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Psychosomatic Medicine 67:964-971 (2005)
© 2005 American Psychosomatic Society

ORIGINAL ARTICLES

Coping Processes and Hemostatic Reactivity to Acute Stress in Dementia Caregivers

Kirstin Aschbacher, BA, Thomas L. Patterson, PhD, Roland von Känel, MD, Joel E. Dimsdale, MD, Paul J. Mills, PhD, Karen A. Adler, MS, Sonia Ancoli-Israel, PhD and Igor Grant, MD

From the Department of Psychiatry, University of California, San Diego, California (K.A., T.L.P., R.v.K., J.E.D., P.J.M., K.A.A., S.A.-I., I.G.); Department of General Internal Medicine, University Hospital Bern, Bern, Switzerland (R.v.K.); San Diego Veterans Affairs Healthcare System, La Jolla, California (T.L.P., S.A.-I., I.G.).

Address correspondence and reprint requests to Igor Grant, MD, Professor and Executive Vice-Chairman, Department of Psychiatry, School of Medicine, University of California, 9500 Gilman Drive, La Jolla, CA 92093-0680. E-mail: igrant{at}ucsd.edu


   ABSTRACT
TOP
 ABSTRACT
INTRODUCTION
 METHODS
 RESULTS
 DISCUSSION
 NOTES
 REFERENCES
 
Background: A hypercoagulable stress response might contribute to the increased cardiovascular risk in Alzheimer’s caregivers.

Objectives: (1) To evaluate whether coping processes affect hemostatic reactivity to acute psychological stress and (2) whether these effects differ substantially between caregivers and noncaregivers.

Methods: Sixty elderly community-dwelling spousal caregivers of patients with Alzheimer’s disease and 33 noncaregiving controls completed the revised Ways of Coping Questionnaire to assess approach/problem-solving versus avoidant coping processes. Participants were administered an acute stress test that required them to deliver a 3-minute speech challenge to the interviewer on an assigned topic. The hypercoagulability marker D-dimer was measured at three time points: baseline, immediately postspeech, and during recovery (15 minutes postspeech).

Results: Multivariate analysis of covariance revealed that subjects who endorsed greater levels of approach coping had decreased levels of D-dimer at all time points (p = .048). A significant three-way interaction between planful problem solving, caregiver status, and the temporal pattern of D-dimer was found (p = .004), indicating that caregivers with low levels of planful problem solving exhibited greater increases in D-dimer from baseline to speech and recovery time points relative to controls. No relationship between avoidant coping and D-dimer was found.

Conclusions: These findings suggest the possibility that approach and problem-solving coping processes buffer the impact of acute psychological stressors on procoagulant activity. It remains to be seen whether interventions that increase approach/problem-solving processes might produce salutary effects among caregiving populations.

Key Words: approach • cardiovascular • caregiving • coping • D-dimer • hemostasis

Abbreviations: APP = approach coping; AVD = avoidant coping; BMI = body mass index; CGS = caregiver status; DD = D-dimer; HAM-D = Hamilton Rating Scale for Depression; HARS = Hamilton Anxiety Rating Scale; MANCOVA = multivariate analysis of covariance; PPS = planful problem solving; WOC = Ways of Coping; UCSD = University of California San Diego; HLM = hierarchical linear modeling.


   INTRODUCTION
TOP
 ABSTRACT
 INTRODUCTION
METHODS
 RESULTS
 DISCUSSION
 NOTES
 REFERENCES
 
Current estimates suggest that approximately 15 to 25 million adults in the United States provide unpaid, informal care to relatives or friends (1,2). The economic value of these services has been estimated at $196 billion, a figure which far exceeds the US national spending for nursing home care and home health care combined (3). Myriad studies have demonstrated that caregivers suffer from greater psychological distress, more health problems, and may even be at increased risk of mortality compared with their noncaregiving counterparts (4–6). Furthermore, previous research has concluded that caregivers who experienced more stressful life events exhibited greater cardiovascular risk, as indexed by elevated levels of the procoagulant molecule D-dimer (DD) (7,8).

