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Effect of Depression on Five-Year Mortality After an Acute Coronary Syndrome

2005; Elsevier BV; Volume: 96; Issue: 9 Linguagem: Inglês

10.1016/j.amjcard.2005.06.052

1879-1913

Sherry L. Grace, Susan Abbey, Moira K. Kapral, Jiming Fang, Robert P. Nolan, Donna E. Stewart,

Mental Health Treatment and Access

Previous research has established a relation between depression at the time of cardiac hospitalization and patient mortality. The objective of this study was to examine the role of depressive history and symptomatology during hospitalization on 5-year all-cause mortality after admission for an acute coronary syndrome. We recruited 750 patients who had unstable angina pectoris and myocardial infarction from 12 coronary care units between 1997 and 1999. Measurements included sociodemographic and clinic data and the Beck Depression Inventory (BDI). Data were linked to an administrative database to determine 5-year all-cause mortality. Survival data were adjusted using a Cox's proportional hazards model. One hundred seventy-four participants (23.2%) self-reported a history of depressed mood for >2 weeks, 235 (31.3%) had elevated BDI scores at index hospitalization, with 105 (14.0%) reporting persistent depressive symptomatology. One hundred fifteen participants (15.3%) died by 5 years after hospitalization. After adjusting for prognostic indicators, such as cardiac disease severity, medical history, and smoking, depressive symptomatology during hospitalization was significantly predictive of mortality, but depressive history was not. Hazard ratios associated with BDI scores 2 weeks, 235 (31.3%) had elevated BDI scores at index hospitalization, with 105 (14.0%) reporting persistent depressive symptomatology. One hundred fifteen participants (15.3%) died by 5 years after hospitalization. After adjusting for prognostic indicators, such as cardiac disease severity, medical history, and smoking, depressive symptomatology during hospitalization was significantly predictive of mortality, but depressive history was not. Hazard ratios associated with BDI scores 2 weeks (yes/no). Survey data were linked with clinical data that were compiled by coronary care unit nurses, which included Killip's class11Killip T. Kimball J.T. Treatment of myocardial infarction in a coronary care unit a two year experience with 250 patients.Am J Cardiol. 1967; 20: 457-464Abstract Full Text PDF PubMed Scopus (1766) Google Scholar as an indicator of illness severity and medical history (i.e., hypertension, diabetes, congestive heart failure, or previous myocardial infarction). Depressive symptoms at the time of hospitalization were assessed by the Beck Depression Inventory (BDI),12Beck A.T. Ward C.H. Mendelson M. Mock J. Erbaugh J. An inventory for measuring depression.Arch Gen Psychiatry. 1961; 4: 561-571Crossref PubMed Scopus (29332) Google Scholar a reliable and well-validated 21-item scale that uses a forced-choice 4-alternative response format that has been widely used in the general population and in populations with long-term illness, including cardiac problems.13Steer R.A. Cavalieri T.A. Leonard D.M. Beck A.T. Use of the Beck Depression Inventory for primary care to screen for major depression disorders.Gen Hosp Psychiatry. 1999; 21: 106-111Abstract Full Text Full Text PDF PubMed Scopus (239) Google Scholar, 14Frasure-Smith N. Lesperance F. Talajic M. Depression following myocardial infarction impact on six-month survival.JAMA. 1993; 270: 1819-1825Crossref PubMed Scopus (1886) Google Scholar, 15Shnek Z.M. Irvine J. Stewart D.E. Abbey S. Psychological factors and depressive symptoms in ischemic heart disease.Health Psychol. 2001; 20: 141-145Crossref PubMed Scopus (60) Google Scholar, 16Beck A.T. Steer R.A. Garbin M.G. Psychometric properties of the Beck Depression Inventory twenty-five years of evaluation.Clin Psychol Rev. 1988; 8: 77-100Crossref Scopus (9501) Google Scholar, 17Frasure-Smith N. In-hospital symptoms of psychological stress as predictors of long-term outcome after acute myocardial infarction in men.Am J Cardiol. 