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Minor Depression as a Cardiac Risk Factor After Coronary Artery Bypass Surgery
Minor Depression as a Cardiac Risk Factor After Coronary Artery Bypass Surgery CHIARA RAFANELLI, M.D., PH.D. RENZO RONCUZZI, M.D. YURI MILANESCHI, PSY.D.
A few studies have investigated the role of psychosocial variables on clinical outcomes in coronary artery bypass grafting patients. The aims of this prospective study were 1) to assess clinical and subclinical distress in a consecutive sample of patients who underwent coronary artery bypass grafting surgery at both a 1-month assessment and a 6- to 8-year follow-up visit; and 2) to investigate the relationship between psychological variables and coronary events. A consecutive series of 47 patients with recent coronary artery bypass grafting surgery was evaluated by means of observer-rated categories (both the Diagnostic and Statistical Manual [DSM] and the new Diagnostic Criteria for Psychosomatic Research [DCPR]), and self-rated scales such as the Psychosocial Index. Survival analysis was used to characterize the clinical course of patients at the 6- to 8-year follow-up. One month after surgery, at the first psychological assessment, 36% of patients received a psychiatric diagnosis, and almost half of the sample met the criteria for a DCPR cluster. At follow-up, only abnormal illness behavior scores varied significantly from those at the first evaluation. Among the variables examined as potential risk factors for coronary events, only minor depression attained statistical significance. Psychological evaluation of patients who underwent coronary artery bypass grafting surgery needs to incorporate both clinical (DSM) and subclinical (DCPR) methods of classification. Furthermore, the data suggest minor depression as a potential cardiac risk factor in coronary artery bypass grafting patients. The clinical approach to coronary artery bypass grafting patients should thus include not only major depressive symptoms but also minor depression. (Psychosomatics 2006; 47:289–295)
I
n the past decade, there has been an increasing awareness of the presence of psychosocial distress, such as anxiety and depression, after coronary artery bypass grafting.1–11 Although there is vast literature regarding the effect of depression on the outcome of acute myocardial infarction,12–15 only a few studies have investigated the role of this psychological variable on clinical outcome of coronary artery bypass grafting.5,8–10,16–21 Most of these studies assessed depression only by self-rated instruments, with different cutoff points, to discriminate between levels of symptomatology; this was likely because of the large number of patients and the consequent lack of time. Only Con-
Psychosomatics 47:4, July-August 2006
nerney et al.,10 who monitored, over 1-year period, 366 patients who had undergone coronary artery bypass grafting, measured major depressive disorder before discharge with a structured psychiatric interview based on DSM– IV.22 None of these studies assessed either psychiatric dis-
Received February 13, 2005; revised July 26, 2005; accepted August 24, 2005. From the Dept. of Psychology, Univ. of Bologna, Bologna, Italy; and the Div. of Cardiology, Bellaria Hospital, Bologna, Italy. Address correspondence and reprint requests to Dr. Rafanelli, Dept. of Psychology, Univ. of Bologna, Viale Berti Pichat 5, 40127 Bologna, Italy. e-mail: [email protected] Copyright 䉷 2006 The Academy of Psychosomatic Medicine
http://psy.psychiatryonline.org
289
Depression as a Cardiac Risk Factor eases or subsyndromal symptomatology as potential risk factors for new cardiac events or cardiac mortality. The aims of this study were 1) to assess, by reliable methods, clinical and subclinical distress in a consecutive sample of patients who underwent coronary artery bypass grafting and to compare results after 1 month with findings after 6 to 8 years; and 2) to investigate the relationship between psychological variables and the clinical outcome on the basis of coronary events (angina pectoris, reinfarction, cardiac death) found at the 6- to 8-year follow-up visit. The assessment included semistructured clinical interviews for evaluating both psychiatric disorders (DSM– IV)22 and psychosomatic syndromes (Diagnostic Criteria for Psychosomatic Research [DCPR]),23 and self-rated instruments (the Psychosocial Index).24 METHOD Subjects The study was approved by the Ethics Committee of Bellaria Hospital. Written informed consent was obtained from all the patients. A consecutive series of 47 patients who underwent recent (1 month earlier) coronary artery bypass grafting surgery, referred by the department of cardio-surgery, S. Orsola Hospital Bologna, to the Cardiac Rehabilitation Program of Bellaria Hospital in Bologna, between the months of January 1996 and November 1997 were included in the study. All the patients agreed to participate. There were 36 men and 11 women. The mean age was 66 years (standard deviation [SD]: 8.5; range: 46–81 years). The patients underwent grafts using veins from the leg or arteries, usually the left or right internal mammary artery. Fourteen patients (29.8%) reported complications during the bypass surgery: four (8.51%) had an acute myocardial infarction; one (2.13%) had atrial fibrillation with arterial embolism; seven patients (14.9%) reported paroxysmal atrial fibrillation, one (2.13%) had paroxysmal atrial fibrillation and hepatic failure; and, in one patient (2.13%), a pacemaker was fitted; 20 patients had three bypasses; 13 patients had two bypasses; 9 had four bypasses; 4 had one bypass; and only 1 patient had five bypasses. Three of these patients had undergone previous coronary artery bypass grafting (two patients in 1993 and one patient in 1996). Seven patients had undergone further valve replacement, five of these during the coronary artery bypass grafting surgery itself. Before the coronary artery bypass grafting, 12 patients (25.5%) had suffered an acute myocardial infarction, 11 patients 290
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(23.4%) by angina postacute myocardial infarction, and 24 (51.1%) by angina pectoris. Assessment Patients were interviewed by the same clinical psychologist who evaluated them both at the initial assessment after coronary artery bypass grafting surgery and at the 6to 8-year follow-up visit. Patients were also asked to complete a self-rating questionnaire both times. Assessment included the following measures: 1)
