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Depression and Cardiac Morbidity 5 Years After Coronary Artery Bypass Surgery
Depression and Cardiac Morbidity 5 Years After Coronary Artery Bypass Surgery LOUIS BOROWICZ, JR., M.S., RICHARD ROYALL, PH.D. MAURA GREGA, M.S.N., OLA SELNES, PH.D. CONSTANTINE LYKETSOS, M.D., GUY MCKHANN, M.D.
The purpose of this study was to determine whether depression 1 month after coronary artery bypass surgery would be associated with greater cardiac morbidity in patients 5 years later. The cardiac symptom most affected by depression was the recurrence of angina. Factors associated with a return of angina at 5 years were depression measured preoperatively, at 1 month, at 1 year, and at 5 years. Additional significant factors were male sex and a preoperative history of smoking, percutaneous transluminal coronary angioplasty, or cerebrovascular accident. When these factors were combined in multiple logistic regression analyses, the score on the Center for Epidemiologic Studies Depression Scale at 1 month was the most significant of all factors. The depression score at 1 month after coronary artery bypass surgery is an important indicator of cardiac morbidity up to 5 years later. (Psychosomatics 2002; 43:464–471)
T
he relief of cardiac symptoms is one of the major indicators of the success of cardiac surgery or of successful revascularization.1 Therefore, any factors that potentially interfere with this symptom relief have important consequences for the estimated 800,000 coronary artery bypass grafting surgeries performed each year worldwide. Depression may be one such factor because of its prevalence in this population. Previous reports indicate that approximately one-third of all patients are depressed at some point shortly after the time of coronary artery bypass surgery.2 Notably, up to 50% of the patients who were depressed before surgery are depressed 1 month after surgery.3 This is important because accumulating evidence suggests that depression is associated not only with a greater risk of developing coronary Received Feb. 28, 2001; revision received Feb. 8, 2002; accepted Feb. 13, 2002. From the Zanvyl Krieger Mind/Brain Institute, the Departments of Neurology and Surgery, and the Department of Biostatistics, Johns Hopkins School of Public Health. Address reprint requests to Mr. Borowicz, Johns Hopkins Hospital, Meyer 1-100, 600 N. Wolfe St., Baltimore, MD 21287; [email protected] (e-mail). Copyright 䉷 2002 The Academy of Psychosomatic Medicine.
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disease4 but also with greater morbidity,5 a risk of heart failure,6,7, and mortality after myocardial infarction.4,6,8 Depression, both before and after coronary artery bypass grafting, has been associated with poorer outcomes. Studies have specifically shown that higher rates of rehospitalization occur within 6 weeks after surgery9 and that higher rates of rehospitalization for cardiac reasons, and death, occur for up to 2 years after the surgery.10,11 As part of a long-term ongoing prospective study of factors associated with neurological deficits after coronary artery bypass grafting, we included the evaluation of depression. We also examined the role of all of these factors in cardiac morbidity after coronary artery bypass grafting. In the present study, we determined the presence of cardiac morbidity, specifically chest pain, at 1 year and 5 years after surgery. We also examined other outcomes, such as hospitalization for cardiac reasons and death. We analyzed these outcomes in relation to preoperative, demographic, and medical factors; operative factors; and preoperative and postoperative depression measures. In this report, we emphasize the longer-term outcome (5 Psychosomatics 43:6, November-December 2002
Borowicz et al. years after surgery) and demonstrate that persons with higher depression scores either before or after surgery, but especially 1 month after surgery, have greater cardiac morbidity. Furthermore, these higher rates of morbidity could not be accounted for by other demographic, medical, or surgical factors. METHOD Patients A total of 172 patients (134 men and 38 women) were enrolled in this study after they had given signed informed consent. They were interviewed before coronary artery bypass grafting and at 1 month (N⳱149), 1 year (N⳱136), and 5 years (N⳱132) after surgery. At each time point, psychological and neuropsychological tests were administered and detailed medical histories were obtained. The group had a mean age of 63.4 years at baseline (range⳱41–86) and a mean 13 years of education (2–18). Patients had several medical disorders normally associated with this population, including hypertension (62%) and diabetes mellitus (24%). Study Design The study protocol has been described in detail elsewhere.12,13 In brief, patients were recruited before surgery, and medical histories and examinations were obtained. Demographic factors included gender, age, and education. Medical factors included history of smoking, history of hypertension, diabetes mellitus, stroke, transient ischemic attack, presence of a carotid bruit, myocardial infarction, peripheral vascular disease, use of anticoagulants, elevated cholesterol, prior percutaneous transluminal coronary angioplasty or redo coronary artery bypass grafting, and apolipoprotein-e genetic status. History of syncope, seizures, and use of antidepressant medications was also obtained. The preoperative cardiac status of the patients was determined with three different measures. The ejection fraction and the left ventricular function were recorded from the patient’s cardiac catheterization report. Both are common measures of cardiac performance. In addition, we designed, with the aid of cardiac surgeons at our institution, a Cardiac Sickness Index13 to provide another measure of cardiac health. The Cardiac Sickness Index rates individuals in one of four categories on the basis of their location and symptom profile just before surgery. These range from the patient being ambulatory at home to being bedridden Psychosomatics 43:6, November-December 2002
in the coronary care unit with angina at rest and requiring cardiac monitoring and intravenous anticoagulation. Information was also collected on other preoperative factors, which included systolic blood pressure, diastolic blood pressure, and mean arterial pressure. Details of operative management were obtained from operative and perfusion notes and included the number of vessels bypassed, time on the cardiopulmonary bypass pump, time of cross-clamping of the aorta, mean arterial pressure during bypass, rate of perfusion flow, partial oxygen level, and time to awaken after surgery. The postoperative course in the hospital was reviewed daily. Interim medical histories were obtained at follow-up examinations at 1 month, 1 year, and 5 years after surgery. Any episodes of rehospitalization, infection, myocardial infarction, cardiac procedure, or neurological problems were noted. Rehospitalizations for cardiac reasons were differentiated from those for other reasons. History of chest pain, shortness of breath, or heart rate irregularities was obtained. All patients were interviewed by one of two individuals (L.B. or M.G.), who used semistructured followup questions to separate cardiac from other reported symptoms. Particular attention was paid to distinguishing the precipitating factors and characteristics of reported chest pain that would indicate that it was of cardiac origin and not from some other source. The functional status of individuals was obtained by using a modified version of the Beth Israel Functional Status Questionnaire.14 Information on mortality was determined for all except two patients (N⳱170), either through direct contact with the patient or with family members of deceased patients. Patients were assessed with the Center for Epidemiologic Studies Depression Scale (CES-D Scale).15 The CES-D Scale is a 20-item self-report questionnaire developed for the study of depression in research applications in the general population. Possible scores range from 0 to 60; a score of equal to or greater than 16 generally indicates clinically significant depression.16 In this study, we analyzed the CES-D Scale both as a continuous variable and by using a CES-D Scale score equal to or greater than 16 as the point that separates individuals with depression from those without depression. Interviewers were blind to the CES-D Scale score until the end of each interview. Specifically, the interviews about chest pain took place before the patients completed the CES-D Scale. Information on a history of depression at any time before surgery was obtained from the patients. For a patient to be classified as having been treated for depression, a 465
