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ORIGINAL ARTICLES |
From the Department of Anesthesia and Intensive Care (A.S.), Department of Rehabilitation Care (E.B.), Research Department (T.B.), Department of Cardiac Surgery (F.H.), Gottsegen György Hungarian Institute of Cardiology, Budapest, Hungary; Institute of Behavioral Sciences (P.B., M.S.K.), School of Ph.D. Studies (T.B.), Department of Anesthesia (M.D.K.), Semmelweis University, Budapest, Hungary; Department of Radiotherapy (J.S.), Mannheim Institute of Public Health, Heidelburg University, Mannheim, Germany; and Department of Psychology (F.H., J.F.T.), Ohio State University, Columbus, Ohio.
Address correspondence and reprint requests to Andrea Székely, Haller u. 29, Budapest, H-1096, Hungary. E-mail: szekelya{at}kardio.hu
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ABSTRACT |
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Methods: In total, 180 patients who underwent cardiac surgery using cardiopulmonary bypass were prospectively studied and followed up for 4 years. Anxiety (Spielberger State-Trait Anxiety Inventory, STAI-S/STAI-T), depression (Beck Depression Inventory, BDI), living alone, and education level along with clinical risk factors and perioperative characteristics were assessed. Psychological self-report questionnaires were completed preoperatively and 6, 12, 24, 36, and 48 months after discharge. Clinical end-points were mortality and cardiac events requiring hospitalization during follow-up.
Results: Average preoperative STAI-T score was 44.6 ± 10. Kaplan-Meier analysis showed a significant effect of preoperative STAI-T >45 points (p = .008) on mortality. In multivariate models, postoperative congestive heart failure (OR: 10.8; 95% confidence interval [CI]:2.9–40.1; p = .009) and preoperative STAI-T (score OR: 1.07; 95% CI: 1.01–1.15; p = .05) were independently associated with mortality. The occurrence of cardiovascular hospitalization was independently associated with postoperative intensive care unit days (OR: 1.41; 95% CI: 1.01–1.96; p = .045) and post discharge 6th month STAI-T (OR: 1.06; 95% CI:1.01–1.13; p = .03).
Conclusions: The results of the present study suggest that the assessment of psychosocial factors, particularly the ongoing assessment of anxiety, could help in risk stratification and identification of patients at risk of mortality and cardiovascular morbidity after cardiac surgery.
Key Words: cardiopulmonary bypass • psychosocial factors • anxiety • depression • mortality • morbidity
Abbreviations: BDI = Beck Depression Inventory; STAI-S = state anxiety subscale; STAI-T = trait anxiety subscale of Spielberger State-Trait Anxiety Inventory; CPB = cardiopulmonary bypass; CABG = coronary artery bypass grafting; CHF = congestive heart failure; CHD = coronary heart disease; ICU = intensive care unit; MI = myocardial infarction; PTSD = posttraumatic stress disorder.
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INTRODUCTION |
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Due to advances in surgical procedures, mortality after cardiac surgery has decreased significantly. Therefore, postoperative quality of life after these operations has become an important measure of the effectiveness of the surgery. Despite good surgical results, some patients report poor health status and need frequent hospitalization after surgery. For example, the negative influence of depression on the long-term outcome has been reported in patients having undergone valve surgery (4). A vast literature on depression and cardiovascular diseases suggests that depression has a direct effect on coronary pathology (5). Some studies have analyzed the influence of phobic anxiety on heart failure (6,7), but the role of anxiety as a personality dimension has rarely been studied. However, to date, few studies have assessed both depressive symptoms and symptoms of anxiety simultaneously (8). Even fewer have done so in Eastern Europe where the risk of cardiovascular mortality and morbidity is even higher and cannot be fully explained by physiological or behavioral factors.
Furthermore, despite increased research activity in the field of postoperative quality of life after cardiac surgery, most of the studies report events during 1-year follow-up (9,10) and only few data are available for the long-term results. Thus, there is need for additional investigation in the long-term consequences of increased psychosocial risk factors on recovery from cardiac surgery.
The aim of the present study was to investigate the influence of psychological factors, particularly depression and anxiety, as well as clinical risk factors and perioperative characteristics on the 4-year mortality and on postoperative hospitalization for cardiovascular reasons in patients, who underwent elective CABG and/or valve surgery. This research was conducted in Eastern Europe where the risk of cardiovascular mortality and morbidity is high and not entirely explained by medical and behavioral factors.
