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Depressive Symptoms and Mortality Two Years After Coronary Artery Bypass Graft Surgery (CABG) in Men

From Veterans Affairs Connecticut Healthcare System (M.M.B., M.C.B., R.S.), West Haven Campus, West Haven, Connecticut 06516; Section of Cardiovascular Medicine (R.S., M.M.B.); Yale University School of Medicine, New Haven, Connecticut 06510; and Mt. Sinai School of Medicine (M.M.B.), New York, New York 10029.

Address reprint requests to: Matthew M. Burg, PhD, VA Connecticut Healthcare System/116B4, 950 Campbell Ave., West Haven, CT 06516. Email: mburg{at}attglobal.net

Received for publication November 19, 2002; revision received April 22, 2003.

	ABSTRACT

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OBJECTIVES: Depression has been related to mortality in patients with CAD and to medical morbidity after CABG; however, prior studies have not examined the contribution of presurgical depressive symptoms to mortality after CABG. The purpose of this study was to determine the independent contribution of presurgical symptoms of depression to 2-year cardiac mortality after CABG.

METHODS: Eighty-nine consecutive veteran nonemergent CABG patients recruited between December 1996 and June 1998 completed the BDI 1 to 7 days before surgery. Mortality risk was assessed by medical co-morbidity and RIS.

RESULTS: Significant univariate contributions to two-year cardiovascular mortality were found for RIS (² = 6.57, p < .01), history of CHF (² = 4.94, p < .02), history of COPD (² = 5.19, p < .02), and elevated depressive symptoms (² = 4.70, p < .03). The multivariate model revealed that the RIS (² = 4.70, p < .03) and elevated depressive symptoms (² = 3.86, p < .05) remained significant in the prediction of 2-year cardiovascular mortality, with no other variables being found significant.

CONCLUSIONS: Elevated depressive symptoms before CABG surgery appear to be an important independent contributor to long-term mortality. Future research should focus on replication with larger, more diverse samples, and identification of pathophysiological mechanisms.

Key Words: depression, • coronary artery bypass graft surgery, • prognosis.

Abbreviations: CABG = coronary artery bypass graft surgery;; CAD = coronary artery disease;; BDI = Beck Depression Inventory;; MI = myocardial infarction;; COPD = chronic obstructive pulmonary disease;; CHF = congestive heart failure;; RIS = Risk Index Score.

	INTRODUCTION

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Elevated depressive symptoms contribute significantly to medical morbidity and mortality in patients with CAD, independent of severity of disease, left ventricular dysfunction, and other prognostic factors (1–4). CABG is a treatment of choice for relief of angina and improvement in quality of life. We have previously reported that pre-CABG depression predicted 6-month medical morbidity (5); others have found major depression after CABG to be associated with increased risk of a cardiac event (excluding death) 1 year after surgery (6). The purpose of the present study was to examine whether pre-CABG depressive symptoms were associated with 2-year cardiac-related mortality.

	METHODS

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Patient Sample
This is a follow-up of a sample described previously (5). In brief, the sample was comprised of 89 consecutive male patients admitted for nonemergent CABG. The mean age was 66.3 years (range 42–83) and mean level of education was 10.5 years (range 4–20 years). Fifty percent were married, 30% were divorced, and 20% were widowed or single. Seventy-one percent were either retired or unemployed. The local Human Investigations Subcommittee approved the study.

Measures
Potential medical contributors to post-CABG mortality included the RIS of Tu et al. (7, 8) (calculated from age, gender, left ventricular function, urgency of CABG surgery, and whether the CABG surgery is a repeat procedure), cardiac history (previous MI, history of CHF, history of arrhythmia) and medical comorbidities (history of COPD, diabetes mellitus, and renal insufficiency). Depression was assessed by using the BDI (2, 9, 10). History of and/or treatment for depression and/or anxiety disorders were not assessed.

Follow up
Survival 2 years after CABG was determined from a review of the patient’s medical record, and through an interview with the patient and/or a family member. Ascertainment of end point and cause of death were available for all patients.

Procedure
Procedures have been described previously (5). In brief, patients provided informed consent and completed the BDI in the week before surgery; demographics, medical history, and risk status were assessed at that time. Two years after CABG, patient medical record was reviewed to determine survival status. When information was incomplete or unclear, the patient and/or family were contacted. In each event of death, the cause was ascertained from medical record and/or death certificate. Survival/death and cause were determined for all patients.