Depression and Cardiac Morbidity physician’s diagnosis and treatment of major depression were required; a family history of depression required such a diagnosis in the patient’s grandparents, parents, or siblings; and major psychiatric disorder required a physician’s diagnosis of such a disorder (other than depression). Information on the use, but not the dose, of antidepressant medications was collected at each interview. Statistical Analyses Univariate logistic regression analyses for demographic, medical, and operative factors as well as CES-D Scale scores and depression status (CES-D Scale score equal to or greater than 16) were performed relative to the described outcomes. The factors with a significant association (p⬍0.05) were then combined in multiple logistic regression analyses. RESULTS We used available data from 147 patients at 1 month, 128 patients at 1 year, and 117 patients at 5 years. Among the 19 missing individuals at 1 year, there were four deaths and 15 patients who refused to continue participation in the study. At 5 years, 15 of the additional 30 missing patients had died, 13 refused to continue, and two could not be located. Nine patients were examined at 5 years but not at 1 year. With a CES-D Scale score equal to or greater than 16 as our criterion for depression, 32% (N⳱55) of the patients were depressed preoperatively, 28% (N⳱41) were depressed at 1 month, 21% (N⳱27) at 1 year, and 16% (N⳱19) at 5 years. Patients who were depressed at 1 month were as likely as nondepressed patients to return for subsequent follow-up interviews. At the time of preoperative testing, 25 patients (15%) indicated that they had been treated for depression, and seven patients (4%) had a history of other psychiatric disorders. Patients with these histories were more likely than those without such histories to be depressed before surgery and more likely to be depressed at one or more interview points after surgery (t⳱5.20, df⳱133, p⳱0.001). A small number of patients were taking antidepressant medications: five before surgery, five at 1 month, 11 at 1 year, and 10 at 5 years. Some patients taking antidepressant medications had scores on the CES-D Scale in the depressed range. Since depressed individuals are often either untreated or treated with inadequate doses of antidepressants, these medications may not be effective markers of depression.17 466
Chest Pain Within 5 Years At 5 years, 44 patients (38%) were considered to have had chest pain of cardiac origin at some time since their previous interview. Care was taken to document the precipitating factors and characteristics that would qualify this pain as angina and distinguish it from other causes of chest pain. A total of 25 of those with chest pain had also been hospitalized for cardiac reasons, including percutaneous transluminal coronary angioplasty, congestive heart failure, cardiac catheterization, myocardial infarction, redo coronary artery bypass grafting, shortness of breath, or multiple reasons. The mean 1-month CES-D Scale score of patients who reported chest pain at 5 years was 17.7 (SD⳱12.0), while the mean score for those without chest pain was 9.7 (SD⳱8.3); the difference was highly statistically significant (t⳱4.24, df⳱115, p⬍0.001). The relation of each of the CES-D Scale scores to the odds in favor of chest pain within 5 years after surgery was examined by using univariate logistic regression analysis. As noted above, the 1month CES-D Scale score was the most significant of the four CES-D Scale scores: preoperative (t⳱2.18, df⳱120, p⳱0.03), 1 month (t⳱3.67, df⳱115, p⳱0.0004), 1 year (t⳱2.86, df⳱105, p⳱0.005), and 5 years (t⳱2.14, df⳱100, p⳱0.03). The 1-month score also had the largest estimated coefficient (beta⳱0.078), indicating that a 9point increase in 1-month CES-D Scale score is associated with more than a doubling of the odds in favor of the occurrence of chest pain. The CES-D Scale score at 1 month was the most statistically significant of the CES-D Scale scores collected at all times (Table 1). This was true when scores at each time were entered, either separately or in combination, into the logistic regression model. Similar univariate logistic reTABLE 1.
Factors Associated With Return of Chest Pain for 117 Patients 5 Years After Coronary Artery Bypass Surgery
Variable
t
df
p
Male sex History of smoking Previous percutaneous transluminal coronary angioplasty Previous cerebrovascular accident
2.42 123 0.02 2.08 123 0.04 2.12 123 0.04 2.04 123 0.04
Score on the CES-D Scale Preoperative 1 month 1 year 5 years
2.18 3.67 2.86 2.14
120 115 105 100
0.03 0.0004 0.005 0.03
Psychosomatics 43:6, November-December 2002
Borowicz et al. gression analyses were performed for each of the variables obtained before surgery. The only additional variables significantly associated with chest pain at 5 years were male sex (t⳱2.42, df⳱123, p⳱0.02), history of smoking (t⳱2.08, df⳱123, p⳱0.04), previous percutaneous transluminal coronary angioplasty (t⳱2.12, df⳱123, p⳱0.04), and previous cerebrovascular accident (t⳱2.04, df⳱123, p⳱0.04). No operative variables were associated. When these four significant variables were added, one at a time, to the logistic regression model with the 1-month CES-D Scale score, none was statistically significant, while the CES-D Scale coefficient remained significant. This continued to be true when the CES-D Scale scores at all four time points were added simultaneously; i.e., none was significant and, after adjustment for these four covariates, the 1-month CES-D Scale score estimated beta coefficient was 0.067 (t⳱2.95, df⳱111, p⳱0.004). Relationship Between Depression and Gender Separate logistic regression analyses for men and for women showed that the results in the overall analysis were determined by the data for men. Accordingly, in the smaller group of women, evidence about the relationship of the 1month CES-D Scale score to chest pain within 5 years is weak. For men (N⳱95), the estimated coefficient was 0.094 (t⳱3.31, df⳱93, p⳱0.001), indicating that the estimated odds in favor of chest pain doubles with an 8-point increase in CES-D Scale score. However, for women (N⳱22), the estimated coefficient was only 0.025 (t⳱0.75, df⳱20, p⳱0.46), indicating that the odds in favor of chest pain doubles with a 28-point increase in CES-D Scale score, but this estimate has a standard error so large that the 95% confidence interval includes both zero and the estimate for men. That is, our data are compatible with values of the women’s CES-D Scale coefficient ranging from zero (there is no relationship between CES-D Scale score and chest pain) to a value as large as the estimate for men. Effect of Depression 1 Year After Surgery We analyzed the association of preoperative factors and CES-D Scale scores at the four time points with chest pain within 1 year. The results were essentially the same, with the CES-D Scale score at 1 month having the strongest association with chest pain within 1 year (t⳱4.34, df⳱126, p⳱0.001). As with the analysis at 5 years, this association persisted after correction for the results of other variables by means of multiple logistic regression models. Psychosomatics 43:6, November-December 2002
Effect of Depression on Other Cardiac Outcomes We also analyzed other cardiac outcomes within 5 years of surgery. For this analysis, we used a CES-D Scale score of equal to or greater than 16 to distinguish those who were depressed from those who were not depressed at 1 month (Table 2). When this method was applied to the patients interviewed at 5 years, we found that 29 of these individuals had been depressed and 88 had not been depressed when they were seen at 1 month (Table 3). Those who had undergone percutaneous transluminal coronary angioplasty were statistically more likely to have been in the depressed group (21% versus 6%) (v2⳱4.05, df⳱1, p⳱0.04). The functional status of patients was also significantly lower for the depressed group (mean⳱28.0, SD⳱6.1) than for the nondepressed group (mean⳱33.0, SD⳱4.5) (t⳱4.63, df⳱114, p⳱0.001). The depressed group also had more dysrhythmias (29% versus 17%), strokes (14% versus 3%), and deaths (17% versus 9%) by 5 years, but these differences were not significant. There were no differences in the number of myocardial infarctions. DISCUSSION We report here that higher depression scores preoperatively, 1 month, 1 year, and 5 years after surgery were associated with chest pain 5 years after surgery, with the CES-D Scale score at 1 month having the strongest association with depression. This association between CES-D Scale score and cardiac morbidity could not be accounted for by other demographic, medical, or surgical factors. This study adds strength to the association of depression and coronary artery disease. Notably, our data indicate that the presence of depression 1 month after surgery is an important risk factor for an outcome occurring many years later. At the 1-month evaluation, very few patients had chest pain, and those who did were more likely to have musculoskeletal pain associated with the surgical procedure than angina. Thus, we think that we were not simply observing patients with unsuccessful responses to surgery at 1 month who then will have poorer outcomes by 5 years. A similar delayed effect of depression is reported in studies of myocardial infarction and depression. Depression after a myocardial infarction is associated with higher rates of mortality in the months and years after the myocardial infarction.8,18 In those studies, the presence of depression has been shown to be a signifi467
Depression and Cardiac Morbidity cant risk factor for coronary artery disease and myocardial infarction independent of other accepted risk factors such as hypertension and hypercholesterolemia.19 Reports also
TABLE 2.
