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(Circulation. 2005;111:271-277.)
© 2005 American Heart Association, Inc.

Cardiovascular Surgery

Patients With Depressive Symptoms Have Lower Health Status Benefits After Coronary Artery Bypass Surgery

Susmita Mallik, MD; Harlan M. Krumholz, MD, SM; Zhen Qiu Lin, PhD; Stanislav V. Kasl, PhD; Jennifer A. Mattera, MPH; Sarah A. Roumains, RN; Viola Vaccarino, MD, PhD

From the Department of Medicine, Division of General Medicine, Emory University School of Medicine, Atlanta, Ga (S.M.); Section of Cardiovascular Medicine, Department of Medicine, Yale University School of Medicine, New Haven, Conn (H.M.K.); Yale–New Haven Hospital Center for Outcomes Research and Evaluation, New Haven, Conn (H.M.K., Z.Q.L., J.A.M., S.A.R.); Department of Epidemiology and Public Health, Yale University School of Medicine, Boston, Mass (S.V.K.); Department of Medicine, Division of Cardiology, Emory University School of Medicine, and the Department of Epidemiology, Rollins School of Public Health, Emory University, Atlanta, Ga (V.V.).

Reprint requests to Susmita Mallik, MD, Department of Medicine, Emory University, Room 473, Faculty Office Bldg, 49 Jesse Hill Jr. Drive, Atlanta, GA 30303. E-mail smallik{at}emory.edu

Received June 23, 2004; revision received October 6, 2004; accepted October 12, 2004.

	Abstract

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Background— Depression is an established independent prognostic factor for mortality, readmission, and cardiac events after CABG surgery. However, limited data exist on whether depression influences functional outcomes after CABG.

Methods and Results— We followed 963 patients who underwent first CABG between February 1999 and February 2001. At baseline and at 6 months after CABG, we interviewed patients to assess depressive symptoms using the Geriatric Depression Scale (GDS) and physical function using the Short Form-36 Physical Component Scale (PCS). The patient’s physical function was considered improved if the PCS score increased 5 points at 6 months. Patients with high GDS scores were younger, were more often female, and had worse physical function and higher comorbidity than patients with low GDS scores. Rates of improvement in physical function were 60.1% for a GDS score <5 (below 75th percentile), 49.8% for a GDS score between 5 and 9 (75th to 90th percentile), and 39.7% for a GDS score 10 (90th percentile; P=0.002 for the trend). Depressive symptoms remained a significant independent predictor of lack of functional improvement after adjustment for severity of coronary artery disease, angina class, baseline PCS score, and medical history. A GDS score 10 was a stronger inverse risk factor for functional improvement after CABG than such traditional measures of disease severity as previous myocardial infarction, heart failure on admission, history of diabetes, and left ventricular ejection fraction.

Conclusions— Higher levels of depressive symptoms at the time of CABG are a strong risk factor for lack of functional benefits 6 months after CABG.

Key Words: coronary artery bypass • coronary disease • depression • outcome

	Introduction

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Coronary artery bypass graft surgery is a common procedure for the treatment of coronary heart disease (CHD). Because CABG yields only a small absolute survival benefit relative to medical therapy, the primary goal of CABG surgery is to improve health status, including symptoms, functional status, and quality of life. Although many patients experience symptomatic and functional improvements after CABG, there is great variation in outcome that remains mostly unexplained.^1,2 At 1 year after CABG, 34% of patients remain symptomatic with angina and 40% of patients have activity limitation.³ Therefore, it is of interest to identify factors that influence the ability of CABG to improve patients’ health status. Identification of these factors, if modifiable, may support interventions to improve the functional response after CABG.

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Depression is a strong and independent risk factor for mortality, recurrent cardiac events, and lower functional status in several CHD patient groups, including patients with myocardial infarction,⁴ unstable angina,⁵ and congestive heart failure.⁶ Depression, present in 20% to 25% of patients undergoing CABG,⁷ is an independent prognostic factor for mortality, readmission, and cardiac events after CABG.^8–10 Therefore, it is likely that depression also influences functional response after CABG. Surprisingly, however, little information is available on this topic. Thus, we examined whether depressive symptoms adversely affect functional improvement at 6 months after CABG.

	Methods

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Participants
The methodology of this study has been described previously.¹¹ Briefly, we screened consecutive patients admitted for their first CABG at Yale–New Haven Hospital between February 1999 and January 2001. We excluded patients with previous CABG, those undergoing concomitant operations, those <30 years of age, and patients with barriers to the interview such as aphasia, impaired mental status, or language other than English. The Institutional Review Board approved the study, and all patients provided informed consent. After surgery, patients were interviewed in person while in the hospital to assess the study variables described below.