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METHODS |
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Clinical Factors
A range of medical and psychosocial factors were collected as potential determinants of outcome. Medical factors included previous myocardial infarction, previous CABG, history of arrhythmia, congestive heart failure, diabetes mellitus, hypercholesterolemia, cerebrovascular disease, chronic renal insufficiency, hypertension, and previous psychiatric hospitalization. Detailed definitions can be accessed at the homepage of the Society of Thoracic Surgeons (11). The additive EuroSCORE was also calculated. This index taps patient-related factors (i.e., age >60 years (one per 5 years or part thereof), female gender, chronic pulmonary disease, extracardiac arteriopathy, neurological dysfunction, previous cardiac surgery, serum creatinine >200 micromol/l, active endocarditis, critical preoperative state), cardiac-related factors (i.e., unstable angina on intravenous nitrates, reduced left ventricular ejection fraction, recent (<90 days) myocardial infarction, pulmonary systolic pressure >60 mm Hg) and operation-related factors (i.e., emergency other than isolated coronary surgery, thoracic aorta surgery, and surgery for postinfarct septal rupture) (12). According to the additive score, a low risk group (EuroSCORE 1–2), a medium risk group (EuroSCORE 3–5), and a high-risk group (EuroSCORE 
6) were formed. Intraoperative characteristics included number of grafted vessels, cardiopulmonary bypass, and aortic cross clamp time. Postoperative complications were defined by key outcomes of the Society of Thoracic Surgeons Database (13), as permanent stroke (new-onset cerebrovascular accident persisting >72 hours), reoperation for any reason, serious infection (positive blood culture, deep sternal wound infection, catheter-related infection), prolonged mechanical ventilation (ventilatory support >48 hours), renal failure requiring dialysis, and myocardial infarction. The diagnosis of heart failure required either the use of intra-aortic balloon pump or the use of continuous intravenous inotropic support for at least 48 hours, or autopsy evidence of heart failure (14). Duration of intensive care unit (ICU) and hospital stay was also analyzed.
Psychosocial Factors
Demographic data collected were age, gender, living status (alone versus with another), and education. Depression was assessed using the Beck Depression Inventory (BDI), a questionnaire previously used with cardiac patients (15). The BDI, a 21-item questionnaire, is an established tool for depression screening with each item evaluating a symptom of depression, such as sad mood, pessimistic outlook, feelings of guilt, and loss of appetite. Each item contains four sentences indicating degree of severity for that particular symptom. Subjects respond by endorsing one sentence from the set of four. The validity and reliability of the BDI are well documented in the Hungarian population (16). The BDI was scored 0 to 60; a cut-off at 10 was selected as indicative for clinically significant symptoms of depression consistent with the literature on depression in patients with coronary disease (17). This cut-off value was applied when data were dichotomized and the BDI as a continuous variable was used in the univariate and multivariate analysis.
The Spielberger State-Trait Anxiety Inventory state and trait scores (STAI-S and STAI-T) (18) were used to characterize anxiety symptoms of the patients. The STAI-S measures the transitional emotional status evoked by a stressful situation, like surgery. The STAI-T score reflects relatively enduring individual differences in anxiety proneness. In the American population, patients with scores >40 are classified as anxious (19). The validity and reliability of the STAI are well documented in the Hungarian population. The mean score established for the Hungarian population (42.6) is higher than that of the American population (20). In our cardiac population, the mean preoperative STAI-T was even higher (44.6). Therefore, we considered 45 as a cut-off, with patients with scores >45 being classified as anxious. This cut-off point was used when data were dichotomized, and the STAI-T was used as a continuous variable in the univariate and multivariate models.
Follow-Up Surveillance
BDI, STAI-S, STAI-T tests were sent to the patients along with an additional sheet with questions regarding hospitalization and the primary cause of their hospital admission from the time of the last contact. The patients were contacted by mail 6, 12, 24, 36, and 48 months after discharge. At the end of the 2nd and 4th years, we telephoned those patients, who did not respond, and we asked for information about their medical history. Psychological questionnaires were not completed by telephone contact to avoid bias resulting from different methodologies. Seven patients died at the hospital and 10 patients died during the 4-year follow-up. The responder rate through mail was 81%, 55.9%, 57.2%, 40.4% and 53.9% at 6, 12, 24, 36, and 48 months after discharge, respectively. We could collect information by mail and by phone from 84% of our study population at the end of the third year and from 82% at the end of the fourth year. The Hungarian registry was searched for mortality information at the end of the fourth year.
End-Point Assessment
We have chosen all cause mortality and hospitalization because of cardiovascular events (angina, congestive heart failure, myocardial infarction, percutaneous coronary angioplasty, survived cardiac arrest, and death due to cardiac causes) as clinical end-points.