The hypercoagulability marker DD is the end product of a cascade of hemostatic events in which stress results in intravascular fibrin formation and lysis of fibrin clots. Thus, DD provides an excellent physiological measure of hemostatic functioning because it indicates that the entire hemostatic system has been activated and fibrin turnover has occurred. Furthermore, DD is highly sensitive, fluctuating in response to acute stress, and has a longer half-life than many other hemostasis factors, rendering it relatively more detectable in human plasma (9). A recent meta-analysis concluded that elevated DD serves as a marker for increased risk of experiencing subsequent coronary events (10).

Investigating hemostatic reactivity in response to an acute stressor can provide a snapshot of the physiological mechanisms underlying the well-documented association between stress and cardiovascular disease. Whereas people with healthy hemostatic systems maintain a balance between fibrinolysis and coagulation, those under chronic stress (e.g., caregivers) may exhibit heightened reactivity to acute stressors (11). Thus, heightened procoagulant reactivity may mediate allostatic load, or cumulative wear and tear on a physiologic system. Previous research has demonstrated that acute stressors such as anger or mental activity can promote plaque rupture in patients with advanced stages of coronary artery disease (12). Following plaque rupture, concomitant hypercoagulability will promote coronary thrombus growth (13). An accumulation of acute stressors over time may pose a significant health risk, particularly among populations with preexisting atherosclerosis or endothelial damage. Furthermore, a study by Holahan et al. (14) concluded that hassles, or ordinary daily stressors, were a stronger predictor of distress and psychosomatic complaints in an elderly population of community residents than major life events. Thus, reactions to an acute laboratory stress test may be a reasonable approximation of the wear and tear caused by daily hassles.

A recent meta-analysis found that certain coping processes appear to buffer the deleterious impact of acute stress on health outcomes (15). Coping, as defined by Lazarus and Folkman (16), consists of cognitive and behavioral efforts to manage demands that exceed the resources of the person. The current study examined the approach/avoidant and problem-focused/emotion-focused coping paradigms, which have been well researched with respect to a wide array of health outcomes. Approach coping (APP) is generally characterized as active attempts to deal with a stressor (e.g., strategizing, seeking social support, or gathering additional information), while avoidant coping (AVD) involves emotionally distancing oneself from a stressor (e.g., denial, escape, or disengagement). The problem-focused coping process is best captured by the PPS subscale of APP, while emotion-focused coping is largely synonymous with avoidant strategies (17). Previous research suggests that higher proportions of APP versus AVD are associated with better health in caregivers (18,19). Whereas several studies have reported that active coping techniques (e.g., problem solving, positive reappraisal, and support seeking) are associated with greater self-reported health (20), research suggests that AVD is not associated with long-term, physical health outcomes (15,21). Furthermore, problem solving, an approach-based strategy, was the only strategy found to correlate positively with health outcomes in the case of an acute stressor (15). We examined hemostatic reactivity in relation to the broad approach-avoidant distinction while utilizing the planful problem-solving (PPS) subscale to investigate the problem-focused component of APP.

Based on the existing body of literature regarding caregivers, coping, and cardiovascular reactivity, the following hypotheses were proposed. (1) APP and problem-solving processes would buffer the hemostatic response to stress. (2) Because caregivers suffer from chronic stress and are likely to exhibit greater allostatic load, we hypothesized that the buffering effect of APP processes might be more salient in caregivers than in controls (manifesting as an interaction between coping and caregiving status). (3) As AVD has generally been found to be associated with greater psychological distress but not with physical distress, we expected to observe no main effects of AVD processes on hemostasis. However, given that AVD may exert short-term benefits (22), we anticipated there could be an association between AVD and hemostatic reactivity. The model proposed here examines multiple interactions between caregiving status (i.e., caregivers versus noncaregivers), coping processes, and procoagulant reactivity to acute psychological stress. Such a model helps disentangle the effects of multiple factors and evaluate the relative benefits of coping mechanisms as moderators of the link between stress and cardiovascular disease in dementia caregivers.


