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ORIGINAL ARTICLES |
From the Research Center, Montreal Heart Institute, Montreal, Canada (N.F.-S., F.L., M.J., M.T., M.G.B.); Department of Psychiatry, McGill University, Montreal, Canada (N. F.-S., F.L.); School of Nursing and Department of Epidemiology and Biostatistics, McGill University, Montreal Canada (N.F.-S.); Departments of Psychiatry (N.F.-S., F.L.) and Medicine (M.J., M.T., M.G.B.), University of Montreal, Montreal, Canada
Address reprint requests to: Nancy Frasure-Smith, Research Center, Montreal Heart Institute, 5000 Belanger St. E, Montreal, Quebec, Canada, H1T 1C8. E:mail: frsm{at}icm.umontreal.ca
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ABSTRACT |
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 TOP ABSTRACT INTRODUCTIONMETHODSRESULTSDISCUSSIONACKNOWLEDGMENTSREFERENCES |
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METHODS: Secondary analysis was performed on data from two studies that used the Beck Depression Inventory (BDI) to assess depression symptoms during hospitalization: a prospective study of post-MI risk and a randomized trial of psychosocial intervention (control group only). The sample included 896 patients (283 women) who survived to discharge and received usual posthospital care. Multivariate logistic regression analysis was used to assess the risk of 1-year cardiac mortality associated with baseline BDI scores.
RESULTS: There were 290 patients (133 women) with BDI scores 
10 (at least mild to moderate symptoms of depression); 8.3% of the depressed women died of cardiac causes in contrast to 2.7% of the nondepressed. For depressed men, the rate of cardiac death was 7.0% in contrast to 2.4% of the nondepressed. Increased BDI scores were significantly related to cardiac mortality for both genders [the odds ratio for women was 3.29 (95% confidence interval (CI) = 1.02–10.59); for men, the odds ratio was 3.05 (95% CI = 1.29–7.17)]. Control for other multivariate predictors of mortality in the data set (age, Killip class, the interactions of gender by non-Q wave MI, gender by left ventricular ejection fraction, and gender by smoking) did not change the impact of the BDI for either gender.
CONCLUSIONS: Depression in hospital after MI is a significant predictor of 1-year cardiac mortality for women as well as for men, and its impact is largely independent of other post-MI risks.
Key Words: depression, • myocardial infarction, • women, • prognosis.
Abbreviations: BDI = Beck Depression Inventory;; PSSS = Perceived Social Support Scale;; CI = confidence interval;; EPPI = Emotions and Prognosis Post-Infarct;; MCS = Marlowe-Crowne Social Desirability Scale;; M-HART = Montreal Heart Attack Readjustment Trial;; MI = myocardial infarction;; STAI = State-Trait Anxiety Inventory.
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INTRODUCTION |
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TOPABSTRACTINTRODUCTIONMETHODSRESULTSDISCUSSIONACKNOWLEDGMENTSREFERENCES |
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METHODS |
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After discharge, patients in the EPPI study received usual care from their physicians, whereas M-HART patients were randomly assigned to a psychosocial intervention program or usual care. Because the results of the M-HART study showed evidence of a harmful impact of the program on prognosis in women, the present combined sample includes only those M-HART patients who were randomly assigned to usual care (control group). In addition, because of the current focus on depression, the pooled sample excludes patients who did not complete the BDI during admission (four from the EPPI study, and six from the M-HART control group).
Procedures
Patients meeting sample selection requirements were asked to participate as soon as possible after transfer from coronary care to medical wards. After explanation of the study and obtaining informed consent, study research assistants conducted baseline psychosocial interviews. These interviews assessed a variety of demographic, medical history, and psychosocial variables including age, education, daily smoking at the time of the MI, previous MI, previous treatment for hypertension, current marital status, and measures of social network (whether the patient was living alone; number of close friends). The 21-item self-report BDI (9) was used to assess symptoms of depression, and the 20-item state scale of Spielberger’s STAI (11) was administered to assess anxiety. The 24-item Spielberger Anger Expression Scale including subscales for anger-in (the tendency to avoid expressing anger, even when appropriate) and anger-out (the tendency to express anger by directing it outward toward other people or objects) (12) was also used, as was the PSSS (13), a 12-item self-report measure of perceived availability of social support. The tendency to respond to interview questions with socially acceptable rather than objective responses (social desirability response set) was assessed using the 13-item version of the MCS, developed by Reynolds (14).
Medical data obtained from hospital charts included whether the index MI was a Q wave or a non-Q wave MI, Killip class (15), left ventricular ejection fraction (N = 868), thrombolytic treatment at the time of admission, whether the patient had a revascularization procedure (angioplasty or bypass) during the index admission, and prescription of medication for diabetes (hypoglycemics or insulin).
