The relationship between health-related quality of life and frequency of spells in patients with syncope

Journal of Clinical Epidemiology 53 (2000) 1209–1216

The relationship between health-related quality of life and frequency of spells in patients with syncope M. Sarah Rosea,*, Mary Lou Koshmanb, Sheila Sprenga, Robert Sheldona,b a

Health Research Group, University of Calgary, 3330 Hospital Drive N.W., Calgary, Alberta, T2N 4N1 Canada b Cardiovascular Research Group, University of Calgary, Calgary, Alberta, Canada Received 26 August 1998, received in revised form 20 March 2000; accepted 20 March 2000

Abstract Chronic syncope has a wide range of symptom burden, and anecdotal data suggest substantial but variable physical and psychosocial morbidity. We hypothesized that health-related quality of life (HRQL) is impaired in syncope patients and the degree of impairment is proportional to syncope frequency. The EuroQol EQ-5D was completed by 136 patients (79 female and 57 male) with mean age 40 (SD ⫽ 17) prior to assessment. HRQL was substantially impaired in syncope patients compared to population norms in all five dimensions of health measured by the EQ-5D. In patients with six or more lifetime syncopal spells there was a significant (P ⬍ 0.001) negative relationship between the frequency of spells and overall perception of health, which was not evident in those who had a history of less than six lifetime spells. These relationships were maintained after controlling for comorbid conditions. © 2000 Elsevier Science Inc. All rights reserved. Keywords: Syncope; Health-related quality of life (HRQL); EuroQol; Population norms; Symptom burden; Comorbidity

1. Introduction

2. Methods

Recurrent syncope can have a substantial impact on a patient’s life. Although previous studies have shown that patients with syncope have no increased risk of early mortality [1] or sudden death [2,3], the severity of the impact of syncope ranges from inconvenience and embarrassment to restrictions on driving and the use of heavy machinery, which may in turn result in an inability to work. The measurement of health-related quality of life (HRQL) provides a vehicle with which we can systematically measure the impact of disease on day-to-day living. Results from an earlier study have suggested that physical and psychosocial impairment in patients with syncope is similar to that reported by patients with other chronic diseases [4,5]. We designed this study to measure HRQL in patients with syncope and to examine the relationship between HRQL and symptom burden. We hypothesized that HRQL is impaired in patients with syncope compared to general population norms, and that the degree of impairment is related to the frequency of syncopal spells. We also investigated which specific concepts of health contribute to overall perceptions of health and well-being in patients with syncope.

2.1. Patient population

* Corresponding author. Tel.: (403) 220-4297; fax: (403) 270-7307.

We employed a cross-sectional study design of all patients presenting sequentially to the syncope clinic for initial assessment and tilt table testing who had no other identified cause of syncope (such as complete heart block or ventricular tachycardia). The sample consisted of 145 patients. Patients underwent tilt table testing if they had: 1) two or more lifetime syncopal episodes, or 2) one syncopal episode and four presyncopal episodes, or 3) one syncopal episode causing serious injury. No patients declined to participate but nine patients were excluded from the analysis due to incomplete data. Patients completed the questionnaires on arrival at the clinic before any clinical interaction with either the physician or the nurses. Therefore, the information was collected prior to tilt table testing and all patients were naive to any counselling or treatment that was subsequently offered. 2.2. Tilt table test Patients underwent tilt table testing in the absence of beta adrenoceptor blocking agents, disopyramide, or drugs with anticholinergic activity in a quiet room after they had fasted for 4–8 h, according to one of two previously published protocols [6,7]. Tilt tests were deemed to be positive if they