a modified version of the Structured Clinical Interview for DSM–IV (SCID).25 The diagnosis of minor depression was also included. 2) the Italian version26 of the semistructured interview for the DCPR,23 to detect subclinical psychological syndromes, which allows for identification of 12 psychosomatic clusters, such as: alexithymia, type A behavior, irritable mood, demoralization, disease phobia, thanatophobia, health anxiety, illness denial, functional somatic symptoms secondary to a psychiatric disorder, persistent somatization, conversion symptoms, and anniversary reaction. Data from different studies have shown that the system has good levels of reliability and validity and that the joint application of the DCPR and DSM–IV (Diagnostic and Statistical Manual of Mental Disorders, 4th Edition) improved the identification of psychological problems in patients with a variety of medical disorders;26–32 DCPR syndromes were formulated independently of DSM–IV findings. 3) The Psychosocial Index,24 a short test tailored to a busy clinical setting, which would be easy to use while providing adequate individual information. This index was largely derived from well-established methods, such as Kellner’s Screening List for Psychosocial Problems. It is a simple, self-rated test including 55 items for assessing four dimensions: acute and chronic stress, psychological distress, abnormal illness behavior, and psychological well-being. It enables evaluation of the psychosocial dimensions on the basis of both patients’ answers and interviewers’ comments. In our study, we used only the self-report data. Patients were seen by the cardiologists involved in the program once a year during the follow-up visits. Data about coronary events were also collected from medical records. For the diagnosis of instable angina, the patients met the following criteria: recent onset of chest pain with evidence Psychosomatics 47:4, July-August 2006
Rafanelli et al. of reversible ischemic ST–T modifications. For the diagnosis of reinfarction, the patients met at least two criteria of the following three: 1) typical ischemic symptoms (chest pain or shortness of breath) lasting for more than 10 minutes; 2) creatin kinase isoenzyme MB (CK-MB) levels more than twice the upper limit of normal; 3) electrocardiographic (ECG) evidence of ischemic ST-segment depression, ST-segment elevation, or new pathological Qwaves. The event listed as cardiovascular death involved death in the hospital due to acute myocardial infarction or heart failure. Statistical Analysis We used t-tests for paired samples to compare Psychosocial Index scoring 1 month and 6 to 8 years after coronary artery bypass grafting. Survival analysis was used for coronary events (angina pectoris, reinfarction, cardiac death). The following risk factors were considered as potential predictors of outcome: age, sex, number of cardiovascular risk factors (smoking habits, diabetes mellitus, arterial hypertension, blood total and LDL cholesterol, vascular diseases), number of bypasses, low left-ventricular ejection fraction (ⱕ40%), previous myocardial infarction, valve replacement concomitant to coronary artery bypass grafting, presence of a DSM diagnosis, presence of a DCPR cluster, self-rated stress, psychological distress, abnormal illness behavior, and psychological well-being. Each factor considered was dichotomized for measurement-type factors with a selected cutoff point around the median. Subsequently, for each factor, we performed the following procedure: the new dichotomous variable was applied to the sample, dividing it into two groups; the Kaplan-Meier method for estimating survival curves for the two groups was also used; by the end-point, the logrank test to compare the two survival curves was utilized. For all tests performed, the significance level was set at 0.05, two-tailed. RESULTS One month after coronary artery bypass grafting, at the first psychological assessment, 17 of 47 patients (36.1%) received a psychiatric diagnosis according to DSM–IV criteria. The 19 diagnoses (two patients had a double diagnosis) are listed in Table 1. The diagnoses of “adjustment disorders” were excluded from the assessment interview. The prevalence of mood disorders was 23.4%. There were six patients (12.8%) with minor depression, five (10.6%) with major depression, three (6.4%) with agoraPsychosomatics 47:4, July-August 2006
phobia, two (4.3%) with social phobia, two (4.3%) with undifferentiated somatoform disorder, and one (2.1%) with obsessive-compulsive disorder. Only two patients were taking lorazepam (one patient both at the time of entering the study and at the follow-up visit, the other only at the follow-up visit), and one patient was taking bromazepam as prescribed at the follow-up visit. None of the patients had ever taken any psychotropic drugs or had ever undergone psychological treatment for mood disorders. Twenty-three of the 47 patients (48.9%) had a DCPR cluster, with a total of 28 DCPR diagnoses (Table 2). There were eight patients (17%) with type A behavior, seven (14.9%) with irritable mood, four (8.5%) with health anxiety, three (6.4%) with demoralization, two (4.3%) with illness denial, two (4.3%) with persistent somatization, one (2.1%) with alexithymia, and one (2.1%) with nosophobia. There was an overlap between the two classification systems. Nine (52.9%) of the 17 patients with DSM–IV diagnoses had an associated DCPR cluster. In 14 of 23 cases (60.9%), therefore, there was a DCPR cluster without any associated psychiatric diagnosis. The mean scores of the Psychosocial Index were: 7.0 (SD: 5) for psychological distress, 1.6 (SD: 2.2) for abnormal illness behavior, 1.7 (SD: 1.8) for stress, and 5 (SD: 1.4) for psychological well-being (Table 3). After the 6- to 8-year period, 13 patients could not be reassessed: 6 patients had died, 6 had severe illnesses, and 1 patient refused the follow-up visit. During the first evaluation, these 13 patients had reported the following diagnoses: minor depression (N⳱3), major depressive disorder associated with type A behavior (N⳱1), and nosophobia (N⳱1). Among the remaining 34 patients, 7 of 13 (53.8%) with a DSM diagnosis at first evaluation maintained at least one of the first assessment DSM diagnoses (Table 1). There was one patient (2.9%) with minor depression; there were two (5.9%) with major depression, two (5.9%) with agoraphobia, two (5.9%) with social phobia, two (5.9%) with undifferentiated somatoform disorder, one (2.9%) with obsessive-compulsive disorder, one (2.9%) with panic disorder with agoraphobia, and one (2.9%) with bipolar disorder. At the time of the follow-up evaluation, there were two new DSM diagnoses: panic disorder with agoraphobia and bipolar disorder type II. Nineteen of the 21 patients (90.5%) with a DCPR diagnosis at first evaluation maintained at least one of the first assessment diagnoses (Table 2). There were five patients (14.7%) with type A behavior, five (14.7%) with irritable mood, four (11.8%) with health anxiety, three http://psy.psychiatryonline.org