   METHODS
TOP
 ABSTRACT
 INTRODUCTION
 METHODS
RESULTS
 DISCUSSION
 NOTES
 REFERENCES
 
Subjects and Study Design
The data presented here come from an ongoing longitudinal study investigating health outcomes related to immune and cardiovascular functioning in elderly caregivers of spouses with Alzheimer’s disease. Seventy caregiver/spouse pairs were recruited through community support groups or referrals from the University of California San Diego (UCSD) Alzheimer Disease Research Center. All caregivers provided in-home care for their spouse at the time of their enrollment in the study. In order to provide a control comparison group, we recruited 38 demographically matched participants whose spouses did not require caregiving. Data for 10 caregivers and five noncaregivers were excluded for the following reasons: several participants dropped the study due to death of a spouse or development of illness, one was missing coping data, and the rest were unable to provide blood at all time points due to vein clotting. Thus, the total sample for this study was composed of 93 total participants (60 caregivers and 33 noncaregivers). Participants were 68% female, 92% Caucasian (1% African-American, 3% Asian, 3% Hispanic, and 1% other) and ranged in age from 51 to 88 years (M ± SD: 70.7 ± 8.5). Demographic and medical descriptive information, as well as statistical tests evaluating equivalence for caregiving and noncaregiving samples, is summarized in Tables 1 and 2. With the exception of age (caregivers being older; t (91) = –2.36, p = 0.02), caregivers and noncaregivers did not significantly differ on demographic variables or factors potentially related to hemostatic functioning (e.g., body mass index [BMI], smoking, and potentially relevant preexisting morbidities; Table 2). Socioeconomic status was assessed using the well known Hollingshead Two-Factor Index of Social Position, which combines scaled scores assessing the occupation and education of the head of the household (23). All volunteers provided written consent to participate in the study, which was approved by the UCSD institutional review board.


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  		TABLE 1. Demographic Comparisons Between Caregivers and Noncaregivers

 

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  		TABLE 2. General Health Characteristics of Caregivers and Noncaregivers

 

Measures of Participant Health
For the purposes of evaluating the possible influence of participant health on the findings, the presence of medical conditions potentially related to hemostatic functioning was assessed through self-reports (Table 2). Vascular disease was defined as previous history of coronary artery disease or previous cerebrovascular disease, an aggregate measure which has been acceptable in similar studies of hemostasis (8,24). In order to provide general measures of health beyond BMI and smoking habits, participants were asked whether they had experienced an extended illness (i.e., had they "suffered from a physical illness or disability lasting a month or more, not requiring hospitalization") or hospitalization (i.e., were they "seen at a hospital in the last 6 months as an inpatient?").

Assessment of Coping
Coping was measured with the 66-item revised Ways of Coping Questionnaire (WOC; 17,25). The questionnaire describes a broad range of cognitive and behavioral strategies, which people use to cope with the demands of a stressful encounter. Each item is measured on a 4-point Likert Scale, ranging from 0 (i.e., "Does not apply/not used") to 3 (i.e., "Used a great deal"). Participants are asked to rate how much each coping strategy was used with regard to the most stressful interpersonal conflict in the past month. Given that spousal problem behaviors (e.g., disruptive and aggressive behaviors) have been linked to caregiver burden (26), as well as psychiatric and physical morbidity (27), there is reason to believe that coping with interpersonal conflict may affect caregiver physiology. Nonetheless, coping with interpersonal conflict is a universal experience.

The WOC is divided into eight subscales on the basis of factor analysis (17,25), which include confrontive coping (e.g., "I express anger to the person(s) who caused the problem"), distancing (e.g., "Try to forget the whole thing"), self-control (e.g., "I try to keep my feelings to myself"), seeking social support (e.g., "Accept sympathy and understanding from someone"), accepting responsibility (e.g., "Criticize or lecture myself"), escape-avoidance (e.g., "Try to make myself feel better by eating, drinking, smoking, using drugs or medications, etc."), planful problem solving (e.g., "I’m making a plan of action and am following up on it"), and positive reappraisal (e.g., "I’ll come out of the experience better than when I went in"). APP represents the cumulative total of 4 subscales that conceptually represent gravitation toward the problem (i.e., confrontive coping, seeking social support, planful problem solving, and positive reappraisal). In contrast, AVD represents the total of four subscales involving a movement away from the problem (i.e., distancing, self-controlling, accepting responsibility, and escape-avoidance).

