Department of General Practice, Amsterdam
Department of Psychiatry, Institute for Research in Extramural Medicine, VU University Medical Centre, Amsterdam
Department of Psychiatry, Leiden University Medical Centre, Leiden
Department of Psychiatry, Amsterdam, The Netherlands
Department of General Practice, Amsterdam, The Netherlands
Department of Psychiatry, Institute for Research in Extramural Medicine, VU University Medical Centre, Amsterdam, The Netherlands
Correspondence: Mr Hein van Hout, Department of General Practice, Institute for Research in Extramural Medicine, VU University Medical Centre, Van der Boechorststraat 7,1081 BT Amsterdam, The Netherlands. Tel: +31 20 4448199; fax: +31 20 4448361; e-mail: Hpj.vanhout{at}vumc.nl
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ABSTRACT |
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Aims To determine whether anxiety disorders predict mortality in older men and women in the community.
Method Longitudinal data were used from a large, community-based random sample (n=3107) of older men and women (5585 years) in The Netherlands, with a follow-up period of 7.5 years. Anxiety disorders were assessed according to DSMIII criteria in a two-stage screening design.
Results In men, the adjusted mortality risk was 1.78 (95% CI 1.013.13) in cases with diagnosed anxiety disorders at baseline. In women, no significant association was found with mortality.
Conclusions The study revealed a gender difference in the association between anxiety and mortality. For men, but not for women, an increased mortality risk was found for anxiety disorders.
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INTRODUCTION |
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The main objective of this study was to determine whether anxiety disorders predict mortality in older people in the community. Subsidiary objectives were to filter out the effect of comorbid depression, to compare men and women, and to explore the effects of potential explanatory (lifestyle) and confounding variables.
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METHOD |
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Participants with anxiety disorders were identified using a two-stage screening design (Duncan-Jones & Henderson, 1978). The Center for Epidemiological Studies Depression Scale (CESD; Radloff, 1977) was used as the screening instrument, using the generally recommended cut-off score of 16 or over. This scale was found to be a good screen for both anxiety and depression (sensitivity 0.79). The second stage of case-finding involved a diagnostic interview, held 28 weeks after the first LASA assessment, with everyone who screened positive and an equally large random subsample of participants who screened negative. The response at this stage was 86.0% and attrition was related to age but not to gender, leaving a study sample of 659 persons interviewed, of whom 332 were screen positives and 327 screen negatives (Beekman et al, 1995b).
Informed consent was obtained from everyone who participated in the study. Participants were interviewed in their homes by well-trained and intensively supervised interviewers. These interviewers were trained to conduct only the baseline assessment or the diagnostic interview, ensuring that no participant was interviewed by the same person twice.
Measurements
Psychopathology
Both anxiety disorders and comorbid major depressive disorder were defined
according to DSMIII criteria
(American Psychiatric Association,
1980) and assessed by means of the Diagnostic Interview Schedule
(DIS; Robins et al,
1981). In this study four anxiety disorders were assessed: phobic,
panic, generalised anxiety and obsessivecompulsive disorders. The
analyses were based on anxiety disorders and major depression experienced in
the 6 months prior to interview.
Death
Death certificates were traced through the registries of the municipalities
in which the respondents were registered. Vital status ascertainment was
complete. All deaths were recorded that occurred between the baseline
interview (September 1992 to September 1993) and 1 January 2000. The average
follow-up period lasted 7.5 years (s.d.=0.3).
Covariates
Potential explanatory variables included the lifestyle variables smoking,
drinking, body mass index and physical activity (walking, cycling, light and
heavy household activities, and sports;
Visser et al,
1997).
