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ORIGINAL ARTICLES |
From the Department of Psychiatry, Washington University School of Medicine, St. Louis, MO (R.M.C., K.E.F.); Department of Psychiatry, Duke University Medical Center, Durham, NC (J.A.B); Department of Biostatistics, University of North Carolina, Chapel Hill, NC (M.Y.); Department of Psychiatry, University of Washington, Seattle WA (R.C.V.); Department of Psychiatry, Yale University, New Haven, CT (M.M.B.); Department of Psychiatry, University of Alabama Birmingham, AL (C.C.); Department of Psychiatry, University of Miami, Miami FL (P.G.S.); National Heart, Lung, and Blood Institute, Bethesda, MD (P.G.K., S.M.C.); Department of Medicine, Mayo Clinic, Rochester, MN (A.S.J.).
Address correspondence and reprint requests to Robert M. Carney, PhD, Behavioral Medicine Center, Washington University School of Medicine, 4625 Lindell Avenue, Suite 420, St. Louis, MO 63108. E-mail: carneyr{at}bmc.wustl.edu
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ABSTRACT |
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 TOP ABSTRACT INTRODUCTIONMETHODSRESULTSDISCUSSIONAPPENDIX 1ACKNOWLEDGMENTSREFERENCES |
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6 months after the myocardial infarction) mortality among initially depressed patients who had a Beck Depression Inventory score 10 and a past history of major depression, and who completed the 6-month post-treatment assessment. It also examines the relationship between change in depression and late mortality. METHODS: Out of the 1,165 (47%) of the Enhancing Recovery in Coronary Heart Disease study participants who met our criteria, 57 died in the first 6 months, and 858 (409 usual care, 449 intervention) completed the 6-month assessment. Cox regression was used to analyze survival.
RESULTS: The intervention did not affect late mortality. However, intervention patients whose depression did not improve were at higher risk for late mortality than were patients who responded to treatment.
CONCLUSIONS: Patients whose depression is refractory to cognitive behavior therapy and sertraline, two standard treatments for depression, are at high risk for late mortality after myocardial infarction.
Key Words: depression, • depressive disorder, • myocardial infarction, • mortality, • cognitive therapy.
Abbreviations: MI = myocardial infarction;; ENRICHD = the Enhancing Recovery in Coronary Heart Disease study;; UC = usual care;; INT = intervention;; CBT = cognitive behavior therapy;; BDI = Beck Depression Inventory;; DSM-IV = Diagnostic and Statistical Manual IV;; HR = hazard ratio;; LVEF = left ventricular ejection fraction.
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INTRODUCTION |
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There are several important questions that the ENRICHD primary analysis did not address. One concerns the effects of INT on the subgroup of patients whose depression would probably have persisted without treatment. Patients were recruited for ENRICHD within a few days of their MI so that they could receive INT as soon as medically possible. This was done because the risk of mortality is highest in the first few weeks or months after the onset of MI. Also, to maximize the number of subjects available for enrollment, patients with as few as two depression symptoms with an onset as recent as 1 week before the eligibility evaluation were enrolled. Consequently, the sample included patients with relatively mild, transient depression that would probably have resolved without treatment within weeks after the MI, in addition to patients with more persistent depression. Although there were sound reasons for including the mildly depressed patients, the persistently depressed subgroup might have benefited more from INT.
Another question not addressed by the primary analysis is whether INT succeeded in improving survival among patients who lived long enough to complete it. It often takes months to successfully treat depression. However, many patients were too medically ill to participate for several weeks or even months after enrollment, and some patients died during the INT phase of the trial. These patients were included in the trial’s primary survival analysis (9). Therefore, it did not address the question of whether completion of INT decreased the risk of mortality among patients who survived the first 6 months after MI, or whether there was a relationship between improvement in depression during the first 6 months and subsequent survival.
