Psychosomatics 40:286-292, August 1999
© 1999 The Academy of Psychosomatic Medine
Depression in Coronary Heart Disease
What Is the Appropriate Diagnostic Threshold?
Mark Sullivan, M.D., Ph.D.,
Andrea LaCroix, Ph.D.,
Joan Russo, Ph.D.,
Eamonn Swords, M.D.,
Michael Sornson, M.D., and
Wayne Katon, M.D.
Received August 19, 1998; revised November 24, 1998; accepted December 4, 1998. From the Center for Health Studies and Group Health Cooperative and University of Washington, Seattle, Washington. Address correspondence and reprint requests to Dr. Sullivan, Psychiatry and Behavioral Sciences, University of Washington, Box 356560, Seattle, WA 98195; e-mail: sullimar{at}u.washington.edu
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ABSTRACT
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The purpose of this study was to determine the threshold at which depression becomes important for the daily functioning of patients with heart disease. Data from a 1-year prospective cohort study of health maintenance organization patients undergoing coronary angiography for coronary heart disease were analyzed for differences in a standardized composite measure of functioning. Patients with major depression (N=19) and patients with minor depression (N=28) were significantly more functionally impaired at baseline and at 1-year follow-up than those with no depression (N=110). The major and minor depression groups did not differ significantly. The significance of the depression group differences was reduced, but not eliminated, when controlling for differences in reported heart symptoms.
Key Words: Depression • Diagnostic Tools • Syndromes Secondary to General Medical Disorders
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INTRODUCTION
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The role of depression in coronary artery disease is receiving increasing attention in the medical and psychiatric literature.1 However, the bulk of the attention has been directed toward depression as a risk factor for the development of coronary artery disease2 and as a risk factor for mortality from coronary artery disease.3,4 Some attention has also been given to depression as a risk factor for cardiac events (such as myocardial infarction [MI] and arrhythmia) in those with coronary disease.5 We recently published a study of patients with coronary disease undergoing angiography, providing evidence that anxiety and depressive symptoms significantly affect physical function and role function for the following 1-year period. Effects were strongest in the top quartile of anxiety and depressive symptoms, but many in this group did not have symptoms of a magnitude typical for a depressive disorder.6 It is not clear how severe depression must be before it has significant effects on functional outcomes in coronary patients.
There is evidence from clinical7,8 and population-based studies9,10 that depressive symptoms below the threshold for major depression have significant effects on daily function, ability to work, and health care utilization. This information is important because the prevalence of subthreshold depressive symptoms is at least equal to that of major depression and may be as much as two to three times that of major depression. The impact of subsyndromal, or minor, depression on daily function has not been prospectively studied in patients with a specific and well-defined medical illness.
In this study, we prospectively examined the role of major and minor depression in the functional status (composed of physical function, activity interference, social, family, and work disability) of a group of patients with documented coronary artery disease. We hypothesized that 1) patients with major and minor depression would show greater functional impairment over a 1-year follow-up period than those who met criteria for no depression diagnosis and 2) this difference in functional impairment was not solely due to differences in reported heart symptoms.
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METHODS
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Patients were recruited from Group Health Cooperative (GHC) of Puget Sound, a consumer-owned health maintenance organization (HMO) in Western Washington, and Group Health Northwest. Between December 1991 and February 1993, all GHC members 45 to 80 years of age undergoing elective cardiac catheterization for suspected coronary artery disease were screened for study participation. Inclusion criteria were as follows: 1) at least 50% occlusion of one major coronary vessel by angiography, 2) a Bruce-protocol treadmill stress test within the past year, 3) coronary disease must be subject's most disabling disease, and 4) subject must be ambulatory at the time of catheterization. Of 409 patients undergoing catheterization, 270 (66%) were eligible, and 232 (86% of those eligible) provided consent and completed the initial psychosocial interview. Of these, 157 subjects completed all relevant measures at baseline and 12 months.
Potential subjects were contacted by phone before their scheduled cardiac catheterization by the study coordinator, who described the study and obtained preliminary consent to meet with them in the hospital. After complete description of the study to subjects, written informed consent was obtained at the time of the interview. Research procedures were approved by the Human Subjects Committees of the University of Washington, GHC of Puget Sound, and Group Health Northwest.
