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Psychosomatic Medicine 61:729-737 (1999)
© 1999 American Psychosomatic Society

ORIGINAL ARTICLE

Depression and Risk of Sudden Cardiac Death After Acute Myocardial Infarction: Testing for the Confounding Effects of Fatigue

Jane Irvine, DPhil, CPsych, Antoni Basinski, MD, PhD, CCFP, Brian Baker, MBChB, FRCP(C), Stacey Jandciu, BSc, Miney Paquette, MA, John Cairns, MD, FRCP(C), Stuart Connolly, MD, FRCP(C), Robin Roberts, MTech, Michael Gent, DSc and Paul Dorian, MD, FRCP(C)

From the Toronto General Hospital, University Health Network (J.I., B.B., S.J.); Departments of Psychiatry (J.I., B.B.) and Medicine (P.D.), University of Toronto, Toronto; Institute for Clinical Evaluative Sciences in Ontario (A.B.), Toronto; St. Michael’s Hospital (M.P., P.D.), Toronto, Ontario; Faculty of Medicine, University of British Columbia (J.C.), Vancouver, British Columbia; and Departments of Medicine (S.C.) and Clinical Epidemiology and Biostatistics (R.R., M.G.), McMaster University, Hamilton, Ontario, Canada.

Address reprint requests to: Jane Irvine, DPhil, CPsych, College Wing-2-330, Toronto General Hospital, University Health Network, 200 Elizabeth St., Toronto, Ontario, Canada, M5G 2C4. Email: jane.irvine{at}utoronto.ca


   ABSTRACT
TOP
 ABSTRACT
INTRODUCTION
 MATERIALS AND METHODS
 RESULTS
 DISCUSSION
 ACKNOWLEDGMENTS
 REFERENCES
 
OBJECTIVES: This study examined the impact of depressive symptoms and social support on 2-year sudden cardiac death (SCD) risk, controlling for fatigue symptoms.

METHODS: Myocardial infarction (MI) patients (N = 671) participating in the Canadian Amiodarone Myocardial Infarction Arrhythmia Trial completed measures of depression, hostility, and social support.

RESULTS: After controlling for significant biological predictors, psychosocial predictors of increased SCD risk in the survival analysis were greater social network contacts (RR = 1.04; 95% CI = 1.01–1.06; p < .007), lower social participation (RR = 0.98; 95% CI = 0.96–1.00; p < .05), and, in placebo-treated patients, elevated depressive symptoms (RR = 2.45; 95% CI = 1.14–5.35; p < .02). Fatigue was associated with SCD (RR = 1.31; 95% CI = 1.11–1.53; p < .001), and, when included in the model, diminished the influence of depression (RR = 1.73; 95% CI = 0.75–3.98; p = .20). When the cognitive-affective depressive symptoms were examined separately from somatic symptoms, there was a trend for an association between cognitive-affective symptoms and SCD in placebo-treated patients after controlling for fatigue (RR = 1.09; 95% CI = 0.99–1.19, p < .06).

CONCLUSIONS: Symptoms of depression and fatigue overlap in patients with MI. The trend for the cognitive-affective symptoms of depression to be associated with SCD risk, even after controlling for dyspnea/fatigue, suggests that the association between depression and mortality after AMI cannot be entirely explained as a confound of cardiac-related fatigue. The independent contribution of social participation suggests a role of both depressive symptomatology and social factors in influencing mortality risk after MI.

Key Words: depression • social support • cardiac mortality • acutemyocardial infarction

Abbreviations: AMI = acute myocardial infarction; BDI = Beck DepressionInventory; CAMIAT = Canadian Amiodarone Myocardial InfarctionArrhythmia Trial; CHF = congestive heart failure; MI =myocardial infarction; SCD = sudden cardiac death.