Obviously, it is not possible to identify with certainty the patients in the INT arm whose depression would have persisted without treatment. However, longer duration, greater severity, and prior history of major depression predict persistent depression (10). Although it would be desirable to restrict the analysis to patients with major depression, the sample size would be too small to test the present hypotheses. However, nearly half of coronary heart disease patients with minor depression go on to develop major depression, and the severity and duration of minor depression, along with prior history of major depression, predict progression from minor to major depression (11).
This manuscript therefore focuses on the subgroup of ENRICHD participants who had at least one prior episode of major depression, who met the full Diagnostic and Statistical Manual IV (DSM-IV) criteria for major or minor depression, including a duration 14 days, and who had a BDI score 10 at baseline. We hypothesized that in this subgroup, the risk of late mortality was lower in the INT than in the UC arm. We also hypothesized that improvement in depression over the first 6 months after the index MI was associated with a lower risk of late mortality in both arms. These are exploratory hypotheses in the sense that we formulated them after examining the primary results of the ENRICHD trial. However, they are a priori hypotheses in the sense that we proposed them before viewing the subgroup data or conducting the analyses reported below.
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METHODS |
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The sample for the present analysis is further limited to patients who met the DSM-IV criteria for a current major or minor depressive episode of at least 14 days duration and had a BDI score 10 at enrollment, who had a past history of at least one prior major depressive episode, who survived at least 6 months after their index MI, and completed the 6th month depression assessment. Depressed patients who did not meet these criteria, and non-depressed patients who were enrolled in ENRICHD solely on the basis of low perceived social support, were excluded from the analysis.
Procedure
Depression Assessment
Depression Interview and Structured Hamilton
The Depression Interview and Structured Hamilton (12) is a semi-structured interview developed for ENRICHD to diagnose current depressive episodes in cardiac patients according to the DSM-IV criteria, to determine the severity of depression using the 17-item Hamilton Rating Scale for Depression, and to screen for other psychiatric disorders. We have previously reported a high level of diagnostic agreement between Depression Interview and Structured Hamilton interviews administered to cardiac patients by trained research nurses and structured interviews administered by trained clinicians (weighted 
=.86) (12). The Depression Interview and Structured Hamilton was administered at baseline and repeated 6 months later.
BDI
The BDI (13) is a 21-item measure of the self-reported severity of depression. It was administered at baseline and at 6 months after enrollment.
Treatment
The participants were randomly assigned within 28 days of their index MI by an automated system located at the ENRICHD coordinating center, to receive either the intervention (INT) or usual care (UC). Both groups received the American Heart Association’s Active PartnershipTM health education booklet. The UC patients received no further contact from study personnel except for follow-up.
The intervention was guided by two standard cognitive behavior therapy manuals (13,14). The Beck Institute for Cognitive Therapy and Research provided the training and quality control for the intervention. The therapists were supervised by clinical investigators at each site and by Beck Institute personnel. The intervention, training, and quality control procedures are described in detail elsewhere (15). Participants randomized to the INT arm who were severely depressed (Hamilton Rating Scale for Depression score >24) at enrollment or who did not respond quickly enough to cognitive behavioral INT (<50% improvement in depression within 5 weeks of randomization) were referred to a study psychiatrist for concurrent pharmacotherapy. Unless contraindicated, sertraline was initiated at 50 mg per day and subsequently increased, if necessary, to a maximum of 200 mg per day. Patients who were unable to tolerate or who did not respond to sertraline were switched to an alternative antidepressant. The maximum duration of the intervention was 6 months for the cognitive behavioral therapy (CBT) component and 12 months for the sertraline component. Patients who required maintenance pharmacotherapy after 12 months were referred to their own physicians. CBT sessions continued for 6 months or until the patient met the ENRICHD criteria for early termination because of successful completion of treatment. These criteria included the following: (1) completion of at least 6 therapy sessions; (2) demonstration of adequate cognitive behavioral skills to maintain treatment gains and prevent relapse; (3) BDI 
7 for at least 2 consecutive weeks. Patients who met the criteria for successful completion of treatment before 6 months were contacted weekly until the 6 months elapsed. Patients who relapsed within the 6-month treatment window were scheduled for further treatment sessions.