Potentially confounding or effect-modifying variables, assessed at the study baseline, included demographic characteristics (age, gender, socio-economic status, marital status and urbanisation). As a measure of socio-economic status we used a weighted score composed of level of education, occupation and income (range 0100) (van Tilburg et al, 1995; Visser et al, 1997). Psychiatric treatment status was measured and concerned contacts with a psychiatrist or psychological and appropriate psychotropic medication. An earlier account described the treatment rates (de Beurs et al, 1999). Functional limitations (restrictions in performing daily physical activities) were measured using an adaptation of an Organisation for Economic Co-operation and Development (OECD) questionnaire (van Sonsbeek, 1988). Cognitive functioning was assessed with the Mini-Mental State Examination (Folstein et al, 1975). Chronic physical diseases were assessed in detail, including cardiac diseases, arteriosclerosis, stroke (excluding transient ischaemic attacks), diabetes mellitus, cancer, lung diseases (chronic obstructive pulmonary disease) and arthritis. Other chronic diseases were assessed in less detail. The validity of the instrument was supported in a previous study by cross-checking responses with the respondents general practitioners (Kriegsman et al, 1996; Visser et al, 1997).
Statistical analyses
The socio-demographic, morbidity, treatment status and lifestyle
characteristics of survivors and deceased were compared by means of
2 or t-tests. Mortality rates per 1000 person-years
were calculated according to anxiety status. When the 95% confidence intervals
of the hazard ratio did not include the value 1, the association was
considered to be statistically significant.
Cox proportional hazard regression models were used to examine the association between anxiety disorders and time to death in men and women and with adjustment of the explanatory (lifestyle) and confounding variables (age, disease, disability, cognition). We explored potential effect modification of the relation between anxiety and mortality by the socio-demographic, comorbid depression, physical morbidity, physical disability, cognitive functioning and lifestyle variables, by interactions in Cox survival models. For the same variables we checked whether these confounded the relation between mortality and anxiety. Significant interaction was only found between gender, anxiety and mortality. The survival curve for men showed a positive association between anxiety and mortality rate, whereas for women it did not. We therefore present the outcomes separately for men and women. Also the confounders were analysed separately for men and women.
Additional sensitivity analyses were performed to investigate whether the effects were maintained when controlling for depression (both for depressive disorder and depressive symptoms) and for ongoing psychiatric treatment.
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RESULTS |
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Compared with the non-anxious group, people with an anxiety disorder were older, more likely to be female, less likely to be married, more often living in urban areas, had lower socio-economic status, suffered more from chronic physical illnesses and were less physically active. The number of anxious persons treated by a psychiatrist or psychotropic medication was low (Table 1). Women with anxiety disorder were more likely to be treated at follow-up than men.
After 7.5 years, in total 199 (30.2%) persons had died. Of the men, 110 (39.4%) had died compared with 89 (23.4%) of the women. Univariate analyses between mortality and socio-demographic characteristics, chronic diseases, lifestyle and the anxiety screening score at baseline revealed significant associations on all variables except for urbanisation and arthritis. This indicates that the association between anxiety and mortality may be confounded by several variables.
Table 2 shows the number of cases of anxiety, the number deceased, the number of person-years and the mortality rate at 7.5-year follow-up. The unadjusted mortality rates suggest that the mortality risk is (slightly) elevated in respondents with an anxiety disorder. There was a substantial difference between men and women. The genderxanxiety interaction term in the age-adjusted model was found to be statistically significant (Wald test 6.3, d.f.=1, P=0.04).
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Anxiety disorder and mortality
Three (potential) confounders were found, and these were similar for men
and women: age, functional limitations and the number of chronic diseases.
Neither the chronic diseases alone nor cognitive impairment affected the
relationship between anxiety and mortality. In our sample, 26% of people with
an anxiety disorder also met criteria for major depression. In men 14.7% of
the patients with anxiety disorder had comorbid depression compared with 31.2%
in women. However, adjustment for baseline depression did not change the
mortality risk of anxiety.
Activity level was the only explanatory variable that substantially changed the magnitude of the relation between anxiety and mortality; smoking, drinking and body mass index hardly affected it (Table 3). Adjustment for ongoing treatment status had no effect on the hazard ratios.
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Finally, in the fully adjusted model, anxiety disorders had a hazard ratio for subsequent mortality in men of 1.78 (95% CI 1.013.13) and in women of 0.89 (95% CI 0.511.56) (Table 3). The survival curves according to the adjusted Cox model are shown in Fig. 1 for men and in Fig. 2 for women.