indicate that depression increases the risk of a myocardial infarction fourfold.20 Additionally, the risk of death or a second infarction has been shown to be much higher in
Preoperative Characteristics of Patients, by Depression Status 1 Month After Coronary Artery Bypass Grafting Patients Who Underwent Coronary Artery Bypass Grafting Not Depressed (Nⴔ106)
Variable
N
Male sex Caucasian Hypertension Hypercholesteremia Diabetes mellitus Cerebrovascular accident Transient ischemic attack Myocardial infarction Percutaneous transluminal coronary angioplasty Left ventricular functiona Poor Fair Good Past history of depression Family history of depression Age (years) Education (years) Ejection fraction (%) Mean arterial pressure (mm Hg) Functional status (0–36) Cardiac sickness index (1–4)
%
Depressed (Nⴔ41) N
Analysis %
90 100 60 62 62 3 4 58 17
85 94 57 58 58 3 4 55 16
27 36 29 31 31 4 1 23 12
66 88 71 76 76 10 2 56 29
1 27 64 9 15
1 29 70 8 14
2 6 25 11 11
6 18 76 27 27
Mean 63 13.5 56.5 94.7 30.4 1.9
SD 9.8 3.0 15.8 11.6 4.1 1.0
Mean 62.0 12.0 59.1 96.0 27.1 1.8
SD 8.9 3.6 17.2 11.0 5.9 1.1
v2
df
p
5.49
1
0.02
6.97
1
0.008
t
df
p
2.54
145
0.01
4.20
145
0.002
a
Data were not available for all patients.
TABLE 3.
Five-Year Morbidity and Mortality of Patients, by Depression Status 1 Month After Coronary Artery Bypass Grafting Patients Who Underwent Coronary Artery Bypass Grafting Not Depressed (Nⴔ88)
Depressed (Nⴔ29)
Analysis
Variable
N
%
N
%
v2
df
p
Male sex Angina Dysrhythmias Myocardial infarction Percutaneous transluminal coronary angioplasty Rehospitalization Cerebrovascular accident Transient ischemic attack Deatha
78 27 15 4 5 44 3 3 9
89 31 17 5 6 50 3 3 9
17 17 8 2 6
59 59 28 7 21
10.98 6.11
1 1
0.001 0.01
4.05
1
0.04
4 0 6
14 0 17
Mean 33.0
SD 4.5
Mean 28.0
SD 6.1
t 4.63
df 114
p 0.001
Functional status (0–36) a
Data were not available for all patients.
468
Psychosomatics 43:6, November-December 2002
Borowicz et al. individuals who are depressed after an initial myocardial infarction.21 An association between depression and cardiac surgery is generally accepted and has been reported with an incidence up to 25%–35% at various times postoperatively. However, most studies do not report the incidence of depression before surgery. In a previous study,3 we reported that of the 27% of patients who were depressed before surgery, about 50% were depressed at 1 month and 1 year after surgery. In contrast, of the individuals who were not depressed before surgery, only 13% were depressed at 1 month and 9% at 1 year. Thus, we determined that preoperative depression is a strong predictor of postoperative depression, and newly acquired depression is relatively uncommon. There have been few other reported studies of the relationship between depression and coronary outcomes after coronary artery bypass grafting. Saur et al.9 found that higher levels of depression preoperatively and at 6 weeks postoperatively were associated with higher rates of hospital readmission within 6 months. Baker and colleagues11 reported an association between elevated depressive symptoms before surgery and an increase in mortality over the next 4–38 months (12.5% in the depressed group versus 2.2% in the nondepressed group). This relationship is similar to our finding but is hampered by the small number of deaths (six deaths in a group of 158 patients). We are aware of only one study in which a structured psychiatric interview was given. Connerney et al.10 used cardiac readmission or cardiac death as outcomes. They found that those with major depression after surgery, but before hospital discharge, were 2.3 times more likely to have a cardiac event in the following 12 months and that this association could not be accounted for by other medical risk factors. The reasons for an association between depression and cardiac morbidity are unclear.22 One possibility is that depressed patients have more severe coronary artery disease at the time of surgery, which then results in poorer outcomes. In the present study, however, the cardiac variables, measured preoperatively, were similar between groups. The ejection fraction and left ventricular function, measures of cardiac performance, were the same for both depressed and nondepressed patients. Also, the Cardiac Sickness Index was effectively the same for both groups, indicating that in this population, depressed patients did not have more severe cardiac illness before coronary artery bypass grafting. Another possibility is that patients with depression are less likely to comply with medical care, follow physician Psychosomatics 43:6, November-December 2002
advice, or participate in cardiac rehabilitation programs.23,24 We do not have specific data with which to respond to this issue except that depressed patients were as likely to return for follow-up interviews in this study. Also, patients who were depressed at 1 month had more hospitalizations by 1 and 5 years, reported use of more cardiac medications at 1 year, and had almost four times the rate of percutaneous transluminal coronary angioplasty by 5 years, suggesting continued contact with the health care system. Patients with depression may also be more likely to report symptoms or more likely to misinterpret nonanginal pain as angina.25 This is a serious consideration in a study like this that relies on patient reports as an outcome measure. Two interviewers familiar with the symptoms of angina made particular efforts to characterize the patient complaints of chest pain. Also, these characterizations were made at times when the interviewers were not aware of an individual’s CES-D Scale score. In addition, the patients with depression had a higher incidence of several other symptoms or procedures associated with poorer cardiac performance. Nevertheless, even though the association of depression with subsequent chest pain was statistically significant, we cannot rule out the possibility that patients with depression respond to and report chest pain differently from those without depression. Other possible reasons proposed to explain the relationship between depression and the outcome in