1991; 67: 121-127Abstract Full Text PDF PubMed Scopus (245) Google Scholar Higher scores reflect greater depressive symptomatology, with scores >10 reflecting mild to severe symptomatology. The internal consistency of the BDI had an α value of 0.87 in the present sample. Based on the universal and centralized health care system in the province, we were able to obtain comprehensive follow-up information on the sample of participants using the Registered Persons Database. Linkage to a Discharge Abstract Database enabled determination of co-morbidity to compute the Charlson Comorbidity Index.18Charlson M. Pompei P. Ales K. MacKenzie C. A new method of classifying prognostic comorbidity in longitudinal studies development and validation.J Chron Dis. 1987; 40: 373-383Abstract Full Text PDF PubMed Scopus (37038) Google Scholar Consecutive patients who were diagnosed with myocardial infarction or unstable angina in 12 coronary care units across south-central Ontario, Canada, were approached for the study. Characteristics of participants and nonparticipants are listed in Table 1. Of the almost 1,800 patients who were approached, participants were significantly younger than those who refused or were ineligible to participate (t = −13.08, p <0.001). Significantly more men than women agreed to participate (chi-square 14.00, p <0.001), and more married and fewer widowed patients agreed to participate (chi-square 21.46, p <0.001).Table 1Nurse-reported characteristics of participants versus nonparticipants (ineligible, refused) at time of index hospitalizationVariableParticipants (n = 910)Nonparticipants (n = 890)Women320 (35.0%)385 (43.7%)⁎p <0.001.Married667 (73.1%)551 (62.5%)⁎p <0.001.Myocardial infarct478 (52.4%)490 (55.6%)Age (yrs)62 (12.00)69 (12.25)⁎p <0.001. p <0.001. Open table in a new tab Nine hundred ten patients (590 men and 320 women, 69% response rate) consented to participate in the study. Patients were 31 to 93 years old (mean 61.9 ± 12.0). Seventy-four percent of participants (n = 664) were married, and 45% (n = 340) had a family income above $50,000 Canadian (i.e., ∼$32,000 United States) annually. Fifty-three percent (n = 482) had a confirmed myocardial infarction, and 47% (n = 424) were diagnosed as having unstable angina after appropriate diagnostic tests. From the initial cohort of 910 participants who were recruited, we were able to match 867 of these participants with unique encrypted identifiers (43 participants lost, 4.7%), and link 856 to the Canadian Institute of Health Information Discharge Abstract Database (11 patients lost, 1.2% of overall cohort). No cases were lost while linking to the Registered Persons Database. Of this cohort, 836 had complete baseline BDI depression scores (20 patients lost, 2.2% of overall cohort), and 750 had a valid history of depression responses (86 patients lost, 9.5% of overall cohort). Statistical analyses were performed with SAS 8.2 (SAS Institute, Cary, North Carolina). Data were cleaned and screened to evaluate statistical assumptions. A descriptive examination of the variables was performed, and baseline participant characteristics were compared based on differences in mortality and depressive symptomatology (BDI score 130 mm Hg), previous myocardial infarction or congestive heart failure, diabetes, and the Charlson Co-morbidity Index (0 vs ≥1 co-morbid condition). As presented in Table 2, participants who had a BDI score ≥10 during hospitalization were more likely to be women, have lower family income, be widowed, separated, or divorced, have fewer years of education, be a smoker, have a diagnosis of unstable angina, have greater disease severity (as operationalized by Killip's class), have more co-morbid conditions, and have a medical history of diabetes and congestive heart failure.Table 2Participant characteristics of those with subthreshold depressive symptomatology (Beck Depression Inventory <10) versus those with depressive increased symptomatology (Beck Depression Inventory ≥10) at index hospitalizationOverallDepressive Symptomsp