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Ann Thorac Surg 2004;77:597-603
© 2004 The Society of Thoracic Surgeons

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Original article: cardiovascular

Predictors of cognitive decline following coronary artery bypass graft surgery

^a Denver Veterans Affairs Medical Center, Denver, Colorado, USA
^b Department of Medicine, University of Colorado Health Sciences Center, Denver, Colorado, USA
^c Department of Surgery, University of Colorado Health Sciences Center, Denver, Colorado, USA
^d Department of Neuropsychiatry, University of Colorado Health Sciences Center, Denver, Colorado, USA
^e Department of Preventive Medicine and Biometrics, and the Colorado Health Outcomes Program, University of Colorado Health Sciences Center, Denver, Colorado, USA
^f The Feinberg School of Medicine, Northwestern University, Chicago, Illinois, USA
^g Department of Veteran Affairs Central Office, Washington, DC, USA
^h Veterans Affairs Cooperative Studies Program Coordinating Center, Hines VAMC, Hines, Illinois, USA
ⁱ Cardiothoracic Surgery, Tucson VAMC, USA
^j Department of Surgery, University of Arizona, Tucson, Arizona, USA
^k Anesthesia Service, San Francisco VAMC, USA
^l Department of Anesthesia and Perioperative Care, University of California, San Francisco, San Francisco, California, USA

Accepted for publication July 17, 2003.

^* Address reprint requests to Dr Ho, 1055 Clermont St (111B), Denver, CO 80220, USA.
e-mail: michael.ho{at}uchsc.edu

	Abstract

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BACKGROUND: A significant number of patients develop cognitive impairment that persists for months following coronary artery bypass grafting (CABG) surgery. Our objectives were to identify patient-related risk factors, processes of care, and the occurrence of any perioperative complications associated with cognitive decline.

METHODS: Nine hundred thirty-nine patients enrolled in the Processes, Structures, and Outcomes of Care in Cardiac Surgery study undergoing CABG-only surgery at 14 Veterans Administration medical centers between 1992 and 1996 completed a short battery of cognitive tests at baseline and 6-months post-CABG. The composite cognitive score was based on the sum of errors for each individual item in the battery. Multiple linear regression analyses were used to identify independent predictors of the 6-month composite cognitive score.

RESULTS: In multivariable analyses, patient characteristics associated with cognitive decline included cerebrovascular disease (p = 0.009), peripheral vascular disease (p = 0.007), history of chronic disabling neurologic illness (p = 0.016), and living alone (p = 0.049), while the number of years of education (p = 0.001) was inversely related to cognitive decline. After adjustment for baseline patient risk factors, the presence of any postoperative complication(s) (p = 0.001) was also associated with cognitive decline while cardiopulmonary bypass time (p = 0.008) was inversely related to cognitive decline.

CONCLUSIONS: Patients with noncoronary manifestations of atherosclerosis, chronic disabling neurologic illness, or limited social support are at risk for cognitive decline after CABG surgery. In contrast, more years of education were associated with less cognitive decline. Preoperative assessment of risk factors identified in this study may be useful when counseling patients about the risk for cognitive decline following CABG surgery.

	Introduction

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Cognitive decline frequently occurs following coronary artery bypass grafting (CABG) surgery. A recent meta-analysis of both cohort and randomized controlled trials estimated the incidence to be 22.5%, but rates within individual studies ranged from a low of 4% to a high of 47% [1]. Some of the identified patient risk factors include age, diabetes, and the presence of the apolipoprotein E-4 (APOE-4) allele [2–5]. Many observational studies have also evaluated the effects of processes of care during CABG and perioperative complications on subsequent cognitive functioning. The use of cardiopulmonary bypass and the total microembolic load, as assessed by transcranial Doppler monitoring have been shown to be associated with cognitive decline [6, 7].