   INTRODUCTION
TOP
 ABSTRACT
 INTRODUCTION
MATERIALS AND METHODS
 RESULTS
 DISCUSSION
 ACKNOWLEDGMENTS
 REFERENCES
 
Psychological distress (measured as symptoms of depression, anxiety, or anger) has been associated with increased mortality, independent of biological risk factors, in patients with (1–6) and without coronary heart disease (7–11). On the other hand, social contacts, evaluated in terms of perceived support (12–14), social network size/scope (15–18), not being socially isolated (19–22), and social participation/contact (12, 18, 23–27) have been associated with decreased mortality in individuals with (12, 13, 16, 19, 20–22, 24, 25) and without documented coronary heart disease (14, 15, 17, 18, 23, 26–28). Despite these associations, few studies have simultaneously investigated the mortality risk associated with distress and the degree to which this risk is reduced with various amounts and forms of social contacts. The studies involving cardiac patients have produced inconsistent results. Life stress and social isolation were both independently associated with higher mortality risk after AMI in one study, with patients high in both stress and isolation manifesting the highest mortality risks (19). Three other studies, however, found that perceived social support was not associated with mortality independent of psychological distress, which was measured as depressive symptomatology (1), anxiety (6), or emotional functioning (13). Given these findings, it is reasonable to question whether reductions in social isolation, measured in terms of varying levels and forms of social contact/support, actually reduce the negative effects of stress and psychological distress. Along these lines of inquiry, the purpose of this study was to clarify the relationship of distress and social contact in predicting the mortality of patients who suffer an AMI. We hypothesized that 1) elevated distress (at baseline) would be associated with higher 2-year mortality from SCD, independent of other clinical variables known to predict SCD, and 2) greater social contacts/support would be associated with lower 2-year mortality from SCD. Because a number of different psychosocial constructs have been related to mortality in previous studies, a subsidiary aim was to identify which of these were the best predictors of mortality. Because symptoms of fatigue are common in both heart disease and depression, this study also sought to determine whether depressive symptomatology was associated with mortality, after controlling for cardiac-related fatigue symptoms. Previous studies of psychological distress in the AMI population have not controlled for symptoms of fatigue. Our final aim was to test whether the association between psychosocial factors and mortality was influenced by antiarrhythmic treatment status (amiodarone vs. placebo). This study was conducted in conjunction with the CAMIAT study (29).


   MATERIALS AND METHODS
TOP
 ABSTRACT
 INTRODUCTION
 MATERIALS AND METHODS
RESULTS
 DISCUSSION
 ACKNOWLEDGMENTS
 REFERENCES
 
Subjects
The University of Toronto Ethics Committee and those of the participating hospitals approved the procedures of this study. The methods for the CAMIAT study have been reported in detail (29). In brief, inclusion criteria for CAMIAT were survivors of an AMI found, within 6 to 45 days of infarction, to have frequent (>=10/hour) or repetitive ventricular depolarizations on ambulatory electrocardiograms (>=18 hours of monitoring required). The determination of MI was based on the presence of two of the three following criteria: 1) characteristic ischemic pain in the precordium or associated referral areas for at least 20 minutes during physical and emotional rest, 2) activities of creatine kinase or aspartate aminotransferase more than two times the upper limit of the normal range levels for a given laboratory in the absence of any other explanation or the presence of creatine kinase MB of 6% or more than that of the total activity of creatine kinase; and 3) the development of new 40-ms Q waves in at least two adjacent electrocardiographic leads or the development of a dominant R wave in V1 (R >= 1 mm and S >= 1 mm in V1). The only exclusion criteria used for the psychosocial study were inability to read English or French well enough to complete the questionnaires and death before the 2-week postrandomization clinic visit for CAMIAT.

Written consent for the psychosocial study was obtained at the 2-week postrandomization clinic visit for CAMIAT. If the patient consented to participate in the psychosocial study, the CAMIAT study nurse administered a brief rating scale assessing the patient’s symptoms of dyspnea/fatigue (Yale Scale) (30), and the patient was given the psychological questionnaire battery to complete at home and return by mail within 2 weeks. Patients were called by the psychosocial research coordinator if they had not returned their questionnaire battery by 2 weeks.