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ended in syncope, or presyncope and a drop in rate-systolic pressure product to 9000 mmHg/min. Tilt tests were stopped only with syncope or at the end of a 10-min headup tilt. 2.3. Definitions Syncope was defined as a transient state of unconsciousness characterized by spontaneous recovery or by recovery during the supine position. Presyncope was defined as a state of lightheadedness usually associated with one or more symptoms of decreased vision, the sensation of hearing voices distantly, slow response times to verbal stimuli, nausea, vomiting, or partial loss of postural tone, which substantially reproduced the clinical presyncope of the patient. Symptom burden was measured using the total lifetime number of syncopal spells, the duration of symptoms, and the frequency of syncopal spells (total lifetime number divided by the duration of symptoms) prior to assessment. Duration of symptoms refers to the number of months elapsed between the first historical syncopal spell and the tilt table test. Our primary objective index of illness severity was frequency of syncopal spells per month. We also divided patients into high and low recurrent syncope risk groups, because this guides our approach to treating them. In previous work [8,9] we have shown that patients with a history of at least six lifetime syncopal spells preceding a positive tilt table test have a risk of syncope in the next year of at least 50%. Patients with less than six lifetime syncopal spells have a risk of syncope in the next year of 18%. This criterion was used to select high recurrent syncope risk patients for the recently completed North American Vasovagal Pacemaker Study [10]. Furthermore, this prognostic factor has the same weight for patients with negative or positive tilt table tests [11]. Therefore, patients who had experienced six or more lifetime syncopal spells were defined as being at high risk of experiencing a recurrent syncopal spell within the next year.

was to examine whether there was a difference in comorbidity between the two groups of syncope severity, which might ultimately affect the relationship between HRQL and the frequency of syncope spells. To measure comorbidity in the sample, we used the Charlson comorbidity index [14], using a retrospective chart review. This index is a weighted index that takes into account the number and seriousness of comorbid diseases and was designed to classify comorbid conditions that might alter the risk of mortality for use in longitudinal studies. The conditions and respective weights are included in Table 1. We also considered the Charlson age-morbidity score, in which each decade of life over 40 adds 1 point to the Charlson comorbidity index [15]. It is possible that comorbid conditions may affect HRQL without being risk factors for mortality. Therefore, we have included in Table 1 other conditions that were measured in the development of the Charlson comorbidity index but were not included because they were not predictive of mortality. For each individual the total number of comorbid conditions was also calculated. 2.6. Statistical analysis We first determined whether each variable was normally distributed or skewed. The skewed distributions were analyzed following natural logarithmic transformation. Means (⫾SD) were calculated for normally distributed continuous variables. Geometric means (with 95% confidence intervals) were calculated for skewed variables by backtransforming the logarithmic mean and 95% confidence interval. Frequencies were measured for categorical variables. Differences between high and low recurrent syncope risk groups were examined for statistical significance by a two-sample t-test for continuous variables (using a logarithmic transformation on skewed distributions where appropriate) and by Fisher’s exact test for categorical variables. All P-values are two-tailed without adjustment for multiple P-values.

2.4. Health-related quality of life assessment

2.7. The relationship between frequency of syncopal spells and HRQL

To measure HRQL we used the EQ-5D, which has been designed as an international, standardized, generic instrument for describing and valuing health-related quality of life [12]. The EQ-5D produces an overall index of health status, using a visual analogue scale (the “thermometer”) and classifies health-related quality of life according to five dimensions: mobility, usual activities, self-care, anxiety or depression, and pain or discomfort. Each dimension has three levels that reflect increasing levels of impairment: no problem, some or moderate problems, and extreme problems. In our sample very few patients indicated the latter category. Therefore, we collapsed the categories to indicate either no limitations or problems or any limitations or problems.

We used least squares regression to relate the frequency of syncopal spells (number of lifetime spells divided by the duration of symptoms) to overall perception of health (measured by the EQ-5D thermometer). Patients were stratified by recurrent syncope risk group and the regression analysis repeated within each stratum. For the five categorical dimensions of health, we compared the distribution of the frequency of syncopal spells in patients with impaired health to patients without impaired health, using a two-sample t-test and applying a logarithmic transformation to the frequency. Differences between the groups were described using the geometric mean with 95% confidence intervals.