Much is still unknown with respect to potential risk factors associated with, and possible mechanisms of cognitive dysfunction following CABG. The majority of prior studies addressing these issues enrolled patients from single centers and some may have been limited by small sample sizes. Furthermore, given recent advances in percutaneous coronary revascularization techniques, patients may have alternatives to bypass surgery if their risk for cognitive dysfunction is substantially based on preoperative assessment. Identification of additional factors can help clinicians to select the mode of revascularization and to better counsel patients about the risks and benefits of surgery. Therefore, our objectives were to identify patient-related risk factors, processes of care, and the occurrence of any perioperative complications associated with cognitive decline following CABG.

	Material and methods

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Patients
The patient sample was derived from the Veterans Administration (VA) Cooperative Study in Health Services #5, Processes, Structures, and Outcomes of Care in Cardiac Surgery (PSOCS), a multicenter, prospective, observational study investigating the links between processes and structures of care and risk adjusted outcomes [8]. Details of the PSOCS study are published elsewhere and are only reported here as relevant to the current analyses. Data on 734 variables, including patient-related risk factors, processes, structures, and outcomes of care were collected for a representative sample of patients who underwent cardiac surgery 14 VA medical centers between September 1992 and December 1996. The 14 VA medical centers were chosen from the total 43 VA medical centers that perform open-heart surgery to be representative of the spectrum of risk-adjusted operative mortality by center. Data were prospectively collected by full-time, trained research nurses located at each of the 14 sites. Patient-related risk data were obtained by patient interview and chart review within 72 hours prior to surgery. The baseline cognitive evaluation was also conducted within 72 hours before the surgery, using a standard protocol.

All patients enrolled in the PSOCS study, who had CABG only surgery and who completed both a baseline and 6-month postoperative cognitive evaluation, were included. Of the 3,998 patients who underwent CABG only, 1,677 patients completed a baseline cognitive evaluation and 939 patients completed both a baseline and 6-month postoperative cognitive evaluation. A primary reason for not completing the baseline cognitive evaluation was urgent or emergent surgical priority that precluded time to complete the evaluation.

Description of neurocognitive tests and assessment protocol
Three tests comprised our battery of neurocognitive measures: the Short Form of the Blessed Orientation-Memory-Concentration Test, two tasks from the Behavioral Dyscontrol Scale, and the Trail Making Test–Part A from the Halstead-Reitan battery [9–13]. The appendix lists all of the items included in the evaluation. These measures were chosen because they are brief, simple to administer, and assess a broad range of cognitive processes. In addition, they have well-established validity and reliability characteristics [10–12, 14–16].

A standardized testing protocol was used to evaluate patients at both time points. The initial teams of research nurses were trained in the administration of all three sets of measures before the study began. Research nursing staff hired during the latter stages of the study were individually trained by the study coordinator and supervised practice sessions were conducted before the new nurses were allowed to assess study patients.

Predictor and outcome variables
The dependent or outcome variable of interest was the 6-month composite cognitive evaluation score, adjusted for the baseline composite cognitive score. The Short Form of the Blessed Orientation-Memory-Concentration Test and the two tasks from the Behavioral Dyscontrol Scale were scored as the number of errors made. The time in seconds to complete the Trail Making Test–Part A was converted to an error score using the mean and standard deviation for the cohort at baseline as reference: less than reference mean + 1 standard deviation = 0 errors; reference mean + 1 to 2 standard deviations = 1 error; reference mean + 2 to 3 standard deviations = 2 errors; reference mean + 3 standard deviations = 3 errors.

The composite score was based on the sum of errors for each individual item. The possible range of the composite score was 0 to 22. A higher composite score represented worse cognitive performance. A composite score was calculated for each patient at baseline and at 6 months after CABG.

A panel of four cardiovascular clinicians and a health services researcher reviewed the PSOCS data and selected a subset of 24 patient-related risk, processes of care (what is actually done in giving and receiving care), and perioperative complication variables as potential predictors of cognitive decline, based on the published literature and clinical experience [1–7, 17–20].