coronary disease are that depressed patients have reduced heart variability,26,27 increased platelet aggregability, and/or elevated catecholamine levels.28 We did not collect data that might help clarify these proposed mechanisms. Since numerous studies have reported higher rates of mortality and morbidity in women after coronary artery bypass grafting,29,30 and since women have higher rates of depression in the general population,31 we examined the relationship between depression at 1 month and chest pain at 5 years, stratified by gender. Somewhat to our surprise, we found a significant relationship between depression and cardiac outcomes in men but not in women. Nondepressed women report approximately the same level of chest pain, as do depressed women at 5 years. Moreover, both depressed and nondepressed women report relatively high levels of chest pain at both 1 year and 5 years. The reason for this lack of association in women is unclear. One possibility is that a score of 16 on the CES-D Scale is sufficient to distinguish depressed from nondepressed men but that perhaps a different, probably higher, score may be required for women. When we analyzed the CES-D Scale score as a continuous variable, however, we 469
Depression and Cardiac Morbidity still found this gender difference. There is also evidence of gender differences in the reporting of angina32 that may bias the interpretation of symptoms between men and women. Finally, depression may not be a risk factor for ischemic heart disease in women.33 We are cautious in interpreting these data because of the relatively few women in this study. The CES-D Scale score at 1 month, rather than at other time points, provided the strongest association with subsequent cardiac morbidity. From a practical viewpoint, 1 month is convenient for reevaluation because at our hospital, patients return for surgical postoperative evaluation at this time. The 1-month time point also provides a distinct opportunity for intervention. By use of the CES-D Scale, patients with depression who are thus at risk for poorer outcomes can be identified. Particular attention could be paid to this at-risk group in terms of compliance with medical management and postsurgery cardiac rehabilitation. Pharmacological and/or psychotherapeutic interventions34 could be introduced for depressed patients with the goal of minimizing both depressive and cardiac symptoms over the succeeding years. At this time, however, there is no evidence that pharmacologically treating depression will influence cardiac outcomes for those with coronary artery disease. Physicians have been reluctant to prescribe tricyclic antidepressants to cardiac patients because of potential cardiac side effects.35 There is evidence, however, that selective serotonin reuptake inhibitors are safe for these patients.36 Prospective controlled studies in patients after myocardial infarction are in progress to determine whether the use of such agents is effective in reducing cardiac morbidity. We are aware that there are limitations in this study. These findings are incidental to a study of the effects of
coronary artery bypass grafting on cognition in which depression was measured as a possible confounding agent. Depression was defined by the CES-D Scale score, and although this questionnaire is validated and reliable, it cannot substitute for formal psychiatric diagnosis. Even though efforts were made by interviewers to screen for noncardiac or psychosomatic complaints, self-reports are less definitive than a diagnosis made by a physician and supported by other studies, e.g., stress echocardiography. In summary, the present results, coupled with several other studies, indicate that patients depressed preoperatively and at 1 month after surgery are at significantly higher risk of poorer outcomes after coronary artery bypass grafting. These findings, combined with recent findings regarding the apparent causal relationship between depression and the incidence of coronary artery disease and poorer outcomes after myocardial infarction, strongly suggest that depression is an important but commonly ignored or underestimated risk factor for cardiac outcomes.21 Studies are needed to determine whether, once depression is identified after coronary artery bypass grafting, better outcomes can be achieved for those with depression by the use of more aggressive cardiac rehabilitation, supportive psychotherapy,20,21 and/or pharmacological intervention. Supported by the Research Network on Successful Aging of the John D. and Catherine T. MacArthur Foundation, the Charles A. Dana Foundation, the Seaver Institute, and NIH grant NS 35610 from the National Institute of Neurological and Communicative Disorders and Stroke. The authors thank Pamela Talalay, Ph.D., for her editorial reviews and the cardiac surgeons at the Johns Hopkins Hospital for their collaboration.
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Borowicz et al. and 12-month outcome: a prospective study. Lancet 2001; 358: 1766–1771 11. Baker RA, Andrew MJ, Schrader G, Knight JL: Preoperative depression and mortality in coronary artery bypass surgery: preliminary findings. Aust NZ J Surg 2001; 71:139–142 12. McKhann GM, Goldsborough MA, Borowicz LM: Cognitive outcome after coronary artery bypass: a 1-year prospective study. Ann Thorac Surg 1997; 63:510–515 13. McKhann GM, Goldsborough MA, Borowicz LM Jr, Mellits ED, Brookmeyer R, Quaskey SA, Baumgartner WA, Cameron DE, Stuart RS, Gardner TJ: Predictors of stroke risk in coronary artery bypass patients. Ann Thorac Surg 1997; 63:516–521 14. Jette AM, Davies AR, Cleary PD, Calkins DR, Rubenstein LV, Fink A, Kosecoff J, Young RT, Brook RH, Delbanco TL: The Functional Status Questionnaire: reliability and validity when used in primary care. J Gen Intern Med 1986; 1:143–149 15. Radloff LS: The CES-D Scale: a self-report depression scale for research in the general population. J Applied Psychol Measurement 1977; 1:385–401 16. Devins GM, Orme CM: Center for Epidemiologic Studies Depression Scale, in Test Critiques, vol II. Edited by Keyser DW, Sweatland RC. Kansas City, Mo, Westport, 