Study Measures
Assessment of Depressive Symptoms
Depressive symptoms were assessed during hospitalization after CABG with the Geriatric Depression Scale, Short Form (GDS-S), which is a validated 15-item depressive symptoms scale designed to screen for current depression in older adults.¹² Because this scale focuses on the nonsomatic symptoms of depression, it is well suited to measure depression in severely ill hospitalized patients. The GDS-S score ranges from 0 to 15 and represents the sum of the total number of depressive symptoms. Because there is a lack of consensus for categorization of GDS scores, we selected GDS cutoff values corresponding to the 75th and 90th percentiles in our population (5 and 10, respectively).^13,14

Baseline Health Status, Physical Function, and Clinical Variables
Patients were interviewed about their level of physical and psychological functioning in the month before CABG with the Medical Outcomes Trust Short Form 36-Item Health Survey (SF-36). This established survey instrument, which is validated in patients with CHD, has recognized validity in CABG patients.^15–17 A higher score indicates better functioning. Social support was evaluated with the Enhancing Recovery in Coronary Heart Disease Social Support Inventory (ENRICHD SSI).¹⁸ Medical records were abstracted with the Society of Thoracic Surgery instrument and clinical definitions.¹⁹

Outcome Variables
All patients were interviewed by phone at 6 months about their physical and psychological functioning with the same instrument used at baseline. The primary outcome variable of interest was physical function measured by means of the Physical Component Scale (PCS) of the SF-36. The SF-36 consists of a total of 36 questions and measures 8 health constructs using 8 scales with 2 to 10 items per scale.²⁰ The PCS is a summary scale constructed from the SF-36 scales, giving greater weight to those relevant for physical function (physical functioning, role functioning, bodily pain, and general health).^15,21 Use of this summary measure makes it possible to reduce the number of statistical comparisons and thus the role of chance in hypothesis testing. In addition, the PCS has the advantage of greater sensitivity to change over the original 8 scales of the SF-36, as well as elimination of floor and ceiling effects.^21,22 The PCS allows easy norm-based interpretation because the scores are standardized to the general US population (mean score, 50; SD, 10). Scoring of the PCS followed the methods described by Ware et al.²¹ Our outcomes included a continuous variable indicator of the change in PCS scores between baseline and 6 months (a positive change indicated improvement) and a categorical variable indicating whether the patients improved in physical function from baseline. The latter was defined as a positive change of 5 units in the PCS scores at 6 months compared with baseline. A 5-unit difference corresponds to half the SD for the PCS, a difference considered "moderate" according to statistical standards, and thus should be clinically and socially relevant to measure change.^22,23

Data Analysis
We used ANCOVA models to calculate the mean changes in physical function scores from baseline to follow-up after adjusting for baseline functional status and the other baseline factors listed in the footnote in Table 2. We also used logistic regression models to calculate adjusted probabilities of improvement in physical function after adjusting for the same factors, as well as adjusted ORs that were transformed into relative risks (RRs).²⁴ All tests for statistical significance were 2 tailed with =0.05. All analyses were conducted with SAS software, release 8.02.

View this table: [in this window] [in a new window]   TABLE 2. Unadjusted* and Adjusted Comparisons of Changes in Physical Function (PCS) 6 Months After CABG Surgery According to Number of Depressive Symptoms

	Results

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Study Population
In the study period, 1369 patients met the eligibility criteria. Of these, 1168 (85%) were enrolled. A total of 32 patients died before 6 months; the distribution of deaths was similar in patients with (2.9%) and without (2.4%) depressive symptoms. An additional 61 patients were excluded because they could not be reached at follow-up, and 112 patients were excluded because of missing information on depressive symptoms at baseline or on physical function either at baseline or at follow-up. Among patients for whom information on depressive symptoms was not missing, these exclusions did not substantially differ according to depressive symptom status, except that more patients with depressive symptoms (9.0%) than patients without depressive symptoms (4.6%) had missing data on physical function at follow-up. After these exclusions, 963 patients were included in the present analysis.

Baseline Characteristics
Younger age, less education, less social support, unmarried status, and living alone were associated with higher depressive symptom scores (Table 1). Women also had higher GDS-S scores compared with men.

View this table: [in this window] [in a new window]   TABLE 1. Comparison of Baseline Characteristics According to Level of Depressive Symptoms

View this table: [in this window] [in a new window]   TABLE 1. Continued

Compared with those with lower levels, patients with higher depressive symptom scores were more likely to be referred for CABG because of worsening or new onset of symptoms and less often as a result of test results only. They also had more comorbid conditions, higher Canadian Cardiovascular Society (CCS) angina class, and lower physical function. Interestingly, however, there was no association between depressive symptom scores and severity of coronary atherosclerosis as shown by coronary angiographic findings. There was also no association between depressive symptom scores and hospital complications after CABG. Not surprisingly, patients with higher depressive symptom scores were more likely to have ever been prescribed medications for depression (from lower to higher depressive symptoms category, 7.5%, 15.2%, and 38.5%).