Follow-up Evaluations
Follow-up assessments were performed annually beginning 6 months after enrollment. The assessments included a medical history, physical examination, and a resting electrocardiograph to detect otherwise unrecognized recurrent MI. Medical endpoints were ascertained by follow-up visits and phone calls, routine hospital surveillance, and contacts with the patient’s physician. Copies of the records of every identified hospitalization were obtained for review.
Endpoints
The primary endpoint for the present analysis was death from any cause. Because this report focuses on the effects of change in depression on late mortality, and because depression outcomes were not assessed until 6 months after randomization, only deaths that occurred at least 6 months after randomization were counted as end points.
Statistical Analysis
2 Tests and analyses of variance were used to determine whether the demographic and medical variables differed between INT and UC patients. Smoking status was classified as "current," "ever," or "never." Ejection fraction was reported as both a 3-level ordinal variable (<40%, 40–50%, >50%), and as a continuous measure in the hazard models. Age and body mass index were treated as continuous variables.
The first hypothesis was tested by generating survival curves with the Kaplan–Meier method to compare covariate-adjusted late mortality rates between the INT and UC groups using a log-rank statistic to test for a mean difference in survival time.
Cox proportional hazards regression (16) was used to model the covariate-adjusted effect of change in depression between enrollment and the 6-month follow-up on survival beyond 6 months. Separate analyses were performed for the INT and UC groups. The hazard ratio (HR) was set at 1.0 for patients whose 6-month BDI score remained the same as their baseline BDI score. The hazard estimates were adjusted for the demographic and medical variables that predicted all-cause mortality in the ENRICHD trial (17) including age, minority status, diabetes, left ventricular ejection fraction (LVEF), creatinine level, prior MI, history of pulmonary disease, prior transient ischemic attack or stroke, history of congestive heart failure, and coronary artery bypass graft surgery for the index MI.
Because LVEF was missing on 20% of the ENRICHD participants on a study-wide basis, we used a multiple imputation procedure with 50 iterations to impute missing LVEF data from known risk factors, characteristics of the index MI, and clinical and lifestyle factors. No medical outcome measures were used in the imputation. LVEF was then used after multiple imputation as a covariate in a proportional hazard model along with other predictors to generate parameter estimates and standard errors. SAS software (SAS Institute, Raleigh, NC) was used to perform the multiple imputation and the statistical analyses.
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RESULTS |
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Table 1 compares the baseline demographic and medical characteristics of these patients. There were no differences between the INT and UC patients on any of these variables. The mean BDI scores at baseline and at 6 months were 19.0 ± 7.8 and 9.9 ± 8.9 in the INT arm vs. 18.7 ± 7.3 and 13.0 ± 9.1 in the UC arm (p < .0001 for the 6-month group difference). During the first 6 months, 22.6% of the INT patients and 14.1% of the UC patients were on antidepressants (p < .0003).
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HRs and confidence intervals, adjusted for the baseline BDI score, medical covariates, and use of antidepressants, were calculated to determine the relationship of change in BDI during the first 6 months to survival beyond 6 months. The association was significant in the INT arm (HR = 1.05 [1.01, 1.08], p < .007), but not in the UC arm (HR = 0.99 [0.95, 1.03], p = .76). Figure 1 displays the adjusted hazard estimates for late mortality by change in depression from baseline to 6 months in both arms. The figure is derived from a series of covariate-adjusted Cox proportional hazard models. The extreme values are based on small numbers of patients and should be interpreted with caution.
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0) INT patients with respect to demographic and medical variables. The adjusted HR for patients who improved during treatment compared with those who did not was 0.37 ([0.20–0.72], p < .003).
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To determine whether the patients in the INT arm who did not improve were more likely to have dropped out of treatment or to have become too medically ill to continue or benefit from INT, they were compared with patients who improved. Neither of these events were more common among the unimproved than the improved patients. In addition, the improved and unimproved patients within the INT arm were compared with respect to their progress during treatment and to their psychiatric history. The unimproved patients were more likely to have had at least one psychiatric hospitalization before enrollment, and they were more likely to be on antidepressant maintenance therapy. These comparisons are presented in Table 3.