Statistical methods
All analyses were performed using the SAS statistical software package (SAS Institute Inc, Cary, NC). Baseline characteristics were compared between patients who underwent CABG only included in the study population (ie, those with a baseline and 6-month postoperative cognitive evaluation) and excluded patients (missing one or both cognitive evaluations) using the t test for continuous variables and the ² test for categorical variables. Scores for the individual items in the battery and the composite scores were compared at baseline and at 6 months after CABG, using the McNemar's ² test for categorical variables and the paired t test, for continuous variables.

Multiple linear regression models were used to identify patient-related risk factors, processes of care, and the occurrence of any perioperative complication(s) predictive of the 6-month composite cognitive score, adjusting for the baseline composite cognitive score. In our risk baseline model, we assessed the effects of patient characteristics on the 6-month composite score. Significant variables, with p less than 0.05, were kept in the model. Subsequent models evaluated the effects of processes of care and any intra or postoperative complications on the 6-month composite score after adjusting for base line patient characteristics. This substudy was approved by the Colorado Multiple Institutional Review Board on August 25, 2002.

	Results

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Characteristics of patients who completed the cognitive evaluations and those who did not
Table 1 shows that patients who completed the cognitive evaluation had a lower risk profile compared with patients who did not complete the evaluation. For example, fewer patients included in the current analyses underwent emergent or urgent surgery, required preoperative intraaortic balloon support, or had Canadian Cardiovascular Society (CCS) class III or IV angina. Despite these differences, the mean age was similar and the number of patients with three-vessel coronary artery disease and prior CABG was comparable between the two groups.

	Comment

Top Abstract Introduction Material and methods Results Comment Acknowledgments References

Prior cohort studies have identified only a few patient characteristics that are associated with cognitive decline following CABG. These risk factors include older age, diabetes, and the presence of the apolipoprotein E-4 (APOE-4) allele [2–5]. Hammon and colleagues noted the degree of atherosclerosis of the ascending aorta as a risk factor for postoperative cognitive change [23]. In addition, a study by Heyer and colleagues showed that patients undergoing carotid artery surgery also have declines in neuropsychometric performance [24]. Our finding that cerebrovascular disease and peripheral vascular disease were associated with cognitive decline suggests that patients with any noncoronary manifestation of atherosclerosis are at risk for cognitive dysfunction following CABG.

Population-based studies among community dwelling older adults have noted a correlation between a lack of social support and subsequent development of dementia [25, 26]. Single people and those living alone had an adjusted relative risk of 1.9 for developing dementia [26]. Our finding that a patient living alone before CABG was associated with cognitive decline after surgery is consistent with community-based findings.

Patients with chronic disabling neurologic illness, defined as those requiring assistance with ambulation or ADLs or those with baseline cognitive dysfunction or dementia were also at risk for cognitive decline following CABG. These patients have less neurocognitive reserve and may not be able to compensate for acquired cognitive deficits. This is in contrast to patients with higher levels of education who have more neurocognitive reserve and can compensate for acquired cognitive problems [17].

After adjustment for baseline patient characteristics, the occurrence of any postoperative complication(s) was associated with cognitive decline in our study. Selnes and colleagues previously noted that length of stay was associated with cognitive change on tests of language at 1 year [4]. They postulated that length of stay might be a surrogate marker for another medical or neurologic complication. One of the most frequent postoperative complications among our cohort of patients was low cardiac output requiring intraaortic balloon support or continuous inotropic support for greater than or equal to 6 hours. This finding along with patient risk factors such as peripheral vascular disease and cerebrovascular vascular disease suggests that cerebral hypoperfusion may be an important mechanism underlying cognitive decline after CABG.