Measures
Consenting subjects were interviewed by a research nurse in their hospital rooms after their catheterization while they waited for hemostasis of their groin wound. Interview after catheterization is convenient for subject and spouse, since they must wait in the hospital for up to 6 hours. This interview protocol has been shown to yield reliable and valid psychosocial data in prior studies.11 These interviews included assessment of 1) depression diagnoses by using the National Institute of Mental Health Diagnostic Interview Schedule for DSM-III-R12 (DIS); 2) Hamilton Depression Rating Scale13 (Ham-D); 3) Hamilton Anxiety Rating Scale (Ham-A)14; 4) sociodemographic characteristics, including age, gender, educational level, and occupation (used to derive a Hollingshead-Redlich social class score15); 5) physical functioning (8 items) from the Medical Outcomes Study Short Form-3616 (SF-36); 6) symptom severity (3 items) and 7) activity interference (11 items), both from an adapted version of the Multidimensional Pain Inventory17 (MPI) ; 8) role dysfunction in social and family/home domains (2 Likert scales) using Sheehan's Disability Scales;18 and 9) a single item about work disability from the RAND-UCLA Functional Status Questionnaire (FSQ).19 Whenever possible, the subject's spouse also filled out the MPI activity interference scale to rule out reporting bias due to the subject's emotional state. Each of these measures has well-documented reliability and validity in patients with chronic medical illnesses.
Standard clinical indices of cardiac disease severity were obtained from the patients' outpatient testing records and hospital charts. Various measures derived from coronary angiography were considered as objective measures of disease severity. Number of main vessels occluded >70% was chosen for further analyses because 1) at this level coronary occlusion becomes hemodynamically significant and 2) it showed the strongest relation of all disease severity measures examined to self-reported physical function. Left-ventricular ejection fraction by angiography and amount of ST-segment depression achieved during Bruce-protocol treadmill stress testing were also considered. A pharmacy-derived chronic disease score was used to control for differing levels of medical comorbidity. This chronic disease score has been found to correlate highly with primary care physician ratings of severity of patients' illnesses, as well as with hospitalization and mortality in the subsequent year.20
Scoring procedures for the DIS were modified as follows. Because the DIS probe procedure for determining whether somatic symptoms, such as fatigue, originated from depression or heart disease produced arbitrary and inconsistent results, we elected to use an "inclusive" diagnostic strategy in which all somatic symptoms of depression counted toward a possible diagnosis. This approach to depression diagnosis in the medically ill has been advocated to prevent underdiagnosis,21 which may be especially appropriate in heart disease because prior studies have suggested that symptoms like fatigue in heart disease patients are more closely associated with emotional distress than cardiovascular fitness.22
Despite Hamilton Depression scores and total depression symptom counts indicating a major depression prevalence similar to that of other studies of heart disease patients,23 only one patient in our sample was coded as persistently dysphoric on the DIS. It is well known that elderly males (who form the majority of our sample) underreport dysphoria or attribute the dysphoria to medical illness.24 Therefore, we elected to allow a positive response to the either the DIS dysphoria item or the dysphoria item from the Ham-D (which allows for interviewer observation as well as subject self-report) to qualify as a symptom for depression diagnosis.
Subjects were divided into three groups based on results of the DIS Schedule (as amended earlier), according to DSM-IV criteria for major depressive episode and minor depressive disorder (DSM-IV appendix): 1) major depression: 5 or more DSM symptoms, including either dysphoria or anhedonia; 2) minor depression: 2–4 DSM symptoms, including either dysphoria or anhedonia; and 3) no depression diagnosis: 0–1 DSM symptoms.
Statistical Analyses
Descriptive statistics for the study variables were examined. We performed a principal components analysis on the four functional measures at each assessment : 1) SF-36 physical functioning scale; 2) activity interference scale adapted from the MPI; 3) average score from Sheehan social and family disability scales; and 4) a work item from the UCLA-RAND FSQ, from which one factor was extracted. All four measures were loaded with equal weight (0.8) on a single global functional disability factor accounting for 60% of the total variance. Because of the results of the principal component analysis and the large bivariate correlations among the four functional measures (average correlation 0.50 at baseline and 0.44 at the 12-month follow-up), we formed a single composite functioning variable for baseline and 12-month assessments. The four functional measures were each converted into a standard score (Z-score) by subtracting the baseline mean and dividing by the standard deviation. The Z-scores were then averaged into a composite functioning score. This score is representative of global patient functioning, in which positive composite scores represent more impairment or poorer functioning.
