Abstract
Purpose
To determine whether chronic medical conditions mediate the association between depression and cardiovascular disease (CVD) mortality.
Methods
Data analyzed were from 6,394 subjects aged 25–74 years who participated in extensive health examinations in the NHEFS conducted between 1971 and 1975 and follow-up studies to 1992. CVD mortality was the endpoint. Depression predictors were clinically significant depressive symptoms at baseline by the GWB-D, and/or at 1982–1984 by the CES-D (‘baseline’, ‘new’, or ‘twice’ depression). Chronic conditions were prevalent/incident high blood pressure, diabetes, and non-fatal CVD by examination and/or self-report. Mediation effects were assessed by stepwise adjustments of covariates and additive interactions in competing risks regression models (accounting for other mortality causes) and logit models.
Results
Baseline, new, and twice depression were significant predictors of CVD mortality in competing-risks models adjusted for demographics (HRs 1.3, 1.4, and 2.0), but effects were progressively weakened and became non-significant after adjustment for lifestyle factors, prevalent and incident medical conditions, respectively. CVD mortality risk was 80% higher for depression plus incident non-fatal CVD than without (HR 4.0 vs. 3.2, additive interaction), and mediation effects of depression via chronic medical conditions (particularly via incident non-fatal CVD) increased the risk by 2–11% in logit models, independent of all covariates.
Conclusions
Several levels of evidence suggest that the association between depression and CVD mortality is partially mediated by prevalent/incident chronic medical conditions, as well as unhealthy lifestyle behaviors. Patients presenting with clinically significant depressive symptoms, particularly if persistent, should be assessed for both chronic conditions and lifestyle risk factors.
Similar content being viewed by others
References
Nicholson A, Kuper H, Hemingway H (2006) Depression as an aetiologic and prognostic factor in coronary heart disease: a meta-analysis of 6362 events among 146 538 participants in 54 observational studies. Eur Heart J 27:2763–2774
Van der Kooy K, van Hout H, Marwijk H, Marten H, Stehouwer C, Beekman A (2007) Depression and the risk for cardiovascular diseases: systematic review and meta analysis. Int J Geriatr Psychiatry 22:613–626
Gallo JJ, Bogner HR, Morales KH, Post EP, Lin JY, Bruce ML (2007) The effect of a primary care practice-based depression intervention on mortality in older adults: a randomized trial. Ann Intern Med 146:689–698
Berkman LF, Blumenthal J, Burg M, Carney RM, Catellier D, Cowan MJ, Czajkowski SM, DeBusk R, Hosking J, Jaffe A, Kaufmann PG, Mitchell P, Norman J, Powell LH, Raczynski JM, Schneiderman N, Enhancing Recovery in Coronary Heart Disease Patients I (2003) Effects of treating depression and low perceived social support on clinical events after myocardial infarction: the Enhancing Recovery in Coronary Heart Disease Patients (ENRICHD) Randomized Trial. JAMA 289:3106–3116
de Jonge P, Honig A, van Melle JP, Schene AH, Kuyper AMG, Tulner D, Schins A, Ormel J, Investigators M-I (2007) Nonresponse to treatment for depression following myocardial infarction: association with subsequent cardiac events. Am J Psychiatry 164:1371–1378
Thombs BD, de Jonge P, Coyne JC, Whooley MA, Frasure-Smith N, Mitchell AJ, Zuidersma M, Eze-Nliam C, Lima BB, Smith CG, Soderlund K, Ziegelstein RC (2008) Depression screening and patient outcomes in cardiovascular care: a systematic review. JAMA 300:2161–2171
Marzari C, Maggi S, Manzato E, Destro C, Noale M, Bianchi D, Minicuci N, Farchi G, Baldereschi M, Di Carlo A, Crepaldi G (2005) Depressive symptoms and development of coronary heart disease events: the Italian longitudinal study on aging. J Gerontol Ser A Biol Sci Med Sci 60:85–92
Haukkala A, Konttinen H, Uutela A, Kawachi I, Laatikainen T (2009) Gender differences in the associations between depressive symptoms, cardiovascular diseases, and all-cause mortality. Ann Epidemiol 19:623–629
Ferketich AK, Schwartzbaum JA, Frid DJ, Moeschberger ML (2000) Depression as an antecedent to heart disease among women and men in the NHANES I study. Arch Intern Med 160:1261–1268
Rasul F, Stansfeld SA, Hart CL, Davey Smith G (2005) Psychological distress, physical illness, and risk of coronary heart disease. J Epidemiol Commun Health 59:140–145
Wouts L, Oude Voshaar RC, Bremmer MA, Buitelaar JK, Penninx BW, Beekman AT (2008) Cardiac disease, depressive symptoms, and incident stroke in an elderly population. Arch Gen Psychiatry 65:596–602