Initial 1-year survival status was obtained from contacts with patients or family members at 12 months postdischarge, and from Quebec Medicare data. The Commission d’accès à l’information du Québec provided study investigators with the right to access Medicare data for study participants, all of whom provided informed consent for access. All readmissions for 2 or more days shown by the Medicare data were investigated additionally to determine whether there had been a reinfarction. Data on enzyme levels, chest pain, and EKG changes were obtained from files in the hospital where each admission occurred. Information about causes and dates of death was abstracted from hospital charts, ambulance records, death and autopsy reports (when available), and supplemented by interviews with family members. Survival status was obtained for all patients at 365 days postdischarge. Causes of death were independently classified as cardiac and noncardiac by two cardiologists, who were blinded to baseline data and, in the case of the M-HART study, to treatment group. Cardiac deaths were classified additionally as secondary to arrhythmias (definite or probable), MI (definite or probable), congestive heart failure, or a cardiac procedure (coronary bypass surgery, coronary angioplasty, thrombolysis). Survived MI recurrences were defined using study eligibility criteria for MI, and were also independently rated by the study cardiologists. Disagreements in classification of deaths and MI recurrences were resolved by discussion.
Data Analysis
Data were analyzed using SPSS for Windows (version 7.5) (16). All statistical tests were two-sided. p values 
.05 were considered statistically significant; those .10 and > .05 were considered marginal. The baseline characteristics of women and men were compared using the 
2 statistic for categorical variables. Continuous variables were compared using independent t tests. The primary outcome was cardiac death over 12 months after hospital discharge. Multiple logistic regression analysis and the 2 statistic were used to assess the odds ratio for cardiac mortality associated with gender and with depression. Logistic regression was also used to examine the relationship between other baseline variables and cardiac mortality, and between baseline variables and depression. To facilitate interpretation of interactions, continuous variables were dichotomized at clinically relevant points. As in our previous work, because there was no literature to suggest cutoff values for most of the baseline psychological variables (anxiety, anger-in, anger-out, perceived social support, and social desirability) the highest or lowest quartile was selected. The two-way interactions between gender and baseline variables, between depression and baseline variables, and between gender and depression were assessed using the likelihood ratio test. Significant interactions were examined additionally by performing separate logistic regressions for the groups involved in the interactions.
To examine the impact of depression on cardiac mortality in relation to the impact of other baseline variables, a model predictive of cardiac mortality in both women and men without including depression was built, which began by forcing in age and the significant gender by baseline interactions as well as their component main effects. Then multivariate backward stepwise analyses were performed for the remaining baseline variables to produce a model to predict cardiac mortality for both genders. The degree to which this model was improved by the addition of depression was assessed, using the likelihood ratio test.
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RESULTS |
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35% did not differ. Thus, it is unlikely that there was a clinically meaningful gender difference in cardiac pump function. Approximately 25% of each gender underwent revascularization procedures in hospital before discharge. Although women had significantly higher mean anxiety scores and higher social desirability scores, anger-out scores were higher for men. Finally, the perceived adequacy of social support was about the same for the two genders. Because of women’s higher social desirability scores, the gender comparisons for the other psychological variables were made a second time after controlling for social desirability. The pattern of gender differences remained unchanged.
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10, indicative of at least mild to moderate symptoms of depression [the odds ratio for depression associated with gender was 2.57 (95% CI = 1.92–3.46); p < .00001]. To more fully explore the degree to which gender was related to post-MI depression independently of other factors associated with gender, we performed a multivariate logistic regression analysis using gender to predict depression after controlling for the background factors which differed between men and women. The results showed that gender was significantly related to post-MI depression even after controlling for age, education, marital status, living alone, history of treatment for hypertension, diabetes, previous infarct, thrombolytic treatment, Killip class, left ventricular ejection fraction, anxiety, anger-out, and social desirability score [adjusted odds ratio for depression associated with gender was 2.00 (95% CI = 1.30-3.09); p = .0017]. Thus, women’s higher rate of post-MI depression could not be accounted for by background differences between the genders, including differences in other psychological variables.
Baseline Characteristics in Relation to Depression
Table 2 shows the relationship between depression (BDI 10) and baseline characteristics for the overall sample for variables that did not have a significant interaction with gender, that is, for which the relationship with depression was similar for men and women. Variables with significant interactions with gender are shown in Table 3. Regardless of gender, depression was associated with previous treatment for hypertension, advanced Killip class, and impaired left ventricular ejection fraction. Thus, depressed patients of both genders tended to have somewhat more advanced cardiac disease. Depression was also associated with lower levels of education, not having close friends, lower perceived social support, higher anxiety, higher anger-out, and lower social desirability response style.
