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Depression, Anxiety, and Neuropsychological Performance in Coronary Artery Bypass Graft Patients: A Follow-Up Study

Received September 21, 2006; revised January 22, 2007; accepted January 29, 2007. From the Laboratory for Neuropsychology, Dept. of Internal Medicine–Neurology, Ghent University; Ghent, Belgium. Send correspondence and reprint requests to Dr. Nathalie Stroobant, University Hospital, Ghent, Laboratory for Neuropsychology, 4K3, De Pintelaan 185, B-9000, Ghent, Belgium. e-mail: Nathalie.Stroobant{at}UGent.be
© 2008 The Academy of Psychosomatic Medicine

ABSTRACT

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BACKGROUND: Undergoing coronary-artery bypass surgery (CABG) remains a significant life-event, with an important psycho-emotional impact on patients and their families. OBJECTIVE: The authors examined the incidence and course of depression and anxiety in CABG patients before and after surgery. METHOD: The long-term relationship between mood disorders and neuropsychological deficits was studied 1 day before and 6 days (N=53), 6 months (N=37), and 3–5 years (N=43) after the procedure. RESULTS: Before surgery, one-third of the patients showed mild-to-moderate cognitive-affective symptoms of depression. After surgery, one-fourth still showed elevated depression scores, whereas anxiety was significantly decreased at all post-operative time-points. Patients with higher pre-operative symptoms of depression showed sustained feelings of depression after surgery. Visuomotor performance was most affected by mood. CONCLUSION: Data indicated that patients with preoperative moderate cognitive-affective depression could be at risk for sustained feelings of depression even up to 5 years after surgery.

INTRODUCTION

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Coronary-artery bypass graft (CABG) surgery is a widely used interventional method for the relief of coronary-artery disease symptoms, and improvements in surgical management have significantly reduced mortality rates. Nevertheless, undergoing CABG surgery remains a significant life-event, with an important psycho-emotional impact on patients and their families. Elevated levels of depression and anxiety are reported in 25% to 30% of CABG patients before surgery.^1–3 In up to 20% of the patients, these elevated preoperative mood states persist after cardiac surgery, with potentially adverse effects on quality of life.⁴ Early postoperative depression is even considered an important and independent risk factor for subsequent cardiac events.⁵

Neuropsychological impairment is another common complication of CABG surgery, and the incidence of these deficits ranges from 25% to 80%.⁶ Because emotional states such as depression and anxiety can influence neuropsychological test performance,^7,8 researchers are warned to control for mood states when assessing the pre- and postoperative neuropsychological deficits associated with CABG.⁹ Postoperative decrements are being studied up to 5 years after surgery,^10–12 but only a few studies have examined the association between cognitive dysfunction, on one hand, and long-term depression and anxiety on the other.¹³

The aim of the present study was to examine, in a longitudinal perspective, the incidence and course of depression and anxiety in CABG patients before and after surgery. Also, we investigated the association between mood states and cognitive performance.

METHOD

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Sample
Participants were randomly recruited from the Center for Cardiac Surgery of the University Hospital, Ghent, Belgium. Exclusion criteria were a history of head trauma, seizures, stroke, or other neurological or psychiatric disease. None of the subjects took psychoactive medication. Also, no patients requiring emergency treatment or valve repair entered the study. All patients were scheduled for first-time CABG surgery. The incidence of dementia and other neurological disturbances with associated cognitive impairment increases dramatically with advancing age. Therefore, we excluded patients over age 70 years. Each patient who qualified for the study signed an informed consent document that had been approved by our institutional ethical committee. During the collection phase, 76 patients gave informed consent. Of the initial 76 patients, 2 could not be tested because of scheduling problems; 7 had incomplete inventories preoperatively; and 14 returned incomplete inventories postoperatively. Complete pre- and postsurgical (after 6 days) psychological and neuropsychological measures were available for 53 patients. Patients had cardiac surgery with (on-pump: N=36; 67.9%) and without extracorporeal circulation (ECC; off-pump: N=17; 32.1%). Anesthesia and surgical management are described elsewhere.¹⁴

More information about the demographic, pre-, and peri-operative characteristics of the 53 patients is shown in Table 1. At 6 months and at 3–5 years after surgery, we obtained data from 36 and 43 patients, respectively.