ValueSubthreshold (BDI <10)High (BDI ≥10)Sample750515 (68.7%)235 (31.3%)Men486/750 (64.8%)376/515 (73%)110/235 (46.8%)0.0001Age (yrs)61.57 ± 11.8861.94 ± 11.8760.74 ± 11.890.2009Killip's class <I591/711 (83.1%)414/486 (85.2%)177/225 (78.7%)0.0309Family income <$50,000 Canadian359/646 (55.6%)231/451 (51.2%)128/195 (65.6%)0.0007Married555/744 (74.6%)399/510 (78.2%)156/234 (66.7%)0.0008Education level below high school506/738 (68.6%)336/510 (65.9%)170/228 (74.6%)0.0189Index diagnosis of myocardial infarction392/750 (52.3%)294/515 (57.1%)98/235 (41.7%)0.0001Systolic blood pressure <130 mm Hg309/719 (43%)214/490 (43.7%)95/229 (41.5%)0.5807Charlson Co-morbidity Index 4 times more likely to die (hazard ratio 4.6).Table 3Participants who were alive versus those who died five years after dischargeVariableOverallStatusp ValueAliveDiedSample750635 (84.7%)115 (15.3%)Men486/750 (64.8%)418/486 (86%)68/486 (14%)Women264/750 (35.2%)217/264 (82.2%)47/264 (17.8%)0.1665Age (yrs)61.57 ± 11.8860.09 ± 11.5869.74 ± 10.140.0001Killip's class I120/711 (16.9%)86/120 (71.7%)34/120 (28.3%)0.0001Family income>$50,000359/646 (55.6%)298/359 (83%)61/359 (17%)<$50,000287/646 (44.4%)255/287 (88.9%)32/287 (11.1%)0.0356Marital statusNot married189/744 (25.4%)145/189 (76.7%)44/189 (23.3%)Married555/744 (74.6%)485/555 (87.4%)70/555 (12.6%)0.0004Education levelBelow high school506/738 (68.6%)418/506 (82.6%)88/506 (17.4%)Above high school232/738 (31.4%)206/232 (88.8%)26/232 (11.2%)0.0309Index diagnosisUnstable Angina392/750 (52.3%)331/392 (84.4%)61/392 (15.6%)Myocardial Infarction358/750 (47.7%)304/358 (84.9%)54/358 (15.1%)0.8562Systolic blood pressure 130 mm Hg410/719 (57%)357/410 (87.1%)53/410 (12.9%)0.024Charlson Co-morbidity Index 1219/750 (29.2%)151/219 (68.9%)68/219 (31.1%)0.0001Diabetes mellitus182/750 (24.3%)143/182 (78.6%)39/182 (21.4%)0.0087Previous myocardial infarction537/750 (71.6%)445/537 (82.9%)92/537 (17.1%)0.0299Congestive heart failure88/750 (11.7%)45/88 (51.1%)43/88 (48.9%)0.0001Smoker241/745 (32.3%)216/241 (89.6%)25/241 (10.4%)0.0098Length of hospital stay4.38 ± 3.094.41 ± 3.114.18 ± 30.4648BDI8.63 ± 7.488.32 ± 7.3710.36 ± 7.840.0071History of depressed mood174/750 (23.2%)155/174 (89.1%)19/174 (10.9%)0.0652BDI score<10515/750 (68.7%)446/515 (86.6%)69/515 (13.4%)0.0294≥10235/750 (31.3%)189/235 (80.4%)46/235 (19.6%)History of depressed mood × BDI⁎1 = no history of depression and BDI score <10; 2 = no history of depression and BDI score ≥10; 3 = history of depression and BDI score <10; 4 = history of depression and BDI score ≥10.1 (0 → 0)446/750 (59.5%)381/446 (85.4%)65/446 (14.6%)0.00622 (0 → 1)130/750 (17.3%)99/130 (76.2%)31/130 (23.8%)3 (1 → 0)69/750 (9.2%)65/69 (94.2%)4/69 (5.8%)4 (1 → 1)105/750 (14%)90/105 (85.7%)15/105 (14.3%)Values are means ± SD or numbers of patients (percentages). 1 = no history of depression and BDI score <10; 2 = no history of depression and BDI score ≥10; 3 = history of depression and BDI score <10; 4 = history of depression and BDI score ≥10. Open table in a new tab Table 4Pairwise comparisons of interaction between history of depression and presence of increased depressive symptomatology at index hospitalizationPairwise Comparison⁎0 = depression absent; 1 = depression present.Chi-squarep ValueHazard Ratio95% Confidence Interval(0,1) vs (0,0)6.590.0101.751.14–2.69(1,0) vs (0,0)3.510.0610.380.14–1.05(1,1) vs (0,0)0.000.9520.980.56–1.72(0,1) vs (1,0)8.240.0044.591.62–13.01(0,1) vs (1,1)3.370.0661.780.96–3.30(1,0) vs (1,1)2.830.0920.390.13–1.17 0 = depression absent; 1 = depression present. Open table in a new tab Values are means ± SD or numbers of patients (percentages). The stepwise Cox's proportional hazards models for all-cause mortality across 5 years after index hospitalization are presented in Table 5, after adjusting for gender, age, family income, marital status, education level, diagnosis, high systolic blood pressure, smoking, Killip's class, co-morbid conditions, and a medical history of diabetes, myocardial infarction, or congestive heart failure. Depressive symptomatology at the time of index