Stress–vulnerability factors as long-term predictors of disease activity in early rheumatoid arthritis
Introduction
In recent decades, the role of stressors and stress modulating factors has been repeatedly proposed in chronic inflammatory diseases, such as rheumatoid arthritis (RA) [1], [2], [3], [4]. In line with stress–vulnerability models [4], [6], [7], various stressors and stress modulating factors have been suggested to affect the course of RA disease activity, which is only modestly predicted by biomedical factors [5]. However, empirical findings are far from conclusive concerning the essential factors and the direction of their effects on disease activity. Comprehensive study of the extent to which different stressors and vulnerability factors contribute to the course of disease activity may provide a more integrated understanding of psychosocial factors that affect disease activity in RA.
Most attention in RA stress research has focused on the occurrence of stressful events, particularly major life events, which are assumed to precede and increase an unfavorable course of RA. Although relationships between the occurrence of major events at onset and unfavorable disease outcomes have occasionally been reported [8], [9], other studies have indicated inconclusive results [10], [11], and a relationship to major events could hardly be supported when clinical indicators of disease activity were applied [9], [12], [13]. Aside from major stressful events, minor daily stressors have been supposed to primarily affect short-term disease fluctuations in RA, but research findings have also been inconsistent [11], [14], [15]. Little attention has been directed to the role of more long-lasting stressors that are a direct consequence of the disease itself, such as pain and functional disability, and the impact of the disease on daily life, e.g. limited possibilities in terms of work and daily activities and changes in social relationships [16], [17]. Due to their lasting impact on nearly every aspect of life, chronic disease-related stressors could particularly affect the long-term course of the disease, resulting in a vicious circle of increased inflammation and chronic stress [18], [19].
Aside from environmental stressors, individual and social vulnerability factors, such as personality characteristics, social support and the manner of coping with stress, have been assumed to have direct, mediating or moderating effects on RA disease activity. While personality characteristics were originally assumed to directly enhance vulnerability to the onset of RA, without gaining much support [1], [20], their impact on the course of disease activity has been less extensively studied. So far, the results of relationships to clinical indicators of disease activity or progression are inconclusive [8], [21], [22]. Studies on physical and psychological health outcomes rather support a mediating or modifying role for specific personality characteristics, such as neuroticism and extraversion, on exposure and reactivity to stressors [14], [23], [24], [25], [26], [27]. The role of social support in predicting health outcomes has been widely accepted [28], [29], [30], and favorable direct or buffer effects of quantitative and qualitative aspects of social support, such as the size of the social network or the availability of perceived support, have been demonstrated in prospective studies for physical and psychological symptoms in RA [17], [31], [32]. Regarding disease activity, a social support buffer effect has been suggested by the finding that the quality of spousal support moderates changes in immunological parameters in periods of interpersonal stress [33]. Another possible source of vulnerability is the coping responses individuals use when faced with stress. Based on the general distinction between active, problem-focused coping and passive avoidance coping, research has repeatedly demonstrated that the use of more passive coping, and incidentally also the use of less active coping, prospectively predicts physical and psychological symptoms in RA [32], [34], [35]. In addition, there is preliminary evidence from prospective studies for harmful effects of passive avoidance coping on RA disease activity after 3 years [36] and on self-reported disease flare-ups after 1 year [34]. Due to the generally modest relationships found for these psychosocial factors, biomedical variables have also been posited as having a moderating effect on the stress–vulnerability relationship to disease activity. Specifically, patients without a rheumatoid factor have been reported to be more vulnerable to the stress–illness relationship [21], [22], [37].
So far, empirical evidence supports a link between stressors and vulnerability factors and the course of disease activity in RA. However, definite conclusions about the specific kind of variables affecting disease activity and their relative contributions cannot be drawn from present research, since a comprehensive test of various stressors and vulnerability factors that enables the investigation of direct, mediating or modifying effects on disease activity has rarely been conducted (cf. Ref. [13]). In addition, inconclusive results found in the literature may be ascribed to differences between studies in outcome measures, time periods assessed and stages of the disease. For example, a wide range of outcome measures has been used and researchers do not always distinguish between indicators of disease activity, such as inflammatory activity and swelling of joints, and indicators of disease outcome, such as functional disability [36], [38]. However, disease activity and disease outcome measures may be differently modulated by psychosocial factors [9]. In addition, the kind of variables and the direction of effects recently found for short-term disease fluctuations [14], [15] may be irrelevant to long-term outcomes [14], [38]. In contrast to short-term changes from incidental stress encounters and responses, long-term effects may be primarily influenced by chronic stressors and relatively stable personality, coping and social support characteristics. Also the strength and direction of relationships between stress and vulnerability factors and disease activity may vary over time and be different for short- and long-term outcomes. Some effects may become evident only in the long term and factors may even work in opposite directions in different time periods, e.g. due to a biphasic pattern of immunological or behavioral responses that is differently related to disease activity during and after the occurrence of major stress [2], [3], [38], [39], [40]. Finally, effects may also depend on the stages of disease assessed [3], [38]. Preliminary evidence suggests that stressors and vulnerability factors are differently related to physical and psychological symptoms in early and longstanding RA [41], possibly due to changes brought about by the disease itself. Stressors and vulnerability factors in established RA have been shown to be affected by the inflammatory processes of the disease, its biopsychosocial consequences and the pharmacological treatment with prolonged medication [17], [42], [43], [44], [45], and they may be consequently more validly assessed in recently diagnosed patients [3], [19], [41].