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Depression as a Cardiac Risk Factor (8.8%) with demoralization, three (8.8%) with illness denial, two (5.9%) with persistent somatization, and one (2.9%) with alexithymia. Regarding the Psychosocial Index scores at the followup assessment, patients obtained the following mean scores: 7.4 (SD: 4.7) for psychological distress, 0.6 (SD: 0.9) for abnormal illness behavior, 1.5 (SD: 1.4) for stress, 5.1 (SD: 1.2) for psychological well-being (Table 3). Only abnormal illness behavior scores were significantly different (p⬍0.01) from those at the first evaluation. Follow-up ranged from 6 to 8 years (median: 6 years). Of the total sample, 10 patients (21.3%) reported 13 cardiovascular events: 6 patients (12.8%) reported 7 episodes of angina pectoris (1 patient had 2 episodes); 2 patients (4.3%) reported acute myocardial infarction with angina pectoris; and 2 (4.3%) suffered cardiovascular death. Among the coronary-event variables examined (angina pectoris, myocardial infarction, cardiac death), only minor depression attained statistical significance (v2[1]⳱9.92; p⬍0.01). Kaplan-Meier survival curves are shown in Figure 1. Sociodemographic, psychological, and cardiovascular characteristics of patients with minor depression did not differ significantly from those without. DISCUSSION In our study, mood disorders were diagnosed in more than 20% of patients. These findings, although limited by the fact that the sample was taken only from the rehabilitation program, are in accordance with those in the literature1–10 referring to coronary artery bypass graft patients. Unlike those studies, ours included the diagnosis of minor depression such as was detected in a previous study on acute myocardial infarction patients.26 Furthermore, in almost half of our sample, we found at least one DCPR diagnosis with prevalence of type A behavior and irritable mood, in accordance with our previous study.26 Even though there TABLE 1.
are a large number of potentially overlapping DCPR categories, these data lend support to the integration of both clinical (DSM) and subclinical (DCPR) criteria for assessing psychological distress in medically ill persons.26–32 Moreover, the results of this study outlined, with respect to current knowledge and literature, the need for an integration of methodological tools, both observer and selfrated. The comparison between psychological assessment at 1 month and at 6–8 years after coronary artery bypass grafting revealed that most of the DCPR clusters were still present over this period of time in the same patients. DCPR clusters could thus represent subsyndromal traits; even though the sample was small, the evaluations were carried out over a lengthy period of time, establishing that the DCPR categories remain stable in individuals over time. Our results on Psychosocial Index scores show higher abnormal illness behavior scores at the first assessment than those at the follow-up visits. Given that the construct of abnormal illness behavior has been defined by Pilowsky33 as the persistence of a maladaptive mode of perceiving, experiencing, evaluating, and responding to one’s health status, despite the fact that a physician has provided a lucid and accurate appraisal of the situation and its management, we could suppose a synergic effect of anxiety, because of the recent invasive surgery, on abnormal illness behavior scores. Results from survival analysis show that observerrated minor depression is a potential risk factor for cardiac events 6–8 years after coronary artery bypass grafting surgery. The available data suggest that depression, in general, assessed by self-rated methods, could be a risk factor for cardiac events in this population. In the study by Connerney and colleagues,10 only major depression was evaluated, by clinical interview, in coronary artery bypass graft patients, and was found to be related to cardiac events at the 1-year follow-up. Despite the limits of our study, based on
Psychiatric Diagnoses According to DSM–IV at First Evaluation and at Follow-Up Intake (Nⴔ47)
Psychiatric Diagnosis
N
Minor depression Major depression Agoraphobia Social phobia Undifferentiated somatoform disorder Obsessive-compulsive disorder Panic disorder with agoraphobia Bipolar disorder type II
6 5 3 2 2 1 0 0
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Follow-Up (Nⴔ34)
% Patients (Nⴔ47)
% Diagnoses (Nⴔ19)
12.8 10.6 6.4 4.3 4.3 2.1
31.6 26.3 15.8 10.5 10.5 5.3
N
% Patients (Nⴔ34)
% Diagnoses (Nⴔ12)
1 2 2 2 2 1 1 1
2.9 5.9 5.9 5.9 5.9 2.9 2.9 2.9
8.3 16.7 16.7 16.7 16.7 8.3 8.3 8.3
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Rafanelli et al.
TABLE 2.
Psychosomatic Diagnoses According to Diagnostic Criteria for Psychosomatic Research (DCPR) Cluster at First Evaluation and at Follow-Up Intake (Nⴔ47)
Psychosomatic Diagnosis
N
% Patients (Nⴔ47)
Type A behavior Irritable mood Health anxiety Demoralization Illness denial Persistent somatization Alexithymia Nosophobia
8 7 4 3 2 2 1 1
17.0 14.9 8.5 6.4 4.3 4.3 2.1 2.1
TABLE 3.
Comparison Between Mean Scores of Psychosocial Index at Intake With Those at Follow-Up Intake (Nⴔ47)
Psychosocial Index Psychological distress Abnormal illness behavior Stress Psychological well-being
Follow-Up (Nⴔ34)
Mean
SD
Mean
SD
7.0 1.6 1.7 5.0
5.0 2.2 1.8 1.4
7.4 0.6 1.5 5.1
4.7 0.9 1.4 1.2
p ⬍0.01
SD: standard deviation.
FIGURE 1.