Assessment of Depressive and Anxious Symptomology
Though peripheral to the hypotheses of this study, we assessed depressive and anxious symptomology in order to investigate its potential impact on coping, given that psychological distress may influence both coping and hemostasis (19,21,28). Mood symptomology was assessed using the Hamilton Rating Scale for Depression (HAM-D; 29) and the Hamilton Anxiety Rating Scale (HARS; 30), both of which were administered by trained research nurses. The thresholds used to determine whether participants met criteria for clinically significant levels of depressive and anxious symptomology were based on several well-controlled studies (31–32).

Stress Protocol
Participants were requested to deliver a speech that involved 3 minutes of preparation and 3 minutes of speaking on an assigned topic to the interviewer. Because the parent study is longitudinal, participants were randomly assigned to one of two speech topics to ensure that a given subject will not extemporize on identical topics 2 years in a row. The first topic regards a standard "stolen belt" paradigm (34), whereas the second involves a conflict with a disreputable car salesman. Previous research has indicated that these tasks provoke equivalent stress reactivity (35,36). Furthermore, in the current study the two stress tasks were comparably distributed between caregivers and noncaregivers. Blood was drawn at three time points along the stress-response temporal continuum. Baseline measures were taken after the subject had rested for 20 minutes in a sitting position. The first 2 ml of blood was discarded to ensure measures were not contaminated by artificial coagulation activation due to drawing blood. The second blood sample was extracted directly following the speech, and the third, after 14 minutes of recovery time.

Medical and Hemostasis Measures
A research nurse conducted in-home interviews, in which medical histories of all participants were assessed. The stress-testing and blood-draw procedures were conducted between 8 and 10 AM on a separate day from the interviews. Blood was drawn using an indwelling 22-gauge venous forearm catheter. Participants were asked to identify certain health factors potentially relevant to hemostasis such as high blood pressure, elevated blood cholesterol levels, or history of myocardial infarction or stroke. Participants taking ß-blockers or anticoagulant medications were excluded from the study as these medications may affect hemostatic activity (37). Within 3 hours of the blood draw, plasma samples were obtained by centrifugation, which entailed double spinning at 1600g for 10 minutes at room temperature. Platelet-poor plasma samples were kept frozen at –80°C until assayed for DD using commercially available enzyme linked immunosorbent assay (ELISA) kits.

Data Analyses
All statistical analyses except the hierarchical linear modeling (HLM) analyses were run using SPSS 11.5 for Windows, p values of 0.05 or less were considered statistically significant for a priori hypotheses, and type I error protection methods were employed for post hoc tests. HLM results were obtained using HLM 5 for Windows. Multivariate analysis of covariance (MANCOVA) was utilized to assess the impact of coping and caregiver status (CGS) on DD across all three time points while covarying for age. In order to utilize coping factors as independent variables in MANOVA, all coping factors were split at the sample median (PPS = 9.5, APP = 32.5, AVD = 24.5) yielding high/low dichotomous variables. The mean and median coping scores found in this study fall in a similar range (within 1 SD) as norms from previous studies (17), with the exception of greater positive reappraisal reported in the current study, which may reflect the gender distribution of our sample (38). While the dichotomization of continuous coping variables tends to reduce power (39), the power advantages of a within-subjects design over a between-subjects design are substantial, such that a pre-/post-ANOVA requires two to four times as many subjects to equal the power of a within-subjects design (40). This design also facilitated comparison of linear and nonlinear trends across all three time-points, while maintaining practical relevance in terms of high/low coping distinctions. All DD measurements were screened for normality and logarithmically transformed in order to approximate normal distributions. {chi}2 (For categorical data), two-sided Fisher exact tests (for categorical data with small cell sizes), and t tests (for continuous data) were performed to evaluate whether caregivers and noncaregivers differed on demographic variables or factors potentially relevant to DD levels. Equal variance was assumed for all t-tests based on the results of Levene’s test and a lack of significant heteroscedasticity of variance, except where otherwise noted.


