects of life such as physical, social and mental health [1,2]. Many studies have tried to describe and examine predictors of HRQoL in addition to evaluating the impact of pharmacological and non-pharmacological interventions on HRQoL in patients with CHF [2,3]. Studies have also reported that patients with CHF are willing to improve their HRQoL at the cost of a shorter survival [4]. Other studies have reported that HRQoL is an independent predictor of rehospitalisation and mortality [5-8].

HRQoL can be measured using different types of generic and/or disease-specific instruments. The most commonly used instruments among patients with CHF are the generic Short-Form-36 (SF-36) and the disease-specific Minnesota Living with Heart Failure questionnaire [2,3]. Another approach is to use a battery of different instruments measuring specific aspects of physical, social and mental health [9]. Instruments that measure global perceived health (GPH) by using a single-item question can be an alternative for patients with CHF [2]. Such instruments are regarded as a simple, direct and global means of assessing an unknown array of perceptions, values and preferences related to a respondent's health status in a unique manner [10]. A recent study found that such a single-item question concerning GPH was the strongest variable linked to perceived HRQoL in patients with CHF [11].

Despite their popularity in research, HRQoL instruments are rarely used in routine clinical practice. The major reason is that the scoring and interpretation of these instruments are believed to be time-consuming and too complex for the patients and the clinicians [12,13]. In one study, patients with CHF needed about 15 min to answer the SF-36. In addition, 25% of the group needed assistance to complete the instrument [12]. To facilitate the implementation of HRQoL measurements in clinical practice, two studies reported that a single-item question concerning GPH provided prognostic information in patients with CHF during follow-up periods of 12 weeks and 36 months, respectively [13,14]. However, these studies included patients recruited from clinical trials who had a mean age of less than 65 years [13,14]. Since the majority of patients with CHF in the community have a mean age of around 75 years, studies examining the prognostic information of GPH for patients in the corresponding category are needed. The aim of this study was therefore to examine whether GPH can provide prognostic information concerning cardiovascular (CV) mortality over 10 years of observation in elderly patients with possible CHF in primary health care.


   2. Method
Top
 Abstract
 1. Introduction
 2. Method
3. Results
 4. Discussion
 References
 
2.1. Study population
Baseline data were collected during 1996 in a patient population described previously [15]. In short, the medical records of all patients aged 65-82 years, who had contacted a primary health-care centre in the south east of Sweden due to symptoms and/or signs associated with CHF (shortness of breath and/or peripheral oedema and and/or fatigue), were included. All records (n=1168) were carefully scrutinized by a cardiologist (UA). Those in whom CHF could not be excluded were offered a clinical and echocardiographic examination. A total of 548 patients were contacted, of these 38 decided not to participate because of distance, severe illness, mental insufficiency, or incapacity. Thus 510 patients agreed to participate in the study.

2.2. Clinical examination, echocardiography and peptide measurements
All patients were examined by the same cardiologist. The examination included a new patient history, clinical examination, and Doppler echocardiography (Accuson XP-128c). The echocardiographic examination was performed with the patient in the left-supine position. Systolic function was divided semi-quantitatively by visual estimation into three classes, as follows: normal systolic function corresponded to a left ventricular ejection fraction (LVEF) ≥50%; slightly impaired systolic function, LVEF 40-49%; and impaired systolic function, LVEF <40%. Blood samples were drawn after an overnight fast and seated rest for 30 min. Patients were instructed not to take any medication on the day of sampling until the blood samples had been collected. Blood samples for evaluation of B-type natriuretic peptide (BNP) levels were collected into pre-chilled plastic tubes containing EDTA, placed on ice and centrifuged at 3000 g for 10 min at +4 °C, and then stored at –70 °C. BNP was analyzed by non-extraction immunoradiometric assay (Shionoria, Osaka, Japan) [16].

2.3. Global perceived health
GPH was measured using the question concerning current health status from the SF-36: "In general, would you say your health is...?" [17]. For this question, patients ranked their health as excellent, very good, good, fair or poor. This question has previously been used as a health status indicator in patients with CHF [11,14]. The question has also been used as a determinant of criterion validity for the different domains of the SF-36 [18].