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DISCUSSION |
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Explanations
Several plausible mechanisms for the link between affective disorders and
mortality exist, of which pathophysiological and behavioural explanations are
the most important. Physiological alterations have been described which
include impairment of platelet function and decreased heart rate variability
as a consequence of an imbalance in the autonomic tone
(Kawachi et al, 1995; Musselman et al,
1998). Also, immune activation and hypercortisolaemia as stress
responses may result in decreased insulin resistance and increased steroid
production and blood pressure, thereby increasing the risk of cardiac disease
(Musselman et al,
1998). However, these studies investigated people with affective
disorders, thus combining anxiety and depressive disorders. We are not aware
of any pathophysiological study on specific anxiety disorders. It is likely
that anxious people are less compliant with treatment recommendations and are
less willing to exercise and eat healthily, which may partly explain our
results (DiMatteo et al,
2000).
A possible explanation for the gender difference is that men have more cardiovascular disorders, the course of which could be affected more strongly by comorbid anxiety. A psychological explanation might be that men are less capable of dealing with feelings of anxiety and hopelessness than women. Women are more inclined to discuss such feelings with others, are more open to accepting support from others, and may therefore be better able to cope with feelings of anxiety (Verbrugge, 1985). Also, men are less inclined than women to report feelings of anxiety. If they nevertheless do report them, their condition may be worse than that of their female counterparts, which can have a greater impact on their physical health and may lead to earlier death. Another explanation might be that anxious elderly men more often die by suicide than their female counterparts. However, causes of death were studied in our sample in an earlier account, but suicide did not explain the excess mortality (Penninx et al, 1999).
Earlier studies
The (weighted) prevalence of anxiety disorders in our study is comparable
with other community-based studies among the elderly
(Flint, 1994). Mortality
figures for people with anxiety disorders in community-based samples are rare
and conflicting. In a large German cohort study with 5 years of follow-up,
anxiety symptoms were associated with improved survival (Hermann et
al, 2000). In contrast, in a large community-dwelling cohort with a
follow-up period of 17 years
(Joukamaaet al,
2001), the authors were unable to find significant associations
between phobias and mortality rate. In an earlier study among in-patients with
anxiety disorders excess mortality was reported, of which a third was due to
suicide (Allgulander & Lavori,
1991). Studies of out-patients with anxiety disorders confirmed
the excess mortality but found a much lower suicide rate
(Coryell, 1988; Johnsson Fridell et al,
1996; Warshaw et al,
2000). Two small US studies among out-patients with panic disorder
reported a doubled mortality rate (Coryell
et al, 1982; Weissman
et al,1990). However, a confirmation study some years
later by Coryell et al
(1986) found less evidence for
this relationship.
Strengths and limitations
Our study was the first to combine a long follow-up period (7.5 years) with
formal diagnosis of anxiety in a general population sample and complete
mortality data. Also, our extensive biological, psychological and sociological
baseline measurements enabled identification and adjustment for confounders. A
first limitation was that the diagnoses were based on DSMIII nosology;
the results therefore cannot be extrapolated to people meeting DSMIV
criteria for anxiety disorders (American
Psychiatric Association, 1994). This is especially relevant since
a large portion of the sample were diagnosed with generalised anxiety
disorder, for which the DSMIV criteria are more stringent. Second,
generalisation of our findings is limited by non-response; this was largely
due to oversampling of the older old, who were more likely to
withdraw from the study because of health problems, cognitive problems or
death. Thus, the sample may underrepresent the frailest group, and
generalisation of our findings to this section of the population is limited.
However, for the studys purpose of investigating the associations
between variables, good representation on all variables is far more important.
Also, it should be noted that selective attrition of the most frail is more
likely to have resulted in too conservative an estimate, rather than
exaggerating the impact of anxiety on mortality. Third, with our data it is
difficult to disentangle cause and effect: it remains unclear whether a worse
health status leads to anxiety, or conversely whether anxiety leads to a worse
health status and subsequent greater mortality. Finally, further analyses
should take the cause of death into account as well. This might shed more
light on the mechanism of increased mortality rates among men.