1985, pp 144–160 17. Hirschfeld RM, Keller MB, Panico S, Arons BS, Barlow D, Davidoff F, Endicott J, Froom J, Goldstein M, Gorman JM, Marek RG, Maurer TA, Meyer R, Phillips K, Ross J, Schwenk TL, Sharfstein SS, Thase ME, Wyatt RJ: The National Depressive and Manic-Depressive Association consensus statement on the undertreatment of depression. JAMA 1997; 277:333–340 18. Frasure-Smith N, Lesperance F, Talajic M: Depression and 18month prognosis after myocardial infarction. Circulation 1995; 91:999–1005 19. Glassman AH, Shapiro PA: Depression and the course of coronary artery disease. Am J Psychiatry 1998; 155:4–11 20. Pratt LA, Ford DE, Crum RM, Armenian HK, Gallo JJ, Eaton WW: Depression, psychotropic medication, and risk of myocardial infarction: prospective data from the Baltimore ECA follow-up. Circulation 1996; 94:3123–3129 21. Frasure-Smith N, Lesperance F, Talajic M: Depression following myocardial infarction: impact on 6-month survival. JAMA 1993; 270:1819–1825 22. Lavoie KL, Fleet RP: The impact of depression on the course and outcome of coronary artery disease: review for cardiologists. Can J Cardiol 2000; 16:653–662 23. Blumenthal JA, Williams RS, Wallace AG, Williams RB, Needles TL: Physiological and psychological variables predict compliance to prescribed exercise therapy in patients recovering from myocardial infarction. Psychosom Med 1982; 44:519–527
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24. Carney RM, Freedland KE, Eisen SA, Rich MW, Jaffe AS: Major depression and medication adherence in elderly patients with coronary artery disease. Health Psychol 1995; 14:88–90 25. Katon WJ, Walker EA: Medically unexplained symptoms in primary care. J Clin Psychiatry 1998; 59:15–21 26. Carney RM, Saunders RD, Freedland KE, Stein P, Rich MW, Jaffe AS: Association of depression with reduced heart rate variability in coronary artery disease. Am J Cardiol 1995; 76:562–564 27. Carney RM, Freedland KE, Stein PK, Skala JA, Hoffman P, Jaffe AS: Change in heart rate variability during treatment for depression in patients with coronary heart disease. Psychosom Med 2000; 62:639–647 28. Musselman DL, Evans DL, Nemeroff CB: The relationship of depression to cardiovascular disease. Arch Gen Psychiatry 1998; 55:580–592 29. O’Connor GT, Morton JR, Diehl MJ, Olmstead EM, Coffin LH, Levy DG, Maloney CT, Plume SK, Nugent W, Malenka DJ, Hernandez F, Clough R, Birkmeyer J, Marrin CAS, Leavitt BJ (Northern New England Cardiovascular Disease Study Group): Differences between men and women in hospital mortality associated with coronary artery bypass graft surgery. Circulation 1993; 88:2104–2110 30. Edwards FH, Carey JS, Grover FL, Bero JW, Hartz RS: Impact of gender on coronary bypass operative mortality. Ann Thorac Surg 1998; 66:125–131 31. Patel RL, Turtle MR, Chambers DJ, James DN, Newman S, Venn GE: Alpha-stat acid-base regulation during cardiopulmonary bypass improves neuropsychologic outcome in patients undergoing coronary artery bypass grafting. J Thorac Cardiovasc Surg 1996; 111:1267–1279 32. Harris RB, Weissfeld LA: Gender differences in the reliability of reporting symptoms of angina pectoris. J Clin Epidemiol 1991; 44:1071–1078 33. Hippisley-Cox J, Fielding K, Pringle M: Depression as a risk factor for ischaemic heart disease in men: population based casecontrol study. Br Med J 1998; 316:1714–1719 34. Peden JG, Kathol R: Mood disorders and general medical illness, in Synopsis of Treatment of Psychiatric Disorders, 2nd ed. Edited by Gabbard GO, Atkinson SD. Washington, DC, American Psychiatric Press, 1998, pp 565–573 35. Glassman AH, Rodriguez AI, Shapiro PA: The use of antidepressant drugs in patients with heart disease. J Clin Psychiatry 1998; 59(suppl 10):16–21 36. Roose SP, Glassman AH, Attia E, Woodring S, Giardina E-GV, Bigger JT Jr: Cardiovascular effects of fluoxetine in depressed patients with heart disease. Am J Psychiatry 1998; 155:660–665
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The purpose of this study was to determine whether depression 1 month after coronary artery bypass surgery would be associated with greater cardiac morbidity in patients 5 years later. The cardiac symptom most affected by depression was the recurrence of angina. Factors associated with a return of angina at 5 years were depression measured preoperatively, at 1 month, at 1 year, and at 5 years. Additional significant factors were male sex and a preoperative history of smoking, percutaneous transluminal coronary angioplasty, or cerebrovascular accident. When these factors were combined in multiple logistic regression analyses, the score on the Center for Epidemiologic Studies Depression Scale at 1 month was the most significant of all factors. The depression score at 1 month after coronary artery bypass surgery is an important indicator of cardiac morbidity up to 5 years later. (Psychosomatics 2002; 43:464–471)
T
he relief of cardiac symptoms is one of the major indicators of the success of cardiac surgery or of successful revascularization.1 Therefore, any factors that potentially interfere with this symptom relief have important consequences for the estimated 800,000 coronary artery bypass grafting surgeries performed each year worldwide. Depression may be one such factor because of its prevalence in this population. Previous reports indicate that approximately one-third of all patients are depressed at some point shortly after the time of coronary artery bypass surgery.2 Notably, up to 50% of the patients who were depressed before surgery are depressed 1 month after surgery.3 This is important because accumulating evidence suggests that depression is associated not only with a greater risk of developing coronary Received Feb. 28, 2001; revision received Feb. 8, 2002; accepted Feb. 13, 2002. From the Zanvyl Krieger Mind/Brain Institute, the Departments of Neurology and Surgery, and the Department of Biostatistics, Johns Hopkins School of Public Health. Address reprint requests to Mr. Borowicz, Johns Hopkins Hospital, Meyer 1-100, 600 N. Wolfe St., Baltimore, MD 21287; [email protected] (e-mail). Copyright 䉷 2002 The Academy of Psychosomatic Medicine.