   RESULTS
TOP
 ABSTRACT
 INTRODUCTION
 METHODS
 RESULTS
DISCUSSION
 NOTES
 REFERENCES
 
In order to investigate the possibility that the act of caregiving might be associated with changes in coping processes and mood, we compared caregivers and noncaregivers on these factors. Independent t tests revealed that caregivers exhibited significantly lower levels of all coping processes examined relative to their noncaregiving peers (Table 3). As expected, caregivers exhibited significantly more depressive and anxious symptomology than noncaregivers; however, clinically significant mood symptomology was not prominent in either group (Table 3). Eighty-two percent of caregivers and 94% of noncaregivers fell below the generally accepted threshold on the HAM-D for clinically significant levels of depressive symptoms (≤7 points). Fifteen percent of caregivers scored in the mild on the HAM-D (see 28,29 for ranges), compared with 6% of noncaregivers. Of the remaining 3% of the caregiver sample, one scored in the moderate and another in the severe range. Ninety-eight percent of caregivers and 100% of noncaregivers and fell below generally accepted criteria (≥14 points) for clinical anxiety on the HARS (33). One caregiver exhibited clinically significant levels of anxious symptoms. Furthermore, univariate analysis of variance tests established that the high/low coping groups did not significantly differ on symptom scores for depression or anxiety, independent of CGS.


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  		TABLE 3. Coping and Mood Symptoms in Caregivers and Noncaregivers

 

The primary hypotheses were investigated using 3 split-plot MANCOVA analyses (one per coping variable), employing caregiving status and coping processes as independent variables, controlling for age as a covariate, and examining linear and quadratic interaction contrasts within the 3 DD time points (this within-subjects factor was designated "Time"). A main effect of APP on procoagulant response was found, indicating that greater use of APP was associated with decreased levels of DD across all time points (F(1,88) = 4.04, p = .048, {eta}2 = 0.04; see Figure 1). Caregiving status exhibited a nonsignificant main effect on DD, with caregivers exhibiting a nonsignificant trend toward greater procoagulability than noncaregivers (F(1,88) = 3.08, p = .083, {eta}2 = 0.03). No relationship was found between AVD and DD, although in this analysis, a main effect for CGS emerged, such that caregivers consistently had higher levels of DD than noncaregivers (F(1,88) = 5.39, p = .023, {eta}2 = 0.06). When depression and anxiety were added as covariates, all factors were insignificant, perhaps due to insufficient power.



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  		Figure 1. Procoagulant differences between caregivers and noncaregivers at high versus low levels of approach coping.

 

A significant linear 3-way interaction was found between PPS, CGS, and Time (F(1,88) = 8.94, p = .004, {eta}2 = 0.09; see Figure 2) accounting for the significant multivariate omnibus test of the 3-way interaction (F(2,87) = 4.46, p = .014). The main effects of PPS (F(1,88) = 3.78, p = .055, {eta}2 = 0.04), CGS (F(1,88) = 4.21, p = .043, {eta}2 = 0.05), and the linear trend of Time (F(1,88) = 10.82, p = .001, {eta}2 = 0.11) were also significant, though not interpretable in light of the significant interaction. Two separate simple-effects analyses (i.e., exploring two-way interactions at each level of the third factor) were performed to clarify the meaning of the 3-way interaction. Significant findings within these simple-effect analyses were further explored using specific contrast comparisons. These follow-up analyses indicated that caregivers who engage in fewer problem-solving strategies exhibit greater hemostatic reactivity than their noncaregiving counterparts, whereas caregivers with higher levels of problem-solving strategies exhibit similar hemostatic reactivity to noncaregivers. Table 4 provides group comparisons on the untransformed DD reactivity means.



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  		Figure 2. Procoagulant differences between caregivers and noncaregivers at high versus low levels of problem-solving coping.

