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ORIGINAL ARTICLES |
From the Department of Psychiatry (K.E.F., J.A.S, R.M.C.), Cardiovascular Imaging and Clinical Research Core Laboratory (V.G.D.-R.), and Cardiovascular Division, Department of Medicine (M.W.R, V.G.D.-R.), Washington University School of Medicine, St. Louis, Missouri; and the Cardiovascular Division, Department of Medicine (A.S.J.), Mayo Clinic, Rochester, Minnesota.
Address reprint requests to: Kenneth E. Freedland, PhD, Department of Psychiatry, Washington University School of Medicine, 4625 Lindell Blvd., Suite 420, St. Louis, MO 63124. Email: freedlak{at}bmc.wust.edu
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ABSTRACT |
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 TOP ABSTRACT INTRODUCTIONMETHODSRESULTSDISCUSSIONCONCLUSIONSACKNOWLEDGMENTSREFERENCES |
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METHODS: A modified version of the Diagnostic Interview Schedule was administered to a series of 682 hospitalized patients with CHF to determine the prevalence of DSM-IV major and minor depression; 613 patients also completed the Beck Depression Inventory. Medical, demographic, and social data were obtained from hospital chart review, echocardiography, and patient interview.
RESULTS: In the sample as a whole, 20% of the patients met the DSM-IV criteria for a current major depressive episode, 16% for a minor depressive episode, and 51% scored above the cutoff for depression on the Beck Depression Inventory (
10). However, the prevalence of major depression differed significantly between strata defined by the functional severity of heart failure, age, gender, employment status, dependence in activities of daily living, and past history of major depression. For example, the prevalence ranged from as low as 8% among patients in New York Heart Association class I failure to as high as 40% among patients in class IV.
CONCLUSIONS: The prevalence of depression in hospitalized patients with CHF is similar to rates found in post-myocardial infarction patients. However, it is considerably higher in certain subgroups, such as patients with class III or IV heart failure. Further research is needed on the prognostic importance and treatment of comorbid depression in CHF.
Key Words: comorbidity • depression • depressive disorder • heart failure • congestive • prevalence.
Abbreviations: ADLs = activities of daily living; BDI = Beck Depression Inventory; CES-D = Center for Epidemiological Studies Depression Scale; CHF = congestive heart failure; COPD = chronic obstructive pulmonary disease; DIS = Diagnostic Interview Schedule; DSM-IV = Diagnostic and Statistical Manual of Mental Disorders, fourth edition; HRDS = Hamilton Rating Scale for Depression; LVEF = left ventricular ejection fraction; MI = myocardial infarction; NYHA = New York Heart Association.
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INTRODUCTION |
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TOPABSTRACTINTRODUCTIONMETHODSRESULTSDISCUSSIONCONCLUSIONSACKNOWLEDGMENTSREFERENCES |
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Most of the existing studies of depression in patients with CHF have focused on outpatients and have relied exclusively on cutoff scores on instruments such as the CES-D (19–21). The prevalence of depression defined in this manner may be as high as 42% (21). The prevalence of depressive disorders defined by the DSM-IV criteria has not been established in outpatients with CHF.
There have been only two studies in which standardized interviews were used to establish the diagnosis of major depression in hospitalized patients with CHF. The first, a small (N = 60) study of patients age 70 years or older, found a point prevalence of major depression of 17% (22). More recently, Koenig (23) reported a 37% rate of major depression and 22% rate of minor depression in 107 patients age 60 or older with CHF. The exclusion of younger patients and the striking difference in prevalence estimates between these two relatively small studies reveals the need for a larger study to establish reliable estimates and to identify demographic, medical, and psychosocial factors that may affect the prevalence of depression in this patient population.
This study defines depression in several different ways to facilitate comparison of prevalence rates with ones reported elsewhere. It examines whether the prevalence of depression differs between strata defined by demographic, medical, and psychosocial characteristics. It also identifies variables that are independently related to the likelihood of depression in hospitalized patients with CHF. Unlike the Freedland et al. (22) and Koenig (23) studies, our sample includes both middle-aged and elderly patients, thus permitting analysis of the effects of age on comorbid depression in CHF.