Measures
The primary outcome event was SCD over 2 years of follow-up. A blinded external validation committee reviewed outcome events. SCD was defined as arrhythmic death or resuscitated ventricular fibrillation (29). Resuscitated ventricular fibrillation was defined as loss of consciousness and pulse, ventricular fibrillation documented electrocardiographically, administration of direct-current countershock, establishment of spontaneous cardiac output, and survival of at least 7 days. Arrhythmic death was defined as death due to rapid ventricular tachycardia or fibrillation with the likelihood that the patient would have probably survived for at least 4 months had this rhythm not occurred; sudden loss of cardiac output and pulse that precedes collapse of the circulation (defined as a state of very low cardiac output, poor peripheral perfusion, systolic blood pressure of <80 mm Hg, or dependence on intravenous inotropic support) or severe pulmonary edema, characterized by severe respiratory distress of sudden onset without evidence of noncardiac cause; and the absence of shock or pulmonary edema at the time of onset of the arrhythmia. Secondary outcomes were cardiac deaths and all-cause mortality.

The questionnaire battery included measures that had been related to cardiac mortality or morbidity in previous studies: depressive symptomatology, BDI (31); psychological distress, 90-item Symptom Check List (32); hostility, Cook-Medley Hostility Scale (33); perceived support, Multidimensional Scale of Perceived Social Support (34); and social network contacts and social participation, Health and Daily Living Form (35). The perceived social support measure asked patients to rate the degree of support experienced from family, friends, and significant others. The social network contacts measure assessed the frequency of interaction with one’s social network as well as network size (eg, number of close friends and number of memberships in clubs and associations). The social participation measure asked patients to indicate the number of times, in the month before hospitalization, that they had participated in any of the 15 pleasurable activities listed (eg, concert, play, opera, or museum) and, if they answered "yes," whether they were accompanied by a family member and/or friend. The total score was the sum of activities participated in with family and friends.

Patients’ reports of dyspnea/fatigue were assessed by the Yale Scale (30). This scale has been shown to be sensitive to drug treatment for CHF (30, 36) and to correlate satisfactorily with the 12-minute walking test (r = 0.60) (37). It is a rating scale similar to the New York Heart Association classification system except that it asks patients about symptoms of dyspnea/fatigue with both magnitude of task (eg, patient becomes symptomatic only with such major activities as walking up a steep hill, climbing more than three flights of stairs, or carrying a moderate load on the level) and pace of task (eg, major tasks such as walking up a steep hill, climbing more than three flights of stairs, or carrying a moderate load on the level are performed at reduced pace, taking longer to complete; less strenuous tasks can be done at a normal pace). There are five levels rated for both magnitude and pace of task corresponding to the ability to perform activities of extraordinary effort, major effort, moderate effort, light effort, and no effort (ie, symptomatic at rest). A third domain asks patients if dyspnea/fatigue has caused functional impairment and to what degree (eg, moderate impairment is defined as the patient having to change jobs or abandon at least one usual activity). The total dyspnea/fatigue score is the sum of scores across the three domains, ranging from 0 (extremely symptomatic) to 12 (not symptomatic). To express the relative risk ratio for the association between dyspnea/fatigue and mortality as a number >1, the scale was recoded so that 0 represented no impairment and scores >0 represented increasing severity of symptoms.

The following cardiac prognostic variables were obtained from the CAMIAT data files (29): study treatment status (ie, amiodarone or placebo); age, dichotomized at >=70 years or <70 years; previous MI; history of CHF, defined by history and assignment of New York Heart Association functional class or a documented history of interstitial or airspace pulmonary edema); CHF at the time of hospitalization for the index AMI, defined as pulmonary edema evidenced by intersitial or airspace disease on at least one in-hospital chest x-ray; ventricular premature depolarization runs on baseline 24-hour Holter monitoring; high ventricular premature depolarization rate, defined as >=20/hour; history of diabetes mellitus; and randomization to CAMIAT within 28 days of the index MI. The cardiac history variables were extracted from the patients’ medical records by the CAMIAT study nurses.

Statistical Analysis
The primary analysis was by Cox proportional hazards for the survival to SCD. The first set of analyses identified biological variables associated with SCD with inclusion defined by a significance level of >=0.20. Patients were retained in the amiodarone group regardless of whether they stopped taking the medication (ie, intention-to-treat analysis). Variables were assessed by the backward elimination method. This method enables identification of the variables that were most strongly and independently associated with SCD risk in this study. After identifying the subset of associated biological variables, models including psychosocial and demographic variables were analyzed. For the latter analyses, a two-tailed p value of <.05 was considered the minimum level of statistical significance for retaining a psychosocial variable in the model predicting SCD. In the test of the psychosocial variables, the first models were tested for interaction effects with treatment group (amiodarone or placebo). In the event of interaction effects, the variables were modeled separately for each treatment group. Both SAS version 6 (38) and SPlus 3.3 (39) were used for the statistical analyses.