Implications
An important consequence of our findings for health policy is that it is
important to treat anxiety in older people. In our study few elderly people
with anxiety disorders received treatment. There are several treatment options
available for anxiety disorders. Although there are only a few treatment
effect studies among elderly people, there is no reason to expect the efficacy
of treatment to diminish with age. The next steps for research are to look
into the causes of death associated with anxiety, to explore further the
sociopsychological and pathophysiological differences between men and women,
and to test the effect of interventions.
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Clinical Implications and Limitations |
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LIMITATIONS
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ACKNOWLEDGMENTS |
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REFERENCES |
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![]() ![]() ![]() ![]() ![]() ![]() ![]() ![]() ![]() |
---|
American Psychiatric Association (1980) Diagnostic and Statistical Manual of Mental Disorders (3rd edn) (DSMIII). Washington, DC: APA.
American Psychiatric Association (1994) Diagnostic and Statistical Manual of Mental Disorders (4th edn) (DSMIV). Washington, DC: APA.
Beekman, A. T., Bremmer, M. A., Deeg, D. J., et al (1998) Anxiety disorders in later life: a report from the Longitudinal Aging Study Amsterdam. International Journal of Geriatric Psychiatry, 13, 717 -726.[CrossRef][Medline]
Beekman, A. T., Deeg, D. J., Smit, J. H., et al (1995a) Predicting the course of depression in the older population: results from a community-based study in The Netherlands. Journal of Affective Disorders, 34, 41-49.[CrossRef][Medline]
Beekman, A. T., Deeg, D. J., van Tilburg, T., et al (1995b) Major and minor depression in later life: a study of prevalence and risk factors. Journal of Affective Disorders, 36, 65 -75.[CrossRef][Medline]
Coryell, W. (1988) Panic disorder and mortality. Psychiatric Clinics of North America, 11, 433 -404.[Medline]
Coryell, W., Noyes, R. & Clancy, J. (1982) Excess mortality in panic disorder. A comparison with primary unipolar depression. Archives of General Psychiatry, 39, 701 -703.[Abstract]
Coryell, W., Noyes, R. & House, J. D. (1986) Mortality among outpatients with anxiety disorders. American Journal of Psychiatry, 43, 508 -510.
Cuijpers, P. (2001) Mortality and depressive symptoms in inhabitants of residential homes. International Journal of Geriatric Psychiatry, 16, 131 -138.[CrossRef][Medline]
de Beurs, E., Beekman, A. T., van Balkom, A. J., et al (1999) Consequences of anxiety in older persons: its effect on disability, well-being and use of health services. Psychological Medicine, 29, 583 -593.[CrossRef][Medline]
DiMatteo, M. R., Lepper, H. S. & Croghan, T. W.
(2000) Depression is a risk factor for noncompliance with
medical treatment: meta-analysis of the effects of anxiety and depression on
patient adherence. Archives of Internal Medicine,
160, 2101
-2107.
Duncan-Jones, P. & Henderson, S. (1978) The use of a two-phase design in a prevalence survey. Social Psychiatry, 13, 231 -237.
Flint, A. J. (1994) Epidemiology and comorbidity of anxiety disorders in the elderly. American Journal of Psychiatry, 151, 640 -649.[Abstract]
Folstein, M. F., Folstein, S. E. & McHugh, P. R. (1975) Mini-Mental State: a practical method for grading the cognitive state of patients for the clinician. Journal of Psychiatric Research, 12, 189 -198.[CrossRef][Medline]
Geerlings, S. W., Beekman, A. T., Deeg, D. J., et al (2000) Physical health and the onset and persistence of depression in older adults: an eight-wave prospective community-based study. Psychological Medicine, 30, 369 -380.[CrossRef][Medline]
Herrmann, C., Brand-Driehorst, S., Buss, U., et al (2000) Effects of anxiety and depression on 5-year mortality in 5,057 patients referred for exercise testing. Journal of Psychosomatic Research, 48, 455 -462.[CrossRef][Medline]
Honig, A., Pop, P., de Kemp, E., et al (1992) Physical illness in chronic psychiatric patients from a community psychiatric unit revisited. A three-year follow-up study. British Journal of Psychiatry, 161, 80-83.[Abstract]
Johnson, J., Weissman, M. M. & Klerman, G. L. (1990) Panic disorder, comorbidity, and suicide attempts. Archives of General Psychiatry, 47, 805 -808.[Abstract]
Johnsson Fridell, E., Ojehagen, A. & Traskman-Bendz, L. (1996) A 5-year follow-up study of suicide attempts. Acta Psychiatrica Scandinavica, 93, 151 -157.[Medline]
Joukamaa, M., Heliövaara, M., Knekt, P., et al
(2001) Mental disorders and cause-specific mortality.