2.4. Mortality
All mortality was registered during the 10-year follow-up period and was collected from the National Board of Health and Welfare, Stockholm, Sweden and from autopsy records. The primary outcome of CV mortality was defined as deaths caused by CHF and/or fatal arrhythmias, sudden deaths due to ischaemic heart disease (IHD), or cerebrovascular deaths. No patients were lost during the follow-up period.

2.5. Statistical analyses
Categorical variables were examined with the Chi-square test whereas continuous variables were examined with Student's t-test. The plasma concentration of BNP was analyzed using Student's t-test after log10 transformations to normality. Quartiles of BNP plasma concentrations were used in the prognostic models. For the question concerning GPH, the patients ranked their health as excellent, very good, good, fair or poor. Since none of the patients in the group with excellent GPH died during the follow-up period, and to facilitate statistical analysis, we amalgamated the groups "excellent" and "very good" GPH into one group: "very good GPH". Those reporting good health were labelled as "good GPH" and those reporting fair or poor health were amalgamated to "poor GPH". In a subsequent analysis we again divided the modified "poor GPH" group into "fair" and "poor" groups. Survival curves for all-cause and CV mortality were obtained by Kaplan-Meier analysis and Log-rank estimations. Univariate logistic regression analyses were done to identify predictors of all-cause and CV mortality. Predictors having an association (p<0.15) with the outcomes were used in the prognostic models. Cox proportional regression hazard analysis was used to evaluate potential predictors of all-cause and CV mortality. A p value of <0.05 was considered statistically significant. Statistical analyses were performed with the SPSS, version 16.0 (SPSS Inc, Chicago, Illinois, USA).

2.6. Ethical aspects
The study protocol was approved by the ethics committee of the Faculty of Health Sciences, University of Linköping. All patients provided written informed consent.


   3. Results
Top
 Abstract
 1. Introduction
 2. Method
 3. Results
4. Discussion
 References
 
3.1. Study population
Of the 510 patients included at baseline, 464 (91%) responded to the question concerning GPH. Due to poor image quality of the Doppler echocardiography, 16 of these patients were excluded. Thus a total of 448 patients were included in the study. Baseline characteristics are described in Table 1. The mean age of the study population was 73 years and 52% were males. Almost 90% of the patients had hypertension and 12% had LVEF <40%. The mean plasma concentration of BNP was 23.2 (SD 33) pmol/l. Sixteen percent of the population rated GPH as very good, whereas 43% rated good and 41% poor GPH. Patients not responding to the question concerning GPH (n=46) did not differ in respect to sex, IHD, LVEF <40% or plasma concentration of BNP. They were, however, older (75 years±5 vs. 72 years±6, p=0.001), a higher percentage were in NYHA functional class III (28% vs. 12%, p=0.002, {chi}2=9.7), and more suffered from diabetes (33% vs. 20%, p=0.038, {chi}2=4.3). A higher percentage also suffered all-cause (70% vs. 38%, p=0.0001, {chi}2=17.6) or CV mortality (50% vs. 24%, p=0.0001, {chi}2=14.1).


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  		Table 1 Baseline characteristics for patients included in the study (n=448) and univariate odds ratios for all-cause and cardiovascular mortality