2.5. Comorbidity

2.8. Contributory factors to decreased HRQL

It is well recognized that comorbidity has an impact on HRQL [13]. Our primary reason to measure comorbidity

We used multiple linear regression modeling, stratified by recurrent syncope risk group, to identify the relative im-

M.S. Rose et al. / Journal of Clinical Epidemiology 53 (2000) 1209–1216 Table 1 The medical conditions that contribute to the Charlson comorbidity index, with weights where applicable Conditions Myocardial Angina Arrhythmia Valvular Myocardial infarction Congestive heart failure Vascular Hypertension Peripheral vascular Cerebrovascular Pulmonary Mild Severe-moderate Neurologic Other Neurologic Dementia Hemiplegia Endocrine Other endocrine Diabetes Diabetes with end organ Renal Mild insufficiency Moderate–severe Liver Mild Moderate–severe Gastrointestinal GI bleeding Inflammatory bowel Peptic ulcer Cancer/immune Tumor Lymphoma Leukemia AIDS Metastatic Cancer Miscellaneous Rheumatologic Coagulopathy

Charlson index weight

Number of syncope patients

1 1

4 10 10 8 2

1 1

10 2 3

1

9 3

1 2

3 0 0

1 2

0 4 1

2

1 0

1 3

0 0 0 1 3

2 2 2 6 6

1 0 0 0 1 1 0

Those conditions without weights were evaluated for the Charlson comorbidity index but not included.

portance of each of the five health concepts in determining overall perception of health. The dependent variable was the EQ-5D thermometer and the independent variables were the five dichotomous health dimensions and the comorbidity index. Using a manual stepwise regression approach, variables were retained in the model if they were significant at the 5% level. We then examined whether the frequency of syncopal spells was a significant predictor of perceptions of overall health by including the frequency in this multiple regression model. 2.9. HRQL in syncope patients compared to population norms To examine our secondary hypothesis the prevalence and age-adjusted prevalence of impaired health for each of the

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five categorical dimensions of health were compared to published UK population norms [16]. The age-adjusted prevalence rate of impaired health reflects the prevalence of impaired health we would expect to see if our sample had the same age distribution as the reference population with which it was being compared. We note the limitations of this comparison due to the different country of origin of the comparison and reference population. Population norms for the EQ-5D are not yet available in Canada.

3. Results 3.1. Patient characteristics The sample consisted of 136 (79 female and 57 male) patients with mean age of 40 years (SD ⫽ 17). Patient characteristics are presented in Table 2 for the group as a whole and stratified according to recurrent syncope risk group (high vs. low 1-year risk of recurrent syncope). The distribution of all three measures of symptom burden were highly skewed and therefore described using the geometric mean with 95% confidence interval. Patients in the high recurrent syncope risk group had a frequency of syncopal spells twice that of patients in the low recurrent syncope recurrent syncope risk group (P ⫽ 0.02) and the duration of their symptoms was substantially longer (P ⬍ 0.001). There were more women in the high recurrent syncope risk group (P ⫽ 0.053), but no significant differences between the two groups were observed due to age or the outcome of the tilt table test. The number of patients in the sample with each of the comorbid conditions is included in Table 1. A summary of the distribution of the comorbidity variables is provided in Table 3. There was no significant difference between the two syncope severity groups in the Charlson comorbidity index (Fishers exact test, P ⫽ 0.261), the age-comorbidity index (Fishers exact test, P ⫽ 0.097), or the total number of comorbid conditions (Fishers exact test, P ⫽ 0.229). 3.2. Impaired health in syncope patients compared to population norms The percentage of patients with impaired health in each of the five health concept variables is presented in Table 4. Results are presented for the groups as a whole because there were no significant differences between the recurrent syncope risk groups in the prevalence of impaired health for any of the five dimensions of health (Fishers exact test, P-values ranging from 0.103 to 0.540). There was evidence of substantially impaired HRQL in syncope patients, irrespective of recurrent syncope risk group, compared to the reference population norms in all five dimensions of health, measured by the EQ-5D. The increase in the prevalence of impaired health was approximately 10-fold for mobility, usual activities, and self-care, and twofold for anxiety/depression. There was no evidence

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Table 2 Characteristics of patients grouped according to illness severity Low risk ( ⬍6 spells)

All patients No. of patients Age (mean ⫾ SD, years) Men Tilt-test (negative) No. of syncopal episodes Median (95% CI) Geometric mean (95% CI) Duration (months) Median (95% CI) Geometric mean (95% CI) Frequency (spells/month) Median (95% CI)

136 40 ⫾ 17 57 (42%) 38 (28%)

a

74 38 ⫾ 16 25 (34%) 16 (22%)

3 (2.6–3.4) 2.5 (2.2–2.9)

0.090 0.053 0.117

16 (9–23) 27.3 (19–38)