hospitalization remained a significant predictor of all-cause mortality across years 2 through 5; however, depressive history and its interaction with depressive symptomatology at the time of hospitalization did not remain in the adjusted models during any year of follow-up. The hazard ratio associated with subthreshold symptomatology (BDI score 130 mm Hg5.660.0170.450.24–0.87Charlson Co-morbidity Index >19.810.0023.081.52–6.212BDI score ≥105.610.0181.901.12–3.24Age21.19<0.00011.071.04–1.10Congestive heart failure21.93<0.00013.812.18–6.663BDI score ≥104.020.0451.611.01–2.57Age29.09 130 mm Hg8.270.0040.510.32–0.81Congestive heart failure18.27<0.00012.991.81–4.944BDI score ≥105.870.0151.761.11–2.79Gender4.960.0260.560.34–0.93Age30.72 130 mm Hg7.160.0080.560.37–0.865Congestive heart failure18.80<0.00012.781.75–4.40BDI score ≥104.620.0321.531.04–2.24Age39.28 130 mm Hg6.140.0130.620.43–0.91Charlson Co-morbidity Index >16.820.0091.871.17–2.99Congestive heart failure8.200.0042.041.25–3.33 Open table in a new tab Depressive symptomatology and major depressive disorders are common among patients who have ACS.10Grace S.L. Abbey S. Pinto R. Shnek Z. Irvine J. Stewart D.E. Longitudinal course of depressive symptomatology following a cardiac event effect of gender and cardiac rehabilitation.Psychosom Med. 2005; 67: 52-58Crossref PubMed Scopus (79) Google Scholar, 19Abbey S.E. Stewart D.E. Gender and psychosomatic aspects of ischemic heart disease.J Psychosom Res. 2000; 48: 417-423Abstract Full Text Full Text PDF PubMed Scopus (41) Google Scholar Similar to previous findings,5Lesperance F. Frasure-Smith N. Talajic M. Major depression before and after myocardial infarction its nature and consequences.Psychosom Med. 1996; 58: 99-110Crossref PubMed Scopus (455) Google Scholar 23% of participants reported a history of depressed mood. The prevalence of major depression at the time of hospitalization ranges from ∼15% to 20% in the literature,20Lett H. Blumenthal J. Babyak M. Sherwood A. Strauman T. Robins C. Newman N.F. Depression as a risk factor for coronary artery disease evidence, mechanisms, treatment.Psychosom Med. 2004; 66: 305-315Crossref PubMed Scopus (672) Google Scholar which is approximately threefold higher than those of age-matched community-based prevalence studies.21Blazer D.G. Kessler R.C. McGonagle K. Swartz M. The prevalence and distribution of major depression in a national community sample the national comorbidity survey.Am J Psychiatry. 1994; 151: 979-986PubMed Google Scholar, 22Lavie C. Milani R. Cassidy M. Gilliland Y. Effects of cardiac rehabilitation and exercise training programs in women with depression.Am J Cardiol. 1999; 83: 1480-1483Abstract Full Text Full Text PDF PubMed Scopus (102) Google Scholar In our sample, 31% had increased depressive symptomatology at the time of hospitalization, 14% of whom had a persistent depressed mood before the index hospitalization. We were interested in the prognostic significance of historical and persistent depressive symptomatology on mortality to build on the findings of Lesperance et al.1Lesperance J. Frasure-Smith N. Talajic M. Bourassa M. Five-year risk of cardiac mortality in relation to initial severity and one-year changes in depression symptoms after myocardial infarction.Circulation. 2002; 105: 1049-1053Crossref PubMed Scopus (634) Google Scholar, 5Lesperance F. Frasure-Smith N. Talajic M. Major depression before and after myocardial infarction its nature and consequences.Psychosom Med. 1996; 58: 99-110Crossref PubMed Scopus (455) Google Scholar Although a strong body of literature demonstrates that depressive history is related to onset of ACS,7Hemingway H. Marmot M. Evidence based cardiology: psychosocial factors in the aetiology and prognosis of coronary heart disease: systematic review of prospective cohort studies.BMJ. 1999; 318: 1460-1467Crossref PubMed Google Scholar, 8Rugulies R. Depression as a predictor for coronary heart disease a review and meta-analysis.Am J Prev Med. 2002; 23: 51-61Abstract Full Text Full Text PDF PubMed Scopus (922) Google Scholar, 9Wulsin