Changes in Physical Function
At 6 months, a strong and graded association was found between number of depressive symptoms at baseline and improvement in physical function. The rate of physical function improvement was 60.1% in the absence of clinically relevant depressive symptoms, 49.8% for 5 to 9 depressive symptoms, and 39.7% for 10 depressive symptoms (P=0.002 for trend) (Table 2).

After adjustment for baseline physical function and other baseline covariables listed in Table 2, increasing levels of depressive symptoms retained a strong and significant trend toward a lower improvement in functional status as both a continuous and a categorical variable (Table 2). In multivariable analysis, 10 depressive symptoms (RR, 0.62; 95% CI, 0.19 to 0.82) tended to be a stronger inverse risk factor for functional improvement after CABG than traditional measures of disease severity such as previous myocardial infarction (RR, 0.86; 95% CI, 0.70 to 1.02), heart failure on admission (RR, 0.70; 95% CI, 0.45 to 0.96), history of diabetes (RR, 0.78; 95% CI, 0.63 to 0.93), and even left ventricular ejection fraction, which was not associated with functional improvement (RR for ejection fraction <40% compared with ejection fraction 40%, 1.09; 95% CI, 0.95 to 1.25). Being prescribed antidepressant treatment was not associated with functional changes.

The association between depressive symptoms and improvement in functional status was stronger in women than in men (see the Figure). In women, the likelihood for improved function was 75% lower for GDS scores of 10 compared with women with GDS scores <5; in men, the corresponding number was 30% (P=0.03 for the interaction between depression category and sex).

View larger version (9K): [in this window] [in a new window]   RRs for improved physical function at 6 months by sex. RRs are adjusted for factors listed in footnote in Table 2. P=0.03, interaction between sex and depression category.

	Discussion

Top Abstract Introduction Methods Results Discussion Conclusions References

 
Our findings indicate that depressive symptom severity at baseline is strongly and significantly associated with lower improvement in functional status at 6 months after CABG. Depressive symptoms, a modifiable risk factor, were more strongly associated with functional status changes than traditional measures of disease severity such as left ventricular ejection fraction, history of myocardial infarction, history of diabetes, and congestive heart failure. These findings demonstrate that depressive symptoms are at least as important as traditional measures of cardiac function in predicting health status outcomes of patients undergoing CABG.

Patients with higher depressive symptom scores did not have worse coronary atherosclerosis at the time of the CABG than patients with no depressive symptoms. However, they had a higher CCS angina class and lower physical function and were more likely to be referred for CABG for worsening clinical status. After adjustment for these and other baseline characteristics, depressive symptom level retained a strong and independent association with functional status improvement at 6 months.

Studies have shown consistently that depressive symptoms predict adverse outcomes²⁵ and hospital readmission^8,9 and increase the frequency of cardiac events independently of traditional risk factors after CABG.^10,26 However, only a few studies have investigated whether depressive symptoms also influence the ability of patients to improve functionally after CABG. These studies have been limited by either small samples or examination of selected end points such as cardiac-related symptoms,^8,27 return to presurgical activity level,⁸ sleep problems,²⁷ and return to work.²⁸ Surprisingly, no previous studies have evaluated the impact of depression on a global measure of functional status after CABG with a standardized assessment. This relationship, however, has been consistently reported in other CHD patient populations such as patients with stable coronary disease,²⁹ acute coronary syndromes,⁵ and congestive heart failure.⁶ Our study not only confirms the association between depressive symptoms and functional status in patients with CHD but also indicates that depressive symptoms represent a critical factor in predicting outcome after CABG.

An intriguing finding of our study is that the negative effect of depressive symptoms on functional status after CABG was stronger in women than in men. Although this finding needs to be confirmed in future studies, it is consistent with previous investigations in which depression had a greater impact on poor cardiovascular outcomes in women than in men.^30,31 This suggests a greater vulnerability of women not only toward depression, which is well-established,³² but also toward the adverse effects of depression on the cardiovascular system.