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METHODS |
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TOPABSTRACTINTRODUCTIONMETHODSRESULTSDISCUSSIONCONCLUSIONSACKNOWLEDGMENTSREFERENCES |
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Assessment of Depression and Functional Status
Trained research interviewers administered a modified version of the depression section of the National Institute of Mental Health Diagnostic Interview Schedule (DIS) developed by Carney et al. to diagnose depressive disorders in cardiac patients (1). This instrument was selected rather than the Structured Clinical Interview for DSM-IV (SCID) or other alternatives because the majority of studies on depressive disorders in patients with coronary heart disease (1, 4, 7, 26–29) and both previous studies of major depression in hospitalized patients with heart failure (22, 23) have used modified or standard versions of the DIS. Unlike the standard DIS, the Carney et al. modified version starts the depression section of the interview with somatic rather than cognitive or mood-related symptoms. It also focuses on current rather than lifetime symptoms, and it probes for the duration (chronicity) of current symptoms. Also, the DIS is designed for trained lay interviewers; because of the sample size and the setting of the interviews, it was not feasible to use an instrument designed for administration by clinicians. However, to minimize the possibility of overdiagnosis of depression in this seriously medically ill patient population, the interviews were independently reviewed by two clinicians (K.E.F., R.M.C.) following the DSM-IV criteria for major and minor depression, with 98% interrater agreement. Disagreements were resolved by consensus.
In addition to current depression symptoms, the interview documented the patient’s psychiatric history, marital and employment status, living arrangement, activities of daily living (ADLs), and need for assistance with self-care or other activities. The patients were also asked to complete the Beck Depression Inventory (BDI) to assess the severity of 21 symptoms of depression (30). The BDI is frequently used in research on depression in patients with heart disease, diabetes, and other chronic medical illnesses (31–35).
Medical Evaluation
Medical history.
The patient’s hospital chart was reviewed and a standardized medical data collection form was used to document 1) whether this was the patient’s initial hospital admission for CHF or if there had been at least one prior CHF admission, 2) medical history and comorbid medical conditions, and 3) prescribed medications. The patient’s New York Heart Association (NYHA) functional classification during the 2-week period immediately preceding the hospitalization was determined by integrating data from the interview and the medical chart. An experienced cardiac research nurse (J.A.S.) supervised the collection of medical data in consultation with a study cardiologist with particular expertise in geriatric cardiology and CHF (M.W.R.)
Left ventricular dysfunction.
Transthoracic 2-dimensional, Doppler, and color flow echocardiography (Acuson Sequoia or Hewlett-Packard) was performed in the four standard views (parasternal long- and short-axis views, and apical 4- and 2-chamber views) within 48 hours of hospital admission if logistically feasible. The images were stored on 
-inch videotape (S-VHS), and digitized in a cine-loop format (Acuson KinetDx) for off-line analysis. All studies were performed by experienced cardiac sonographers to ensure optimal visualization of the left ventricular endocardial borders and cardiac chambers. The left ventricular volumes and ejection fraction (LVEF) were calculated by the method of summation of disks (modified Simpson’s rule) from the apical 4-chamber view at end-diastole and end-systole at end-expiration. All measurements were obtained and averaged from five consecutive cardiac cycles by an expert echocardiographer (V.G.D.-R.) who was blinded to other medical and psychodiagnostic findings.
Statistical Analysis
Patients were classified as having major depression, minor depression, or no current depressive disorder according to the DSM-IV criteria, and as "probably depressed" or "not depressed" according to whether their BDI score was 10 or higher. Chi-square tests were used to determine whether the prevalence of depression differed among subgroups defined by a selected set of demographic, medical, and psychosocial variables. Age was dichotomized at 60 years to compare depression rates in younger vs. older patients, and LVEF was dichotomized at 35% to compare patients with relatively poor vs. preserved left ventricular function. 
was set at 0.05 per comparison.
Logistic regression analyses were conducted to determine which of the variables identified in the univariate comparisons are independently associated with the presence of depression. In the first analysis, patients were categorized with respect to the presence or absence of major depression; those with minor depression or no current depressive disorder were combined into a single comparison group. All variables except LVEF that were significantly associated with the DSM-IV diagnosis of depression in the univariate comparisons were entered simultaneously into this model. Nonsignificant variables were then dropped, and a reduced model was fitted to the remaining variables. All effects were adjusted for every other variable in the model. Similar analyses were conducted to model clinically significant depression (ie, having either major or minor depression on the modified DIS) and depression as defined by a score of 10 or higher on the BDI. Because 19% of the patients did not undergo echocardiography, the sample sizes for these analyses would have been reduced if LVEF were included. Consequently the effects of LVEF were tested in secondary analyses determining whether it was significantly related to depression after controlling for the variables retained in the reduced models described above. SAS 8.1 software was used for all statistical analyses.