 

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  		TABLE 4. Change in D-dimer From Pre- to Postspeech Among Caregivers and Noncaregivers With High Versus Low Coping Processes

 

In the follow-up tests using simple effects analyses, the simple two-way Time x CGS interaction within each level of PPS ({alpha} = 0.025) remained significant only for low levels of PPS (Wilk’s {lambda}; F(2,46) = 4.32, p = .019). Thus, within the group of participants with low PPS scores, a specific contrast test was performed to assess the interaction of CGS and global reactivity (defined as change from baseline to the average of speech and recovery). This contrast test revealed that low-PPS caregivers exhibited significantly greater reactivity than low-PPS noncaregivers (F(1,47) = 8.81, p = .005), while no difference in DD reactivity was found between caregivers and noncaregivers in the high-PPS group. Similar conclusions are reached by an alternate simple effects analysis at each level of CGS ({alpha} = 0.025). The simple Time x PPS interaction was significant for caregivers (Wilk’s {lambda}; F(2,56) = 4.10, p = .022) but not for noncaregivers. An interaction contrast test examining whether the DD reactivity differed between high- and low-PPS caregivers revealed a significant difference in reactivity between low-PPS and high-PPS caregivers (F(1,57) = 7.90, p = .007).

In the interest of thoroughness, the remaining subscales of APP (i.e., confrontive coping, seeking social support, and positive reappraisal) and all the subscales of AVD were tested individually through MANOVA, but none emerged as significant predictors of procoagulability. When depression and anxiety were added as covariates, the 3-way linear interaction remained significant (F(1,86) = 8.83, p = .004), whereas the covariates were nonsignificant.

In an attempt to maximize the quantitative information from the coping factors, we reanalyzed the series of analyses using multilevel modeling. These HLM analyses examined the main effects of coping and caregiving status, the potential linear change in DD over time, and whether this change differs according to CGS or coping processes. Because of the long half-life of DD (41), a linear increase between postspeech measures was not necessarily expected. Thus, postspeech measures were averaged such that reactivity represented the linear change from baseline to an average postspeech measure. Level 1 in the HLM analysis (within-subjects variables) represented prepost change and the between-subjects main effects. Level 2 represented the interactions of coping and CGS with DD reactivity. All coping variables were centered before analysis.

When all possible main effect and interaction terms were entered into the model, no terms reached significance. This may indicate a lack of power due to the small number of higher-level groups. Whereas the observed power of the linear 3-way interaction in the MANOVA analysis was large (0.84), several researchers have cautioned that power to detect cross-level interactions in HLM is closely tied to the number of higher-level groups (42–44). Whereas 30 is often recommended as a minimum sample size for higher-level units (42), caregivers and noncaregivers constitute only two higher-level groups. Because of these power concerns, the MANOVA results were considered more interpretable. Nonetheless, in the interest of providing a balanced perspective, main effect and reactivity hypotheses were tested in separate analyses, and the nonsignificant 3-way interaction term was omitted to maximize parsimony and power.

Consistent with the MANOVA analyses, HLM analyses revealed a significant main effect of APP (ß = –0.004, SE = 0.001, p = .03) and no effect of AVD. Although PPS and CGS also revealed significant main effects, they are not interpretable in light of the significant interactions found. As might be expected, the results using HLM were similar, but differed somewhat from those found using MANOVA. In HLM, the 3-way interaction term was not significant. However, a significant interaction between CGS x Time was found in all 3 analyses of reactivity: (1. PPS: ß = 0.14, SE = 0.06, p = .02; 2. APP: ß = 0.14, SE = 0.06, p = .02; 3. AVD: ß = 0.15, SE = 0.06, p = .02), indicating that caregivers exhibited greater reactivity than noncaregivers. A marginally significant interaction between PPS x Time (ß = –0.016, SE = 0.01, p = .06) suggested that participants with greater levels of problem-solving might exhibit less reactivity. As in the MANOVA analyses, approach and AVD did not exhibit a significant impact on reactivity.