Statistical Analysis
All analyses were performed using the SPSS 13.0 statistical package (SPSS Inc., Chicago, Illinois). Descriptive statistics (mean, SD or median and interquartile range) were calculated on all continuous variables. Prevalence of baseline characteristics and incidence of adverse events were compared using the 
2 or Fisher’s exact test as appropriate. Univariate logistic regression analysis was used to determine the preoperative characteristics affecting mortality. These factors were controlled with bootstrapping methods. The following factors had an influence on mortality (p 
.20) EuroSCORE, postoperative CHF, postoperative infection, preoperative STAI-T, (measured as a continuous variable) and education years. The EuroSCORE was used instead of preoperarative co-existing diseases, as a summary measure of preoperative risk and condition. Variables found to be significant (p .20) in the univariate screening analysis were entered into the multivariate models. The first block comprised only medical variables; in the second block, BDI and STAI-T scores were added. A p < .05 was considered to be statistically significant.
The demographic and clinical variables that predicted postdischarge hospitalization were included in a series of separate Cox analyses with each of the significant psychosocial variables. Because EuroSCORE proved to be a nonsignificant factor for cardiovascular hospitalization (p = .41), co-existing diseases were separately investigated. The variables that predicted hospitalization with p .20 in the initial Cox model were then combined in one survival analysis. These variables were diabetes, postoperative infection, ICU days, preoperative and postdischarge 6th month STAI-T and BDI scores. An iterative approach was used to create the final model by combining the psychosocial and demographic and clinical variables. For validation, the bootstrapping method was used.
Kaplan-Meier plots and log-rank tests were used to investigate differences in the postoperative survival of the patients (21).
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RESULTS |
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45 on the preoperative STAI-T scale (53.8 ± 7.3). Hence, 42% of this population was classified as presenting clinically significant anxiety symptoms. Baseline characteristics, perioperative variables, clinical factors, and psychosocial factors for those scoring <45 versus 45 on the preoperative STAI-T scale are provided in Table 1. The prevalence of coexisting diseases was similar to the hospital case-mix index and to that reported in other studies.
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Figure 1 shows the time course of scores of the STAI-S and STAI-T scales. Preoperative STAI-S was significantly higher than any of the postoperative values. On the contrary, STAI-T scores remained relatively consistent compared with the preoperative value, except for the score at 12 months postoperatively. The correlation between the preoperative and postoperative STAI-T time points was relatively strong (r = .53–62; p < .0001). Hence, we considered trait anxiety as a more reliable indicator of individual differences in anxiety symptoms, and therefore used STAI-T scores in further analysis instead of STAI-S. Kaplan-Meier analysis showed that patients with preoperative STAI-T >45 points had a significantly higher mortality rate (Figure 2). This effect could be also observed if the model was adjusted for depression (p = .049). Data are not shown.
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Depression
The mean preoperative BDI score was 9.8 ± 7.2 (minimum–maximum 0–46) and the score was 10 points in 44.4% of the 180 patients studied. A significant reduction in depression scores could be observed only at the 1st year compared with the preoperative value (difference: –1.3 ± 4.7; p = .014). Figure 3 shows the time course of BDI scores. Kaplan-Meier analysis showed no significantly higher mortality in patients with preoperative BDI scores >10 compared with patients with BDI scores <10.
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Mortality
Univariate analyses showed that mostly postoperative risk factors were associated with mortality (Table 2). In the multivariable model, only preoperative STAI-T remained an independent determinant of all cause mortality in addition to postoperative heart failure.
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Cardiovascular Hospitalization
During the 4-year follow-up, 26.2% of the patients were hospitalized at least once, 18.8% two times, and 11.5% three times or more. Hospitalization rates for those who had an average postoperative STAI-T score <45 versus 45 are provided in Figure 4. Arrhythmia, myocardial infarction, angina, and congestive heart failure were the main reasons for hospitalization; the incidence of these reasons was significantly higher in the patients who had an average postoperative STAI-T score of 45 points. The results of Cox regression analysis are shown in Table 3.
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DISCUSSION |
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Three large-scale community-based studies reported a significant relationship between anxiety disorders and cardiac death (6,7,22) and two of them also observed a dose-dependent relationship between the level of anxiety and the occurrence of fatal cardiac events (7,22). The long-term negative influence of negative psychosocial stressors increases the severity of cardiovascular diseases. However, the severity or progression of the cardiovascular diseases is difficult to measure by traditional clinical variables, such as hypertension, peripheral vascular diseases, or diabetes, because these categories do not provide any information about the duration and/or stage of these diseases. Therefore, research with harder end-points, such as used in the present study, may help to clarify the associations found between psychosocial factors and cardiovascular disease.