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RESULTS |
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The 682 patients enrolled in the study thus represent 26% of the determinant screening encounters. Of the enrolled patients, 355 (52%) were women and 278 (41%) were African Americans. Their mean age was 66 ± 12 years. The excluded and enrolled patient samples did not differ significantly with respect to gender distribution, but the proportion enrolled was lower among minority patients (23%) than whites (28%; p < .005), and the excluded patients were older than the enrollees (p < .0001). The enrollees were more likely than the excluded patients to have dyspnea on exertion (68% vs. 52%, p < .0001), paroxysmal nocturnal dyspnea (45% vs. 32%, p < .0001), orthopnea (56% vs. 43%, p < .0001), third heart sound (37% vs. 31%, p = .001), jugular venous distention (59% vs. 53%, p = .003), hepatojugular reflux (12% vs. 9%, p = .02), and a response to diuretics (69% vs. 58%, p < .0001). The enrollees were less likely than the excluded patients to have pulmonary rales (84% vs. 88%, p = .005). There was no difference in the proportion of patients with peripheral edema (74% vs. 72%, p = .15).
Prevalence of Depression
Among the 682 enrolled patients, 135 (20%) met DSM-IV criteria for a current major depressive episode, 111 (16%) met DSM-IV criteria for a current minor depressive episode, and 436 (64%) were classified as not currently depressed. Combining the groups with major or minor depression, 245 (36%) of the patients had clinically significant depression.
Among the 613 (90%) patients who completed the BDI, 310 (51%) scored 10 or higher and were classified as probably depressed. Of patients scoring in the depressed range on the BDI, 105 (34%) met DSM-IV criteria for major depression, 65 (21%) met the criteria for minor depression, and 140 (45%) were not currently depressed according to the DIS interview. Among those scoring in the nondepressed (<10) range on the BDI, 15 (5%) met DSM-IV criteria for major depression, 33 (11%) met the criteria for minor depression, and 255 (84%) were classified as nondepressed on the DIS. Thus, only 55% of the patients scoring in the depressed range on the BDI had clinically significant depression according to the DIS, and 16% of patients classified as nondepressed on the BDI were depressed according to the DIS. Nevertheless, there was a strong association between the BDI and DSM-IV classifications (
2 = 111.4, p < .0001).
Univariate Associations with Depression
In Table 1, the sample is stratified by demographic, psychosocial, and medical variables, and the proportion of patients within each stratum meeting DSM-IV criteria for major or minor depression or the BDI 10 criterion for depression is displayed. As expected, the prevalence of current major depression was somewhat elevated in patients with a family history of major depressive disorder and markedly elevated among patients with past history of one or more major depressive episodes. Major depression was also significantly more prevalent among patients who were female, less than 60 years old, unable to work due to disability, unable to perform self-care or other ADLs without assistance, in a higher NYHA class, or admitted with a history of COPD or sleep apnea.
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Contrary to expectation, the prevalence of depression was lower among patients with than without a history of MI. This may be explained by the fact that patients with a history of MI were more likely to be more than 60 years old (2 = 14.6, p < .0001) and male (2 = 11.1, p < .001). Patients with these characteristics were less likely to be depressed than were younger patients and females.
Several classes of drugs commonly used to treat patients with heart disease (ß-blockers, calcium channel blockers, digitalis, angiotensin-converting enzyme inhibitors) have been suspected of causing dysphoric mood in some patients (36–42), but none of these agents were associated with significantly higher prevalence rates of major depression. Among the 551 (81%) patients for whom echocardiographic findings were available, the prevalence of depression was also unaffected by whether there had been previous hospitalizations for CHF or whether the patient had poor left ventricular function (LVEF < 35%).
The rates of minor depression were affected by most of the same variables associated with major depression, but the differences between strata were generally smaller. When depression was defined by a score of 10 or higher on the BDI, the prevalence rates again differed by past history of major depression, age, disability status, dependence in ADLs, NYHA class, and history of chronic obstructive pulmonary disease (COPD). Depression on the BDI tended to be more common among women than men, but the gender difference was not significant, and it also did not differ significantly according to whether there was a family history of major depressive disorder. In contrast to major depression, the prevalence of depression on the BDI was significantly higher among patients who had relatively poor left ventricular function or a history of gastrointestinal disease and significantly lower among patients on ß-blockers.