 
3.2. Global perceived health and mortality
During the 10-year follow-up period, 167 patients (37%) suffered all-cause mortality and 108 patients (24%) suffered CV mortality. Fig. 1 shows the numbers and percentages of all-cause and CV mortality in relation to very good, good or poor GPH. As demonstrated by the Kaplan-Meier analysis (Figs. 2 and 3), there was a significant (p<0.001) association between poor GPH and all-cause and CV mortality. Pair-wise Log-rank comparisons showed that those patients who reported good GPH at baseline had significantly or almost significantly higher rates of all-cause (p=0.02, {chi}2=5.3) and CV mortality (p=0.06, {chi}2=3.5) compared with patients reporting very good GPH. Those patients reporting poor GPH had significantly more all-cause (p=0.003, {chi}2=8.9) and CV mortality (p=0.001, {chi}2=11.8) compared with those reporting good GPH. In the additional analysis of CV mortality (Fig. 4), the group reporting poor GPH were divided into fair (n=167) or poor (n=15) GPH. The groups classified as very good or good GPH were the same as in the previous analysis. CV death during follow-up was significantly higher in patients categorized as poor GPH than in patients categorized as fair GPH (60% vs. 32%, p=0.004, {chi}2=8.2). Patients reporting fair GPH had significantly higher CV mortality compared with patients rating good (32% vs. 20%, p=0.004, {chi}2=8.1) or very good GPH (32% vs. 10%, p<0.001, {chi}2=12.8). The possibility that poor GPH is only a reflection of disease severity cannot be ruled out in these analyses. Therefore, we wanted to analyze whether poor GPH was an independent predictor of CV mortality.


Figure 01
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  		Fig. 1 All-cause and cardiovascular mortality in relation to global perceived health (GPH) defined as very good, good or poor. The numbers in the table represent the number of cases, and the numbers above the bars represent the percentages of all-cause and cardiovascular mortality.

 


Figure 02
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  		Fig. 2 Kaplan-Meier survival curves for 10-year all-cause mortality according to global perceived health (GPH). The p value (p<0.001) is true for the association between poor GPH and all-cause mortality.

 


Figure 03
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  		Fig. 3 Kaplan-Meier survival curves for 10-year cardiovascular mortality according to global perceived health (GPH). The p value (p<0.001) is true for the association between poor GPH and cardiovascular mortality.

 


Figure 04
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  		Fig. 4 Kaplan-Meier survival curves for 10-year cardiovascular mortality according to global health perception score (GPH). In this additional analysis the classification of "poor GPH" was further divided into "fair" and "poor" GPH. The p value (p<0.001) is true for the association between poor GPH and cardiovascular mortality.

 
3.3. Prognostic models for cardiovascular mortality
In Table 2, the prognostic models were adjusted for those variables that were correlated to 10-year CV mortality in Table 1. Model 1 included GPH, sex, age and NYHA class, whereas model 2 included IHD, diabetes, LVEF and quartiles of BNP plasma concentration. In model 3 the variables in models 1 and 2 were combined. Because blood samples were not obtained for all patients studied, models 2 and 3 were only based on patients from whom blood samples had been drawn (n=438).


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  		Table 2 Prognostic model for global perceived health (GPH) and 10-year cardiovascular mortality

 
In model 1 age>75 years was the strongest predictor for CV mortality, with a hazard ratio (HR) of 5.8 (CI 95% 3.0-10.7). Patients with poor GPH or NYHA functional class III had a HR of 3.7 (CI 95% 1.7-8.2) and of 3.6 (CI 95% 2.0-6.3), respectively, for CV mortality. For patients with good GPH, the risk was more than doubled (HR 2.7 CI 95% 1.2-6.0). In model 2 patients with BNP plasma concentrations in the fourth quartile had a more than seven-fold increase in risk (HR 7.2 CI 95% 3.4-15.4), and for those with LVEF<40% the risk of CV mortality was almost trebled (HR 2.6 CI 95% 1.6-4.3). In the model including all variables (model 3), all but two variables, NYHA II and LVEF 40-49%, remained as significant predictors for CV-mortality. BNP plasma concentrations in the fourth quartile (HR 4.4 CI 95% 2.0-9.7) and poor GPH (HR 4.1 CI 95% 1.8-9.4) were found to be the strongest predictors for CV mortality. We also tested models 2 and 3 by adding the variable IHD, however this did not change the results.

In the subsequent analysis, the patient group with poor GPH was divided into fair and poor GPH (Table 3). The analysis revealed more than a seven-fold (HR 7.4 CI 95% 2.3-23.5) increase in the risk of CV mortality among those with poor GPH, whereas those reporting fair GPH were at four times the risk of CV mortality (HR 4.1 CI 95% 2.3-9.3).