The purpose of the present study was to examine the role of stress–vulnerability factors for their ability to predict long-term changes in disease activity in recently diagnosed RA patients. Specifically, we studied the relative contribution of personality characteristics (neuroticism and extraversion), physical and psychological stressors (chronic disease-related stressors of functional disability, pain and disease impact on daily life, as well as major life events), coping and social support at the time of diagnosis to changes in disease activity 1, 3 and 5 years later. In line with preliminary evidence suggested by current theories and research, it was hypothesized that a more unfavorable course in disease activity after 1, 3 and 5 years could be directly predicted by personality characteristics of more neuroticism and less extraversion, higher levels of physical and psychological stressors, more passive avoidant coping, less active problem-focused coping and less social support at the time of diagnosis. In addition to these direct effects, several mediator and moderator effects were exploratively investigated. First, the mediating function of coping and social support for the relationship between personality characteristics and change in disease activity and for the relationship between stressors and change in disease activity was examined. In addition, the mediating function of stressors for the relationship between personality characteristics and change in disease activity, and of coping for the relationship between social support and change in disease activity, was explored. Hypotheses of moderator effects included the moderating function of stressors on vulnerability factors, anticipating that the maladaptive effects of major life events and chronic disease-related stressors on disease activity would be greater in patients with more unfavorable personality characteristics, coping and social support. Moreover, moderator effects of the presence of the rheumatoid factor on all stressors and vulnerability factors were examined, assuming that the relationships of stressors and vulnerability factors to the course of disease activity might be stronger in patients with a negative rheumatoid factor. Finally, possible mediator and moderator effects between demographic variables (gender, age and educational level) and all stress–vulnerability factors were explored.
Section snippets
Sample and procedure
The sample consisted of outpatients with recently diagnosed RA from five hospitals in the Netherlands. All patients participated in one of two medical trials of second-line antirheumatic drugs [45], [46]. Inclusion criteria for the medical trials were a minimum age of 18 years, diagnosis according to the 1987 ACR criteria [47] and a duration of disease of less than 1 year. All incoming patients from the hospitals who met the inclusion criteria were asked to participate in the medical trials.
Change in clinical status during the study period
Disease activity scores at the time of diagnosis were in the normal range for representative samples with recent onset or longstanding RA [52], [53], [65]. During the 5-year period, there was a significant mean decrease in disease activity [F(3,73)=22.2, P<.001 and F(3,73)=10.6, P<.01 for the ESR and joint score, respectively; see Table 1 for means and standard deviations during the study period]. In addition, chronic disease-related stressors of pain and functional disability (grip strength)
Discussion
The present study has examined the potential of stressors and vulnerability factors for predicting long-term disease activity in early RA. Contrary to expectations, none of the psychosocial factors assessed at diagnosis predicted short-term outcomes for disease activity after 1 year. This may be due to the fact that the newly prescribed medication at diagnosis seemed to be largely effective in reducing disease activity, as indicated by the mean decrease in disease activity in the first year and
Acknowledgements
Preparation of this article was supported in part by grants from the Dutch Arthritis Association (“Nationaal Reumafonds”). We thank G.A. van Albada-Kuiper, A.H. Bakker, I. van Booma-Frankfort, E.J. ter Borg, R. Brons, A.A. van Everdingen, H.C.M. Haanen, A.H.M. Heurkens, D.M. Hofman, R. Huisman, C.H.M. van Jaarsveld, A.W.J.M. Jacobs-van Bree, A.A. Kruize, H. van Mourik, I. Nuver-Zwart, Y. Schenk, D.R. Siewertsz-van Reesema, M.J. van der Veen and S. van Wijk for collecting study data.
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