60 (37–83) 50 (40–67)

17 (3–31) 20 (13–32)

144 (100–188) 107 (78–143)

0.17 (0.10–0.23) 0.19 (0.14–0.25)

0.14 (0.08–0.20) 0.13 (0.08–0.19)

0.19 (0.06–0.32) 0.26 (0.17–0.39)

⬍.001

0.020

Data for the total number of spells were missing for three patients.

of a difference in the gender distribution between the reference population sample and our sample, ␹21 ⫽ 0.38, P ⫽ 0.54, but there was a significant difference in age distribution between these two samples, ␹25 ⫽ 12.1, P ⫽ 0.034. To account for this difference in age distribution we calculated the age-adjusted prevalence rate of impaired health in the syncope patients. The age-adjusted values of the prevalence were slightly lower than the crude estimates, reflecting the younger age distribution in the syncope sample. 3.3. The relationship between frequency of syncopal spells and HRQL There was a significant curvilinear relationship (illustrated in Fig. 1), between the overall perception of health as measured by the EQ-5D and the (log) frequency of syncopal spells when the group was analyzed as a whole. Overall, the low recurrent syncope risk group had a slightly higher mean overall perception of health (72.6) than the high recurrent syncope risk group (68.5), but this was not statistically significant (P ⫽ 0.221). When the patients were stratified according to recurrent syncope risk, there was no evidence of this curvilinear relationship in either subgroup (P ⫽ 0.15 and 0.25 for the quadratic terms in the low and high recurrent syncope risk groups, respectively). Moreover, there Table 3 The distribution of the comorbidity variables in the sample

0 1 2 3 4 5 6 7

P

a

59 43 ⫾ 18 30 (51%) 20 (34%)

7.5 (5–10) 9.5 (7–13)

Geometric mean (95% CI)

High risk ( ⭓6 spells)

a

was a significant (P ⬍ 0.001) negative linear relationship between the (log) frequency of syncopal spells and overall perception of health in the high recurrent syncope risk group, but this was not observed in the low risk group. Regression lines for the two groups separately are illustrated in Fig. 2. The frequency of syncopal spells was significantly higher in patients with impaired health in terms of mobility (P ⫽ 0.001) and usual activities (P ⬍ 0.001), but not pain or discomfort (P ⫽ 0.074) or anxiety and/or depression (P ⫽ 0.259). These differences are presented in Table 5. The concept self-care was not included in this table, because too few syncope patients indicated problems with self-care to warrant this analysis. In summary, the negative relationship between the frequency of syncopal spells and overall perception of health was observed only in patients who have experienced a lifetime total of six or more syncopal spells. For these high-risk patients, the frequency of syncopal spells was higher for those who experienced impaired health in terms of mobility and performing their usual activities.

Table 4 Comparison of prevalence of impaired health in patients with syncome to UK population norms for each of the five demensions of the EQ-5D Syncope patients Population norms (UK)

Charlson comorbidity index

Charlson age-comorbidity index

Total number of comorbid conditions

121 (89%) 8 (6%) 5 (4%) 1 (1%) 1 (1%)

100 (74%) 10 (7%) 10 (7%) 6 (4%) 4 (3%) 4 (3%) 1 (1%) 1 (1%)

95 (70%) 23 (17%) 10 (7%) 3 (2%) 2 (1%) 2 (1%) 1 (1%)

Dimensions

Prevalence (%)

Mobility

2.9

Usual activities

3.5

Self-care

0.8

Pain/discomfort

35.9

Anxiety/depression

19.1

Prevalence (%) 95% CI

Age-adjusted prevalence (%)

25.9 (18.9–34.3) 37.2 (29.2–45.9) 9.0 (4.9–15.4) 49.2 (40.6–58.0) 43.4 (35.0–52.1)

25.5 33.6 9.6 46.8 40.8

M.S. Rose et al. / Journal of Clinical Epidemiology 53 (2000) 1209–1216

Fig. 1. Curvilinear relationship between health-related quality of life (measured by the EQ-5D thermometer) and the frequency of symptoms (log spells per month). Higher scores indicate better quality of life. The estimated regression coefficients were ⫺6.5 (SE 1.1, P ⬍ 0.001) for log frequency and ⫺0.8 (SE 0.32, P ⫽ 0.011) for log frequency squared.