Kaplan-Meier Survival Curves in Patients With and Without Minor Depression
N=
At risk, without minor depression 40 39 38
At risk, with minor depression N= 5 4 3
28
7
3
1
Cumulative Survival
1.0
0.8
0.6
0.4
0.2 0
20
40
60 Months
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80
100
Follow-Up (Nⴔ34) % Diagnoses (Nⴔ28) 27.6 24.1 13.8 10.3 6.9 6.9 3.4 3.4
N
% Patients (Nⴔ34)
% Diagnoses (Nⴔ23)
5 5 4 3 3 2 1 0
14.7 14.7 11.8 8.8 8.8 5.9 2.9 0.0
20.8 20.8 16.7 12.5 12.5 8.3 4.2 0.0
a small sample size, our data suggest the relevance of minor depression as potential cardiac risk factor in coronary artery bypass graft patients at the 6- to 8-year follow-up. However, there were only six subjects in the original sample who had minor depression. This poses limitations on interpretation of the data. Despite this, if these results were confirmed by future research with larger samples, the clinical approach to these patients should include not only an accurate investigation of severe depression, as outlined in the literature on cardiovascular patients, but also an assessment of minor depression. Blumenthal and colleagues9 showed that not only patients with moderate-to-severe depression before coronary artery bypass grafting but also patients with mild or moderate-to-severe depression that persisted for 6 months after coronary artery bypass grafting had higher death rates than did those without depression. It is likely that depression is thought of as an understandable and inevitable reaction to the severe circumstances accompanying coronary artery bypass surgery, and, as a result, it is not always treated.10 It is conceivable that minor depression could be underestimated and undertreated even more frequently than major depression and could thus represent a persistent factor increasing psychological and physical vulnerability. Although the basis of the relationship between depression and cardiac morbidity and mortality remains speculative, there are various potential social, behavioral, and biological mechanisms by which depression may confer this increased risk.9 It is not surprising that there is a temporary increase in the incidence of depression immediately after surgery34 and that it causes difficulty in assessing depression because of the overlap between symptoms of depression and those of cardiac disease. Our study, conducting the psychological http://psy.psychiatryonline.org
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Depression as a Cardiac Risk Factor evaluation 1 month after coronary artery bypass, nonetheless shows the presence or persistence of mood diseases and outlines the importance of detecting mood symptomatology in coronary artery bypass patients. Future studies should investigate the association of certain symptoms with other psychological or physical factors that may be responsible for clinical outcomes. Even though the only ran-
domized behavioral intervention trial attempting to reduce morbidity and mortality in depressed patients with existing coronary disease35 showed that changes in depression level did not translate into improved survival, there remains the need to further investigate whether treating depression can reduce the risk of morbidity and mortality in patients who have undergone coronary artery bypass grafting.
References
1. Burker EJ, Blumenthal JA, Feldman M, et al: Depression in male and female patients undergoing cardiac surgery. Br J Clin Psychol 1995; 34:119–128 2. Pirraglia PA, Peterson JC, Williams-Russo P, et al: Depressive symptomatology in coronary artery bypass graft surgery patients. Int J Geriatr Psychiatry 1999; 14:668–680 3. Underwood MJ, Firmin RK, Jehu D: Aspects of psychological and social morbidity in patients awaiting coronary artery bypass grafting. Br Heart J 1993; 69:382–384 4. McKhann GM, Borowicz LM, Goldsborough MA, et al: Depression and cognitive decline after coronary artery bypass grafting: Lancet 1997; 349:1282–1284 5. Burg MM, Benedetto MC, Rosenberg R, et al: Presurgical depression predicts medical morbidity 6 months after coronary artery bypass graft surgery. Psychosom Med 2003; 65:111–118 6. Timberlake N, Klinger L, Smith P, et al: Incidence and patterns of depression following coronary artery bypass graft surgery. J Psychosom Res 1997; 43:197–207 7. Saur CD, Granger BB, Muhlbaier LH, et al: Depressive symptoms and outcome of coronary artery bypass grafting. Am J Crit Care 2001; 10:4–10 8. Baker RA, Andrew MJ, Schrader G, et al: Preoperative depression and mortality in coronary artery bypass surgery: preliminary findings. Aust N Z J Surg 2001; 7:139–142 9. Blumenthal JA, Lett HS, Babyak MA, et al. and NORG Investigators: Depression as a risk factor for mortality after coronary artery bypass surgery. Lancet 2003; 362:604–609 10. Connerney I, Shapiro PA, McLaughlin JS, et al: Relation between depression after coronary artery bypass surgery and 12-month outcome: a prospective study. Lancet 2001; 358:1766–1771 11. Rymaszewska J, Kiejna A, Hadrys T: Depression and anxiety in coronary artery bypass grafting patients. Eur Psychiatry 2003; 18:155–160 12. Carney RM, Rich MW, Freedland KE: Major depressive disorder predicts cardiac events in patients with coronary artery disease. Psychosom Med 1988; 50:627–633 13. Ladwig KH, Kieser M, Konig J, et al: Affective disorders and survival after acute myocardial infarction: results from the postinfarction late potential study. Eur Heart J 1991; 12:959–964 14. Frasure-Smith N, Lesperance F, Talajic M: Depression following myocardial infarction: impact on 6-month survival. JAMA 1993; 270:1819–1825 15. Frasure-Smith N, Lesperance F, Talajic M: Depression and 18month prognosis after myocardial infarction. Circulation 1995; 91:999–1005 16. Rogers WJ, Coggin CJ, Gersh BJ, et al: Ten-year follow-up of quality of life in patients randomized to receive medical therapy or coronary artery bypass graft surgery: The Coronary Artery Surgery Study (CASS). Circulation 1990; 82:1647–1658