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DISCUSSION |
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Because we focused on late mortality and on a subgroup of the depressed patients, we had a total of only 102 deaths during follow-up, far fewer than were modeled in the trial’s primary analysis. Nevertheless, there was a significant relationship between change in depression and late mortality in the intervention arm. That is, the patients who responded to the intervention, as indicated by a decrease in their BDI score, were at lower risk of late mortality than were patients whose depression persisted or worsened. For example, patients in the INT arm who exhibited a 10 point or greater increase (worsening) in BDI scores were 1.6 times more likely to die in the ensuing months than were patients whose BDI score did not change, and 2.5 times as likely to die as those patients whose BDI score decreased (improved) by 10 or more points during treatment. Many of the patients whose depression worsened during the 6 months of intervention met the criteria for minor depression at baseline and later developed major depression. In contrast, there was no significant relationship between change in depression and late mortality in the UC group. These effects were independent of the baseline BDI score, medical and demographic predictors of mortality, and antidepressant use.
It is not clear why lack of improvement in depression predicted mortality only in the INT arm. Fewer INT than UC patients failed to improve (15% vs. 26%), yet the incidence of mortality among non-improvers was higher in the INT arm than in the UC arm (21.2% vs. 10.4%). The patients in the intervention arm who failed to improve did so despite intensive efforts to treat their depression. Thus, they appear to have a treatment-refractory form of depression. In contrast, only about 15% of the patients in the UC arm received any form of non-study treatment for their depression during the first 6 months, and even fewer of the patients in the UC arm who failed to improve received treatment. Some of them might not have remitted even if they had received treatment, but others might have responded well to treatment had it been provided. Thus, it is possible that the study intervention uncovered a subtype of depression that confers a high risk for late mortality, ie, patients who do not respond to standard antidepressant therapies (CBT and sertraline).
Whereas the INT arm appears to have included patients whose depression would only have improved with treatment, most of the patients who improved in the UC arm did so without treatment. The results displayed in Figure 2 support this interpretation. There is a stronger relationship between response to treatment and late mortality among patients who received both sertraline and CBT than among patients who received only CBT. There was a similar relationship of change in depression to survival in the UC arm among patients who received antidepressants, although it was not statistically significant.
Neither the proportion of minority patients nor the level of education differed between the arms. The INT patients whose depression either did not improve or got worse were less likely to have had thrombolytic therapy or coronary artery bypass graft surgery and more likely to have had percutaneous transluminal coronary angioplasty than were the patients whose depression improved. However, none of these patients were judged by their therapists to be too severely medically ill to receive or to benefit from treatment, and the relationship between change in depression to late mortality remained significant after adjustment for medical and demographic predictors of mortality. Nevertheless, it is possible that an undetected decline in the health of these patients might have both undermined improvement in depression and increased the risk of late mortality.
There were no differences between patients in the INT arm who improved and those who did not with regard to logistical barriers to receiving the intervention, such as lack of transportation. There was only a nonsignificant, one-session difference between them in the total number of treatment sessions received. The unimproved patients were no more likely to have dropped out of treatment or to have canceled sessions than were the responders. Although there is no evidence that the patients who failed to improve received qualitatively less adequate treatment than the more successfully treated patients, this possibility cannot be entirely ruled out.
Patients who did not improve were more likely to have had prior psychiatric hospitalizations and to have had electroconvulsive therapy, although such histories were reported in very few cases in either group. Interestingly, however, the patients who failed to improve were slightly less depressed at baseline than were the patients who improved, as indicated by lower BDI scores.
It is possible that the patients who failed to respond to INT might have felt more hopeless than before treatment began. That is, finding that they were still depressed despite completing an intensive INT, they might have felt even more hopeless than they did before beginning treatment. Hopelessness has been shown to be a strong predictor of mortality in post-MI patients, and in one study, it was a stronger predictor of mortality than was depressed mood (18). Unfortunately, hopelessness was not assessed in detail in the ENRICHD trial.