3.4. Contributory factors to decreased HRQL To investigate which aspects of health were most important in determining overall perception of health, we used the EQ-5D thermometer as the dependent variable in a multiple regression model and the comorbidity variables and the five dimensions as binary predictor variables. Analysis was done separately for the low and high recurrent syncope risk groups. The results of the two regression models are presented in Table 6. In the high-risk group all four dimensions of health (mobility, usual activities, anxiety or depression, and pain or discomfort) were simultaneous, independent significant pre-

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dictors of self-perceived health status. The total number of comorbidities also contributed to a decrease in self-perceived health status in the high-risk group (with borderline significance, P ⫽ 0.057), but neither the Charlson comorbidity index (P ⫽ 0.249) nor the age-comorbidity index (P ⫽ 0.184) was significant when included in the model instead of the total number of comorbidities. After including the four dimensions of health and the total number of comorbidities in the regression model, the log frequency of syncopal spells was still a significant predictor of overall perceived health status (P ⬍ 0.001) in the high-risk group. In the low-risk group the dimensions of health that were significant predictors of overall perception of health were pain and impaired mobility. All three measures of comorbidity were significant predictors of poor health perception, but the Charlson comorbidity index provided the best fitting model. After including impaired mobility, pain, and the Charlson comorbidity index, the frequency of syncopal spells was still not a significant predictor in the low-risk group (P ⫽ 0.193). There was no evidence of a significant effect of age, gender, or the outcome of the tilt table test in either regression model.

4. Discussion The primary finding of this study is that HRQL is linearly associated with the log frequency of syncopal spells, but only in patients with six or more lifetime spells. Our initial analysis described a curvilinear relationship between the frequency of syncopal spells and HRQL. Subsequent analysis, however, indicated that the apparent curvilinear rela-

Fig. 2. The relationship between health-related quality of life (measured by the EQ-5D thermometer) and the frequency of symptoms (spells per month) within each risk group separately. For the high-risk group, the fitted regression line has a slope of ⫺5.9 (SE 1.1, P ⬍ 0.001). For the low-risk group the fitted line indicates the mean value of HRQL because the slope of the estimated regression line was not significant from zero (estimated slope 1.9, SE 1.4, P ⫽ 0.21).

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Table 5 Results of the univariate predictor analysis to examine the relationship between the frequency of syncopal spells and each of the five dimensions of the EQ-5D Geometric mean (95% CI) for the frequency of syncopal spells Health concept

Not impaired

Impaired

Mobility

0.14 (0.10–0.19) 0.12 (0.09–0.17) 0.17 (0.11–0.24) 0.14 (0.10–0.20)

0.49 (0.23–1.02) 0.39 (0.22–0.68) 0.24 (0.13–0.38) 0.24 (0.15–0.40)

Usual activities Anxiety/depression Pain/discomfort

P 0.001 ⬍0.001 0.259 0.074

Results are presented as geometric mean and 95% Confidence Interval (CI) of the frequency of syncopal spells for the two (impaired and notimpaired) groups. The unimpaired group includes individuals who indicated no problems for the dimension and the impaired group includes those individuals who indicated medium to severe problems.

tionship was the result of a highly significant negative linear relationship between the frequency of syncopal spells and HRQL for patients in the high recurrent syncope risk group only. In previous work [8,9] we have shown that patients in these two illness severity groups (⬍6 or ⭓6 lifetime syncopal spells) have a very different prognosis in terms of the risk of recurrent syncope. The results of this study indicate that the number of lifetime spells also has a large impact on their HRQL. In both the high and low recurrent syncope risk groups, patients with impaired mobility experienced the greatest decrease in HRQL followed by those who experienced pain or discomfort. The pain or discomfort experienced by patients with syncope is most likely to be caused by peri-syncopal symptoms, which include headache, vertigo, visual symptoms, diaphoresis, dyspnea, chest pain, palpitations, abdominal pain, nausea, and vomiting. In this study we have measured the frequency of frank syncope, which is quantifiable and memorable. However, almost all patients with recurrent