To test the hypothesis that functional disability will differ among patients with major depression, minor depression, or no depression after controlling for relevant covariates, repeated measures analysis of covariance (ANCOVAs) was used. The dependent variable was the composite functioning score assessed at baseline and 12 months later. The within-group factor was time, and the between-groups factor was baseline depression diagnosis at three levels (major, minor, and none). Six covariates were used: age, gender, educational level, number of main coronary arteries stenosed >70%, medical vs. surgical management during the follow-up year, and chronic disease score. In the event of a significant between-groups effect, three a priori two-group comparisons using the same repeated measures ANCOVAs were performed. We hypothesized that the patients with no depression diagnoses would exhibit significantly better functioning than patients with minor or major depression and that patients with minor depression would report less disability than the patients with major depression. We estimated that we had 75% power to detect a large effect size (a difference of 0.8 standard deviations between the groups), but only 39% power to detect a medium effect size (of 0.5 standard deviations), and 10% power to detect a small effect size (of 0.2 standard deviations). To explore the mechanisms that may potentially link depression to functional disability, severity of heart symptoms in the depression groups was examined by using the same repeated measures ANCOVA design and covariates described earlier.
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RESULTS
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Characteristics of the study population are displayed in Table 1. The study population was predominantly male (81%), with a mean±standard deviation (SD) age of 62±9.0 years. Forty-three percent of those enrolled were older than age 65. The majority of participants were white (96%), consistent with the demographic characteristics of the surrounding communities. The sample was otherwise typical of an HMO coronary disease population. The mean±SD chronic disease score was 6.0±2.5. This score points to a substantial burden of chronic illness, since only 12% of the 45–64 age group, 27% of the 65–74 age group, and 39% of the 75+ age group in this HMO have chronic disease scores of 4 or greater. Twenty-nine percent of the sample received some revascularization procedure during the year of follow-up.
Table 2 shows the characteristics of the depression groups formed by the decision rules described earlier. The minor depression group has Ham-D and Ham-A scores, as well as the DSM-IV symptom counts, intermediate between those meeting major depression criteria and those with no depression diagnosis.
Table 3 shows baseline function by baseline depression categories. The subjects with minor depression were slightly more impaired on physical function and ability to do some work but less impaired in activity interference and social/family function than those with major depression. The composite functioning Z-score was therefore nearly equal for the two groups. Symptom severity scores are shown for comparison. At baseline, both subjects and available spouses (N=125) completed the MPI activity interference scale. The responses were closely parallel, with no significant differences between spouse- and subject-reported disability (data not shown).
Table 4 displays 12-month function by baseline depression groups. The composite score for the major depression group showed slightly worse functioning than the minor depression group, but this difference was not statistically significant. Symptom severity scores are shown for comparison.
The repeated measures ANCOVA on the composite functioning score had a significant group effect (F[2,148]=7.91, P<0.001) and time effect (F[1,154]=10.49, P<0.001) after controlling for the six covariates. The time by group effect was not significant (F[2,154]=0.16), indicating that the groups did not exhibit different patterns of change over time. Planned comparisons using the same repeated measures ANCOVAs with pairs of groups revealed that, after controlling for the covariates, the significant group effect was due to functioning differences between the patients with no depression and minor depression (F[1,130]=10.79, P<0.001) and no depression and major depression (F[1,121]=9.66, P<0.002). In each case, those with depressive symptoms reported poorer functioning. There was no significant difference in average functioning between the patients with major and minor depression (F[1,39]=0.08).
Exploratory analyses revealed that the three depression groups differed in severity of reported heart symptoms (chest discomfort, breathlessness, rapid or irregular heart beat) by repeated measures ANCOVA, correcting for age, gender, education, coronary disease severity, medical comorbidity, and medical vs. surgical coronary management (F[2,148]=5.24, P<0.01). There was a significant time effect for symptoms as well (F[2,154]=31.49, P<0.001). There was no group by time interaction (F[1,154]=1.59, P=0.21). Because of the significant difference between the groups in severity of symptoms, we wanted to determine if the observed group differences in functioning were due solely to differences in symptom reporting. To answer this question, we included symptom severity as a time-dependent covariate in the ANCOVAs in addition to the other covariates and performed another repeated measures ANCOVA, with functioning as the dependent variable. The group effect was still marginally statistically significant (F[2,147]=2.97, P=0.05), indicating that differences in composite functioning between the depression groups could not be explained solely by differences in reported symptoms.
Figure 1 displays the composite functioning score for the three depression groups from baseline to 12 months. More negative scores indicate less impairment and better function. All groups improved during follow-up at a similar rate, but the patients with major and minor depression showed greater functional impairment or lower functional status at baseline and at follow-up.