It is also possible that treated patients who did not improve had a qualitatively different form of depression than the patients who showed improvement. For example, there is evidence that some cases of late-onset depression are either caused or exacerbated by cerebrovascular disease (18). Structural and functional brain abnormalities have been documented in patients whose first episode of depression began late in life. Depression that may be the result of cerebrovascular disease has been called "vascular" depression (19). Cerebrovascular comorbidity is common in elderly patients with advanced coronary heart disease, and depression in these patients may not respond to CBT or even to sertraline. However, all of the patients included in the present analysis had at least one prior episode of depression, and there were no differences between the improved and unimproved groups in age at enrollment, age at time of the initial depressive episode (mid-30s, on average), the number of prior episodes, the duration of the current episode, or the proportion of patients with a family history of depression. Cerebrovascular disease is associated with late-onset but not early-onset depression. Nevertheless, the possible contribution of cerebrovascular disease to nonresponse to CBT and sertraline cannot be excluded.
Other potential differences between the patients who improved and those who did not are suggested by studies of treatment-refractory depression. Patients with treatment-refractory depression have evidence of adrenergic and serotonergic disturbances (20), hypothalamic–pituitary–adrenal axis dysregulation (21–23), elevated inflammatory markers suggesting an immunological acute phase response (24,25), and low plasma folate and high homocysteine levels (26). All of these abnormalities have also been suggested as possible mechanisms underlying the effect of depression on mortality in patients with CHD (27). Thus, it is possible that the depressed patients who are at the highest risk for dying as a result of specific physiological abnormalities may be the same ones who are refractory to standard antidepressant treatment. This could also explain the failure of the ENRICHD intervention to reduce mortality and recurrent MI, despite improving depression.
Whatever the explanation for their failure to respond to treatment, patients whose depression does not improve with treatment are at an increased risk for late mortality. As a result, they should be followed more closely and perhaps be given more aggressive cardiological care than other depressed cardiac patients. Every effort should be made to intervene in all other modifiable risk factors, and to treat all comorbid medical disorders to the extent possible. More aggressive treatment for depression may also be warranted, but further research is needed to develop more effective ways to treat depression in patients with CHD who do not respond to first-line interventions.
The results of these secondary analyses must be interpreted with caution. The ENRICHD clinical trial failed to demonstrate that treating depression or improving social support improves survival. We conducted these secondary analyses to determine whether improvement in depression was related to late mortality in a subgroup of patients meeting the full DSM-IV criteria for major or minor depression, including a duration of 14 or more days, with at least one prior episode of major depression, and a BDI of 10 or greater at enrollment. We found that failure to improve despite aggressive treatment for depression is associated with an increased risk for late mortality in post-MI patients. This unexpected finding warrants further investigation.
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APPENDIX 1 |
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TOPABSTRACTINTRODUCTIONMETHODSRESULTSDISCUSSIONAPPENDIX 1ACKNOWLEDGMENTSREFERENCES |
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Rush Presbyterian-St. Luke’s Medical Center, Chicago, Illinois
Lynda H. Powell, PhD (Principal Investigator), James E. Calvin, MD, David C. Clark, PhD, David Cook, MD, Steven Creech, MS, Hugo Cuadros, MD, Gloria Darovic MSN, RN, Pablo Denes, MD, Diane Downs, RN, BSN, Claudia Eaton, MS, RN, W. J. Elliott, MD, Joseph Fanelli, MD, Daniel Fintel, MD, Kristin Flynn, PhD, Pilar Frankowicz, Patricia Hernandez, Layla Kassem, PsyD, Philip Krause, MD, Alice Luten, PhD, Carlos Mendes de Leon, PhD, William S. Miles, PhD, Rocio Munoz–Dunbar, MA, Paige Pfenninger, RN, BSN, Carol Rogers Pitula, PhD, RN, Daniel Rowan, MD, Simona K. Reichmann, PhD, Nancy L. Sampson, BA, Leila Shahabi, RN, BSN, Susan Szeplakay, RN, Darla Vale, RN, Friedman Yaakov, MD, John Zajecka, MD, Joe Zander, PhD, and Alan Zunamon.