Recently, Van Dijk and colleagues reported in a randomized trial that there were no significant differences in cognitive outcomes at 12 months between those undergoing CABG with or without cardiopulmonary bypass [27]. Our finding that cardiopulmonary bypass time was inversely associated with cognitive decline and a previous finding from a cohort study that use of cardiopulmonary bypass was associated with cognitive decline suggests that this issue is still unresolved [6]. A multicenter randomized trial of on-pump versus off-pump CABG is currently being conducted in the VA, with cognitive function as one of its outcomes [28]. Hopefully, this study will shed more light on the effects of cardiopulmonary bypass on subsequent cognitive functioning.

The strengths of our study include the large patient sample from multiple centers, who completed both a baseline and 6-month cognitive evaluation. Furthermore, the wealth of variables in the PSOCS database allowed us to explore many potential patient-related risk factors, processes of care, and complications that are associated with cognitive decline. As a result, we have identified several risk factors that previously have not been associated with cognitive decline, including chronic disabling neurologic disease, cerebrovascular disease, peripheral vascular disease, living alone, and the occurrence of any postoperative complication(s).

There are several potential limitations to our study. Although our patient sample represents a large cohort of patients who underwent cognitive testing in the setting of CABG, this group comprises only about one-quarter of the patients undergoing CABG in the PSOCS study. This group consists mainly of patients undergoing elective CABG only surgery, with a lower preoperative risk profile. However, information about the potential risk for cognitive dysfunction after bypass surgery may be more useful to this subset of patients undergoing elective surgery because there is time to perform preoperative cognitive evaluation, which may lead to other therapeutic options such as multivessel angioplasty. Finally, the study sample consisted mainly of male veterans and may not be generalized to the nonveteran population.

In conclusion, we identified several patient risk factors associated with cognitive decline after CABG. These findings, along with prior work from the literature contribute to the growing list of risk factors that clinicians can use to counsel patients about the potential risk for cognitive dysfunction following CABG.

	Acknowledgments

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This research was supported by the Cooperative Studies Program of the Department of Veteran Affairs Office of Research and Development and a National Research Service Award # 1 F32 HL69596–01.

	Appendix

 
Cognitive Tests^a

Short Orientation-Memory-Concentration Test: Scoring by errors 1. About what time is it (within 1hour)? 0,1 2. What month is it now? 0,1 3. What year is it now? 0,1 4. Say the months in reverse order. 0–2 (2 = 2 or more errors) 5. Count backwards from 20 to 1. 0–2 (2 = 2 or more errors) 6. Repeat the memory phase. "John Brown, 42 Market Street, Chicago" 0–5 Trail Making A Test: 7. Trail Making A Test (time in seconds) Time Mean + 1SD 0 Mean + 1 SD < Time Mean + 2 SD 1 Mean + 2 SD < Time Mean + 3 SD 2 Time > Mean + 3 SD 3 Behavorial Dyscontrol Scale: 8. Tap twice (dominant hand) and once (other hand). 0–4 9. Fist-edge-palm. 0–3 Total composite score 0–22

^aPatients were scored based on the number of errors on each question, except for the Trail Making A Test, where time in seconds was recorded.

Study participants
Chairman's office, Denver VAMC
Karl Hammermeister, MD, (Co-Chairman), Frederick L. Grover, MD (Co-Chairman), Gulshan Sethi, MD (Co-Chairman, Tucson VAMC), A. Laurie Shroyer, PhD (Health Services Researcher), Catherine B. VillaNueva, RN, MS/MBA (National Research Nurse Coordinator), Gary Grunwald, PhD (Biostatistician), Samantha MaWhinney, ScD (Biostatistician), (Guillermo Marshall, PhD (past Biostatistician), Maureen O'Brien, PhD (Data/Statistical Analyst), Josie Loftin (Secretary), Martin J. London, MD (Consultant), Jim Grigsby, PhD, (Consultant)