syncope also experience spells of presyncope. Presyncope is characterized as lightheadedness, accompanied by a number of the above symptoms, without actually losing consciousness. It is likely that the occurrence of presyncope contributes more to the pain and discomfort score in syncope patients than loss of consciousness. Previous studies of impairment in patients with syncope have cautioned that an explanation for the relationship between syncope and impairment may be due to syncope being a marker for the presence of other chronic diseases that cause the impairment [4,17]. This may be true of the lowrisk group but not of the high-risk group. The majority of both our groups consisted of syncope patients with very few comorbid conditions. In the low-risk group, the presence of comorbid disease had a substantial impact on self-perceived health status whereas the frequency of syncopal spells had no impact. Conversely, in the high-risk group the number of comorbid conditions had a minimal impact of self-perceived health status whereas the frequency of syncopal spells showed a dose–response effect on self-perceived health status. Because there was no difference in the presence of comorbid conditions between the two risk groups, this suggests that in the low-risk group syncope is a minor problem compared to the comorbid conditions and that in the high-risk group the converse is true. The negative relationship between frequency of spells and overall perception of health in the high recurrent syncope risk group was observed even after controlling for impaired health in terms of mobility, usual activities, and pain or discomfort and comorbid disease in the multiple regression models. This suggests that for high-risk patients the frequency of syncopal spells has an impact of HRQL over and above that which can be explained by impairment as measured by these core health concepts or by comorbid disease. It is possible that this may be explained by limitations in social activities, which is not measured by the EQ-5D. One of the most important results from this study is that physical impairment has a greater impact than psychological impairment on HRQL. In an earlier study, Linzer et al. [5] suggested that syncope leads to greater psychosocial

Table 6 Multiple linear regression models predicting scores on the EQ-5D thermometer for high-risk and low-risk patients seperately High risk (⭓6 spells)

Low risk (⬍6 spells)

Variables

Estimated coefficient (SE)

P

Constant Log (frequency) Impaired mobility Impaired usual activities Pain/discomfort Anxiety/depression Number of comorbidities Constant Impaired mobility Pain/discomfort Charlson comorbidity index

81.5 (3.2) ⫺3.2 (0.9) ⫺10.2 (4.1) ⫺10.2 (3.6) ⫺10.8 (3.2) ⫺7.0 (3.4) ⫺6.5 (3.4) 78.4 (3.3) ⫺12.1 (5.0) ⫺7.5 (3.5) ⫺18.3 (5.7)

⬍.001 ⬍0.001 0.017 0.006 0.001 0.045 0.057 ⬍.001 0.020 0.036 0.002

For the regression model for the high-risk group the residual SE was 12.22 on the 64 df and the multiple R2 equal to 0.68. For the regression model for the low-risk group the residual SE was 12.0 on 49 df and multiple R2 ⫽ 0.53.

M.S. Rose et al. / Journal of Clinical Epidemiology 53 (2000) 1209–1216

than physical impairment but we consistently found a greater impact of physical impairment rather than psychological impairment in patients with syncope. Linzer et al. used the SCL-90-R to measure mental health status in syncope patients. The SCL-90-R measures psychiatric and psychosomatic morbidity rather than psychological health and well-being, with nine dimensions related to specific types of psychopathology and a Global Severity Index that relates to the general magnitude of psychiatric distress. The subscale of the SCL-90-R on which patients scored highest was the somatization scale, a scale that is designed to measure “distress arising from perceptions of bodily dysfunction.” Derogatis [18] indicates that the symptoms and signs that comprise the items for this scale “all may be reflections of true physical disease.” Specific items in the somatization scale that apply to syncope patients are faintness or dizziness, nausea, or upset stomach. Thus, symptoms attributed to psychological distress may simply be the symptoms of the illness. Linzer also used the Sickness Impact Profile to measure the psychosocial impact of syncope. This scale has four categories, one of which measures the psychological impact of the illness (emotional behavior) and the remaining three measure the social impact of the illness (social interaction, alertness behavior, and communication). The EuroQol group excluded the dimension that measured social relationships because an analysis of the separate contribution of each dimension indicated that social relationships were not, in general, an important contributor to the determining health state valuations [12]. The fact that we were not measuring the social impact of the disease may explain why we obtained such difference results. This suggests that future HRQL studies should separate the psychological effects of syncope from the impact of the disease on the patients’ social interactions and emphasizes the need for a disease-specific measure of HRQL in syncope in addition to a generic measure. The choice of a generic measure enables comparisons to be made with other disease states and facilitates the comparison of different treatments. The EQ-5D has been criticized as less sensitive to subtle changes than other generic measures such as the SF-36 [16]. However, the EQ-5D is preferable in many situations to the SF-36, which provides scores on a number of dimensions but does not provide an overall summary score. The Canadian Center of Health Technology Assessment (CCOHTA) recommended the EQ-5D [19], because the single numeric index provided by the EQ-5D can be interpreted as an estimate of the mean preference score that would be given to that health status by a random sample of the general public. Finally, the EQ-5D is sensitive to changes in disease status. We recently reported that patients with frequent syncope who were successfully treated with pacemakers had a concomitant rise in HRQL measured with the EQ-5D [20,21]. There is a clear need for a disease-specific HRQL scale for syncope. The term disease specific in the context of HRQL can either refer to quality of life concepts that are especially appropriate for particular diseases

