The close, bidirectional relationship between depression and cardiovascular disease is well established. Major depression is associated with an increased risk of coronary artery disease and acute cardiovascular sequelae, such as myocardial infarction, congestive heart failure, and isolated systolic hypertension. Morbidity and mortality in patients with cardiovascular disease and depression are significantly higher than in patients with cardiovascular disease who are not depressed. Various pathophysiological mechanisms might underlie the risk of cardiovascular disease in patients with depression: increased inflammation; increased susceptibility to blood clotting (owing to alterations in multiple steps of the clotting cascade, including platelet activation and aggregation); oxidative stress; subclinical hypothyroidism; hyperactivity of the sympatho-adrenomedullary system and the hypothalamic–pituitary–adrenal axis; reductions in numbers of circulating endothelial progenitor cells and associated arterial repair processes; decreased heart rate variability; and the presence of genetic factors. Early identification of patients with depression who are at risk of cardiovascular disease, as well as prevention and appropriate treatment of cardiovascular disease in these patients, is an important and attainable goal. However, adequately powered studies are required to determine the optimal treatment regimen for patients with both depression and cardiovascular disorders.
Depression is associated with increased risk of coronary artery disease, and increased morbidity and mortality after myocardial infarction, CABG surgery, congestive heart failure, or mitral valve replacement
Depression-associated biological alterations include increased inflammation, a clotting diathesis, decreased variability in heart rate, increased activity of the sympathoadrenal and pituitary–adrenal axes, and a reduction in circulating endothelial progenitor cells
Depression-associated biological alterations might mediate the link between depression and cardiovascular disease
Results are inconclusive from studies designed to determine whether successful treatment of depression in patients with cardiovascular disease is associated with a reduction in subsequent major cardiac events
Further research is required to determine whether normalization of these depression-associated biological alterations, resulting from effective treatment, contribute to a reduced risk of cardiovascular disease
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Maltzberg, B. Mortality among patients with involution melancholia. Am. J. Psychiatry 93, 1231–1238 (1937).
Stapelberg, N. J., Neumann, D. L., Shum, D. H., McConnell, H. & Hamilton-Craig, I. A topographical map of the causal network of mechanisms underlying the relationship between major depressive disorder and coronary heart disease. Aust. N. Z. J. Psychiatry 45, 351–369 (2011).
Thombs, B. D. et al. Probit structural equation regression model: general depressive symptoms predicted post-myocardial infarction mortality after controlling for somatic symptoms of depression. J. Clin. Epidemiol. 8, 832–839 (2008).
Lippi, G., Montagnana, M., Favaloro, E. J. & Franchini, M. Mental depression and cardiovascular disease: a multifaceted, bidirectional association. Semin. Thromb. Hemost. 35, 325–336 (2009).
Musselman, D. L., Cowles, M. K., McDonald, W. & Nemeroff, C. B. In Hurst's The Heart 12th Edn (eds Fuster, V. et al.) 2169–2187 (McGraw-Hill, New York, 2008).
Khan, F. M., Kulaksizoglu, B. & Cilingiroglu, M. Depression and coronary heart disease. Curr. Atheroscler. Rep. 12, 105–109 (2010).
Kessler R. C. et al. Lifetime prevalence and age-of-onset distributions of DSM-IV disorders in the National Comorbidity Survey Replication. Arch. Gen. Psychiatry 62, 593–602 (2005).
Berry. et al. NEJM 366, 321–329 (2012).
Cowles, M., Nemeroff, C. B. & Pariente, C. In Understanding depression: a translational approach (eds Pariente, C. et al.) 7–16 (Oxford University Press, Oxford, 2009).
Janszky, I., Ahnve, S., Lundberg, I. & Hemmingsson, T. Early-onset depression, anxiety, and risk of subsequent coronary heart disease. J. Am. Coll. Cardiol. 56, 31–37 (2010).
Mendes de Leon, C. F. et al. Depression and risk of coronary heart disease in elderly men and women. Arch. Intern. Med. 158, 2341–2348 (1998).
Ruo, B. et al. Depressive symptoms and health-related quality of life: the Heart and Soul Study. JAMA 290, 215–221 (2003).