Convincing evidence supports the hypothesis that an association between psychosocial risks and pathophysiological alterations exists. Dysregulation of the pituary-adrenal axis, sympathoadrenal hyperactivity, alterations in autonomic nervous system activity, alteration in platelet receptors and reactivity, and immunological changes have been reported (5,23,24). Autonomic dysregulation may explain the high incidence of arrhythmia in anxious patients in our population. This pathophysiological alteration and the decreased heart rate variability as a consequence increase the risk for ventricular tachycardia, fatal arrhythmias, and sudden death (25,26). However, future studies in this population that measure heart rate variability will be needed to further explicate the possible mechanisms responsible for the association between anxiety and mortality and morbidity we found.
Since the inhospital mortality after CABG and valve surgery has become relatively low in the last decades, improvement in health status, changes in functioning status, and feeling of well-being have become important indicators of the result of cardiac surgery. A decline in well-being was observed after 12-months in patients post CABG (27). Mental attributes continued to improve at 2 years, but physical function appeared to decline after 12 months (28). Self-perceived health-related quality of life in depressed patients was considerably worse than patients without these symptoms (29). Some investigators found no significant association with medium-term (>6 month) mortality, but an increased risk for new cardiovascular events (9,30). The different results can be explained by the dynamic relationship between risk factors and outcomes such that certain factors lose their importance with time, whereas other factors become stronger predictors only in late assessments (31). Given that the present study included a relatively long follow-up period, the present results might better reflect the longer term consequences of increased psychosocial risk factors. More studies with extended follow-up periods will be necessary before strong conclusions about the long-term effects of anxiety, depression, and other psychosocial factors can be made.
More recent studies have also addressed the problem of comorbid anxiety and depressive disorders (32). Anxiety has been characterized as a strongly negative emotion with a component of fear, and such fear has cognitive, neurobiological, and behavioral manifestations. Frasure-Smith and colleagues reported an increased risk of cardiac events after myocardial infarction associated with anxiety (19), in contrast to Jiang et al., who used the same score and found no relationship with mortality (33). Our finding might be explained by the fact that our study population was not homogenous, because not only CABG patients were enrolled but also patients who underwent valve surgery. Nevertheless, preoperative depression has been reported to be an independent predictor of 6-month mortality after valve surgery (4). Additionally, we have to emphasize that the mean score established for the Hungarian population for anxiety (42.6) is higher than that of the American population (20). In Eastern Europe, the highest rates of premature death have been observed in young and middle-aged men. Traditional risk factors such as bad diet, smoking, and alcohol can only partly explain the growing disparity in life expectancy between East and West Europe (34). Behavioral scientists have argued that psychosocial risk factors such as increased stress, anxiety, and depression may explain additional variance in the cardiovascular mortality and morbidity data in Eastern Europe.
In long-term investigations (3–5 years), anxiety was associated with an increased occurrence of adverse events (35). However, in most of the studies, preoperative scores were utilized for investigating the possible links between anxiety and/or depression and postoperative outcomes. Hospital readmission was found to link preoperative depression and postoperative anxiety after controlling medical factors (36). Consistent with the present findings, Peterson et al. also emphasized that postoperative depressive symptoms better predicted long-term cardiac outcomes than preoperative symptoms (37). Hence, psychosocial factors should be measured and possibly treated during follow-up to better recognize patients at increased risk for cardiovascular events and mortality.
In the present study, the number of days in the ICU was associated with both mortality and morbidity. Postoperative length of ICU stay has been reported as an indicator of physical recovery (38) and as a significant determinant of postoperative depressive symptoms (39). Regardless of the precipitating reason, long ICU stays can lead to symptoms of posttraumatic stress disorder (PTSD), the impact of which has been recently highlighted. PTSD predicted nonadherence to medication after myocardial infarction (40). These long-lasting emotional sequelae influence negatively postdischarge quality of life and should also be recognized before surgery and during rehabilitation (41,42). In contrast, optimism predicted a lower rate of rehospitalization after cardiac surgery (43).
Limitations
The present study has several limitations. For example, a larger and more homogeneous population of patients would be needed to assess more precisely the influence of different psychosocial factors on long-term mortality and morbidity. In addition, rehospitalization and frequency of rehospitalization have not been fully investigated in the present study. Furthermore, using the BDI to assess depression in cardiac patients is problematic because some somatic symptoms of depression may result from physical illness or drug side-effects (i.e., loss of energy, diminished interest of sexual activity, fatigue).
Comment
The present study suggests that future patients be assessed for anxiety to evaluate their risk for cardiovascular morbidity or mortality after cardiac surgery. It may also be useful to assess interventions aimed at reducing anxiety in highly anxious patients to reduce their risk for morbidity and mortality.
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NOTES |
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This study was supported by Grant OTKA-T-035169 from the Hungarian Research Foundation Budapest, Hungary, and Grant NKFP 1b/020/2004 from the National Research and Development Programs, Budapest, Hungary.
DOI:10.1097/PSY.0b013e31814b8c0f
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