Stanford University, Palo Alto, California
Robert F. DeBusk, MD (Principal Investigator), Linda Balenesi, RN, Anna Casteneda, Dianne Christopherson, PhD, RN, Alison Deeter, Susan Duenke, PsyD, Lynda Fisher Forseth, Erika S. Froelicher, University of California, San Francisco, California, PhD, RN, FAAN, Anne Blair Greiner, M.S., Robin Hanna, RN, Heidi Kaiser, Sarah Lamb, RN, Simone Madan, PhD, Margaret Marnell, PhD, Kirsten Martin, RN, Nancy Houston Miller, RN, BSN, Lexa Most, RN, BSN, Kathleen Parker, RN, MSN, Stephen Rao, PhD, Peggy Raymond, Diane Strachowski, PhD, C. Barr Taylor, MD, Marcia Thompson, RN, BSN, Barbara Tremor, RN, BSN, and Carl E. Thoresen, PhD.
University of Alabama at Birmingham, Birmingham, Alabama
James M. Raczynski, PhD (Principal Investigator), Barry Adams, PsyD, Stephanie Allison, RN, Melba Bandy, RN, James Barton, RN, Larry Bates, PhD, Vera Bittner, MD, Dianne Caddell, Martha Cole, Carol E. Cornell, PhD, Vicki DiLillo, PhD, Jeff Dolce, PhD, Angela Fort, RN, M. Janice Gilliland, MA, MSPH, Deborah K. Ingle, RN, Shelly Jordan, JD, BSN, Jerry Markovitz, MD, Dehryl Mason, JD, PhD, John Shuster, MD, MPH, Herman Taylor, MD, Suzanne Thompson, Patricia White, PhD, and Suzan Winders, PhD (ClinSites SORRA Research).
University of Miami, Coral Gables, Florida
Neil Schneiderman, PhD (Principal Investigator), Martha Diaz, Karen Esposito, MD, PhD, Marc Gellman, PhD, M. Gutt, PhD, Gail Ironson, MD, PhD, H. Jimenez, MD, Kristin Kilbourn, PhD, Gervasio Lamas, MD, F. Lopez–Jimenez, MD, MSc, Marta E. Manrique–Reichard, PhD, Judith Rey McCalla, PhD, Thomas Mellman, MD, Caridad V. Mendoza, RN, Robert Meyerburg, MD, F. Penedo, MS, Elsa Velez Robinson, RN, Patrice Saab, PhD, Rafael Sequeira, MD, Pura Teixeiro, RN, and Joy Whitelock, RN, BSN.
University of Washington, Seattle, Washington
Pamela Mitchell, PhD, RN (Principal Investigator), Patricia Betrus, PhD, RN, Elizabeth Bridges, MN, RN, Helen K. Budzynski, PhD, RN, Ann Buzaitis, MN, ARNP, Wan Chen, RN, and Virginia Concannon, RN, BSN. Marie J. Cowan, PhD, RN, FAAN (Principal Investigator 1995–1997), Susanna L. Cunningham, PhD, RN, Frances DeRook, MD, Cecily Erickson, RN, BSN, Peg Hanrahan, MS, RN, Pamela Hardin, RN, Becci Kimball, RN, BSN, Catherine Kirkness, RN, MN, David Kosins, PhD, Donald Kunz, BA, Murray Raskind, MD, Stephen Sholl, PhD, Fendley Stewart, MD, Karen Sturm, RN, Richard C. Veith, MD, Charles Wilkinson, PhD, and Susan L. Woods, RN, PhD.