Rasul F, Stansfeld SA, Smith GD, Shlomo YB, Gallacher J (2007) Psychological distress, physical illness and risk of myocardial infarction in the Caerphilly study. Psychol Med 37:1305–1313
Penninx BWJH, Beekman ATF, Honig A, Deeg DJH, Schoevers RA, van Eijk JTM, van Tilburg W (2001) Depression and cardiac mortality: results from a community-based longitudinal study. Arch Gen Psychiatry 58:221–227
Nicholson A, Fuhrer R, Marmot M (2005) Psychological distress as a predictor of CHD events in men: the effect of persistence and components of risk. Psychosom Med 67:522–530
Whooley MA, de Jonge P, Vittinghoff E, Otte C, Moos R, Carney RM, Ali S, Dowray S, Na B, Feldman MD, Schiller NB, Browner WS (2008) Depressive symptoms, health behaviors, and risk of cardiovascular events in patients with coronary heart disease. JAMA 300:2379–2388
Barton DA, Dawood T, Lambert EA, Esler MD, Haikerwal D, Brenchley C, Socratous F, Kaye DM, Schlaich MP, Hickie I, Lambert GW (2007) Sympathetic activity in major depressive disorder: identifying those at increased cardiac risk? J Hypertens 25:2117–2124
Bao AM, Meynen G, Swaab DF (2008) The stress system in depression and neurodegeneration: focus on the human hypothalamus. Brain Res Rev 57:531–553
Musselman DL, Marzec UM, Manatunga A, Penna S, Reemsnyder A, Knight BT, Baron A, Hanson SR, Nemeroff CB (2000) Platelet reactivity in depressed patients treated with paroxetine: preliminary findings. Arch Gen Psychiatry 57:875–882
Pizzi C, Manzoli L, Mancini S, Costa GM (2008) Analysis of potential predictors of depression among coronary heart disease risk factors including heart rate variability, markers of inflammation, and endothelial function. Eur Heart J 29:1110–1117
Howren BM, Lamkin DM, Suls J Associations of Depression With C-Reactive Protein, IL-1, and IL-6: A Meta-Analysis. SO - Psychosomatic Medicine February/March 2009;71(2):171-186
WRITING GROUP MEMBERS, Lloyd-Jones D, Adams RJ, Brown TM, Carnethon M, Dai S, De Simone G, Ferguson TB, Ford E, Furie K, Gillespie C, Go A, Greenlund K, Haase N, Hailpern S, Ho PM, Howard V, Kissela B, Kittner S, Lackland D, Lisabeth L, Marelli A, McDermott MM, Meigs J, Mozaffarian D, Mussolino M, Nichol G, Roger VL, Rosamond W, Sacco R, Sorlie P, Stafford R, Thom T, Wasserthiel-Smoller S, Wong ND, Wylie-Rosett J, Committee obotAHAS, Stroke Statistics Subcommittee (2010) Heart Disease and Stroke Statistics–2010 Update: A Report From the American Heart Association. Circulation 121:e46-215
Pizzi C, Mancini S, Angeloni L, Fontana F, Manzoli L, Costa GM (2009) Effects of selective serotonin reuptake inhibitor therapy on endothelial function and inflammatory markers in patients with coronary heart disease. Clin Pharmacol Ther 86:527–532
Atlantis E, Browning C, Sims J, Kendig H (2010) Diabetes incidence associated with depression and antidepressants in the Melbourne Longitudinal Studies on Healthy Ageing (MELSHA). Int J Geriatr Psychiatry 25:688–696
Mezuk B, Eaton WW, Albrecht S, Golden SH (2008) Depression and type 2 diabetes over the lifespan: a meta-analysis. Diabet Care 31:2383–2390
Campayo A, de Jonge P, Roy JF, Saz P, de la Camara C, Quintanilla MA, Marcos G, Santabarbara J, Lobo A (2010) Depressive disorder and incident diabetes mellitus: the effect of characteristics of depression. Am J Psychiatry
Centers for Disease Control and Prevention (CDC) National Centre for Health Statistics (NCHS) (2009) National Health and Nutrition Examination Survey (NHANES I Data Files Documentation Codebook, 1971–1975). http://www.cdc.gov/nchs/nhanes/nhanesi.htm Accessed November 2009
Centers for Disease Control and Prevention (CDC) National Centre for Health Statistics (NCHS) (2009) National Health and Nutrition Examination Survey (NHANES I Epidemiologic Followup Study (NHEFS) Public-Use Data Files). http://www.cdc.gov/nchs/nhanes/nhefs/nhefs.htm Accessed November 2009
Rich-Edwards JW, Corsano KA, Stampfer MJ (1994) Test of the National Death Index and Equifax Nationwide Death Search. Am J Epidemiol 140:1016–1019
Stampfer MJ, Willett WC, Speizer FE, Dysert DC, Lipnick R, Rosner B, Hennekens CH (1984) Test of the National Death Index. Am J Epidemiol 119:837–839
Fazio AF (1977) A concurrent validational study of the NCHS General Well-Being Schedule. Vital and Health Statistics Series 73:1–53. http://www.cdc.gov/nchs/products/series.htm Accessed November 2009
Zonderman AB, Costa PT Jr, McCrae RR (1989) Depression as a risk for cancer morbidity and mortality in a nationally representative sample. JAMA 262:1191–1195