   DISCUSSION
TOP
 ABSTRACT
 INTRODUCTION
 METHODS
 RESULTS
 DISCUSSION
NOTES
 REFERENCES
 
These results suggested that approach and problem-solving coping processes buffer the impact of acute psychological stressors on procoagulant activity. Greater levels of APP were associated with lower levels of DD at the baseline and two postspeech time points among the total sample. In contrast, the buffering benefits of problem-solving processes on hemostatic reactivity appeared to be more salient in caregivers, perhaps because they suffer from greater allostatic load (11). The impact of the caregiving burden on health was well illustrated in a study by Schulz and Beach (5), who found that self-reported caregiving strain was an independent risk factor for mortality among elderly spousal caregivers. In a replication and extension of previous findings (45), the present study demonstrated that caregivers exhibited increased fibrin turnover relative to noncaregivers in the avoidant and low problem-solving conditions and exhibited a trend toward significance in the approach analysis. Previous research has also shown an association between increased fibrin turnover and risk of future cardiovascular events (10,46). Taken together, this constellation of findings raises the question of whether an increased procoagulant response to stress in elderly dementia caregivers might serve as a marker for increased risk of subsequent cardiovascular events. If confirmed, our results suggest that approach/problem-solving coping processes may buffer the potentially deleterious effects of procoagulant activity in caregiving populations.

Although caregivers appeared to benefit (i.e., exhibit less procoagulant activity) from approach and problem-solving coping processes, they engaged these coping processes less often than their noncaregiving counterparts. Thus, one manifestation or defining feature of caregiver burden may be a decreased ability to mobilize effective coping mechanisms in response to stress. This theory is supported by several studies (24,47,48), which suggested that higher caregiver burden was associated with fewer problem-solving/approach-type processes and more avoidant-type processes. Given that caregivers exhibited elevations in procoagulant markers (45) associated with increased risk of mortality (49,50), a better understanding of how to mobilize coping processes that could potentially reduce this risk would assist the development of more effective interventions.

Our results supported previous findings (15,51) that APP, but not AVD, was associated with improved physical health and provided insight into a possible mechanism by which coping may impact cardiovascular health specifically. Our results further coincided with the Penley et al. (15) findings in that APP appeared to be more generally associated with better health, whereas problem solving was associated with the dynamic reactivity to an acute psychological stressor. Our results suggest that caregivers exhibit greater procoagulatory tendencies and hemostatic reactivity than noncaregivers; however, it is unclear whether hyperreactivity to an acute stressor is a symptom or a causal mechanism in the dysregulation of caregivers’ hemostatic systems. Nonetheless, previous research has suggested that hyperreactivity in the presence of atherosclerosis or impaired endothelial functioning can increase the risk of an atherothrombotic event (52). The cross-sectional nature of this study prevented us from establishing whether hyperreactivity to an acute stressor was associated with the progression of dementia in the spouses of our caregivers and the attendant caregiver burden. This would have been one way to explore causal interactions between chronic stress and hyperreactivity to acute stress.

Another limitation in this study was that caregivers and noncaregivers differed significantly in age. Although we controlled for age by including it as a covariate in the analyses, future studies should exert greater effort to achieve age matching between samples. The psychological literature attempting to elucidate whether coping changes as a function of age has yielded conflicting results. Some research (38) has concluded that younger people employed more active, interpersonal, problem-solving forms of coping. However, given that both of our study groups were elderly (mean age of caregivers was 72 and noncaregivers 68) and their average age difference was small (4 years), it seems unlikely that the age discrepancy explains the reported results in either the coping or coagulation factors.

Depression was a possible influence on coping, as it has been associated with AVD behaviors in previous studies (19). However, as preliminary analyses revealed that the coping groups did not differ on mood symptomology independent of caregiving status and the inclusion of mood as a covariate did not alter the findings, it is unlikely that mood symptomology is responsible for the effects attributed to coping in the current study. The lack of significant findings associated with mood symptomology may have reflected insufficient power in the design, as well as the fact that depressive and anxious symptomology was not prominent in our sample. Future studies with larger sample sizes should attempt to investigate the gestalt interactions among coping processes, psychological distress, and their combined influence, if any, on hemostasis.