Washington University, St. Louis, Missouri
Robert M Carney, PhD (Principal Investigator), Michael Cox, MD, Linda Beller, RN, MSN, Kathy Bence, RN, MBA, Teresa Benoist, RN, BSN, Stephen Berger, PhD, Sarah Breeden, RN, Laura Brewer, PhD, Iris Csik, MSW, Jerome D. Cohen, MD, Paul R Eisenberg, MD, Kelly Everard, PhD, Jane Finn, RN, BSN, Kenneth E. Freedland, PhD, Patricia Hoffman, PhD, Deirdre Kanakis, PhD, Tiffany Lynch, RN, BSN, Janet Meyer, RN, BSN, Angela Misuraco, RN, BSN, Kathy Petty, RN, BSN, James Preston, Jr., PharmD, BCPS, Michael W. Rich, MD, Stephen Ristvedt, PhD, Carol Sparks, LPN, Kay Schneider, Debbie Sitton, RN, BSN, Judith Skala, RN, MA, Angie Tanner, BS, and Edward S. Weiss, MD.
Yale/Harvard Center, New Haven, Connecticut, and Boston, Massachusetts
Matthew M. Burg, PhD (Principal Investigator), Lisa Berkman, PhD (Harvard University, Boston, MA, Co-Principal Investigator), David Abrams, PhD, Daniel Beck, MBA, LICSW, Paula P. Clark, RN, Susan Farber, PhD, Sandy Ginter, RN, BSN, Keith R. Gonsor, PhD, L. Howard Hartley, MD (Harvard University), Peter Herbert, MD, Selby Jacobs, MD, Renée Kochevar, PhD (Harvard University), Harlan Krumholz, MD, Andrew Littman, MD, MD, Peter Manzo, PhD, Joanne McGloin, MDiv, Thalia Metalides, RN, BSN, James Muller, MD, Sandip Mukherjee, MD, Jane Sherwood, RN, BSN (Harvard University), Thomas Stewart, Andrew Stohl, MD, MD, Peter Stone, MD (Harvard University), and Stuart Zarich, MD.
Coordinating Center: The University of North Carolina at Chapel Hill, North Carolina
James D. Hosking, PhD (Principal Investigator 1995–2001), Diane Catellier, DrPH (Principal Investigator, 2001-present), Hope Bryan, Linda A. Hartig, Jean Johnson, Francis Keefe, PhD (Duke University, Durham, NC), Marc Huber, MS, Varsha Shah, MSE, Kathleen Light, PhD, Lynn Martin, Ravi Mathew, MS, Aluoch Ooro, James Schaefer, David Sheps, MD (University of Florida, Gainsville, FL), Guochen Song, MS, Climmon Walker, and Marston E. Youngblood, MA, MPH.
Project Office: National Heart, Lung and Blood Institute, Bethesda, Maryland
Susan M. Czajkowski, PhD (Project Officer), Robin Hill, PhD (deceased), Sally Hunsberger, PhD, Cheryl A. Jennings, Peter Kaufmann, PhD, Sarah Knox, PhD, James Norman, PhD, Julie Reid, and Carolyn C. Voorhees, PhD.
Center for Therapist Training and Quality Control: Beck Institute for Cognitive Therapy and Research, Bala Cynwyd, Pennsylavania
Judith S. Beck, PhD (Director), Naomi Dank, PhD, Christine Reilly, PhD, RN, and Lesile Sokol, PhD.
Electrocardiogram Reading Center: St. Louis University, St. Louis, Missouri
Bernard Chaitman, MD (Principal Investigator), Theresa Belgeri, RN, P. Cameron, BS, Ihor Gussak, MD, PhD, M. Miller, BA, Karen Stocke, BS, MBA, and Janet Holmes, BSN.
Study Chair and Co-ChairStudy Chair and Co-Chair
Lisa F. Berkman, PhD (Chair; Harvard University), and Allan Jaffe, MD (Co-chair; Mayo Clinic, Rochester, MN).
Data and Safety Monitoring Board
Nanette Wenger, MD (Chair), Baruch Brody, PhD, Luther Clark, MD, James Coyne, PhD, Robert M. Kaplan, PhD, Roger Kathol, MD, and Genell Knatterud, PhD.
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ACKNOWLEDGMENTS |
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This manuscript is dedicated to the memory of Dr. Robin Hill.