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TABLE 1. Demographic, Pre-Operative, and Peri-Operative Characteristics (N=53)

Procedure
The patients were tested in the hospital on the morning of the day before surgery. The postoperative sessions took place on the morning of the 6th postoperative day, 6 months, and 3–5 years after surgery. Data on the patients’ emotional status were derived from two mood scales. Data on cognitive functioning were derived from seven neuropsychological tests, administered by one appropriately-trained investigator (NS).

Emotional Scales
The Beck Depression Inventory (BDI)¹⁵ contains 21 items. Each item shows four statements concerning a particular aspect of the experience and symptomatology of depression. The sum of the first 13 BDI items creates a cognitive–affective subscale for estimating depression in medically ill patients. The sum of the last 8 BDI items creates a subscale that measures somatic–vegetative performance complaints.¹⁵ CABG patients may have vegetative and somatic symptoms that may be due to their postoperative medical condition and are not necessarily related to depression. Previous research⁴ has shown that somatic and vegetative complaints might overestimate the severity of depressive symptoms because they cannot evaluate whether a positive response is due to depression or to the post-surgical physical status of the patient. In line with these findings, we chose to rely on the cognitive–affective BDI subscale only.

State-anxiety reflects the current emotional status of the individual characterized by subjective feelings of stress and tension, on one hand, and increased activity of the autonomic nervous system, on the other. The Spielberger State-Anxiety Inventory¹⁶ has frequently been used in clinical research and reflects an adequate measurement of situation-specific conditions (e.g., in preoperative stress). For both scales, Dutch versions were used.^15,16

Neuropsychological Tests
Tests were selected to sample a broad range of cognitive abilities, including attention and concentration, verbal and nonverbal memory, language, visuospatial functions, executive functions, and motor and psychomotor speed.

1. The Rey Auditory Verbal Learning Test (AVLT) assesses verbal memory. The measures retained are the sum of words immediately recalled over the first five trials and the delayed recall. We also took into account the number of words that were recognized from a list presented after the performance of all neuropsychological tests. To reduce test–retest effects, we used alternate test versions.

2. The Trail-Making Test, Part B (TMT-B) assesses speed for visual search, attention, and mental flexibility. The time-to-completion is the measure taken.

3. The Grooved Pegboard Test (GPT) measures finger and hand dexterity. The sum of the time to completion of the left and right placement of all pegs is the measure taken.

4. The Block Taps Test (TAPS) assesses nonverbal immediate memory and attention. The number of errors is the measure retained.

5. The Line Bisection Test (LBT) assesses unilateral visual inattention. Total deviation from the true center is the measure taken.

6. The Controlled Oral Word Association Test (COWAT, orthographic categories) assesses word fluency. The total number of words (beginning with four given letters) is the measure retained.

7. Judgment of Line-Orientation (JLO) examines the ability to estimate angular relationships between line segments. The measure retained is the correct number of answers.

Data Analysis
Depression and anxiety scores were compared on different time-points by paired-samples t-tests. Associations between emotional scales and neuropsychological test performance were calculated by Pearson correlation coefficients, adopting a significance level of 0.01 to correct for the numerous statistical tests.

RESULTS

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Emotional questionnaires were not returned (N=12) or were incomplete (N=2) in 14 patients. Since neurocognitive dysfunctions were subtle, they are an unlikely cause of possible response-bias. Also, patients with incomplete versus complete data were not different on demographic, peri-operative, neuropsychological, or preoperative emotional variables. Table 2 shows the pre- and post-operative emotional test results of our group of 53 CABG patients.

