Psychosomatics 45:114-118, April 2004
© 2004 The Academy of Psychosomatic Medicine
Vital Exhaustion as a Risk Indicator for First Stroke
G.E. Schuitemaker, Pharm.D.,
G.J. Dinant, M.D., PH.D.,
G.A. Van Der Pol,
A.F.M. Verhelst, M.D., and
A. Appels, PH.D.
Received Nov. 5, 2002; revision received April 22, 2003; accepted May 15, 2003. From the Department of General Practice, the Care and Public Health Research Institute, and the Department of Medical Psychology, University of Maastricht. Address reprint requests to Dr. Dinant, Department of General Practice, University of Maastricht, the Netherlands; geertjan.dinant{at}hag.unimaas.nl (e-mail).
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ABSTRACT
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Fatigue is a common condition after stroke. An unresolved question is whether the fatigue is a consequence of the stroke or is one of the precursors. The authors' objective was to investigate whether vital exhaustion is a precursor of first stroke while controlling for other cardiovascular risk factors. The design was a prospective cohort study. Vital exhaustion was diagnosed with the Maastricht Interview Vital Exhaustion scale. The authors controlled for age, gender, diabetes mellitus, systolic and diastolic blood pressure, total cholesterol, body mass index, and smoking habits as possible confounders. Data were analyzed with Cox regression analysis. The subjects were adults ages 41–66 in an average Dutch village population. Outcome measures included first stroke. Vital exhaustion increased the risk of stroke by 13% per vital exhaustion point on the Maastricht Interview Vital Exhaustion scale. This value remained statistically significant after control for other risk factors. Total cholesterol, diastolic blood pressure, systolic blood pressure, diabetes mellitus, and smoking also increased the risk of stroke significantly. A state of exhaustion is one of the risk indicators for stroke. This means that the fatigue so often seen after stroke was already experienced by many patients before the occurrence of the stroke.
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INTRODUCTION
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Worldwide, stroke is the second most prevalent cause of death after heart disease.1 Identification of risk factors is the mainstay of primary stroke prevention. In the case of stroke, the factor most generally recognized as the principal risk factor is hypertension.2 Other risk factors are myocardial infarction, especially in the first month after the event, diabetes mellitus, and smoking. Dyslipidemia, including hypercholesterolemia, has not been clearly established as a risk factor, although some studies with the lipid-lowering 3-hydroxy-3-methylglutaryl coenzyme A reductase agents (statins) have shown a decrease in the risk of stroke after myocardial infarction.3,4 One study5 reported overweight to be associated with a higher risk of stroke in middle-aged men, and the level of physical activity may be indirectly connected to the risk of stroke.2
Fatigue is a common condition after stroke. In one study, 68% of 88 men and women diagnosed with stroke reported problems with fatigue in contrast to 36% in a comparison group (p<0.001).6 Fatigue was defined as a feeling of physical tiredness and lack of energy.
Similar observations have been made in cardiovascular patients. Many patients feel tired, distressed, or even depressed after a myocardial infarction.7,8 Epidemiological studies investigating the precursors of myocardial infarction showed that these feelings had already existed before the occurrence of myocardial infarction in the majority of patients.9 This prodromal state was labeled by Appels10 as vital exhaustion, a state characterized by unusual fatigue, loss of energy, increased irritability, and feelings of demoralization.
This observation induced us to test the hypothesis that a state of exhaustion precedes the onset of stroke and, consequently, is one of the risk indicators of stroke. This hypothesis was tested in the so-called Mierlo project.
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METHOD
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Design
The Mierlo project was conducted with the adult population of the village of Mierlo in the Netherlands. All inhabitants ages 41 to 66 years received a questionnaire by mail asking for the presence of cardiovascular risk factors (heredity, diabetes mellitus, hypertension, overweight, smoking habits, and a cardiovascular condition). The subjects who answered one or more questions in the affirmative were invited to visit a location in the village that was separate from the health center and specially equipped for this project. Measurements taken at this visit included systolic and diastolic blood pressure, height and weight (used to calculate body mass index), smoking habits, and cholesterol level. In subjects with a total cholesterol >7.0 mmol/liter, cholesterol assessments were repeated twice. The subjects with a mean total cholesterol >7.0 mmol/liter for the three assessments were invited to participate in a randomized clinical trial investigating the effect of a lipid-lowering drug. The subjects who were found to be at a higher risk for cardiovascular disease according to a model adapted from Anggard et al.11 were invited to visit their general practitioner every 3 months over a period of 1 year for surveillance and counseling with regard to their cardiovascular risk profile (a monitoring study). Details about both interventions have been described elsewhere.12
At the first visit to the health center, all subjects were administered the Maastricht Interview Vital Exhaustion scale.13 This measure was administered by a trained nurse practitioner and a trained research nurse, according to current standards. The interview consists of 23 questions regarding unusual fatigue, loss of energy, increased irritability, and feelings of demoralization, all scored as absent or present. Thus, the minimum score is zero, while the maximum score is 23. The duration of one interview was approximately 15 minutes. Those who were interviewed constituted the cohort of the current study.
Endpoint Definition and Statistical Analyses
The endpoint assessed in the present study was the first stroke. If a person was found to have suffered more than one stroke since the original examination, the first event was regarded as the endpoint. The endpoint was assessed in the period between January 1998 and October 1998, based on data from the general practitioner's patient records. The International Classification of Primary Care was used to define "stroke." Endpoint diagnoses were confirmed by a medical specialist.
Patient records were inspected to exclude the possibility that vital exhaustion could have been caused by a previous stroke. One subject was found to have suffered a stroke before the interview and was excluded. None of those who suffered a stroke during the follow-up period had suffered any strokes before enrollment in the study.