Little is known about the mechanisms through which depression affects functional benefits from CABG surgery, although many pathophysiological and behavioral mechanisms have been described as links between depression and morbidity and mortality after CHD. Increased platelet aggregation resulting from the influence of depression may increase the risk of thrombogenic events and therefore increase the risk of recurrent myocardial infarction.³³ Greater autonomic dysfunction is another plausible mechanism linking depression to CHD risk.^34–36 An altered ratio between sympathetic and parasympathetic activity may lead to decreased heart rate variability and baroreflex sensitivity and predisposes to ventricular tachycardia, ventricular fibrillation, and sudden cardiac death.³⁷ Although these may be plausible explanations for the association between depression and increased mortality after myocardial infarction, little is known about the mechanisms through which depression is associated specifically to functional status. Such behavioral factors as poor self-care and compliance with cardiac treatment regimens, continued smoking, low motivation to change lifestyle, and low participation in cardiac rehabilitation may in part link depression to lower functional status in cardiac patients.³⁸ It is possible that similar mechanisms may underlie the association between depression and lower functional benefits after CABG. A better clarification of these mechanisms could help in the development of effective interventions.

Traditionally, patient care after CABG has focused on improvement in cardiac physiology. Our results indicate that future efforts to enhance the functional gains after CABG should also focus on assessment and treatment of depression. Data suggest that depression in cardiac patients is not always treated and is often overlooked,^39,40 even though it can be easily identified, perhaps because it is considered an inevitable reaction to the disease status. Among CHD patients with a clinical diagnosis of depression, some antidepressants such as selective serotonin reuptake inhibitors are well tolerated. Although future trials are needed to evaluate whether treatment of depression improves cardiovascular outcomes,^41,42 treatment of depression is likely to lead to improvement in functional status,^43,44 which may lead to lower mortality and recurrent cardiac events.^29,45

Study Limitations
Our study has several possible limitations. We did not have a clinical diagnosis of depression but rather assessed severity of depressive symptoms using the GDS-S scale. Nonetheless, the importance of depressive symptoms on outcome in CHD patients, even in the absence of a diagnosis of major depression, has been clearly shown.^46,47

Our results could be affected by response bias because willingness to participate was an inclusion criterion. It is also possible that patients with depressive symptoms were more likely to report more physical limitations as a consequence of their depressed mood rather than actual worse health status. This bias, however, is more likely to affect studies in which the link between depression and functional status is assessed cross-sectionally. This study focused on the impact of depressive symptoms on longitudinal changes in physical function, and we took into account the baseline level of reported function in the analysis.

We assessed functional status by using a general functional status measure, the SF-36, instead of instruments specific for CHD that usually focus on angina-related disability. The SF-36 was a more appropriate tool because one third of our patients did not have angina symptoms before CABG, so angina-related instruments would have affected our ability to detect functional changes in these patients. In addition, there was a potential for assessment bias, given that depressed patients more often had a history of angina compared with nondepressed patients. The SF-36 has been extensively validated in patients with CHD^16,48 and has been widely used in CABG patients.^15,17 Therefore, it is an appropriate instrument to use in this population.

Because we assessed preoperative health status only after surgery, inaccurate recall of health status may have biased our findings. To reduce recall bias, baseline health status should ideally be surveyed before the procedure. However, previous research has shown that patient-reported preadmission health status is not significantly affected by whether the data are collected before or after hospitalization when measured with scales similar to those in our study.⁴⁹ Therefore, this method should not have introduced bias.

Another potential limitation is the lack of objective physical performance measures. Although availability of these measures might have enhanced our article, patient self-reported health-related quality of life measurements such as those assessed by the SF-36 may provide better information on health-related quality of life.⁵⁰ In addition, self-perception of health predicts physical performance measured by exercise treadmill better than conventional interpretation of functional capacity by physicians.⁴⁸

Finally, our study population came from 1 major teaching hospital; therefore, the generalizability of our findings to other patient populations is unknown. However, we were able to screen all consecutive CABG admissions for participation and administered detailed questionnaires. This methodology would have been more difficult in the setting of a multicenter study.

	Conclusions

Top Abstract Introduction Methods Results Discussion Conclusions References

 
Depressive symptoms at the time of CABG surgery, particularly at the level of severe depressive symptoms, are associated with a lack of functional benefits 6 months after operation. The negative effects of depressive symptoms on functional status after CABG appear to be stronger in women than in men. Our results are consistent with the growing literature emphasizing a major role of depressive symptoms in the outcome of patients with CHD. Our study emphasizes the substantial importance of detection and treatment of depression in patients after CABG to improve their health status and quality of life.

	Acknowledgments

 
This study was supported by a grant from the Ethel F. Donaghue Women’s Health Investigator Program, New Haven, Conn; by a grant from the Quality Care Research Fund, Aetna Foundation, Hartford, Conn; and by grants from the National Institutes of Health (K24HL077506 and K12RR17643), Baltimore, Md.

	Footnotes

 
Guest Editor for this article was Eugene Braunwald, MD, Brigham and Women’s Hospital, Boston, Mass.

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