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17. Blumenthal JA, Madden DJ, Burker EJ, et al: A preliminary study of the effects of cardiac procedures on cognitive performance. Int J Psychosom 1991; 38:13–16 18. Ebert AD, Walzer TA, Huth C, et al: Early neurobehavioral disorders after cardiac surgery: a comparative analysis of coronary artery bypass graft surgery and valve replacement. J Cardiothorac Vasc Anesth 2001; 15:15–19 19. Bucerius J, Jan F, Gummert JF, et al: Predictors of delirium after cardiac surgery delirium: effect of beating-heart (off-pump) surgery. J Thorac Cardiovasc Surg 2004; 27:57–64 20. Borowicz LM, Goldsborough MA, Selnes OA, et al: Neuropsychologic change after cardiac surgery: a critical review. J Cardiothorac Vasc Anesth 1996; 10:105–112 21. Shaw PJ, Bates D, Cartlidge NE, et al: Neurologic and neuropsychological morbidity following major surgery: comparison of coronary artery bypass and peripheral vascular surgery. Stroke 1987; 18:700–707 22. American Psychiatric Association: Diagnostic and Statistical Manual of Mental Disorders, 4th Edition (DSM-IV). Washington, DC, American Psychiatric Association, 1994 23. Fava GA, Freyberger HJ, Bech P, et al: Diagnostic criteria for use in psychosomatic research. Psychother Psychosom 1995; 63:1–8 24. Sonino N, Fava GA: A simple instrument for assessing stress in clinical practice. Postgrad Med J 1998; 74:408–410 25. First MB, Spitzer RL, Gibbon M, et al: Structured Clinical Interview for DSM–IV. New York, Biometrics Research Department, 1994 26. Rafanelli C, Roncuzzi R, Finos L, et al: Psychological assessment in cardiac rehabilitation. Psychother Psychosom 2003; 72:343– 349 27. Galeazzi GM, Ferrari S, Mackinnon A, et al: Interrater reliability, prevalence, and relation to ICD–10 diagnoses of the Diagnostic Criteria for Psychosomatic Research in consultation–liaison psychiatry patients. Psychosomatics 2004; 45:386–393 28. Porcelli P, De Carne M, Fava GA: Assessing somatization in functional gastrointestinal disorders: integration of different criteria. Psychother Psychosom 2000; 69:198–204 29. Fava GA, Mangelli L, Ruini C: Assessment of psychological distress in the setting of medical disease. Psychother Psychosom 2001; 70:171–175 30. Grandi S, Fabbri S, Tossani E, et al: Psychological evaluation after cardiac transplantation: the integration of different criteria. Psychother Psychosom 2001; 70:176–183 31. Sonino N, Navarrini C, Ruini C, et al: Persistent psychological distress in patients treated for endocrine disease. Psychother Psychosom 2004; 72:343–349 32. Mangelli L, Fava GA, Grandi S, et al: Assessing demoralization and depression in the setting of medical disease. J Clin Psychiatry 2005; 66:391–394
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Rafanelli et al. 33. Pilowsky I: Abnormal illness behavior. Psychother Psychosom 1986; 46:76–84 34. McCrone S, Lenz E, Tarzian A, et al: Anxiety and depression: incidence and patterns in patients after coronary artery bypass graft surgery. Appl Nurs Res 2001; 14:155–164
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35. Writing Committee for the ENRICHD Investigators: Effects of treating depression and low perceived social support on clinical events after myocardial infarction: the Enhancing Recovery in Coronary Heart Disease Patients (ENRICHD) randomized trial. JAMA 2003; 289:3106–3116
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A few studies have investigated the role of psychosocial variables on clinical outcomes in coronary artery bypass grafting patients. The aims of this prospective study were 1) to assess clinical and subclinical distress in a consecutive sample of patients who underwent coronary artery bypass grafting surgery at both a 1-month assessment and a 6- to 8-year follow-up visit; and 2) to investigate the relationship between psychological variables and coronary events. A consecutive series of 47 patients with recent coronary artery bypass grafting surgery was evaluated by means of observer-rated categories (both the Diagnostic and Statistical Manual [DSM] and the new Diagnostic Criteria for Psychosomatic Research [DCPR]), and self-rated scales such as the Psychosocial Index. Survival analysis was used to characterize the clinical course of patients at the 6- to 8-year follow-up. One month after surgery, at the first psychological assessment, 36% of patients received a psychiatric diagnosis, and almost half of the sample met the criteria for a DCPR cluster. At follow-up, only abnormal illness behavior scores varied significantly from those at the first evaluation. Among the variables examined as potential risk factors for coronary events, only minor depression attained statistical significance. Psychological evaluation of patients who underwent coronary artery bypass grafting surgery needs to incorporate both clinical (DSM) and subclinical (DCPR) methods of classification. Furthermore, the data suggest minor depression as a potential cardiac risk factor in coronary artery bypass grafting patients. The clinical approach to coronary artery bypass grafting patients should thus include not only major depressive symptoms but also minor depression. (Psychosomatics 2006; 47:289–295)
I
n the past decade, there has been an increasing awareness of the presence of psychosocial distress, such as anxiety and depression, after coronary artery bypass grafting.1–11 Although there is vast literature regarding the effect of depression on the outcome of acute myocardial infarction,12–15 only a few studies have investigated the role of this psychological variable on clinical outcome of coronary artery bypass grafting.5,8–10,16–21 Most of these studies assessed depression only by self-rated instruments, with different cutoff points, to discriminate between levels of symptomatology; this was likely because of the large number of patients and the consequent lack of time. Only Con-
Psychosomatics 47:4, July-August 2006
nerney et al.,10 who monitored, over 1-year period, 366 patients who had undergone coronary artery bypass grafting, measured major depressive disorder before discharge with a structured psychiatric interview based on DSM– IV.22 None of these studies assessed either psychiatric dis-