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  		Table 3 Additional prognostic model for 10-year cardiovascular mortality for global perceived health (GPH)

 

   4. Discussion
Top
 Abstract
 1. Introduction
 2. Method
 3. Results
 4. Discussion
References
 
This study shows that GPH measured by a single-item question, after adjustment for known risk factors such as impaired NYHA functional class and increased plasma concentrations of BNP, is an independent predictor of CV mortality over 10 years in elderly patients with possible CHF in primary health care. This suggests that a single-item question concerning GPH could be used in routine clinical practice as an aid to identifying patients at risk of adverse CV events and in need of improved management.

The two major goals established in the guidelines for the management of patients with CHF are maintenance or improved quality of life/HRQoL, and increased survival [19]. Therefore, measuring HRQoL and identifying those at risk of adverse outcomes are crucial aspects in the management of CHF patients. One barrier to the implementation of instruments measuring HRQoL in clinical routine, however, is that these instruments are regarded as time-consuming [12,13]. To accomplish the major goals mentioned, utilization of a single question concerning GPH could be a suitable alternative, as it takes only about 15 s to complete and seems to represent an overall assessment of HRQoL [11,20]. Furthermore, GPH has been shown to predict all-cause mortality in middle-aged and elderly people [10]. However, to the best of our knowledge only two studies have evaluated the prognostic ability of a single-item question concerning GPH, in patients with CHF [13,14]. In contrast to the mean age of around 75 years for CHF patients in the community, these two studies were based on patients included in clinical trials with a mean age of 61 and 64 years, respectively. Therefore it is debatable whether these results can be generalized to elderly CHF patients in the community. Another problem is the clinical interpretation, as these studies only reported hazard ratios as a function of the continuous increase within the scales [13,14]. Rumsfeld wrote in an editorial that one problem with HRQoL surveys is that they rarely provide results that suggest a clinical meaning. To achieve this, he suggested that HRQoL scores could be converted into categories, such as poor, good or very good [21]. In our study, a single question concerning GPH was used to evaluate the patients' perception of their own health. The response alternatives to this question also have what could be interpreted as a clinical meaning. After adjustments, we found that patients who scored poor GPH (Table 2) at baseline had a four-fold risk of CV mortality (HR 4.1 CI 95% 1.8-9.4). In the additional prognostic model (Table 3), the risk increased to seven-fold (HR 7.4 CI 95% 2.3-23.5). These results are in accordance with a study evaluating health status and mortality in patients with CHF [22], in which the patients with scores suggesting the highest risk group, or poorest health status, were, after adjustments, at twice the risk of one-year mortality [22]. However, as the risk groups were converted from a 23-item health status questionnaire summary score [22], it is difficult to compare the results obtained from that study with the findings in ours. Recently, another study tested the prognostic significance of three different types of single-item measures of health status (GPH, standard gamble and a "feeling thermometer") in younger patients (mean age 53 years) with advanced CHF who were candidates for heart transplantation [23]. The standard gamble was the only health status measure in this study that remained significant for the combined end-point of heart transplantation or death. As the CHF patients in this study were young, however, the author concluded that the generalizability of the findings to older CHF patients remains to be established.

Another barrier for the implementation of GPH/HRQoL instruments in clinical routines is that some health-care professionals consider them as a reflection of CHF severity as measured by objective clinical findings such as LVEF or BNP [21,24]. There are, however, several reasons to suggest that GPH provides unique information. Support for this comes from studies evaluating the prognostic ability of GPH [13,14]. In one of these studies, GPH remained as an independent predictor of mortality despite adjustment for variables measuring different aspects of CHF severity, such as CHF symptoms, psychological health status (e.g. anxiety and depression), social functioning, activities of daily living, LVEF, age, treatment NYHA functional class, and exercise tolerance [14]. Our study also included plasma concentration of BNP, an established predictor of CV mortality [25,26], as a covariate (Tables 2 and 3). GPH was still found to be an independent predictor of mortality. Luther et al. reported that plasma concentrations of BNP only weakly correlated with the physical aspects of HRQoL, concluding that measures such as BNP and HRQoL may assess different aspects of CHF severity [24]. Moreover, CHF patients with the same degree of physiological impairment may perceive the impact of their CHF differently [24]. Rector et al. had the same experience when reporting that symptoms of CHF and pathologic measures such as low LVEF and increased plasma concentration of BNP only explained 40% and 7%, respectively, of the variation in HRQoL scores. Thus, a substantial part of the CHF patients' scores in HRQoL were not explained by severity as measured by symptoms and pathological measures of CHF [27]. Is it likely that clinical factors are more in focus for the clinician, whereas physical, social and mental functioning are more in focus for the patients? [21] In order to capture all aspects of impairment in the management of patients with CHF, GPH can provide a simple but important complement to clinical measures of CHF severity, because it offers unique, significant information about the patients' own perception of the impact of the disease, which probably goes beyond the objective aspects of CHF.