Hines Va Cooperative Studies Program Coordinating Center, Edward J. Hines Memorial Hospital, Hines, IL
Domenic J. Reda, PhD (Acting Director), William G. Henderson, PhD (Former Director), Thomas E. Moritz, MS (Biostatistician), Nancy K. Ellis, MS (National Data Coordinator), Raslan O. Othman, MS (Systems Analyst), Lizy Thottapurathu, MS (Statistical Programmer)

Consultant, Northwestern University, Chicago, IL
Martin J. McCarthy, Jr., PhD (Health Services Researcher)

Executive committee
Karl Hammermeister, MD, (Chairman), Frederick L. Grover, MD, Gulshan Sethi, MD, Martin J. London, MD, Shukri Khuri, MD, Gareth Tobler, MD, A. Laurie Shroyer, PhD, Gary Grunwald, PhD, Martin McCarthy, Jr., PhD, Maureen O'Brien, PhD, Thomas E. Moritz, MS, William Best, MD, James Gibbs, PhD, Edward L. Hannan, PhD, William G. Henderson, PhD, John G. Demakis, MD, Catherine B. VillaNueva, RN, MS/MBA

Participants (PI = principal investigator)
Ann Arbor
Marvin Kirsh, MD (PI), Constance Newman, RN (Research Nurse); Charleston: John Handy, MD (PI), Lisa Colton, RN, (Research Nurse); Denver: David Fullerton, MD (PI), Janet Baltz, RN (Research Nurse), David Werking, DDS (Follow-up Coordinator); Devra Peterson, RN (past Research Nurse), Shann Ludwig, RN/BSN (past Research Nurse), Sue Bott, MS/RN (past Research Nurse); Hines: Donald DePinto, MD (PI), Louise Barder, RN/MPH (Research Nurse); Little Rock: Kwabena Mawulawde, MD (PI), Gareth Tobler, MD (past PI), Michael Smith, RN, (Research Nurse), Barbara Mitchell, CNOR/RN (past Research Nurse), Brent Higdem, RN (past Research Nurse); Minneapolis: Herbert Ward, MD/PhD (PI), Ellie Carson, RN (Research Nurse); Nashville: Walter H Merrill, MD (PI), Jim Shaw, RN (Research Nurse), Crystal Knight, RN (past Research Nurse); New York: Richard A Esposito, MD (PI), Rosemary Mannix, RN (Research Nurse); Asheville: John Lucke, MD (PI), Stewart Scott, MD (past PI), Sheryl Davis, RN (Research Nurse), Kitty Williams-Wilcox, RN (past Research Nurse); San Diego: Riyad Tarazi, MD (PI), Cecilia Garcia, RN (Research Nurse), Kelly Hartmayer, RN (past Research Nurse); San Antonio: O. LaWayne Miller, MD (PI), Marina Silguero, RN (Research Nurse), Nancy I. Deegan, RN/MSN (past Research Nurse); Tucson: Casey Huston, MD (PI), Gayle Murad, RN (Research Nurse), Robert Alves, RN (past Research Nurse), Sandy Kline, RN (past Research Nurse), Nancy Day, RN (past Research Nurse); West Roxbury: Shukri Khuri, MD (PI), Janet Bannister, RN (Research Nurse); Milwaukee: Hossein Almassi, MD (PI), Tracy Sommer, RN/BSN (Research Nurse)

Data and safety monitoring board
Stephen Plume, MD, (Chairman), Frank Harrell, PhD, Lloyd Fisher, PhD, Paul D. Cleary, PhD, Barbara J. Holtzclaw, PhD/RN

VA headquarters
Philip Lavori, PhD, Acting Director CSP, Steven Berkowitz, PhD, Assistant Director, CSP

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This Article Abstract Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Add to Personal Folders Download to citation manager Author home page(s): Gulshan K. Sethi Martin J. London Frederick L. Grover Karl E. Hammermeister Permission Requests Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Ho, P. M. Articles by Hammermeister, K. E. Search for Related Content PubMed PubMed Citation Articles by Ho, P. M. Articles by Hammermeister, K. E. Related Collections Extracorporeal circulation