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DISCUSSION
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This study provides prospective data showing that both major and minor depression are associated with decreased capacity for physical and role function among those with coronary heart disease. Major and minor depression groups are functionally similar to each other, but significantly different from those with no depression diagnosis, both at the time of depression assessment and 1 year later. The patients with major and minor depression also complain more of cardiac symptoms than the control subjects, even when controlling for severity of coronary disease. This study is consistent with population-based studies that have shown increased functional impairment, symptom reporting, and health care utilization in those with minor depression.9,10 This is the first prospective study, to our knowledge, to demonstrate functional impairment associated with minor depression in a clinical population for whom severity of comorbid medical illness can be carefully controlled. Since coronary disease ranks behind only musculoskeletal disorders in producing activity limitations and work disability,25 it may be important to monitor patients with coronary disease for both minor and major depression.
Earlier studies of depression in heart disease patients have noted the importance of subsyndromal symptoms. Freedland et al.26 noted that even among those patients with coronary disease who have major depression, symptoms tend to be "subtle" and to be in the mild range on the Beck Depression Inventory. Fatigue was reported by nearly 80% of the depressed and nondepressed groups. Insomnia was the only symptom significantly more severe in those with major depression. A series of studies have pointed to "vital exhaustion" as a risk factor for MI and for new cardiac events after coronary angioplasty.27 Vital exhaustion is defined as "lack of energy, increased irritability, and feelings of demoralization." Thus, the concept of "vital exhaustion" may be quite similar to the concept of "minor depression."
There are a number of possible mechanisms by which depression might impair functional capacity in those with coronary disease, including increased severity of physical symptoms, greater fear of physical symptoms, decreased interest in daily activities, or more hopelessness. Our data suggest that depression affects function through symptom amplification and possibly decreased interest in activities. It is also possible that these physical symptoms are an independent confounding factor that covaries with depression and function but does not mediate their relation. Depression has been found to impede habituation to chronic aversive symptoms in other chronic medical illnesses.28 Studies of patients with heart disease have found decreased treadmill stress-test duration,29 increased angina on treadmill testing,30 and increased risk of persistent angina post-MI for those with depression.31 Even subsyndromal depression appears to have direct physiological effects, as suggested by the increased risk for cardiac events in coronary disease patients with anxiety and depressive symptoms.32
Some study limitations, however, must be noted. First, we have limited power to detect differences that might be clinically significant between the major and minor depression groups. Thus, a Type II error may account for our inability to find a significant difference between the major and minor depression groups. Another study with a larger sample size is needed to clarify this issue. More weight should be given to our finding of significant differences between the minor depression and no depression groups. Second, in this study we relied on self-report measures of functional impairment, including capacity for physical exertion (e.g., SF-36 scale), disruption in daily activities, interference with role function, and presence of some impairment in capacity to do work. While differences between the depression groups did not reach statistical significance for each individual measure, a consistent pattern of disability among the groups produced significant differences in the composite measure. These self-report measures of function provide less standardized but more relevant measures of function than those achieved in laboratory situations. It is well known, for example, that treadmill performance of patients with coronary disease does not correlate well with performance of activities of daily living.33 Self-report measures of function are known to be more affected by depression than observational measures.34 However, it is unlikely that there was significant reporting bias among depressed patients in this study, since concurrent administration of the MPI activity interference scale to the subjects and spouses at baseline failed to reveal any differences between the subjects' and spouses' reports of daily function.
An inclusive strategy was used for major and minor depression diagnosis in this study. Because no depression symptoms were excluded as of medical origin, depression rates are higher than if an exclusive or etiologic strategy were used. Furthermore, the dysphoria question on the DIS was supplemented with the dysphoria question from the Hamilton Depression Scale. Nevertheless, the rates found here are similar to other studies and are congruent with the Hamilton Depression scores obtained on the subjects at the same time. More narrowly defined diagnostic groups would have produced smaller groups of patients meeting major and minor depression criteria, but more striking differences between those with major and minor depression and those with no depression diagnosis. Differences in function between the major and minor depression groups approached—but did not achieve—statistical significance (P=0.08). A larger sample size might produce significant differences between these groups.
This is the first prospective study, to our knowledge, of the effects of minor depression on daily function in a clinical sample with single well-defined medical illness. Effects noted on functioning suggest that for coronary disease patients, clinical attention should be directed at minor depression and major depression. There has been some debate in the psychiatric literature about whether all minor depression merits treatment.35 Our study suggests that minor depression may be particularly important in patients with comorbid medical illnesses. Studies underway of pharmacotherapy and psychotherapy for minor depression will further clarify the benefits of identifying medical patients with minor depression.36
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ACKNOWLEDGMENTS
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This study was supported, in part, by a grant-in-aid from the American Heart Association to Dr. Sullivan, a Research Scientist Development Award from the National Institute of Mental Health (Grant No. MH–01351) to Dr. Sullivan, and a Brookdale Foundation Fellowship to Dr. LaCroix.
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ABSTRACT
INTRODUCTION