With the exception of the measure of depressive symptoms, the psychosocial variables were entered as total scores. Consistent with how others have tested for an association between the BDI measure and cardiac deaths (1, 3), scores were dichotomized at >=10 or <10. This cutoff point represents mild to severe levels of depressive symptoms (31) and has also been shown to correspond well with the clinical diagnosis of depression in MI patients (40). Because it is not clear whether a specific level of depressive symptoms increases mortality risk, we also tested for an effect of the total depression score. Finally, because there is overlap between somatic symptoms of depression on the BDI and physical symptoms of heart disease, we repeated the survival analyses, grouping the items into somatic (items 14–21) and cognitive-affective components (items 1–13). Although there have been numerous factor analysis studies of the BDI, there is no universally accepted factor solution (41). Therefore, grouping the items in this way is, of course, speculative. The 13 cognitive-affective items were found to have good internal consistency ({alpha} = 0.81); however, the internal consistency coefficient of the eight somatic items was relatively low ({alpha} = 0.67). The total scores on these components were entered in the survival analysis. Lastly, descriptive analyses were conducted to explore associations between psychosocial markers of SCD and demographic and cardiac prognostic variables.


   RESULTS
TOP
 ABSTRACT
 INTRODUCTION
 MATERIALS AND METHODS
 RESULTS
DISCUSSION
 ACKNOWLEDGMENTS
 REFERENCES
 
Patient Accrual
Of the 36 CAMIAT hospital sites, 31 participated in the psychological substudy. Of the 969 CAMIAT patients available for this study, 87% met the eligibility criteria. Of the eligible patients, 144 (17%) declined participation, and 703 (83%) gave written consent. Of the ineligible patients, 7 died (1 of SCD and 6 of other cardiac causes) before they could be asked to participate in the psychosocial study. Of the 703 who agreed to participate, 671 (95.4%) returned the psychological questionnaires. Missing data reduced the sample size for the multivariate analysis to 634 (90%).

Comparisons of the cardiac prognostic variables between patients who either declined participation or failed to return completed questionnaires and those who participated revealed that patients who declined participation were more likely to be >= 70 years of age ({chi}2 = 12.06, p < .008) and to have been randomized to CAMIAT within 28 days of their qualifying MI ({chi}2 = 13.40, p < .003). Importantly, however, of the patients who were eligible for the psychosocial study, mortality rates at follow-up were not found to differ between patients who agreed to participate and those who either declined or failed to return questionnaires (p > .20).

Patient Characteristics
Most of the patients were men (82.8%); 34.5% had completed trade or technical training or university, 14.4% had completed high school, 30.5% had some high school education, and 20.6% had completed eighth grade or less. Marital status was 5.1% single, 74.4% married, 11% separated or divorced, and 9.6% widowed. Sixty-three percent were unemployed or retired. There was a considerable range of scores on the dyspnea/fatigue scale, from the minimum score of 0 to the maximum score of 12. The mean score was 4.4 ± 2.6. About half of the patients experienced some functional limitations due to dyspnea/fatigue (51.2%); however, only a minority reported symptoms with light activities, such as walking on the level, washing, or standing (10.8%), and very few reported symptoms at rest or while sitting or lying down (0.6%).

The mean age of the sample was 63.8 ± 10.8 years (SD) (range = 32–89 years); mean ventricular premature depolarization rate on 24-hour Holter monitoring was 82.9 ± 149.8; 55.4% had new Q waves; the site of the index MI was inferior in 33.7%, anterior/lateral in 22.8%, posterior in 2.7%, and indeterminate in 40.8%; 10.0% had CHF during hospital admission for the index MI; 33.8% had had a previous MI; 22.7% had a history of CHF; 14.7% had a history of diabetes; and 353 patients were randomized to receive amiodarone, and 318 received placebo. Forty-eight percent reported participation in a diet program, 37.7% in an exercise program, and 6.7% in a stress management program.

Outcome Events
Over the 2-year follow-up period, there were 34 SCDs (5 were resuscitated ventricular fibrillation), 16 other cardiac deaths, 1 vascular death, and 12 noncardiac deaths.