464
disease4 but also with greater morbidity,5 a risk of heart failure,6,7, and mortality after myocardial infarction.4,6,8 Depression, both before and after coronary artery bypass grafting, has been associated with poorer outcomes. Studies have specifically shown that higher rates of rehospitalization occur within 6 weeks after surgery9 and that higher rates of rehospitalization for cardiac reasons, and death, occur for up to 2 years after the surgery.10,11 As part of a long-term ongoing prospective study of factors associated with neurological deficits after coronary artery bypass grafting, we included the evaluation of depression. We also examined the role of all of these factors in cardiac morbidity after coronary artery bypass grafting. In the present study, we determined the presence of cardiac morbidity, specifically chest pain, at 1 year and 5 years after surgery. We also examined other outcomes, such as hospitalization for cardiac reasons and death. We analyzed these outcomes in relation to preoperative, demographic, and medical factors; operative factors; and preoperative and postoperative depression measures. In this report, we emphasize the longer-term outcome (5 Psychosomatics 43:6, November-December 2002
Borowicz et al. years after surgery) and demonstrate that persons with higher depression scores either before or after surgery, but especially 1 month after surgery, have greater cardiac morbidity. Furthermore, these higher rates of morbidity could not be accounted for by other demographic, medical, or surgical factors. METHOD Patients A total of 172 patients (134 men and 38 women) were enrolled in this study after they had given signed informed consent. They were interviewed before coronary artery bypass grafting and at 1 month (N⳱149), 1 year (N⳱136), and 5 years (N⳱132) after surgery. At each time point, psychological and neuropsychological tests were administered and detailed medical histories were obtained. The group had a mean age of 63.4 years at baseline (range⳱41–86) and a mean 13 years of education (2–18). Patients had several medical disorders normally associated with this population, including hypertension (62%) and diabetes mellitus (24%). Study Design The study protocol has been described in detail elsewhere.12,13 In brief, patients were recruited before surgery, and medical histories and examinations were obtained. Demographic factors included gender, age, and education. Medical factors included history of smoking, history of hypertension, diabetes mellitus, stroke, transient ischemic attack, presence of a carotid bruit, myocardial infarction, peripheral vascular disease, use of anticoagulants, elevated cholesterol, prior percutaneous transluminal coronary angioplasty or redo coronary artery bypass grafting, and apolipoprotein-e genetic status. History of syncope, seizures, and use of antidepressant medications was also obtained. The preoperative cardiac status of the patients was determined with three different measures. The ejection fraction and the left ventricular function were recorded from the patient’s cardiac catheterization report. Both are common measures of cardiac performance. In addition, we designed, with the aid of cardiac surgeons at our institution, a Cardiac Sickness Index13 to provide another measure of cardiac health. The Cardiac Sickness Index rates individuals in one of four categories on the basis of their location and symptom profile just before surgery. These range from the patient being ambulatory at home to being bedridden Psychosomatics 43:6, November-December 2002
in the coronary care unit with angina at rest and requiring cardiac monitoring and intravenous anticoagulation. Information was also collected on other preoperative factors, which included systolic blood pressure, diastolic blood pressure, and mean arterial pressure. Details of operative management were obtained from operative and perfusion notes and included the number of vessels bypassed, time on the cardiopulmonary bypass pump, time of cross-clamping of the aorta, mean arterial pressure during bypass, rate of perfusion flow, partial oxygen level, and time to awaken after surgery. The postoperative course in the hospital was reviewed daily. Interim medical histories were obtained at follow-up examinations at 1 month, 1 year, and 5 years after surgery. Any episodes of rehospitalization, infection, myocardial infarction, cardiac procedure, or neurological problems were noted. Rehospitalizations for cardiac reasons were differentiated from those for other reasons. History of chest pain, shortness of breath, or heart rate irregularities was obtained. All patients were interviewed by one of two individuals (L.B. or M.G.), who used semistructured followup questions to separate cardiac from other reported symptoms. Particular attention was paid to distinguishing the precipitating factors and characteristics of reported chest pain that would indicate that it was of cardiac origin and not from some other source. The functional status of individuals was obtained by using a modified version of the Beth Israel Functional Status Questionnaire.14 Information on mortality was determined for all except two patients (N⳱170), either through direct contact with the patient or with family members of deceased patients. Patients were assessed with the Center for Epidemiologic Studies Depression Scale (CES-D Scale).15 The CES-D Scale is a 20-item self-report questionnaire developed for the study of depression in research applications in the general population. Possible scores range from 0 to 60; a score of equal to or greater than 16 generally indicates clinically significant depression.16 In this study, we analyzed the CES-D Scale both as a continuous variable and by using a CES-D Scale score equal to or greater than 16 as the point that separates individuals with depression from those without depression. Interviewers were blind to the CES-D Scale score until the end of each interview. Specifically, the interviews about chest pain took place before the patients completed the CES-D Scale. Information on a history of depression at any time before surgery was obtained from the patients. For a patient to be classified as having been treated for depression, a 465
Depression and Cardiac Morbidity physician’s diagnosis and treatment of major depression were required; a family history of depression required such a diagnosis in the patient’s grandparents, parents, or siblings; and major psychiatric disorder required a physician’s diagnosis of such a disorder (other than depression). Information on the use, but not the dose, of antidepressant medications was collected at each interview. Statistical Analyses Univariate logistic regression analyses for demographic, medical, and operative factors as well as CES-D Scale scores and depression status (CES-D Scale score equal to or greater than 16) were performed relative to the described outcomes. The factors with a significant association (p⬍0.05) were then combined in multiple logistic regression analyses. RESULTS We used available data from 147 patients at 1 month, 128 patients at 1 year, and 117 patients at 5 years. Among the 19 missing individuals at 1 year, there were four deaths and 15 patients who refused to continue participation in the study. At 5 years, 15 of the additional 30 missing patients had died, 13 refused to continue, and two could not be located. Nine patients were examined at 5 years but not at 1 year. With a CES-D Scale score equal to or greater than 16 as our criterion for depression, 32% (N⳱55) of the patients were depressed preoperatively, 28% (N⳱41) were depressed at 1 month, 21% (N⳱27) at 1 year, and 16% (N⳱19) at 5 years. Patients who were depressed at 1 month were as likely as nondepressed patients to return for subsequent follow-up interviews. At the time of preoperative testing, 25 patients (15%) indicated that they had been treated for depression, and seven patients (4%) had a history of other psychiatric disorders. Patients with these histories were more likely than those without such histories to be depressed before surgery and more likely to be depressed at one or more interview points after surgery (t⳱5.20, df⳱133, p⳱0.001). A small number of patients were taking antidepressant medications: five before surgery, five at 1 month, 11 at 1 year, and 10 at 5 years. Some patients taking antidepressant medications had scores on the CES-D Scale in the depressed range. Since depressed individuals are often either untreated or treated with inadequate doses of antidepressants, these medications may not be effective markers of depression.17 466
Chest Pain Within 5 Years At 5 years, 44 patients (38%) were considered to have had chest pain of cardiac origin at some time since their previous interview. Care was taken to document the precipitating factors and characteristics that would qualify this pain as angina and distinguish it from other causes of chest pain. A total of 25 of those with chest pain had also been hospitalized for cardiac reasons, including percutaneous transluminal coronary angioplasty, congestive heart failure, cardiac catheterization, myocardial infarction, redo coronary artery bypass grafting, shortness of breath, or multiple reasons. The mean 1-month CES-D Scale score of patients who reported chest pain at 5 years was 17.7 (SD⳱12.0), while the mean score for those without chest pain was 9.7 (SD⳱8.3); the difference was highly statistically significant (t⳱4.24, df⳱115, p⬍0.001). The relation of each of the CES-D Scale scores to the odds in favor of chest pain within 5 years after surgery was examined by using univariate logistic regression analysis. As noted above, the 1month CES-D Scale score was the most significant of the four CES-D Scale scores: preoperative (t⳱2.18, df⳱120, p⳱0.03), 1 month (t⳱3.67, df⳱115, p⳱0.0004), 1 year (t⳱2.86, df⳱105, p⳱0.005), and 5 years (t⳱2.14, df⳱100, p⳱0.03). The 1-month score also had the largest estimated coefficient (beta⳱0.078), indicating that a 9point increase in 1-month CES-D Scale score is associated with more than a doubling of the odds in favor of the occurrence of chest pain. The CES-D Scale score at 1 month was the most statistically significant of the CES-D Scale scores collected at all times (Table 1). This was true when scores at each time were entered, either separately or in combination, into the logistic regression model. Similar univariate logistic reTABLE 1.