L. Singal B. Do depressive symptoms increase the risk for the onset of coronary disease? A systematic quantitative review.Psychosom Med. 2003; 65: 201-210Crossref PubMed Scopus (602) Google Scholar our results suggest that this history is not as salient to mortality among patients who have established disease compared with depressive severity at the time of hospitalization. This was also shown in a study by Berkman et al,23Berkman L.F. Leo-Summers L. Horwitz R.I. Emotional support and survival after myocardial infarction a prospective, population-based study of the elderly.Ann Intern Med. 1992; 117: 1003-1009Crossref PubMed Scopus (690) Google Scholar where depressive symptomatology was assessed up to 3 years before a myocardial infarction and was not related to mortality 6 months after a myocardial infarction. In addition, Bush et al3Bush D. Ziegelstein R. Tayback M. Richter D. Stevens S. Zahalsky H. Fauerbach J.A. Even minimal symptoms of depression increase mortality risk after myocardial infarction.Am J Cardiol. 2001; 88: 337-341Abstract Full Text Full Text PDF PubMed Scopus (522) Google Scholar found no difference in mortality risk at 4 months based on a history of depression. With regard to the persistence of depressive symptomatology, the prognostic implications of this have been relatively unexplored.24Burg M. Benedetto M. Soufer R. Depressive symptoms and mortality two years after coronary artery bypass surgery in men.Psychosom Med. 2003; 65: 508-510Crossref PubMed Scopus (86) Google Scholar Contrary to expectation, our results reveal that persistent depressive symptomatology that recurs at the time of hospitalization is not of prognostic importance compared with severity only at the time of hospitalization. †We also created a variable for no increased depressive symptomatology at any time point, depressive symptomatology before or at index hospitalization, and depressive symptomatology at the 2 times. This was not related to mortality in the Cox's models. This runs counter to findings from the cohort presented by Lesperance et al,5Lesperance F. Frasure-Smith N. Talajic M. Major depression before and after myocardial infarction its nature and consequences.Psychosom Med. 1996; 58: 99-110Crossref PubMed Scopus (455) Google Scholar in which patients who had recurrent depressive symptomatology at the time of hospitalization were at significantly increased risk of 18-month mortality compared with those who had depressive onset only at the time of hospitalization. However, their analysis was not conducted within an adjusted Cox's model. Further research using longitudinal community cohorts and diagnostic assessments is needed to elucidate the role of depression chronicity and timing in mortality. The significant interaction between history of depressed mood and depressive symptomatology at the time of hospitalization is intriguing and replicates the findings of Lesperance et al.5Lesperance F. Frasure-Smith N. Talajic M. Major depression before and after myocardial infarction its nature and consequences.Psychosom Med. 1996; 58: 99-110Crossref PubMed Scopus (455) Google Scholar They also found that the group with the lowest risk of mortality consisted of patients who had a history of depression and did not report increased depressive symptomatology in the hospital. Lesperance et al speculated that those who had a history of depression and managed to resist the stresses of ACS "had enhanced physical or psychic resources that enabled them to survive." However, in the full Cox's model, this interaction was superceded by the importance of depressive symptomatology at the time of hospitalization. Nevertheless, this interaction deserves further thought and inquiry, particularly with regard to mechanisms. The negative prognostic effect of acute onset depressive symptomatology at the time of hospitalization raises further questions with regard to pathophysiologic,20Lett H. Blumenthal J. Babyak M. Sherwood A. Strauman T. Robins C. Newman N.F. Depression as a risk factor for coronary artery disease evidence, mechanisms, treatment.Psychosom