Received February 13, 2005; revised July 26, 2005; accepted August 24, 2005. From the Dept. of Psychology, Univ. of Bologna, Bologna, Italy; and the Div. of Cardiology, Bellaria Hospital, Bologna, Italy. Address correspondence and reprint requests to Dr. Rafanelli, Dept. of Psychology, Univ. of Bologna, Viale Berti Pichat 5, 40127 Bologna, Italy. e-mail: [email protected] Copyright 䉷 2006 The Academy of Psychosomatic Medicine
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289
Depression as a Cardiac Risk Factor eases or subsyndromal symptomatology as potential risk factors for new cardiac events or cardiac mortality. The aims of this study were 1) to assess, by reliable methods, clinical and subclinical distress in a consecutive sample of patients who underwent coronary artery bypass grafting and to compare results after 1 month with findings after 6 to 8 years; and 2) to investigate the relationship between psychological variables and the clinical outcome on the basis of coronary events (angina pectoris, reinfarction, cardiac death) found at the 6- to 8-year follow-up visit. The assessment included semistructured clinical interviews for evaluating both psychiatric disorders (DSM– IV)22 and psychosomatic syndromes (Diagnostic Criteria for Psychosomatic Research [DCPR]),23 and self-rated instruments (the Psychosocial Index).24 METHOD Subjects The study was approved by the Ethics Committee of Bellaria Hospital. Written informed consent was obtained from all the patients. A consecutive series of 47 patients who underwent recent (1 month earlier) coronary artery bypass grafting surgery, referred by the department of cardio-surgery, S. Orsola Hospital Bologna, to the Cardiac Rehabilitation Program of Bellaria Hospital in Bologna, between the months of January 1996 and November 1997 were included in the study. All the patients agreed to participate. There were 36 men and 11 women. The mean age was 66 years (standard deviation [SD]: 8.5; range: 46–81 years). The patients underwent grafts using veins from the leg or arteries, usually the left or right internal mammary artery. Fourteen patients (29.8%) reported complications during the bypass surgery: four (8.51%) had an acute myocardial infarction; one (2.13%) had atrial fibrillation with arterial embolism; seven patients (14.9%) reported paroxysmal atrial fibrillation, one (2.13%) had paroxysmal atrial fibrillation and hepatic failure; and, in one patient (2.13%), a pacemaker was fitted; 20 patients had three bypasses; 13 patients had two bypasses; 9 had four bypasses; 4 had one bypass; and only 1 patient had five bypasses. Three of these patients had undergone previous coronary artery bypass grafting (two patients in 1993 and one patient in 1996). Seven patients had undergone further valve replacement, five of these during the coronary artery bypass grafting surgery itself. Before the coronary artery bypass grafting, 12 patients (25.5%) had suffered an acute myocardial infarction, 11 patients 290
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(23.4%) by angina postacute myocardial infarction, and 24 (51.1%) by angina pectoris. Assessment Patients were interviewed by the same clinical psychologist who evaluated them both at the initial assessment after coronary artery bypass grafting surgery and at the 6to 8-year follow-up visit. Patients were also asked to complete a self-rating questionnaire both times. Assessment included the following measures: 1)
a modified version of the Structured Clinical Interview for DSM–IV (SCID).25 The diagnosis of minor depression was also included. 2) the Italian version26 of the semistructured interview for the DCPR,23 to detect subclinical psychological syndromes, which allows for identification of 12 psychosomatic clusters, such as: alexithymia, type A behavior, irritable mood, demoralization, disease phobia, thanatophobia, health anxiety, illness denial, functional somatic symptoms secondary to a psychiatric disorder, persistent somatization, conversion symptoms, and anniversary reaction. Data from different studies have shown that the system has good levels of reliability and validity and that the joint application of the DCPR and DSM–IV (Diagnostic and Statistical Manual of Mental Disorders, 4th Edition) improved the identification of psychological problems in patients with a variety of medical disorders;26–32 DCPR syndromes were formulated independently of DSM–IV findings. 3) The Psychosocial Index,24 a short test tailored to a busy clinical setting, which would be easy to use while providing adequate individual information. This index was largely derived from well-established methods, such as Kellner’s Screening List for Psychosocial Problems. It is a simple, self-rated test including 55 items for assessing four dimensions: acute and chronic stress, psychological distress, abnormal illness behavior, and psychological well-being. It enables evaluation of the psychosocial dimensions on the basis of both patients’ answers and interviewers’ comments. In our study, we used only the self-report data. Patients were seen by the cardiologists involved in the program once a year during the follow-up visits. Data about coronary events were also collected from medical records. For the diagnosis of instable angina, the patients met the following criteria: recent onset of chest pain with evidence Psychosomatics 47:4, July-August 2006
Rafanelli et al. of reversible ischemic ST–T modifications. For the diagnosis of reinfarction, the patients met at least two criteria of the following three: 1) typical ischemic symptoms (chest pain or shortness of breath) lasting for more than 10 minutes; 2) creatin kinase isoenzyme MB (CK-MB) levels more than twice the upper limit of normal; 3) electrocardiographic (ECG) evidence of ischemic ST-segment depression, ST-segment elevation, or new pathological Qwaves. The event listed as cardiovascular death involved death in the hospital due to acute myocardial infarction or heart failure. Statistical Analysis We used t-tests for paired samples to compare Psychosocial Index scoring 1 month and 6 to 8 years after coronary artery bypass grafting. Survival analysis was used for coronary events (angina pectoris, reinfarction, cardiac death). The following risk factors were considered as potential predictors of outcome: age, sex, number