Factors Associated With Return of Chest Pain for 117 Patients 5 Years After Coronary Artery Bypass Surgery
Variable
t
df
p
Male sex History of smoking Previous percutaneous transluminal coronary angioplasty Previous cerebrovascular accident
2.42 123 0.02 2.08 123 0.04 2.12 123 0.04 2.04 123 0.04
Score on the CES-D Scale Preoperative 1 month 1 year 5 years
2.18 3.67 2.86 2.14
120 115 105 100
0.03 0.0004 0.005 0.03
Psychosomatics 43:6, November-December 2002
Borowicz et al. gression analyses were performed for each of the variables obtained before surgery. The only additional variables significantly associated with chest pain at 5 years were male sex (t⳱2.42, df⳱123, p⳱0.02), history of smoking (t⳱2.08, df⳱123, p⳱0.04), previous percutaneous transluminal coronary angioplasty (t⳱2.12, df⳱123, p⳱0.04), and previous cerebrovascular accident (t⳱2.04, df⳱123, p⳱0.04). No operative variables were associated. When these four significant variables were added, one at a time, to the logistic regression model with the 1-month CES-D Scale score, none was statistically significant, while the CES-D Scale coefficient remained significant. This continued to be true when the CES-D Scale scores at all four time points were added simultaneously; i.e., none was significant and, after adjustment for these four covariates, the 1-month CES-D Scale score estimated beta coefficient was 0.067 (t⳱2.95, df⳱111, p⳱0.004). Relationship Between Depression and Gender Separate logistic regression analyses for men and for women showed that the results in the overall analysis were determined by the data for men. Accordingly, in the smaller group of women, evidence about the relationship of the 1month CES-D Scale score to chest pain within 5 years is weak. For men (N⳱95), the estimated coefficient was 0.094 (t⳱3.31, df⳱93, p⳱0.001), indicating that the estimated odds in favor of chest pain doubles with an 8-point increase in CES-D Scale score. However, for women (N⳱22), the estimated coefficient was only 0.025 (t⳱0.75, df⳱20, p⳱0.46), indicating that the odds in favor of chest pain doubles with a 28-point increase in CES-D Scale score, but this estimate has a standard error so large that the 95% confidence interval includes both zero and the estimate for men. That is, our data are compatible with values of the women’s CES-D Scale coefficient ranging from zero (there is no relationship between CES-D Scale score and chest pain) to a value as large as the estimate for men. Effect of Depression 1 Year After Surgery We analyzed the association of preoperative factors and CES-D Scale scores at the four time points with chest pain within 1 year. The results were essentially the same, with the CES-D Scale score at 1 month having the strongest association with chest pain within 1 year (t⳱4.34, df⳱126, p⳱0.001). As with the analysis at 5 years, this association persisted after correction for the results of other variables by means of multiple logistic regression models. Psychosomatics 43:6, November-December 2002
Effect of Depression on Other Cardiac Outcomes We also analyzed other cardiac outcomes within 5 years of surgery. For this analysis, we used a CES-D Scale score of equal to or greater than 16 to distinguish those who were depressed from those who were not depressed at 1 month (Table 2). When this method was applied to the patients interviewed at 5 years, we found that 29 of these individuals had been depressed and 88 had not been depressed when they were seen at 1 month (Table 3). Those who had undergone percutaneous transluminal coronary angioplasty were statistically more likely to have been in the depressed group (21% versus 6%) (v2⳱4.05, df⳱1, p⳱0.04). The functional status of patients was also significantly lower for the depressed group (mean⳱28.0, SD⳱6.1) than for the nondepressed group (mean⳱33.0, SD⳱4.5) (t⳱4.63, df⳱114, p⳱0.001). The depressed group also had more dysrhythmias (29% versus 17%), strokes (14% versus 3%), and deaths (17% versus 9%) by 5 years, but these differences were not significant. There were no differences in the number of myocardial infarctions. DISCUSSION We report here that higher depression scores preoperatively, 1 month, 1 year, and 5 years after surgery were associated with chest pain 5 years after surgery, with the CES-D Scale score at 1 month having the strongest association with depression. This association between CES-D Scale score and cardiac morbidity could not be accounted for by other demographic, medical, or surgical factors. This study adds strength to the association of depression and coronary artery disease. Notably, our data indicate that the presence of depression 1 month after surgery is an important risk factor for an outcome occurring many years later. At the 1-month evaluation, very few patients had chest pain, and those who did were more likely to have musculoskeletal pain associated with the surgical procedure than angina. Thus, we think that we were not simply observing patients with unsuccessful responses to surgery at 1 month who then will have poorer outcomes by 5 years. A similar delayed effect of depression is reported in studies of myocardial infarction and depression. Depression after a myocardial infarction is associated with higher rates of mortality in the months and years after the myocardial infarction.8,18 In those studies, the presence of depression has been shown to be a signifi467
Depression and Cardiac Morbidity cant risk factor for coronary artery disease and myocardial infarction independent of other accepted risk factors such as hypertension and hypercholesterolemia.19 Reports also
TABLE 2.
indicate that depression increases the risk of a myocardial infarction fourfold.20 Additionally, the risk of death or a second infarction has been shown to be much higher in
Preoperative Characteristics of Patients, by Depression Status 1 Month After Coronary Artery Bypass Grafting Patients Who Underwent Coronary Artery Bypass Grafting Not Depressed (Nⴔ106)
Variable
N
Male sex Caucasian Hypertension Hypercholesteremia Diabetes mellitus Cerebrovascular accident Transient ischemic attack Myocardial infarction Percutaneous transluminal coronary angioplasty Left ventricular functiona Poor Fair Good Past history of depression Family history of depression Age (years) Education (years) Ejection fraction (%) Mean arterial pressure (mm Hg) Functional status (0–36) Cardiac sickness index (1–4)
%
Depressed (Nⴔ41) N
Analysis %
90 100 60 62 62 3 4 58 17
85 94 57 58 58 3 4 55 16
27 36 29 31 31 4 1 23 12
66 88 71 76 76 10 2 56 29
1 27 64 9 15
1 29 70 8 14
2 6 25 11 11
6 18 76 27 27
Mean 63 13.5 56.5 94.7 30.4 1.9
SD 9.8 3.0 15.8 11.6 4.1 1.0
Mean 62.0 12.0 59.1 96.0 27.1 1.8
SD 8.9 3.6 17.2 11.0 5.9 1.1
v2
df
p
5.49
1
0.02
6.97
1
0.008
t
df
p
2.54
145
0.01
4.20
145
0.002
a
Data were not available for all patients.
TABLE 3.
Five-Year Morbidity and Mortality of Patients, by Depression Status 1 Month After Coronary Artery Bypass Grafting Patients Who Underwent Coronary Artery Bypass Grafting Not Depressed (Nⴔ88)
Depressed (Nⴔ29)
Analysis
Variable
N
%
N
%
v2
df
p
Male sex Angina Dysrhythmias Myocardial infarction Percutaneous transluminal coronary angioplasty Rehospitalization Cerebrovascular accident Transient ischemic attack Deatha
78 27 15 4 5 44 3 3 9
89 31 17 5 6 50 3 3 9
17 17 8 2 6
59 59 28 7 21
10.98 6.11
1 1
0.001 0.01
4.05
1
0.04
4 0 6
14 0 17
Mean 33.0
SD 4.5
Mean 28.0
SD 6.1
t 4.63
df 114
p 0.001
Functional status (0–36) a
Data were not available for all patients.