Radloff LS (1977) The CES-D Scale: a self-report depression scale for research in the general population. Appl Psychol Meas 1:385–401
Lewinsohn PM, Seeley JR, Roberts RE, Allen NB (1997) Center for Epidemiologic Studies Depression Scale (CES-D) as a screening instrument for depression among community-residing older adults. Psychol Aging 12:277–287
Buis ML (2010) Direct and indirect effects in a logit model. Stata J 10:11–29
Luppino FS, de Wit LM, Bouvy PF, Stijnen T, Cuijpers P, Penninx BWJH, Zitman FG (2010) Overweight, obesity, and depression: a systematic review and meta-analysis of longitudinal studies. Arch Gen Psychiatry 67:220–229
Pasco JA, Williams LJ, Jacka FN, Ng F, Henry MJ, Nicholson GC, Kotowicz MA, Berk M (2008) Tobacco smoking as a risk factor for major depressive disorder: population-based study. Br J Psychiatry 193:322–326
Strawbridge WJ, Deleger S, Roberts RE, Kaplan GA (2002) Physical activity reduces the risk of subsequent depression for older adults. Am J Epidemiol 156:328–334
Akbaraly TN, Brunner EJ, Ferrie JE, Marmot MG, Kivimaki M, Singh-Manoux A (2009) Dietary pattern and depressive symptoms in middle age. Br J Psychiatry 195:408–413
Patton GC, Carlin JB, Coffey C, Wolfe R, Hibbert M, Bowes G (1998) Depression, anxiety, and smoking initiation: a prospective study over 3 years. Am J Public Health 88:1518–1522
Patten SB, Williams JVA, Lavorato DH, Eliasziw MA Longitudinal community study of major depression and physical activity. Gen Hosp Psychiatry 31:571–575
Ziegelstein RC, Fauerbach JA, Stevens SS, Romanelli J, Richter DP, Bush DE (2000) Patients with depression are less likely to follow recommendations to reduce cardiac risk during recovery from a myocardial infarction. Arch Intern Med 160:1818–1823
Falk Dahl CA, Dahl AA (2010) Lifestyle and social network in individuals with high level of social phobia/anxiety symptoms: a community-based study. Soc Psychiatry Psychiatr Epidemiol 45:309–317
Atlantis E, Lange K, Goldney RD, Martin S, Haren MT, Taylor A, O’Loughlin PD, Marshall V, Tilley W, Wittert GA (2010) Specific medical conditions associated with clinically significant depressive symptoms in men. Soc Psychiatry Psychiatr Epidemiol
Thurston RC, Kubzansky LD, Kawachi I, Berkman LF (2006) Do depression and anxiety mediate the link between educational attainment and CHD? Psychosom Med 68:25–32
Nabi H, Singh-Manoux A, Shipley M, Gimeno D, Marmot MG, Kivimaki M (2008) Do psychological factors affect inflammation and incident coronary heart disease: the Whitehall II Study. Arterioscler Thromb Vasc Biol 28:1398–1406
Richardson LK, Egede LE, Mueller M, Richardson LK, Egede LE, Mueller M (2008) Effect of race/ethnicity and persistent recognition of depression on mortality in elderly men with type 2 diabetes and depression. Diabet Care 31:880–881
Atlantis E, Grayson DA, Browning C, Sims J, Kendig H (2010) Cardiovascular disease and death associated with depression and antidepressants in the Melbourne Longitudinal Studies on Healthy Ageing (MELSHA). Int J Geriatr Psychiatry (in press)
Sauer WH, Berlin JA, Kimmel SE (2003) Effect of antidepressants and their relative affinity for the serotonin transporter on the risk of myocardial infarction. Circulation 108:32–36
Parker G (2009) Antidepressants on trial: how valid is the evidence? Br J Psychiatry 194:1–3
Beekman AT, Deeg DJ, Van Limbeek J, Braam AW, De Vries MZ, Van Tilburg W (1997) Criterion validity of the Center for Epidemiologic Studies Depression scale (CES-D): results from a community-based sample of older subjects in the Netherlands. Psychol Med 27:231–235
Gunn JM, Ayton DR, Densley K, Pallant JF, Chondros P, Herrman HE, Dowrick CF (2010) The association between chronic illness, multimorbidity and depressive symptoms in an Australian primary care cohort. Soc Psychiatry Psychiatr Epidemiol
Acknowledgments
We are grateful to Tom Sullivan for his contribution in processing of the data.
Conflict of interest
None.
Author information
Authors and Affiliations
Corresponding author
Additional information
The analyses, interpretations, and conclusions reached by the authors’ of this report are independent of the National Center for Health Statistics, Centers for Disease Control and Prevention, which is responsible only for the initial data.
Rights and permissions
About this article
Cite this article
Atlantis, E., Shi, Z., Penninx, B.J.W.H. et al. Chronic medical conditions mediate the association between depression and cardiovascular disease mortality. Soc Psychiatry Psychiatr Epidemiol 47, 615–625 (2012). https://doi.org/10.1007/s00127-011-0365-9
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s00127-011-0365-9