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TABLE 2. Pre- and Post-Operative Emotional Test Scores, Mean (Standard Deviation) and Percentages

Incidence and Change in Cognitive–Affective Depression
Pre- and post-operative percentages of the three subgroups (No, Mild, and Moderate cognitive–affective symptoms of depression according to the BDI scores) are shown in Table 2. Neither preoperative medical nor demographic differences among these three groups were found. The Moderate depression group scored significantly worse on the GPT, TMT, and JLO measures.

Six days after surgery, we found a significant drop in the cognitive–affective depression score (t=2.73; p<0.01), and 83% of the patients remained in the same subgroup of depression. Four percent moved to a group with higher depression scores (No to Mild: 2%; Mild to Moderate: 2%), and 13% moved to a group with lower scores (Mild to No: 11%; Moderate to Mild: 2%).

Six months after surgery, we found no significant drop in the cognitive–affective score, as compared with the preoperative score; 72% of the patients remained in the same depression subgroup; 11% moved to a group with higher depression scores (No to Mild: 5.5%; Mild to Moderate: 5.5%), and 17% moved to a group with lower scores (Mild to No: 11%; Moderate to Mild: 3%; and Moderate to No: 3%).

At 3-to-5 years after the operation, we found no significant drop in the cognitive–affective score, as compared with the preoperative score: 70% of the patients remained in the same depression subgroup; 11.5% of the patients moved to a group with higher depression scores (No to Mild: 11.5%), and 18.5% moved to a group with lower scores (Mild to No: 16%; Moderate to No: 2.5%).

We found a significant difference between the on- and off-pump groups, with off-pump patients showing higher cognitive–affective depression scores at 6 months (mean 2.9 versus 4.1; t = –2.06, p<0.05) and 3–5 years after the surgery (mean 1.8 versus 4.4; t = –2.14, p<0.05).

Incidence and Change in Anxiety Level
Pre- and post-operative percentages of clinically-relevant anxiety scores (50%) are shown in Table 2. Six days (t=3.52, p<0.01), 6 months (t=2.25, p<0.05), and 3–5 years (t = –3.64, p<0.01) after surgery, anxiety decreased significantly, as compared with the immediate pre-operative period. No significant differences were found between early (6 days) post-operative anxiety and 6 months or 3–5-year post-operative anxiety and between 6-month and 3–5-year anxiety.

Anxiety was significantly different (p<0.01) at the different time-points among the three depression groups (No, Mild, and Moderate), with higher anxiety scores in patients with more depression. No differences between on- and off-pump patients were found for anxiety scores.

Pre- and Post-Operative Correlations Between Mood States and Cognitive Test Results
Pre-operatively, we found a significant correlation between the cognitive–affective BDI subscale and GPT (r=0.53, p<0.01) and TMT–B (r=0.39, p<0.01). Higher depression scores were associated with worse performance scores.

Six days after surgery, the cognitive–affective BDI subscale correlated significantly with GPT (r=0.46, p<0.01). Higher depression scores were associated with worse performance scores. At 6 months, however, no significant correlations were found.

At 3–5 years after surgery, the cognitive–affective subscale of the BDI correlated significantly with GPT (r=0.48, p<0.01). Higher depression scores were associated with worse performance scores.

We correlated the pre-operative depression score with all post-operative cognitive results to investigate the predictive value of emotional status on cognition. The pre-operative cognitive–affective depression score was significantly correlated with GPT at 6 months (r=0.43, p<0.01) and GPT at 3–5 years (r=0.43, p<0.01). Anxiety scores showed no significant correlations with neuropsychological test performances on any assessment.

DISCUSSION

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Attrition rate (21%) was comparable to those of other follow-up studies in CABG patients,¹³ and there were no arguments for a response bias because no demographic, pre-, intra-, and post-operative differences were observed between the drop-out group and the included-patient group. Consistent with other studies,^1,2 we found that almost one-third of the CABG patients showed mild-to-moderate cognitive–affective symptoms of depression before surgery. After the operation, approximately one-fourth of the patients still showed mild-to-moderate symptoms of depression. Categorical changes appeared predominantly between No or Mild depressive symptoms, whereas patients classified with Moderate depression remained moderately depressed throughout the follow-up study. This was also found in other research.¹⁷ We conclude that measurements of the pre-operative mood levels remain valuable because most of these patients are at increased risk of suffering from post-operative mood disorders.