Biological Predictors of SCD
The first Cox proportional hazards model evaluated cardiac predictors of SCD. Two variables were significant predictors: previous MI (RR = 2.86; 95% CI = 1.37–5.99; p < .005) and previous CHF (RR = 3.86; 95% CI = 1.89–7.89; p < .0001).

Psychosocial Predictors of SCD
When the psychosocial and demographic variables were added to the model after controlling for previous MI and CHF, the following variables were found to independently predict SCD: in placebo patients, scoring >=10 on the BDI (RR = 2.45; 95% CI = 1.14–5.35; p < .02); and in all patients, having greater social network contacts (RR = 1.04; 95% CI = 1.01–1.06; p < .007) and participating less in social activities (RR = 0.98; 95% CI = 0.96–1.00; p < .05). The interaction term between the depression scores and treatment status was statistically significant (RR = 0.21; 95% CI = 0.06–0.76; p < .02). Furthermore, the relative risk for depressive symptoms in the amiodarone group was not significant (RR = 0.52; 95% CI = 0.15–1.76). Because of the significant interaction between treatment status and depression score, the depression effect was modeled separately for the placebo and amiodarone groups in subsequent analyses. The relative risks are displayed in Table 1, and the survival curves for the depression effect are illustrated in Figure 1.


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  		Table 1. Predictors of SCD: BDI Effect Modeled Separately for Amiodarone- and Placebo-Treated Patients
 


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  		Fig. 1. Cumulative proportion free of SCD (y axis) vs. survival in days (x axis). — = placebo, BDI score < 10; ···· = placebo, BDI score >= 10; —· = amiodarone, BDI score < 10; – – = amiodarone, BDI score >= 10.

 
Greater social participation was associated with a lower risk of SCD; however, greater social network contacts were associated with a greater risk of SCD. In interpreting the size of the effect, it should be noted that these variables were entered as total scores. Thus, the relative risk represents the change in risk associated with a 1-point increase in the social support scale (mean social network contacts score = 6.13 ± 6.17; mean social participation score = 21.23 ± 17.54). Results of tests of the interactions between the social support variables and treatment group were not significant. We also explored interaction effects with sex and age. However, given the small number of women (N = 114) and the fact that only six experienced a SCD, we could not test for interaction effects between sex and the psychosocial variables. There were no interaction effects with age (p > .20).

In the next set of analyses, dyspnea/fatigue was added to the model (Table 2). Dyspnea/fatigue was associated with SCD in all patients (RR = 1.31; 95% CI = 1.11–1.53; p < .001). Because the dyspnea/fatigue score was entered as a total score, the relative risk represents the increase in risk of SCD associated with a 1-point increase in the dyspnea/fatigue scale. The size of the relative risks associated with the depression cutoff point score and the dyspnea/fatigue total score are not directly comparable because they represent different increments in the values of each scale. When dyspnea/fatigue was included in the model, the effect of elevated depressive symptoms in the placebo group was no longer statistically significant, and the relative risk was reduced by about 30% (RR = 1.73; 95% CI = 0.75–3.98; p = .20). The social support factors, on the other hand, were less affected by the inclusion of dyspnea/fatigue: The size of the relative risks was unaltered, and the effect of social network contacts was still statistically significant (p < .004), whereas the effect of social participation remained at borderline significance (p < .06). The pattern of the results was identical when the total BDI score was used in the hazard model.


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  		Table 2. Predictors of SCD: Dyspnea/Fatigue Included
 
When the effects of dyspnea/fatigue within each treatment group were examined, symptoms of dyspnea/fatigue were associated with SCD in both patients taking placebo (RR = 1.29 per 1-point increase; 95% CI = 1.08–1.55; p < .006) and patients taking amiodarone (RR = 1.37 per 1-point increase; 95% CI = 1.10–1.71; p < .005).

These sets of analyses were repeated for the outcomes of cardiac mortality and all-cause mortality. The results were essentially the same with the exception that social participation was not as significant a predictor of all-cause mortality (RR = 0.99, 95% CI = 0.98–1.01, p = .19). When dyspnea/fatigue was entered into the model, the effect of depressive symptoms was nonsignificant (p > .20).