	RESULTS

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Depression
As reported previously (5), the population was grouped based on a cut point of 10 and above on the BDI, selected as indicative of clinically significant depressive symptoms (2). Twenty-five patients scored 10 or greater on the BDI (mean = 16.55, SD = 5.96), whereas 64 scored below 10 (mean = 4.87, SD = 2.70). Also, as reported previously (5), there was no relationship between depressive symptom group and any of the range of demographic variables, traditional risk factors for coronary disease, medications, medical comorbidities, historical aspects of CHD, or other CABG risk related variables (including the RIS).

Mortality
There were a total of seven deaths during the 2-year follow-up period, five among patients scoring 10 or greater on the BDI (4 cardiac deaths, 1 cancer), and two among patients scoring <10 (1 cardiac, 1 cancer). No deaths were due to stroke. Only analyses for cardiac death are reported.

Predictors of Mortality
In a series of univariate logistic regression analyses, significant contributions to 2-year cardiovascular mortality were revealed for RIS (² = 6.57, p < .01), history of CHF (² = 4.94, p < .02), history of COPD (² = 5.19, p < .02), and depressive symptom group (² = 4.70, p < .03). Including these variables in a single multivariate predictor model revealed a significant effect for RIS (² = 4.70, p < .03) and depressive symptom group (² = 3.86, p < .05). No other variables, including 6-month medical morbidity, were found significant in the multivariate model (see Table 1).

	DISCUSSION

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These findings expand on the literature that has demonstrated an association between diagnostic depression and/or significant levels of depressive symptoms in CABG patients assessed either before or after surgery, and 6 to 12 month medical morbidity (5, 6). In recent years, significant improvements in surgical technique have overall reduced mortality after CABG. The findings of this study, in conjunction with earlier findings (5, 6), however, demonstrate that the assessment of depressive symptoms and/or diagnostic depression should be viewed in the context of overall risk assessment for post-CABG medical morbidity and mortality that includes factors such as left ventricular function and medical comorbidity (11–13).

Because it was beyond the scope of the current study to ascertain whether deaths were due to CAD progression in native vessels, to graft occlusion, or to some other process such as ventricular arrhythmia, ascertainment of the key pathway(s) in the observed depressive symptom:mortality relationship will be important in any future studies. For example, deaths due to CAD progression in native vessels can be viewed as consistent with research regarding BDI score and mortality in CAD populations (1–4), while sudden or arrhythmic death can be seen as consistent with the effects of depression on sympathovagal balance (14). Deaths due to occlusions in grafts placed during CABG, which could be viewed as acting through some pathway that rapidly damages bypass grafts, are not supported, given the lack of a relationship between 6-month medical morbidity and 2-year mortality. Determination of the processes relevant to the CABG population will provide important guidance for the design of subsequent clinical trials.

Determination of the cause of death in CABG patients with depression will not necessarily identify the pathophysiological pathway underlying the effects of depression on mortality, however. This identification will require mechanistic substudies in association with a larger replication and/or subsequent clinical trial. Pathways that have been proposed to account for the link between depression and mortality in patients with CAD more generally include poorer self care and lack of adherence to medical therapy, heightened sympathetic tone, and/or impaired sympathovagal balance (14). Recent interest in inflammatory processes and platelet activity also appears promising, given their role both in CAD outcomes (15) and depression (1, 16, 17). Identification of pathophysiological pathways could inform future clinical trials and provide intermediate markers of treatment effects.

The findings of this study are important; however, the selectivity of the sample (older male veterans), and the absence of information regarding psychiatric comorbidity and/or treatment for depression are limitations. Furthermore, the modest size of the cohort and the relatively small number of deaths resulted in a wide confidence interval for the Depression Index’s odds ratio. A replication with a larger and more diverse sample would address these issues and likely yield a narrower confidence interval, and this should be pursued. Replication would also provide an opportunity to examine a range of other issues. For example, in addition to an assessment of depressive symptoms by the BDI, the larger effort should also ascertain whether current and/or historic diagnosis of depressive disorders increases or in any way modifies the risk associated with BDI score. A larger replication would also provide for a more complete evaluation of the effects of gender, age, socioeconomic factors, and psychiatric comorbidity (eg, anxiety), while also examining the potential mitigating effects of treatment for depression, and social support. Successful replication could then pave the way for the pursuit of clinical trials to examine the impact of treating depression and/or depressive symptoms in CABG patients on quality of life, medical outcomes, and longer-term survival.

	ACKNOWLEDGMENTS

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This work was supported by a Veterans Affairs Merit Review Grant award to the first and third authors, and by National Heart, Lung, and Blood Institute Grant 1 R01 HL-59619-01 (to R.S.).

	REFERENCES

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