Data were analyzed by means of Cox regression analyses, using continuous vital exhaustion scores. Since the number of incident cases of stroke was small, which might result in unstable risk estimates, data were analyzed in two steps. The first step involved calculating the risk of exhaustion by using Cox regression analysis and controlling for one possible confounder. In the second step, all factors found to be associated with incident stroke in the first step were simultaneously included in a Cox regression analysis. If the risks computed in the second analysis are comparable with those computed in the first step, one may assume that the estimates of the multivariate model are not seriously invalidated by the small number of incident cases. We also used a dichotomous score for "exhausted versus not exhausted," with a cutoff point between the ranges of 0–7 and 8–23.13
The independent covariates included were age, gender, total cholesterol level, systolic blood pressure, diastolic blood pressure, diabetes mellitus (question 3 of the questionnaire), body mass index, and smoking habits (yes or no). Data were entered into SPSS, version 8.0. All p values were two-tailed.
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RESULTS
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The screening questionnaire was sent to 3,276 subjects. A total of 3,061 questionnaires (93%) were returned. We discovered that 455 subjects (15%) had not answered "yes" to any of the questions. The remaining 2,606 subjects were invited to visit the selection center. This invitation was declined by 147 subjects (6%). Seven subjects (0.2%) did not visit the selection center because they had moved out of Mierlo or had died between the beginning of the study and the assessments. Of those who visited the selection center, 19 (1%) had to be excluded because of language difficulties. This left a cohort of 2,432 subjects, of whom 167 participated in the randomized controlled study and 458 in the monitoring study.
The median duration of follow-up was 50.9 months (SD=6.1, range=9.5–62.7). During this period, 14 subjects suffered a first stroke (seven men and seven women). Table 1 shows the characteristics of the cohort at the time of examination and the administration of the Maastricht Interview Vital Exhaustion scale, as well as univariate analyses using t tests and chi-square tests.
The risk of stroke increased by 13% for each additional vital exhaustion point on the Maastricht Interview Vital Exhaustion scale (Table 2). This figure was statistically significant and hardly changed after control for other possible confounders was instituted. When all possible confounders were included simultaneously in the equation, the relative risk associated with vital exhaustion remained unchanged (relative risk=1.13). The relative risk associated with exhaustion found when we used a dichotomous score and controlled for all possible confounders simultaneously was estimated as 3.52 (95% confidence interval [CI]=0.97–12.73).
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TABLE 2. Vital Exhaustion as a Risk Predictor for Stroke, With Cox Regression Analysis and Control for Single Factors
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Since the Mierlo project included two intervention studies, we checked whether participation in one of these two studies influenced the association between vital exhaustion and stroke. None of the future stroke patients had participated in the randomized controlled study. Furthermore, the results of the randomized controlled study indicated that the lipid-lowering agent had no significant effect compared to placebo.13 Five of the future stroke victims had participated in the monitoring study. Controlling for participation in that study did not influence the results of the Cox regression analysis.
Significant associations were found also for diabetes mellitus, smoking, total cholesterol level, diastolic blood pressure, and systolic blood pressure (Table 2). This implies that an individual with a systolic blood pressure of 160 mm Hg has a 3x65=190% higher risk than an individual with a systolic blood pressure of 95 mm Hg.
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DISCUSSION
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This study tested the hypothesis that feelings of tiredness and distress are among the precursors of stroke. As hypothesized, feelings of vital exhaustion increased the risk of stroke. The increased risk associated with this state could not be attributed to vital exhaustion being a side effect of other risk factors.
The major limitation of this study was the small number of incident cases. This reduced the precision of the estimates of the risk associated with all risk factors, as reflected in the rather large confidence intervals. Because of the small number and the loss of information when the vital exhaustion values were collapsed into an exhausted and a nonexhausted group, the relative risk associated with vital exhaustion as a dichotomous variable just failed to reach the conventional level of statistical significance (95% CI=0.97–12.73). The small number of cases also prevented us from examining whether the association between vital exhaustion and stroke differed between time intervals. We cannot rule out the possibility that some symptoms are markers of subclinical cerebrovascular disease. A second limitation was formed by the fact that the diagnosis of diabetes mellitus was based on self-reports. This may have resulted in an imprecise estimation of diabetes mellitus.
The data from the Mierlo project fit in well with recent observations showing that depression is predictive of stroke.14,15 We cannot answer the question as to whether exhaustion is predictive of stroke because of its overlap with depression. The present study did not measure depression, and no data regarding antidepressive medications were available. An item analysis of the Maastricht Interview Vital Exhaustion scale indicated that the following items (in descending order of strength of the association) were significantly associated with stroke: lack of energy, giving up trying, an inability to accomplish tasks, feeling dejected, decreased energy, crying (or an inclination to cry), and feelings of irritability and hopelessness.
We used the word risk indicator instead of risk factor because pathophysiological aspects of the relation between stroke and vital exhaustion can only be speculated about. An indirect clue may be insulin resistance, as a condition that may be related to both vital exhaustion16 and stroke.17,18 A pattern of pituitary and adrenocortical responses, associated with insulin resistance syndrome, might be an underlying pathophysiological mechanism.
The present study may present an incitement for further studies to find out whether vital exhaustion may be a predictor or even a risk factor for stroke and to try to clarify the pathophysiological nature of this association, focusing on hormonal factors, especially with regard to insulin metabolism.
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ACKNOWLEDGMENTS
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Funded by Steigerwald Arzneimittelwerk GmbH. The authors thank Jan van den Boomen for his help with data collection and Paula Pazo for her help with data analysis.
Dr. Verhelst died in May 2003.
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REFERENCES
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ABSTRACT
INTRODUCTION