Because of the overlap between cardiac symptoms (eg, cardiac-related fatigue) and depressive symptoms, the survival analyses were repeated, grouping the BDI items into somatic and cognitive-affective components. As in the earlier analyses, previous MI, previous CHF, and dyspnea/fatigue were entered before examining the effects of the psychosocial variables. As shown in Table 3, the results revealed a trend for higher scores on the cognitive-affective items to be associated with a higher risk of SCD in placebo-treated patients. The relative risk was 1.09, and the 95% confidence interval straddled 1.00 (0.99–1.19) so that the p value was .06. Paradoxically, there was a trend for the cognitive-affective component to be associated with a lower risk in amiodarone-treated patients (RR = 0.73, 95% CI = 0.52–1.01, p < .06). Because the total scores were entered, the relative risk represents the increase or decrease in risk associated with a 1-point increase in the cognitive-affective depression score. In the survival analyses predicting total cardiac mortality or all-cause mortality, however, the cognitive-affective component was not significant (p > .20). In none of the analyses was the somatic component significantly associated with the mortality outcomes.


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  		Table 3. Predictors of SCD: BDI Somatic vs. Cognitive-Affective Components
 
Lastly, to clarify the apparently contradictory effects of the two social support factors, and to explore potential mechanisms underlying the associations between the psychosocial variables and SCD, we investigated associations between these variables and the cardiac prognostic factors and demographic variables. First, the three social support constructs were only weakly correlated. The correlations were perceived social support with social network contacts (r = 0.24, p < .01) and social participation (r = 0.15, p < .01) and social network contacts with social participation (r = 0.22, p < .01). Also, the BDI score was only weakly correlated with the social support variables (ie, with perceived support, r = -0.25, p < .01; social network contacts, r = -0.02, p = .63; and social participation, r = -0. 13, p < .01). There was only one significant association between the cardiac prognostic variables and elevated depressive symptoms. Patients who scored >=10 on the BDI had greater impairment on the dyspnea/fatigue scale than patients who scored <10 (mean = 5.29 ± 2.63 vs. 3.89 ± 2.41, respectively) (t(592) = 6.41, p < .0001). Greater social network contacts were associated with having had a previous MI (Z = 2.33, p < .03) and having a history of diabetes mellitus (Z = 2.67, p < .01). Greater social participation was associated with less impairment due to dyspnea/fatigue (Z = 2.24, p < .03), marital status (F(3,647) = 3.39, p < .02), and education (F(4,636) = 2.37, p < .05). To test whether these cardiac and demographic variables mediated the association between the social support variables and SCD, the survival analysis was repeated controlling for previous MI, history of diabetes, dyspnea/fatigue, marital status, and education. Controlling for these variables did not alter the size of the relative risks, and the significance level was still significant for social network contacts (p < .006) and only marginally reduced for social participation (p < .07).


   DISCUSSION
TOP
 ABSTRACT
 INTRODUCTION
 MATERIALS AND METHODS
 RESULTS
 DISCUSSION
ACKNOWLEDGMENTS
 REFERENCES
 
Like others (1, 3), we found that elevated depressive symptoms were associated with a two-fold greater risk of mortality in patients after an AMI. However, after controlling for symptoms of dyspnea/fatigue, the relative risk associated with depressive symptoms was reduced by 30% and was no longer statistically significant. Others have not controlled for symptoms of dyspnea/fatigue when evaluating the mortality risk of depressive symptoms in cardiac patients. Thus, our results raise questions about the extent to which cardiac symptoms such as dyspnea/fatigue confound the assessment of depression in the AMI population. Both somatic symptoms (eg, fatigue and sleep problems) and cognitive-affective symptoms (eg, trouble making decisions, guilt, and sadness) make up depressive symptomatology. Therefore, it is possible that symptoms of the physical illness simulate depressive symptoms in the medically ill. Conversely, depression may overlay or amplify self-reports of physical symptoms. Furthermore, depression and illness may be directly related, such that more severely ill patients may experience more depressive symptoms (2).