This study has some limitations. Health is a dynamic concept and may vary over time. A major limitation of this study is that GPH was measured on only one occasion. Further, in the additional prognostic model, only a limited group of patients rated GPH as poor. Therefore, this analysis should be interpreted with caution. Another limitation is that sociological variables such as marital status, educational level, and financial situation were not evaluated at the time of inclusion. This prevented us from adjusting for these variables. Other studies, however, have found GPH to be an independent predictor for mortality after adjustments for such variables [10]. In our study, only 12% of the study population had an LVEF <40%. As echocardiography has a substantial grade of uncertainty, and considering that the patients in this study had visited the primary health-care physician because of symptoms and signs associated with CHF, it is possible that a number the patients might have had CHF which was undetected by Doppler echocardiography. However, if plasma concentration of BNP is used as an objective measure of LV function instead, 75% of patients had a plasma concentration (median 14.2 pmol/L) above the median value (7.0 pmol/L) as measured in a normal reference population of corresponding age and sex, and in the same geographical area. Since we also included BNP plasma concentrations in our analysis, this might mitigate the limitation to some extent. On the other hand, using both LVEF and BNP plasma concentrations might be viewed as over-adjustment, which might reduce the effect of GPH on mortality. Another criticism may be the fact that we included patients in NYHA class I, who could be regarded as not having CHF. However, these patients were included because it is well-known that many patients with decreased systolic function are asymptomatic [28]. In addition, the guidelines for the management of patients with CHF state that CHF patients can be regarded as NYHA class I, if they have objective evidence of cardiac dysfunction, have a past history of CHF symptoms and are on treatment [19]. Diastolic heart failure was not taken into consideration in our analysis, because only thirteen patients had severely reduced diastolic function (pseudonormal pattern or restrictive filling pattern). The patients who did not respond to the GPH question (n=46) were older and had higher NYHA class and higher mortality. However, as the majority (91%) of the patients responded, we do not believe that these few drop-outs had any significant influence on the result. Taking all of these limitations into consideration, we still believe that the results show that GPH is an important aspect in the management of older patients with CHF.

In conclusion, in this study of elderly primary care patients with possible CHF, GPH was found to be an independent predictor of CV mortality. In the management of patients with CHF, identifying those at risk of adverse events is of great importance. We suggest the use of GPH as it is a simple and inexpensive tool to help identify such patients. We also propose that patients with CHF reporting poor GPH should be given priority in the evaluation of HRQoL and a more individualized treatment of their CHF. Such a strategy could help to streamline management, improve HRQoL, and possibly increase the survival of patients with CHF. However, more research is needed to examine the benefit of GPH in clinical practice.


   Acknowledgements
 
The authors wish to thank Maurice Devenney for linguistic assistance and Mats Fredriksson for advice on the statistics in the manuscript. The study was also supported by grants from the Health Research Council in the South-East of Sweden Grant no. F2004-233 and Linköping University Research Foundation CIRC.


   References
Top
 Abstract
 1. Introduction
 2. Method
 3. Results
 4. Discussion
 References
 

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J. Farkas, S. Nabb, L. Zaletel-Kragelj, J. G.F. Cleland, and M. Lainscak
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