of cardiovascular risk factors (smoking habits, diabetes mellitus, arterial hypertension, blood total and LDL cholesterol, vascular diseases), number of bypasses, low left-ventricular ejection fraction (ⱕ40%), previous myocardial infarction, valve replacement concomitant to coronary artery bypass grafting, presence of a DSM diagnosis, presence of a DCPR cluster, self-rated stress, psychological distress, abnormal illness behavior, and psychological well-being. Each factor considered was dichotomized for measurement-type factors with a selected cutoff point around the median. Subsequently, for each factor, we performed the following procedure: the new dichotomous variable was applied to the sample, dividing it into two groups; the Kaplan-Meier method for estimating survival curves for the two groups was also used; by the end-point, the logrank test to compare the two survival curves was utilized. For all tests performed, the significance level was set at 0.05, two-tailed. RESULTS One month after coronary artery bypass grafting, at the first psychological assessment, 17 of 47 patients (36.1%) received a psychiatric diagnosis according to DSM–IV criteria. The 19 diagnoses (two patients had a double diagnosis) are listed in Table 1. The diagnoses of “adjustment disorders” were excluded from the assessment interview. The prevalence of mood disorders was 23.4%. There were six patients (12.8%) with minor depression, five (10.6%) with major depression, three (6.4%) with agoraPsychosomatics 47:4, July-August 2006
phobia, two (4.3%) with social phobia, two (4.3%) with undifferentiated somatoform disorder, and one (2.1%) with obsessive-compulsive disorder. Only two patients were taking lorazepam (one patient both at the time of entering the study and at the follow-up visit, the other only at the follow-up visit), and one patient was taking bromazepam as prescribed at the follow-up visit. None of the patients had ever taken any psychotropic drugs or had ever undergone psychological treatment for mood disorders. Twenty-three of the 47 patients (48.9%) had a DCPR cluster, with a total of 28 DCPR diagnoses (Table 2). There were eight patients (17%) with type A behavior, seven (14.9%) with irritable mood, four (8.5%) with health anxiety, three (6.4%) with demoralization, two (4.3%) with illness denial, two (4.3%) with persistent somatization, one (2.1%) with alexithymia, and one (2.1%) with nosophobia. There was an overlap between the two classification systems. Nine (52.9%) of the 17 patients with DSM–IV diagnoses had an associated DCPR cluster. In 14 of 23 cases (60.9%), therefore, there was a DCPR cluster without any associated psychiatric diagnosis. The mean scores of the Psychosocial Index were: 7.0 (SD: 5) for psychological distress, 1.6 (SD: 2.2) for abnormal illness behavior, 1.7 (SD: 1.8) for stress, and 5 (SD: 1.4) for psychological well-being (Table 3). After the 6- to 8-year period, 13 patients could not be reassessed: 6 patients had died, 6 had severe illnesses, and 1 patient refused the follow-up visit. During the first evaluation, these 13 patients had reported the following diagnoses: minor depression (N⳱3), major depressive disorder associated with type A behavior (N⳱1), and nosophobia (N⳱1). Among the remaining 34 patients, 7 of 13 (53.8%) with a DSM diagnosis at first evaluation maintained at least one of the first assessment DSM diagnoses (Table 1). There was one patient (2.9%) with minor depression; there were two (5.9%) with major depression, two (5.9%) with agoraphobia, two (5.9%) with social phobia, two (5.9%) with undifferentiated somatoform disorder, one (2.9%) with obsessive-compulsive disorder, one (2.9%) with panic disorder with agoraphobia, and one (2.9%) with bipolar disorder. At the time of the follow-up evaluation, there were two new DSM diagnoses: panic disorder with agoraphobia and bipolar disorder type II. Nineteen of the 21 patients (90.5%) with a DCPR diagnosis at first evaluation maintained at least one of the first assessment diagnoses (Table 2). There were five patients (14.7%) with type A behavior, five (14.7%) with irritable mood, four (11.8%) with health anxiety, three http://psy.psychiatryonline.org
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Depression as a Cardiac Risk Factor (8.8%) with demoralization, three (8.8%) with illness denial, two (5.9%) with persistent somatization, and one (2.9%) with alexithymia. Regarding the Psychosocial Index scores at the followup assessment, patients obtained the following mean scores: 7.4 (SD: 4.7) for psychological distress, 0.6 (SD: 0.9) for abnormal illness behavior, 1.5 (SD: 1.4) for stress, 5.1 (SD: 1.2) for psychological well-being (Table 3). Only abnormal illness behavior scores were significantly different (p⬍0.01) from those at the first evaluation. Follow-up ranged from 6 to 8 years (median: 6 years). Of the total sample, 10 patients (21.3%) reported 13 cardiovascular events: 6 patients (12.8%) reported 7 episodes of angina pectoris (1 patient had 2 episodes); 2 patients (4.3%) reported acute myocardial infarction with angina pectoris; and 2 (4.3%) suffered cardiovascular death. Among the coronary-event variables examined (angina pectoris, myocardial infarction, cardiac death), only minor depression attained statistical significance (v2[1]⳱9.92; p⬍0.01). Kaplan-Meier survival curves are shown in Figure 1. Sociodemographic, psychological, and cardiovascular characteristics of patients with minor depression did not differ significantly from those without. DISCUSSION In our study, mood disorders were diagnosed in more than 20% of patients. These findings, although limited by the fact that the sample was taken only from the rehabilitation program, are in accordance with those in the literature1–10 referring to coronary artery bypass graft patients. Unlike those studies, ours included the diagnosis of minor depression such as was detected in a previous study on acute myocardial infarction patients.26 Furthermore, in almost half of our sample, we found at least one DCPR diagnosis with prevalence of type A behavior and irritable mood, in accordance with our previous study.26 Even though there TABLE 1.