It is well known that fatigue is a symptom of depression and a common symptom of physical illness (eg, CHF). Statistically controlling for such disease severity factors as previous MI and CHF may not completely control for the "biological" effects of heart disease on SCD risk. The most important biological predictor of outcome after AMI is ejection fraction (25). Because ejection fraction was not measured on patients participating in CAMIAT, we could not control for this important prognostic variable. However, we were able to control for symptoms of dyspnea/fatigue. Cardiac-related symptoms as indexed by New York Heart Association class (ie, dyspnea, fatigue, and chest pain) have been found to predict mortality in cardiac patients independent of more objective measures of heart function, such as ejection fraction (20, 42–46). Thus, both objective measures of heart function and subjective symptoms seem to provide independent prognostic information. The dyspnea/fatigue score is analogous to the New York Heart Association class.

To further address the question about the overlap in measuring symptoms of cardiac illness and depression, we repeated the survival analyses, dividing the depression items into somatic vs. cognitive-affective components. Our assumption was that the cognitive-affective items would be less confounded with cardiac symptoms and thus provide an opportunity to better test the independent effects of depression. In support of the hypothesis that depression is independently associated with higher SCD risk, the results revealed a trend for higher scores on the cognitive-affective component to be associated with a greater risk of SCD in placebo-treated patients even after controlling for dyspnea/fatigue. Higher scores on the cognitive-affective component, on the other hand, were associated with a lower risk in the amiodarone-treated patients. The results in the placebo-treated patients, therefore, suggest that the association between depressive symptoms and increased SCD risk cannot be entirely explained as an artifact of illness-related fatigue. Rather, the association may well be a specific effect of depressed mood. Although the mechanisms by which depressed mood could affect survival of patients after an AMI have not been established, possible mechanisms include altered autonomic tone and/or poor adherence to medical treatment regimens (47, 48).

Additional evidence suggesting that the depression and fatigue scales were likely measuring related but not synonymous constructs comes from the differences observed in the influence of depression vs. dyspnea/fatigue on SCD risk in amiodarone-treated patients. Although the proportion of SCDs in the placebo group clearly differed between depressed (10.9%) and nondepressed (5.6%) patients, in the amiodarone group, the proportions of SCDs were very similar (2.5% vs. 3.3%, respectively). On the other hand, the relative risks associated with elevated fatigue symptoms and SCD risk were similar between placebo-treated patients and amiodarone-treated patients, and both were statistically significant.

Why did amiodarone seem to protect in the presence of depressive symptoms and yet not confer protection in the presence of fatigue symptoms? Altered neuroendocrine function has been proposed as a possible mechanism for the increased cardiac mortality associated with depression in cardiac patients (47). Therefore, it is possible that the antiarrhythmic properties of amiodarone (29) helped to protect the diseased heart against the neuroendocrine effects of depression. The risk related to fatigue symptoms, being perhaps more a marker of poor cardiac function, may not have been so amenable to the antiarrhythmic properties of amiodarone. There is, however, another potential explanation for the discrepant effects. Patients were recruited into this study approximately 2 weeks after they had started taking amiodarone. Therefore, it is possible that being on amiodarone in some way influenced patients’ endorsement of depression items, thereby disrupting the assessment of the relationship between depression and mortality in this group. For example, side effects of amiodarone may have mimicked depressive symptoms in the amiodarone group. We did not have the side effects data to test this hypothesis directly; however, we do know from the full CAMIAT sample that patients treated with amiodarone experienced more sleep disturbance and gastrointestinal problems than patients in the placebo group (29). Also, scores on the BDI differed between patients on placebo and those on amiodarone (7.7 ± 6.13 and 8.7 ± 6.3, respectively, (t(643) = 2.26, p < .04), although the 1.6-point difference is unlikely to be of clinical significance. Moreover, the difference in the depression-SCD association between the placebo and amiodarone groups was much more striking for the cognitive-emotional symptoms of depression than for the somatic symptoms. It is hard to imagine how the cognitive-emotional symptoms of depression would be affected by amiodarone. Future studies are needed to determine whether amiodarone does indeed protect against the effects of depression on the heart.