Received for publication May 29, 2003.
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 K. A. Riekert, S. J. Bartlett, M. P. Boyle, J. A. Krishnan, and C. S. Rand The Association Between Depression, Lung Function, and Health-Related Quality of Life Among Adults With Cystic Fibrosis Chest, July 1, 2007; 132(1): 231 - 237. [Abstract] [Full Text] [PDF]
|
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 J. L. Steel, D. A. Geller, T. C. Gamblin, M. C. Olek, and B. I. Carr Depression, Immunity, and Survival in Patients With Hepatobiliary Carcinoma J. Clin. Oncol., June 10, 2007; 25(17): 2397 - 2405. [Abstract] [Full Text] [PDF]
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 J. J. Gallo, H. R. Bogner, K. H. Morales, E. P. Post, J. Y. Lin, and M. L. Bruce The Effect of a Primary Care Practice-Based Depression Intervention on Mortality in Older Adults: A Randomized Trial Ann Intern Med, May 15, 2007; 146(10): 689 - 698. [Abstract] [Full Text] [PDF]
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T. Rutledge, V. A. Reis, and S. E. Linke Reply J. Am. Coll. Cardiol., April 3, 2007; 49(13): 1504 - 1504. [Full Text] [PDF]
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 A. Sherwood, J. A. Blumenthal, R. Trivedi, K. S. Johnson, C. M. O'Connor, K. F. Adams Jr, C. S. Dupree, R. A. Waugh, D. R. Bensimhon, L. Gaulden, et al. Relationship of Depression to Death or Hospitalization in Patients With Heart Failure Arch Intern Med, February 26, 2007; 167(4): 367 - 373. [Abstract] [Full Text] [PDF]
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S. Parashar, J. S. Rumsfeld, J. A. Spertus, K. J. Reid, N. K. Wenger, H. M. Krumholz, A. Amin, W. S. Weintraub, J. Lichtman, N. Dawood, et al. Time course of depression and outcome of myocardial infarction. Arch Intern Med, October 9, 2006; 166(18): 2035 - 2043. [Abstract] [Full Text] [PDF]
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 A. Ahmed, M. Ali, C. M. Lefante, M. S. I. Mullick, and F. C. Kinney Geriatric Heart Failure, Depression, and Nursing Home Admission: An Observational Study Using Propensity Score Analysis Am J Geriatr Psychiatry, October 1, 2006; 14(10): 867 - 875. [Abstract] [Full Text] [PDF]
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K. W. Davidson, D. J. Kupfer, J. T. Bigger, R. M. Califf, R. M. Carney, J. C. Coyne, S. M. Czajkowski, E. Frank, N. Frasure-Smith, K. E. Freedland, et al. Assessment and treatment of depression in patients with cardiovascular disease: national heart, lung, and blood institute working group report. Psychosom Med, September 1, 2006; 68(5): 645 - 650. [Abstract] [Full Text] [PDF]
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M. M. Burg, J. Barefoot, L. Berkman, D. J. Catellier, S. Czajkowski, P. Saab, M. Huber, V. DeLillo, P. Mitchell, J. Skala, et al. Low Perceived Social Support and Post-Myocardial Infarction Prognosis in the Enhancing Recovery in Coronary Heart Disease Clinical Trial: The Effects of Treatment Psychosom Med, November 1, 2005; 67(6): 879 - 888. [Abstract] [Full Text] [PDF]
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G. E. Miller, N. Rohleder, C. Stetler, and C. Kirschbaum Clinical Depression and Regulation of the Inflammatory Response During Acute Stress Psychosom Med, September 1, 2005; 67(5): 679 - 687. [Abstract] [Full Text] [PDF]
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A. J.M. Broadley, M. P. Frenneaux, V. Moskvina, C. J.H. Jones, and A. Korszun Baroreflex Sensitivity Is Reduced in Depression Psychosom Med, July 1, 2005; 67(4): 648 - 651. [Abstract] [Full Text] [PDF]
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