Independent Predictors of Depression
Variables that were related to the DSM-IV diagnosis of major depression in the univariate analyses were then entered into a multiple logistic regression analysis. Family history of depression and patient history of COPD, MI, or sleep apnea were not independently associated with major depression in this analysis. A reduced model was then fitted, including the variables remaining after the initial logistic regression. Gender, age, past history of major depression, NYHA class, dependence in ADLs, and inability to work due to disability were retained. The reduced model is presented in Table 2. Figure 1 displays the prevalence of major depression by its two strongest independent correlates (NYHA class and age.)
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Finally, the variables that were related to depression as defined by the BDI cutoff (10) were entered into a separate logistic regression analysis. Age, disability status, LVEF, COPD, and ß-blockade dropped out of this analysis, and past history of major depression, NYHA class, gastrointestinal disease, and dependence in ADLs were retained. The reduced model of depression as defined by the BDI is displayed in Table 2.
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DISCUSSION |
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These differences may be due to methodological factors. In our reports, depressive disorders were defined only by DSM-IV criteria. Koenig’s report used both DSM-IV criteria and scores on the CES-D and the HRSD. Nondepressed control subjects had to score 
10 on the CES-D and the HRSD and to have fewer than two DSM-IV symptoms. Thirty-seven percent of screened patients did not meet the criteria to be either a depressed case or a nondepressed control. If the additional CES-D and HRSD criteria excluded more nondepressed and marginally depressed patients than patients with major depression, the net effect would have been to increase the prevalence of major depression. This is supported by the fact that in the whole CHF sample (which included depressed cases, nondepressed controls, and patients in neither category), the prevalence of major depression decreased to 26% and that of minor depression increased to 32%.
Many studies of medically ill patients use standard cutoff scores on self-report questionnaires such as the BDI or CES-D to define cases of depression. In general, prevalence estimates based on this approach are higher than ones based on structured psychodiagnostic interviews and DSM-IV criteria. This is clearly evident in the present study, because 51% of the patients scored 10 or higher on the BDI. Forty-five percent of the patients scoring in the depressed range on the BDI were classified as nondepressed by DSM-IV criteria. The low specificity of the BDI helps to explain why it yields such a high prevalence of "depression" in this patient population.
However, different cutoff scores can yield very different specificities, sensitivities, and predictive values when the BDI is used to screen for depressive disorders in medically ill patients (34, 44). A score of 10 was chosen for this study because it is the most widely used cutoff in research and clinical practice, but it might not be optimal when screening hospitalized patients with CHF. Regardless of the cutoff score that is used, the BDI cannot substitute for a careful clinical interview. A detailed analysis of the screening performance of the BDI is outside the scope of this article, but it is the subject of a report in progress.
Correlates of Depression
The prevalence of comorbid depression in hospitalized patients with CHF depends not only on the definition of depression but also on the characteristics of the sample. In this study major depression was significantly more common in patients less than 60 years than in older patients (29% vs. 16%). Koenig’s (23) sample was limited to patients age 60 or older, which further highlights the difference in prevalence rates between these studies.
Several other characteristics also affect prevalence rates. Major depression is more common in women and in patients who are disabled, who have a history of depression, or who have comorbid COPD or sleep apnea. In addition, there is a strong relationship between major depression and NYHA class. Patients in class IV are at very high risk for major depression. Alternatively, because depression predicts functional impairment in patients with coronary disease, it might exacerbate functional impairment in CHF (13, 14).
In contrast to its strong association with NYHA class, major depression is unrelated to LVEF, prior hospitalization for CHF, and medical comorbidity. COPD and sleep apnea were associated with major depression in univariate analyses but were not retained as independent correlates. The prevalence of major depression differed by race in our earlier, smaller study (22) but not in this one. It did not differ by education, marital status, living arrangement, or ß-blockade. We reported a similar finding concerning ß-blockade in patients with coronary disease (45). ß-Blockers improve prognosis in CHF (46–50), but physicians may be reluctant to prescribe them for depressed patients. Whether this increases the risk of morbidity and mortality deserves investigation.
Several univariate correlates of major depression dropped out of the multivariable analysis. Independent predictors include NYHA class, age below 60 years, depression history, dependence in ADLs, disability status, and gender. Most correlates of major depression also correlate with minor depression, but not as strongly. For example, major depression affected 29% of younger vs. 16% of older patients; for minor depression, the difference was only 18% vs. 16%. Most predictors of major depression also predicted clinically significant (major or minor) depression, but neither gender nor disability predicted the latter.