British Journal of Psychiatry,
179, 498
-502.
Kawachi, I., Sparrow, D., Vokonas, P. S., et al (1995) Decreased heart rate variability in men with phobic anxiety (data from the Normative Aging Study). American Journal of Cardiology, 75, 882 -885.[CrossRef][Medline]
Kriegsman, D. M., Penninx, B. W., van Eijk, J. T., et al (1996) Self-reports and general practitioner information on the presence of chronic diseases in community dwelling elderly. A study on the accuracy of patientsself-reports and on determinants of inaccuracy. Journal of Clinical Epidemiology, 49, 1407 -1417.[CrossRef][Medline]
Lasser, K., Boyd, J. W., Woolhandler, S., et al
(2000) Smoking and mental illness: a population-based
prevalence study. JAMA,
284, 2606
-2610.
Musselman, D. L., Evans, D. L. & Nemeroff, C. B.
(1998) The relationship of depression to cardiovascular
disease: epidemiology, biology, and treatment. Archives of General
Psychiatry, 55, 580
-592.
Penninx, B. W., Geerlings, S. W., Deeg, D. J., et
al (1999) Minor and major depression and the risk of
death in older persons. Archives of General
Psychiatry, 56, 889
-895.
Radloff, L. S. (1977) The CESD Scale: a self-report depression scale for research in the general population. Journal of Applied Psychological Measurement, 1, 385-401.
Robins, L. N., Helzer, J. E., Croughan, J., et al (1981) National Institute of Mental Health Diagnostic Interview Schedule. Its history, characteristics, and validity. Archives of General Psychiatry, 38, 381 -389.[Abstract]
Van Exel, E., Stek, M. L., Deeg, D. J., et al (2000) The implication of selection bias in clinical studies of late life depression: an empirical approach. International Journal of Psychiatry, 15, 488 -492.[CrossRef]
van Sonsbeek, J. L. A. (1988) Methodological and content related aspects of the OECD indicator of chronic functional limitations. Maandbericht Gezondheid, 88, 4-17.
van Tilburg, T., Dykstra, P., Liebroer, A. C., et al (1995) Sourcebook of Living Arrangements and Social Networks of Older Adults in the Netherlands. Amsterdam: VU University Press.
Verbrugge, L. M. (1985) Gender and health an update on hypotheses and evidence. Journal of Health and Social Behaviour, 26, 156 -182.[Medline]
Visser, M., Launer, L. J., Deurenberg, P., et al (1997) Total and sports activity in older men and women: relation with body fat distribution. American Journal of Epidemiology, 145, 752 -761.[Abstract]
Warshaw, M. G., Dolan, R. T. & Keller, M. B.
(2000) Suicidal behavior in patients with current or past
panic disorder: five years of prospective data from the Harvard/Brown Anxiety
Research Program. American Journal of Psychiatry,
157, 1876
-1878.
Weissman, M. M., Markowitz, J. S., Ouellette, R., et al (1990) Panic disorder and cardiovascular/cerebrovascular problems: results from a community survey. American Journal of Psychiatry, 147, 1504 -1508.[Abstract]
Received for publication September 15, 2003. Revision received April 16, 2004. Accepted for publication May 31, 2004.