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or to limitations in a particular component of HRQL that are attributed to that condition [22]. For syncope patients, examples of the former might be ability to drive and fear of recurrence and an example of the latter may be fatigue specifically attributed to a syncopal spell. Other factors such as presyncopal spells, fear of fainting, or fear and embarrassment as a result of fainting may play a role in overall perceptions of health. Results from this study indicate that the Charlson comorbidity index may be a useful measure of comorbidity in the context of HRQL. The Charlson comorbidity index is usually used to control for the confounding effect of comorbid conditions on overall survival. We used a cross-sectional study design, which means that we can only imply association and not causation between frequency of spells and HRQL. Another limitation of our study is that the patients were recruited from a referral clinic. Therefore, these patients may not be representative of all individuals with syncope (neurally mediated and of unknown cause), but could be considered as patients at the more severe end of the spectrum or those who are not coping well with the disease. Our sample was, however, heterogeneous with the frequency of syncopal spells lying between 0.02 spells/month and 4.5 spells/month in 95% of the sample, suggesting that this sample captured patients with a wide spectrum of disease. Our sample represented a less severe patient group than Linzer’s, because our patients had a median of seven syncopal spells in a median duration of 60 months, compared to Linzer’s patients who had experienced a median number of 10 syncopal spells in a median duration of 11 months [4]. We note that almost 40% of our patients had a negative tilt table test, which adds to the heterogeneity of this sample. However, the outcome of the tilt table test was not a significant predictor of HRQL in this sample, nor was it related to the frequency of syncopal spells. Therefore, for the purpose of this article we feel that it is appropriate to include patients with both positive and negative tilt table tests. The patient population predominantly consisted of young to middle aged adults, with a mean age of 40 years. Therefore, our results may be most relevant to patients of the same ages, although we found no effect of age on any of our measures of health-related quality of life. This is noteworthy, as there is a wide range of reported ages in publications dealing with syncope, from adolescents to the elderly. Illustrative recent papers document mean ages of 21 [23], 34 [24,25], 44 [26,27,28], 49 [29], 57 [30], and 65 [29] years. However, because we did not have a sufficient sample size to perform analyses in prespecified age groups, this does remain a limitation. The current study validates the use of HRQL as an outcome measure in clinical research in this high-risk group of syncope patients. Although we have evidence to support our secondary hypothesis that HRQL is impaired in syncope patients compared to the general population., we must be cautious in the interpretation of these results, due to the nature of the reference group.

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These results provide valuable information for both clinicians and researchers. HRQL is becoming increasingly recognized as an important outcome measure in clinical trials and clinical epidemiology. It is patient oriented, not disease oriented, in that it measures the patient’s perception of his/ her disease. HRQL can be used to evaluate treatments in clinical trials, assess provider performance, monitor the progress of patients receiving treatment for a chronic disease where cure is not a possible outcome, and can be used for cost–utility analysis. HRQL is much easier to measure than the frequency of syncopal spells, especially within a realistic time frame.

[11]

[12] [13] [14]

[15] [16]

Acknowledgments

[17]

Supported in part by a grant from the Medical Research Council of Canada, Ottawa, Canada (PG11188) to R.S.

[18] [19]

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