Two forms of analysis were investigated, each offering advantages and disadvantages. Repeated-measures designs offer substantial power advantages and the capacity to investigate nonlinear trends in the dependent variable over time (40). However, readers are advised that dichotomization of the continuous coping variables is often inadvisable as it may result in a loss of power and information regarding individual differences (39). As might be expected, the findings manifested somewhat differently through the lens of MANOVA versus HLM analyses. Given that the full model in HLM yielded no significant predictors, it is likely that power was insufficient in these analyses, which may explain why the 3-way interaction was not duplicated in HLM. We incline to this explanation because the observed power of the linear 3-way interaction in the MANOVA analysis was large (0.84), suggesting the findings are probably not spurious. In considering why the results of the MANOVA and HLM analyses did not correspond fully, we note that a number of researchers have cautioned that power to detect higher-order, cross-level interactions may require a larger number of higher-level groups (42–44). Nonetheless, the HLM analyses revealed important patterns of similarity, whereby higher APP was associated with lower DD overall, and higher problem solving and being a noncaregiver were associated with lower DD reactivity. Future studies with increased power and sample size will be required to resolve this issue.

The findings raise the question of the extent to which coping processes may be situation-specific versus generalizable (i.e., the organismic-environmental dichotomy). The underlying assumption was that people exhibit some level of consistency in their coping responses to interpersonal personal conflict (i.e., the event participants chose while completing the WOC and the acute stress test). Previous research using coping processes to predict psychological and physical outcomes implies some degree of consistency in coping processes may exist across similar situations (51,53–55). However, the degree to which coping can be considered specific versus generalizable within specified domains of interpersonal interactions is a subject that bears further research and replication in longitudinal studies.

This study did not attempt to elucidate the physiologic mechanism presumed to underlie associations between coping processes and procoagulant activity. Secretion of catecholamines (e.g., epinephrine and norepinephrine) by the sympatho-adrenal-medullary system is believed to mediate the impact of acute stress on the cardiovascular system. Previous studies of dementia caregivers demonstrated that acute stress (e.g., an acute speech stressor) elicited a significant increase in plasma epinephrine and norepinephrine (56) and that increases in epinephrine were positively associated with an increase in procoagulation factors (e.g., the von-Willebrand factor; 52). Future studies could examine whether the SAM system mediates the association between coping processes and hemostasis. The fact that DD levels did not return to baseline is an exciting finding that merits further investigation. A likely explanation for this phenomenon is the long biological half-life of DD in circulation, which is up to 48 hours (41).

In conclusion, coping processes appear to have a direct relationship with the procoagulant response to acute psychological stress. Approach and problem-solving coping processes may be particularly salutary approaches to dealing with the problems of caregiving stress, if one accepts that increases in procoagulant activity might place caregivers at risk for future cardiovascular events. If confirmed, these results may provide the foundation for potential therapeutic interventions. Future studies are needed to investigate whether interventions that increase approach/problem-solving coping processes with respect to the stresses of caregiving reduce hemostatic activity. Future studies could also benefit from longitudinal designs to evaluate whether repetitive episodes of acute stress in combination with poor coping mechanisms contribute to allostatic load and increased risk of cardiovascular events.

The authors are grateful to Christopher Archuleta, MS, Carolyn Swenerton, RN, Sharyn Wilenski, RN, and Christy J. Perez, BS.


   NOTES
TOP
 ABSTRACT
 INTRODUCTION
 METHODS
 RESULTS
 DISCUSSION
 NOTES
REFERENCES
 

Supported by NIA 5 R01 AG15301-15; P50 AG05131 ADRC; NIA AG08415; P50 AG05131; GCRC grant M01 RR00827.

DOI:10.1097/01.psy.0000188458.85597.bc


   REFERENCES
TOP
 ABSTRACT
 INTRODUCTION
 METHODS
 RESULTS
 DISCUSSION
 NOTES
 REFERENCES
 

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