Although the BDI is not very specific vis-a-vis DSM-IV diagnoses, it correlates with most of the same variables. BDI scores are affected by age, depression history, CHF severity, medical comorbidity, disability, and dependence in ADLs. Unlike major depression, BDI-defined depression is not higher among women, but is associated with worse left ventricular dysfunction. However, the LVEF relationship is modest (55% for LVEF < 35 vs. 45% for LVEF 35.) Age, disability, LVEF, and COPD dropped out of the multivariable analysis, leaving NYHA class, gastrointestinal disease, depression history, and dependence in ADLs as independent predictors of depression on the BDI. It is not clear why gastrointestinal disease was the only independent medical predictor of depression on the BDI. It could be an artifact because the BDI includes items assessing appetite and weight loss. It is also not clear why age and disability are independently associated with clinically significant depressive disorders but not with depression as defined by the BDI. Perhaps having CHF when relatively young and being too ill to maintain employment increases vulnerability to depressive disorders. Other patients may be just as vulnerable to subclinical depressive symptoms, but they are less likely to develop clinically significant depression.
Causal Relationships
This study shows that there is a strong association between depression and the functional severity of heart failure, but it does not define the direction of this relationship. However, it provides some interesting clues. Functional severity, as measured by NYHA class, is the strongest correlate of depression in this sample. This raises the possibility that CHF is "depressogenic," particularly when the heart failure has advanced to the stage at which the patient is severely functionally impaired and is experiencing severe dyspnea and other exertional symptoms. It is also possible, however, that depression might exacerbate the symptoms of heart failure and increase the severity of functional impairment. This latter possibility is consistent with the finding that depression correlates with NYHA class but not with LVEF. This finding suggests that in a group of patients with equally severe left ventricular dysfunction, those who are depressed are likely to report worse symptoms of heart failure and worse functional impairment in everyday activities than are those who are not depressed. Because the present findings are consistent with both causal models, further research is needed to resolve this question. It will be necessary to conduct longitudinal studies in which multiple markers of the physiological and functional severity of CHF are obtained. Clinical trials are also needed to determine the effects of depression treatment on the course and outcome of CHF as well as the effects of treating CHF on the course and outcome of depression.
Limitations
Unlike the previous studies of depressive disorders in hospitalized patients with CHF, both of which were restricted to elderly patients, this one includes patients as young as 40 years of age. Because of its larger and more inclusive sample, the present findings provide better estimates of the prevalence of depression in the population of patients hospitalized with congestive heart failure when compared with the earlier studies. Furthermore, this report identifies a number of patient characteristics that help to explain why the observed prevalence of major depression has varied so widely across studies.
Nevertheless, the enrolled sample includes only about one fourth of the patients who were screened for participation. Twenty percent of patients who were screened refused to participate because they felt too fatigued or too ill, and 6% refused for other reasons. Depressed patients may be more likely than nondepressed patients to feel extremely fatigued, ill, or socially withdrawn, which may make them more likely refuse to participate in clinical research. If so, the prevalence of depression might have been underestimated. Most of the excluded patients were objectively too seriously ill or too cognitively impaired to participate. Dementia, delirium, and other neuropsychiatric complications were the most common reason for exclusion, particularly among older patients. This is unfortunate because depression is a common and treatable problem in the early stages of Alzheimer’s and vascular dementia (51–54). The depression measures used in the present study were designed for cognitively intact subjects, so it was necessary to exclude patients with cognitive impairment. In future studies, however, it might be possible to assess depression in CHF patients with mild cognitive impairment by using specialized techniques developed for use with patients in early dementia (55–57).
Although there are limits to the generalizability of the present findings, there was no viable alternative to excluding patients who were too ill or cognitively impaired to participate. This limitation is inherent in virtually every study in psychiatric epidemiology, but it is more obvious in studies of psychiatric comorbidity in severely medically ill patients. Despite this limitation, we were able to recruit 47 patients who, although in class IV heart failure, had physician approval to participate. Most of these patients were too ill even to sit up. Thus, our findings extend not only to hospitalized patients in mild heart failure but, with due caution, to those in severe heart failure as well.
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CONCLUSIONS |
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ACKNOWLEDGMENTS |
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TOPABSTRACTINTRODUCTIONMETHODSRESULTSDISCUSSIONCONCLUSIONSACKNOWLEDGMENTSREFERENCES |
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Received for publication August 10, 2001.
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