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Depression and Prognosis in Men and Women
A total of 42 patients died by 1 year, with 37 being cardiac deaths. This included 15 cardiac deaths among women and 22 among men. The causes of cardiac death for women included 7 MIs (definite or probable), 2 arrhythmic deaths (definite or probable), 5 deaths from heart failure, and 1 periprocedural death. For men there were 6 MIs, 15 arrhythmic deaths, and 1 death from heart failure. In addition, 19 women and 24 men had survived reinfarctions, and 1 woman and 4 men survived cardiac arrests. Results of the logistic regressions for cardiac death and other cardiac events in relation to gender and depression are shown in Table 4. Although there was no significant gender difference for overall cardiac deaths, women were significantly more likely to experience reinfarctions, and marginally less likely to have arrhythmic events than men. The gender difference for the combined end point of any hard event, including cardiac death, survived MI recurrences, and survived cardiac arrests, was not significant. Similarly, there was no difference between men and women in terms of revascularization after discharge. Depressed patients were significantly more likely to die of cardiac causes and to have an arrhythmic event than nondepressed patients. They were also marginally more likely to have MI recurrences, and significantly more likely to experience the combined end point of any hard cardiac event. There was no difference in revascularization between depressed and nondepressed patients. It is also of interest that, as suggested in our previous work (17), the impact of depression tended to be more marked for cardiac deaths (particularly arrhythmic deaths) than for MI recurrences. Consequently, when MI recurrences and arrhythmic events were added together to form the variable "any hard cardiac event," the depression-related risk for the combined outcome was less marked than the risk for the primary outcome, cardiac mortality.
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As mentioned previously, there was no evidence of an interaction of gender and depression for any outcome, including the primary outcome, cardiac death (p = .92). For women, the 1-year odds ratio for cardiac death associated with depression was 3.29 (95% CI = 1.02–10.59), and for men it was 3.05 (95% CI = 1.29–7.17). The same pattern also occurred when the BDI score was analyzed as a continuous variable. The odds ratio for cardiac mortality associated with a 1-point increase in the BDI score was 1.03 (95% CI = 0.98–1.08) for women and 1.06 (95% CI 1.02–1.10) for men. Figure 1 includes the percent cardiac mortality for women and men in relation to the level of their in-hospital BDI score, which reflects increasing severity of depressive symptoms. There is a nearly linear increase in risk of cardiac mortality with increasing BDI scores for both genders. The exception to this linear increase is for women with BDI scores 19, for whom the risk, although higher than that for women who were not depressed at all, was less than the risk for women with scores between 15 to 18. However, although women classified as depressed (BDI scores 10) did not differ in age from nondepressed women, the women with very high scores (19) were, on average, 4 years younger than women with scores < 19 (p = .025). Thus, their lower age may partially explain their lower mortality.
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49). However, the impact of anxiety on cardiac mortality in women remained nonsignificant [odds ratio was 0.74 (95% CI = 0.20–2.71); p = .65].
The Independent Relationship Between Depression and Cardiac Mortality
To assess the strength of the relationship between depression and cardiac mortality after taking into account other predictive factors, stepwise procedures were used to build a combined model to predict cardiac mortality in both women and in men without the inclusion of depression. The final model included age, Killip class, the interaction of gender and left ventricular ejection fraction, the interaction of gender and non-Q wave MI, and the interaction of gender and smoking. Overall, this model had a Hosmer and Lemeshow Goodness of Fit 2 value of 8.79 (8 df; p = .36). The addition of depression significantly improved the model (p = .0008; Goodness of Fit 2 = 5.15; p = .74), and the interaction of gender by depression remained nonsignificant (p = .30), supporting the interpretation that the impact of depression is independent of measures of disease severity for both genders. The final model including depression is shown in Table 7.
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DISCUSSION |
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In their recent review of the literature concerned with gender differences in mortality after MI, Vaccarino et al. (7) reported that despite the large amount of variability among the more than 20 studies examined, women MI patients tended to be older, and were more likely than men to have a history of hypertension, congestive heart failure, and diabetes. They experienced more complications at the time of the MI including congestive heart failure and cardiogenic shock, but there was also evidence of greater preservation of left ventricular function in women. Men, however, were more likely to have had a previous infarct, to smoke, and to have arrhythmic complications. With the exception of smoking (women and men in the current sample were about equally likely to have smoked before the index MI), these differences closely parallel our results. Our data also indicate that, as in the few studies that have assessed social factors (7, 21), women, partially because of their older age, are more likely to be unmarried and living alone, and to have less education than men. The current data now add to this pattern by documenting gender-related differences in psychological factors. We found that women report more depression and anxiety symptoms than men, and that men tend to report more anger directed outward. The observation that anxiety increased the risk of cardiac mortality for men and not for women was of only marginal statistical significance, but may be of some clinical importance, and deserves additional study. However, depression was the only psychological factor with a significant survival impact over the first post-MI year for both genders. This may indicate that depression is more important than other psychological factors, or it may reflect the fact that depression was better measured than anxiety and anger.