Med. 2004; 66: 305-315Crossref PubMed Scopus (672) Google Scholar rather than behavioral, mechanisms. These results corroborate that even mild depressive symptoms at the time of cardiac hospitalization are not benign symptoms solely attributable to a life-threatening event, somatic complaints, or hospital setting but are robust symptoms with important prognostic implications for years to follow. They also highlight the importance of early identification of depressive symptomatology during hospitalization. Once identified, patients who have increased symptomatology should be offered evidence-based treatments.25Swenson J. O'Connor S. Barton D. Van Zyl L. Swedberg K. Forman L.M. Gaffney M. Glassman A.H. Influence of depression and effect of treatment with sertraline on quality of life after hospitalization for acute coronary syndrome.Am J Cardiol. 2003; 92: 1271-1276Abstract Full Text Full Text PDF PubMed Scopus (123) Google Scholar Although treating depression in the context of ACS does improve quality of life and functional capacity,25Swenson J. O'Connor S. Barton D. Van Zyl L. Swedberg K. Forman L.M. Gaffney M. Glassman A.H. Influence of depression and effect of treatment with sertraline on quality of life after hospitalization for acute coronary syndrome.Am J Cardiol. 2003; 92: 1271-1276Abstract Full Text Full Text PDF PubMed Scopus (123) Google Scholar it is unclear whether treating depression may have beneficial effects on cardiac prognosis.20Lett H. Blumenthal J. Babyak M. Sherwood A. Strauman T. Robins C. Newman N.F. Depression as a risk factor for coronary artery disease evidence, mechanisms, treatment.Psychosom Med. 2004; 66: 305-315Crossref PubMed Scopus (672) Google Scholar, 26Davidson K. Rieckmann N. Lesperance J. Psychological theories of depression potential application for the prevention of acute coronary syndrome recurrence.Psychosom Med. 2004; 66: 165-173Crossref PubMed Scopus (62) Google Scholar There is much current research that is examining potential behavioral and physiologic mechanisms that link depression to prognosis and how psychotherapeutic and psychopharmacologic treatment might mitigate this relation. Caution is warranted when interpreting these results. First, the generalizability of the study is limited by the differences between participants and refusers and the loss of participants in the linkage process. However, we adjusted for these differences in the Cox's model to statistically control for these biases. Second, our self-report measurement of depressive symptomatology assessed severity only and does not provide diagnostic information. Moreover, our self-report measurement of depressive history may be hampered by retrospective bias and was not verified through a structured diagnostic interview. However, 2 recent meta-analyses concluded that assessments by self-report questionnaires of symptomatology and clinical interviews based on diagnostic criteria are related to mortality and that, for these purposes, neither type of depressive assessment is superior.27Barth J. Schumacher M. Herrmann-Lingen C. Depression as a risk factor for mortality in patients with coronary heart disease a meta-analysis.Psychosom Med. 2004; 66: 802-813Crossref PubMed Scopus (1111) Google Scholar, 28van Melle J. De Jonge P. Spijkerman T. Tjisssen J. Ormel J. van Veldhuisen D. van den Brink R.H.S. van den Berg M.P. Prognostic association of depression following myocardial infarction with mortality and cardiovascular events a meta-analysis.Psychosom Med. 2004; 66: 814-822Crossref PubMed Scopus (873) Google Scholar Our outcome of mortality was not broken down by cardiac and noncardiac causes but was based on all-cause mortality only. Third, our results are limited by the small number of deaths in the group of participants who had a history of depressed mood and BDI scores >10. Further examination and replication in a larger population-based sample is warranted. We acknowledge Linda Green, PhD, and the coronary care unit nurses for their diligence in participant recruitment and Claus Wall, MSc, for data linkage.