468
Psychosomatics 43:6, November-December 2002
Borowicz et al. individuals who are depressed after an initial myocardial infarction.21 An association between depression and cardiac surgery is generally accepted and has been reported with an incidence up to 25%–35% at various times postoperatively. However, most studies do not report the incidence of depression before surgery. In a previous study,3 we reported that of the 27% of patients who were depressed before surgery, about 50% were depressed at 1 month and 1 year after surgery. In contrast, of the individuals who were not depressed before surgery, only 13% were depressed at 1 month and 9% at 1 year. Thus, we determined that preoperative depression is a strong predictor of postoperative depression, and newly acquired depression is relatively uncommon. There have been few other reported studies of the relationship between depression and coronary outcomes after coronary artery bypass grafting. Saur et al.9 found that higher levels of depression preoperatively and at 6 weeks postoperatively were associated with higher rates of hospital readmission within 6 months. Baker and colleagues11 reported an association between elevated depressive symptoms before surgery and an increase in mortality over the next 4–38 months (12.5% in the depressed group versus 2.2% in the nondepressed group). This relationship is similar to our finding but is hampered by the small number of deaths (six deaths in a group of 158 patients). We are aware of only one study in which a structured psychiatric interview was given. Connerney et al.10 used cardiac readmission or cardiac death as outcomes. They found that those with major depression after surgery, but before hospital discharge, were 2.3 times more likely to have a cardiac event in the following 12 months and that this association could not be accounted for by other medical risk factors. The reasons for an association between depression and cardiac morbidity are unclear.22 One possibility is that depressed patients have more severe coronary artery disease at the time of surgery, which then results in poorer outcomes. In the present study, however, the cardiac variables, measured preoperatively, were similar between groups. The ejection fraction and left ventricular function, measures of cardiac performance, were the same for both depressed and nondepressed patients. Also, the Cardiac Sickness Index was effectively the same for both groups, indicating that in this population, depressed patients did not have more severe cardiac illness before coronary artery bypass grafting. Another possibility is that patients with depression are less likely to comply with medical care, follow physician Psychosomatics 43:6, November-December 2002
advice, or participate in cardiac rehabilitation programs.23,24 We do not have specific data with which to respond to this issue except that depressed patients were as likely to return for follow-up interviews in this study. Also, patients who were depressed at 1 month had more hospitalizations by 1 and 5 years, reported use of more cardiac medications at 1 year, and had almost four times the rate of percutaneous transluminal coronary angioplasty by 5 years, suggesting continued contact with the health care system. Patients with depression may also be more likely to report symptoms or more likely to misinterpret nonanginal pain as angina.25 This is a serious consideration in a study like this that relies on patient reports as an outcome measure. Two interviewers familiar with the symptoms of angina made particular efforts to characterize the patient complaints of chest pain. Also, these characterizations were made at times when the interviewers were not aware of an individual’s CES-D Scale score. In addition, the patients with depression had a higher incidence of several other symptoms or procedures associated with poorer cardiac performance. Nevertheless, even though the association of depression with subsequent chest pain was statistically significant, we cannot rule out the possibility that patients with depression respond to and report chest pain differently from those without depression. Other possible reasons proposed to explain the relationship between depression and the outcome in coronary disease are that depressed patients have reduced heart variability,26,27 increased platelet aggregability, and/or elevated catecholamine levels.28 We did not collect data that might help clarify these proposed mechanisms. Since numerous studies have reported higher rates of mortality and morbidity in women after coronary artery bypass grafting,29,30 and since women have higher rates of depression in the general population,31 we examined the relationship between depression at 1 month and chest pain at 5 years, stratified by gender. Somewhat to our surprise, we found a significant relationship between depression and cardiac outcomes in men but not in women. Nondepressed women report approximately the same level of chest pain, as do depressed women at 5 years. Moreover, both depressed and nondepressed women report relatively high levels of chest pain at both 1 year and 5 years. The reason for this lack of association in women is unclear. One possibility is that a score of 16 on the CES-D Scale is sufficient to distinguish depressed from nondepressed men but that perhaps a different, probably higher, score may be required for women. When we analyzed the CES-D Scale score as a continuous variable, however, we 469
Depression and Cardiac Morbidity still found this gender difference. There is also evidence of gender differences in the reporting of angina32 that may bias the interpretation of symptoms between men and women. Finally, depression may not be a risk factor for ischemic heart disease in women.33 We are cautious in interpreting these data because of the relatively few women in this study. The CES-D Scale score at 1 month, rather than at other time points, provided the strongest association with subsequent cardiac morbidity. From a practical viewpoint, 1 month is convenient for reevaluation because at our hospital, patients return for surgical postoperative evaluation at this time. The 1-month time point also provides a distinct opportunity for intervention. By use of the CES-D Scale, patients with depression who are thus at risk for poorer outcomes can be identified. Particular attention could be paid to this at-risk group in terms of compliance with medical management and postsurgery cardiac rehabilitation. Pharmacological and/or psychotherapeutic interventions34 could be introduced for depressed patients with the goal of minimizing both depressive and cardiac symptoms over the succeeding years. At this time, however, there is no evidence that pharmacologically treating depression will influence cardiac outcomes for those with coronary artery disease. Physicians have been reluctant to prescribe tricyclic antidepressants to cardiac patients because of potential cardiac side effects.35 There is evidence, however, that selective serotonin reuptake inhibitors are safe for these patients.36 Prospective controlled studies in patients after myocardial infarction are in progress to determine whether the use of such agents is effective in reducing cardiac morbidity. We are aware that there are limitations in this study. These findings are incidental to a study of the effects of
coronary artery bypass grafting on cognition in which depression was measured as a possible confounding agent. Depression was defined by the CES-D Scale score, and although this questionnaire is validated and reliable, it cannot substitute for formal psychiatric diagnosis. Even though efforts were made by interviewers to screen for noncardiac or psychosomatic complaints, self-reports are less definitive than a diagnosis made by a physician and supported by other studies, e.g., stress echocardiography. In summary, the present results, coupled with several other studies, indicate that patients depressed preoperatively and at 1 month after surgery are at significantly higher risk of poorer outcomes after coronary artery bypass grafting. These findings, combined with recent findings regarding the apparent causal relationship between depression and the incidence of coronary artery disease and poorer outcomes after myocardial infarction, strongly suggest that depression is an important but commonly ignored or underestimated risk factor for cardiac outcomes.21 Studies are needed to determine whether, once depression is identified after coronary artery bypass grafting, better outcomes can be achieved for those with depression by the use of more aggressive cardiac rehabilitation, supportive psychotherapy,20,21 and/or pharmacological intervention. Supported by the Research Network on Successful Aging of the John D. and Catherine T. MacArthur Foundation, the Charles A. Dana Foundation, the Seaver Institute, and NIH grant NS 35610 from the National Institute of Neurological and Communicative Disorders and Stroke. The authors thank Pamela Talalay, Ph.D., for her editorial reviews and the cardiac surgeons at the Johns Hopkins Hospital for their collaboration.
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