It is also worth noting that the approximate doubling in rates of post-MI depression associated with female gender is similar to the ratio reported in many epidemiological studies of psychiatric disorder in the general community (22, 23). Although some authors have speculated that women are more willing to report depressive symptoms than men (24), and others have suggested that there is a gender difference in tendencies to ruminate about interpersonal interactions that leads women to be more easily depressed (25), the reasons for the higher rates of depression among women remain controversial. However, our finding of similar increases in mortality risk associated with increased BDI scores in women and men suggests that mild to moderate symptoms of depression have an intrinsic clinical value for both genders. Patients reporting this level of symptoms deserve closer psychiatric evaluation, regardless of gender.
Not only did depression have a similar degree of impact for women and men, but also the baseline factors related to depression were almost identical for the two genders. Both men and women who were depressed were significantly more likely to have a history of hypertension, advanced Killip class, and impaired ventricular function, and marginally more likely to be diabetic. Although statistically significant, the differences in disease severity between the depressed and nondepressed were relatively small, and the impact of depression remained after control for measures of disease severity.
We found two interrelated gender differences in the correlates of depression. Men who lived alone and who were unmarried were significantly more likely to be depressed than others. This suggests that depression may be a mechanism explaining previously reported links between social isolation with mortality in cardiac patients (21, 26), at least among men. However, among women, the unmarried and those living alone were less likely to be depressed. Interestingly, a recent Swedish study that examined gender differences in the characteristics of patients hospitalized for depression found that a greater percentage of women were married than men, and conversely that there were more men who had lived alone before admission (27). The authors suggest that for men marriage provides a special degree of closeness that is not available in other relationships, but that for women the same degree of closeness and support can be obtained from a variety of sources, so that living alone confers no special risk for them.
Our research has several limitations. First, it involved secondary analysis of data sets from two separate studies, neither of which was designed in advance to examine gender differences in prognostic factors. Although the mortality rate was lower in the M-HART control group (3.4%) than in the EPPI study (6.4%; p = .054), and a greater proportion of women were included in M-HART (34.8% vs. 21.6%; p < .0003), there was no evidence that the rates of elevated BDI scores (32.7% vs. 31.2%; p = 0.67) or the predictors of depression or mortality differed between the studies. The second limitation is that women and older patients were significantly more likely to refuse to participate than men and younger individuals. Thus, results cannot be generalized beyond the type of patient who is willing to participate in psychological screening interviews during hospitalization. Thirdly, it must be remembered that the BDI assesses the severity of depressive symptomatology, not the diagnosis of major depression. Although the BDI seems to be a good instrument to screen patients at increased risk of cardiac mortality, it is premature to say that 50% of women and 25% of men who experience MIs also experience a clinically significant depression. Unfortunately, although a measure of depression based on psychiatric criteria (the Diagnostic Interview Schedule; Ref. 28) was included in the EPPI study, it was not part of the M-HART trial. Thus, we cannot evaluate the sensitivity and specificity of different cutoff points of the BDI score for predicting major depression in women in contrast to men. We also do not know how many of the patients with increased BDI scores might have responded to antidepressant or psychotherapeutic treatment. Finally, although the current analyses include a substantial number of women and men who experienced MIs, the absolute number of cardiac deaths was relatively small, limiting our ability to control statistically for multiple variables and higher level interactions.
As the evidence accumulates that depressed post-MI patients are at increased risk for cardiac events, the need to provide effective and safe treatment strategies becomes more and more imperative. However, the risk of poor prognosis is not the only reason to want to be able to treat post-MI depression. In fact, with current cardiac treatment regimens, the prognosis after MI is quite good, even for depressed patients. We need to remember that beyond its impact on prognosis, depression results in considerable suffering for patients and families. This fact in and of itself justifies continued research into safe and efficacious treatments for post-MI depression for both women and men.
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ACKNOWLEDGMENTS |
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In addition to all of the people who helped with the EPPI and M-HART projects whom we have acknowledged in previous publications, we particularly want to thank our research assistants Ginette Gravel, Aline Masson, and Mélanie Richard, and to express our thanks to Jean Lambert, PhD, for his suggestions on an earlier version of the manuscript. We also are indebted to the Régie de l’assurance maladie du Québec for providing information on psychiatric contacts.
Received for publication September 22, 1997.
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REFERENCES |
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