The contradictory effects of the two social support factors are puzzling. More social network contacts were associated with greater risk of mortality, whereas more social participation was associated with lower risk. It is possible that the apparently contradictory effects arose because of the influence of confounding factors. Greater social network contacts were associated with previous illness factors (eg, previous MI and diabetes mellitus), whereas social participation was unrelated to these variables. Therefore, social network contacts may have been tapping an unmeasured illness effect. In other words, contacts with family and friends may increase around times of illness. To test this explanation, the survival analyses were repeated, controlling for all demographic and disease-related variables associated with the social support variables. The relative risks for the effects of social network contacts and social participation were essentially unaltered by the inclusion of the potential mediating factors, and the statistical significance was only marginally diminished. However, unavoidable residual confounding remains a possible explanation for increased mortality risk associated with greater social network contacts. The association between social network contacts and mortality risk is at variance with both the social participation results in our study as well as with the beneficial effects of social network contacts observed in other studies (15–18).

We also did not find that marital status or socioeconomic resources (as indexed by educational level and employment) predicted mortality. Ruberman et al. (19) found in cardiac patients that educational level predicted mortality. Williams et al. (21) found that a higher mortality rate was associated with income but not with educational level or employment. Also, other studies in cardiac patients (3, 20, 22, 25) have not found an association between educational level and mortality. Similarly, in a recent large sample of 5201 older men and women in the United States who did not necessarily have coronary heart disease at entry, income predicted mortality, whereas educational level was not predictive in the multivariate model (49). The inconsistencies among studies suggest that when examined as individual factors, educational level and employment may not reliably measure the mortality risk associated with lower socioeconomic resources. The more consistent findings with income suggest that income may be a better measure of socioeconomic resources than either education or employment. As regards marital status, being married has been associated with a lower risk of mortality in some studies of community samples (15, 23, 28) and cardiac samples (21); however, a lack of an association with marital status has also been reported (12, 14, 24, 25). Because marital status per se does not assess the availability, quality, or quantity of social connections, it may not be as sensitive an index of social resources as are measures of social network and social participation.

In conclusion, symptoms of depression and fatigue overlap in patients with MI. The trend for the cognitive-affective symptoms of depression to be associated with higher SCD risk in the placebo group, even after controlling for dyspnea/fatigue, suggests that the association between depression and mortality after AMI cannot be entirely explained as a confound of cardiac-related fatigue. Lastly, the contribution of social participation in predicting SCD, independent of depressive symptoms and dyspnea/fatigue, suggests a role for of depressive symptomatology and social factors in influencing mortality risk in post-AMI patients.


   ACKNOWLEDGMENTS
TOP
 ABSTRACT
 INTRODUCTION
 MATERIALS AND METHODS
 RESULTS
 DISCUSSION
 ACKNOWLEDGMENTS
REFERENCES
 
This study was funded by a research grant from the Heart and Stroke Foundation of Ontario and by a scholarship award from the Heart and Stroke Foundation of Canada (J.I.). We thank the study patients for their cooperation and the CAMIAT study nurses and investigators from the following participating CAMIAT centers: Royal Victoria Hospital, Barrie, Ontario; Foothills Hospital, Calgary, Alberta; Gray Nuns Hospital, Royal Alexandra Hospital, and University Hospital, Edmonton, Alberta; Chedoke McMaster Hospital, Hamilton General Hospital, Henderson General Hospital, and St. Joseph’s Hospital, Hamilton, Ontario; Hotel Dieu Hospital, and Kingston General Hospital, Kingston, Ontario; University Hospital and Victoria Hospital, London, Ontario; Ottawa Civic Hospital, Ottawa, Ontario; Peterborough Civic Hospital, Peterborough, Ontario; L’Enfant Jesus Hospital and L’Hotel Dieu Hospital, Quebec City, Quebec; Credit Valley Hospital, Queensway General Hospital, Scarborough Centenary Hospital, Scarborough General Hospital, Scarborough Grace Hospital, St. Michael’s Hospital, Sunnybrook Medical Sciences Center, and Toronto East General Hospital, Toronto, Ontario; St. Paul’s Hospital, Vancouver; and St. Boniface General Hospital, Winnipeg, Manitoba. We would also like to acknowledge our appreciation of Janice Smith for her excellent work on the data analysis of the results from this study.

Received for publication July 21, 1998.

Revision received June 3, 1999.


   REFERENCES
TOP
 ABSTRACT
 INTRODUCTION
 MATERIALS AND METHODS
 RESULTS
 DISCUSSION
 ACKNOWLEDGMENTS
 REFERENCES
 

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