One-third of the pre-surgical candidates showed clinically significant state-anxiety scores. Six days after surgery, only 13.2% still showed elevated anxiety scores. These results are consistent with other literature.^4,18 Later, after surgery, the amount of anxiety in this group further decreased, to 2.8% at 6 months and 7% at 3–5 years. The state-anxiety scale assesses a temporal rise in physical and psychological arousal and is therefore more sensitive to the stress experienced immediately before surgery.

The pattern of significant decrease in state-anxiety after surgery is in contrast with the course of depression that frequently persists at preoperative levels for years after surgery.^4,17 We concluded that the more trait-like depression follows another pattern—namely, a decrease immediately after the surgery ("the honeymoon effect"), but then a return to the preoperative level.

Remarkably, we found that off-pump patients showed higher cognitive–affective depression scores than on-pump patients. On-pump patients generally showed no depression, whereas off-pump patients showed a mild depression (according to the subgroups) at 6 months and 3–5 years after the surgery. Because it appears unlikely that surgical procedures would have an effect on long-term depression outcome, this finding is difficult to explain and warrants further exploration.

Emotions such as depression and anxiety can impair neuropsychological test performance,⁸ and the cognitive domains of memory,^19,20 attention,⁷ executive functioning, and general functioning²¹ are most vulnerable in non-cardiac patients. In CABG patients, the relationship between depression and anxiety, on the one hand, and various neuropsychological tests, on the other, has also been investigated.^2,17,18,22 This research revealed no significant correlations between preoperative depression and preoperative neuropsychological test scores^2,18 and between postoperative depression and postoperative neurocognitive test scores.^2,17,18,22 In this study, the association between emotional scores and most neuropsychological tests is rather limited, as well, except for the GPT (at all time-points) and TMT (preoperatively). The lack of relationship for the majority of the tests confirms the validity of neurocognitive measurements in stressful conditions such as immediately before a surgical procedure. In contrast, Andrew and colleagues,¹⁷ reported that the degree of preoperative depression and anxiety was predictive of specific postoperative neuropsychological deficits after 6 days. In our study, higher preoperative depression was associated with GPT at 6 months and 3–5 years postoperatively. Slowed visuomotor functioning is one of the cardinal features of depression, and reduced mental and motor speed have been among the most frequent findings in the cognitive literature on depression.²² The fact that higher depression scores were associated with worse performance scores on the GPT and TMT affirms the hypothesis that cognitive–affective symptoms of depression may be associated with performance on visuomotor tests. Moreover, these two tests, together with the AVLT, constitute the core neuropsychological battery as recommended by the Statement of Consensus on assessment of neurobehavioral outcomes after cardiac surgery.⁹

In conclusion, for the majority of patients, emotional functioning did not appear problematic. However, our research indicated that patients with preoperative moderate cognitive–affective depression could be at risk for sustained feelings of depression even up to 5 years after surgery. Elevated emotional arousal (in about 10% of the patients in this study) was also found to be an independent risk factor for increased mortality and morbidity in the cardiovascular system.^23,24 Selection of these patients for pre- and post-operative treatment could decrease the impact of depression and reduce both medical and economic costs.¹⁸

Our findings support the hypothesis that the mood disorders reported by patients do not show a relevant association with neuropsychological performance except for visuomotor tasks. This relationship was noticed at different time-points after the surgery. To our knowledge, this is one of the first studies that examines these associations between neurocognitive decline and mood disorders in a longitudinal perspective and for different types of surgery.

ACKNOWLEDGMENTS

 
This work was supported by a research grant from the University of Ghent and a postdoctoral research grant from the Fund for Scientific Research–Flanders, both awarded to Nathalie Stroobant.

REFERENCES

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