are a large number of potentially overlapping DCPR categories, these data lend support to the integration of both clinical (DSM) and subclinical (DCPR) criteria for assessing psychological distress in medically ill persons.26–32 Moreover, the results of this study outlined, with respect to current knowledge and literature, the need for an integration of methodological tools, both observer and selfrated. The comparison between psychological assessment at 1 month and at 6–8 years after coronary artery bypass grafting revealed that most of the DCPR clusters were still present over this period of time in the same patients. DCPR clusters could thus represent subsyndromal traits; even though the sample was small, the evaluations were carried out over a lengthy period of time, establishing that the DCPR categories remain stable in individuals over time. Our results on Psychosocial Index scores show higher abnormal illness behavior scores at the first assessment than those at the follow-up visits. Given that the construct of abnormal illness behavior has been defined by Pilowsky33 as the persistence of a maladaptive mode of perceiving, experiencing, evaluating, and responding to one’s health status, despite the fact that a physician has provided a lucid and accurate appraisal of the situation and its management, we could suppose a synergic effect of anxiety, because of the recent invasive surgery, on abnormal illness behavior scores. Results from survival analysis show that observerrated minor depression is a potential risk factor for cardiac events 6–8 years after coronary artery bypass grafting surgery. The available data suggest that depression, in general, assessed by self-rated methods, could be a risk factor for cardiac events in this population. In the study by Connerney and colleagues,10 only major depression was evaluated, by clinical interview, in coronary artery bypass graft patients, and was found to be related to cardiac events at the 1-year follow-up. Despite the limits of our study, based on
Psychiatric Diagnoses According to DSM–IV at First Evaluation and at Follow-Up Intake (Nⴔ47)
Psychiatric Diagnosis
N
Minor depression Major depression Agoraphobia Social phobia Undifferentiated somatoform disorder Obsessive-compulsive disorder Panic disorder with agoraphobia Bipolar disorder type II
6 5 3 2 2 1 0 0
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Follow-Up (Nⴔ34)
% Patients (Nⴔ47)
% Diagnoses (Nⴔ19)
12.8 10.6 6.4 4.3 4.3 2.1
31.6 26.3 15.8 10.5 10.5 5.3
N
% Patients (Nⴔ34)
% Diagnoses (Nⴔ12)
1 2 2 2 2 1 1 1
2.9 5.9 5.9 5.9 5.9 2.9 2.9 2.9
8.3 16.7 16.7 16.7 16.7 8.3 8.3 8.3
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TABLE 2.
Psychosomatic Diagnoses According to Diagnostic Criteria for Psychosomatic Research (DCPR) Cluster at First Evaluation and at Follow-Up Intake (Nⴔ47)
Psychosomatic Diagnosis
N
% Patients (Nⴔ47)
Type A behavior Irritable mood Health anxiety Demoralization Illness denial Persistent somatization Alexithymia Nosophobia
8 7 4 3 2 2 1 1
17.0 14.9 8.5 6.4 4.3 4.3 2.1 2.1
TABLE 3.
Comparison Between Mean Scores of Psychosocial Index at Intake With Those at Follow-Up Intake (Nⴔ47)
Psychosocial Index Psychological distress Abnormal illness behavior Stress Psychological well-being
Follow-Up (Nⴔ34)
Mean
SD
Mean
SD
7.0 1.6 1.7 5.0
5.0 2.2 1.8 1.4
7.4 0.6 1.5 5.1
4.7 0.9 1.4 1.2
p ⬍0.01
SD: standard deviation.
FIGURE 1.
Kaplan-Meier Survival Curves in Patients With and Without Minor Depression
N=
At risk, without minor depression 40 39 38
At risk, with minor depression N= 5 4 3
28
7
3
1
Cumulative Survival
1.0
0.8
0.6
0.4
0.2 0
20
40
60 Months
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80
100
Follow-Up (Nⴔ34) % Diagnoses (Nⴔ28) 27.6 24.1 13.8 10.3 6.9 6.9 3.4 3.4
N
% Patients (Nⴔ34)
% Diagnoses (Nⴔ23)
5 5 4 3 3 2 1 0
14.7 14.7 11.8 8.8 8.8 5.9 2.9 0.0
20.8 20.8 16.7 12.5 12.5 8.3 4.2 0.0
a small sample size, our data suggest the relevance of minor depression as potential cardiac risk factor in coronary artery bypass graft patients at the 6- to 8-year follow-up. However, there were only six subjects in the original sample who had minor depression. This poses limitations on interpretation of the data. Despite this, if these results were confirmed by future research with larger samples, the clinical approach to these patients should include not only an accurate investigation of severe depression, as outlined in the literature on cardiovascular patients, but also an assessment of minor depression. Blumenthal and colleagues9 showed that not only patients with moderate-to-severe depression before coronary artery bypass grafting but also patients with mild or moderate-to-severe depression that persisted for 6 months after coronary artery bypass grafting had higher death rates than did those without depression. It is likely that depression is thought of as an understandable and inevitable reaction to the severe circumstances accompanying coronary artery bypass surgery, and, as a result, it is not always treated.10 It is conceivable that minor depression could be underestimated and undertreated even more frequently than major depression and could thus represent a persistent factor increasing psychological and physical vulnerability. Although the basis of the relationship between depression and cardiac morbidity and mortality remains speculative, there are various potential social, behavioral, and biological mechanisms by which depression may confer this increased risk.9 It is not surprising that there is a temporary increase in the incidence of depression immediately after surgery34 and that it causes difficulty in assessing depression because of the overlap between symptoms of depression and those of cardiac disease. Our study, conducting the psychological http://psy.psychiatryonline.org
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Depression as a Cardiac Risk Factor evaluation 1 month after coronary artery bypass, nonetheless shows the presence or persistence of mood diseases and outlines the importance of detecting mood symptomatology in coronary artery bypass patients. Future studies should investigate the association of certain symptoms with other psychological or physical factors that may be responsible for clinical outcomes. Even though the only ran-
domized behavioral intervention trial attempting to reduce morbidity and mortality in depressed patients with existing coronary disease35 showed that changes in depression level did not translate into improved survival, there remains the need to further investigate whether treating depression can reduce the risk of morbidity and mortality in patients who have undergone coronary artery bypass grafting.
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