Whooley, M. A. et al. Depressive symptoms, health behaviors, and risk of cardiovascular events in patients with coronary heart disease. JAMA 300, 2379–2388 (2008).
Cohen, B. E., Panguluri, P., Na, B. & Whooley, M. A. Psychological risk factors and the metabolic syndrome in patients with coronary heart disease: findings from the Heart and Soul Study. Psychiatry Res. 175, 133–137 (2010).
Holahan, C. J. et al. Depression and vulnerability to incident physical illness across 10 years. J. Affect. Disord. 123, 222–229 (2010).
Anda, R. et al. Depressed affect, hopelessness, and the risk of ischemic heart disease in a cohort of US adults. Epidemiology 4, 285–294 (1993).
Ford, D. E. et al. Depression is a risk factor for coronary artery disease in men: the precursors study. Arch. Intern. Med. 158, 1422–1426 (1998).
Janszky, I., Ahlbom, A., Hallqvist, J. & Ahnve, S. Hospitalization for depression is associated with an increased risk for myocardial infarction not explained by lifestyle, lipids, coagulation, and inflammation: the SHEEP Study. Biol. Psychiatry 62, 25–32 (2007).
Surtees, P. G. et al. Depression and ischemic heart disease mortality: evidence from the EPIC–Norfolk United Kingdom prospective cohort study. Am. J. Psychiatry 165, 515–523 (2008).
Jakobsen, A. H., Foldager, L., Parker, G. & Munk-Jørgensen, P. Quantifying links between acute myocardial infarction and depression, anxiety and schizophrenia using a care register database. J. Affect. Disord. 109, 177–181 (2008).
Kendler, K., Gardner, C. O., Fiske, A. & Gatz, M. Major depression and coronary artery disease in the Swedish Twin Registry: phenotypic, genetic, and environmental sources of comorbidity. Arch. Gen. Psychiatry 66, 857–863 (2009).
Egede, L. E., Netert, P. J., & Zheng D. Depression and all-cause and coronary heart disease mortality among adults with and without diabetes. Diabetes Care 28, 1339–1345 (2005).
Fiedorowicz, J. G., He, J. & Merikangas, K. R. The association between mood and anxiety disorders with vascular diseases and risk factors in a nationally representative sample. J. Psychosom. Res. 70, 145–154 (2010).
Callaghan, R. C. & Khizar, A. The incidence of cardiovascular morbidity among patients with bipolar disorder: a population-based longitudinal study in Ontario, Canada. J. Affect. Disord. 122, 118–123 (2010).
Ramsey, C. M., Leoutsakos, J. M., Mayer, L. S., Eaton, W. W. & Lee, H. B. History of manic and hypomanic episodes and risk of incident cardiovascular disease: 11.5 year follow-up from the Baltimore Epidemiologic Catchment Area Study. J. Affect. Disord. 125, 35–41 (2010).
Nabi, H. et al. Combined effects of depressive symptoms and resting heart rate on mortality: the Whitehall II prospective cohort study. J. Clin. Psychiatry 9, 1199–1206 (2011).
Sheline, Y. et al. Support for the vascular depression hypothesis in late-life depression: results of a 2-site, prospective, antidepressant treatment trial. Arch. Gen. Psychiatry 67, 277–285 (2010).
Wassertheil-Smoller, S. et al. Change in depression as a precursor of cardiovascular events. SHEP Cooperative Research Group (Systoloc Hypertension in the elderly). Arch. Intern. Med. 156, 553–561 (1996).
Peters, R. et al. Association of depression with subsequent mortality, cardiovascular morbidity and incident dementia in people aged 80 and over and suffering from hypertension. Data from the Hypertension in the Very Elderly Trial (HYVET). Age Aging. 39, 439–445 (2010).
May, H. et al. Depression after coronary artery disease is associated with heart failure. J. Am. Coll. Cardiol. 53, 1440–1447 (2009).
Kato, N. et al. Relationship of depressive symptoms with hospitalization and death in Japanese patients with heart failure. J. Card. Fail. 15, 912–919 (2009).
Lesman-Leegte, I. et al. Depressive symptoms and outcomes in patients with heart failure: data from the COACH study. Eur. J. Heart Fail. 11, 1202–1207 (2009).
Frasure-Smith, N. et al. Elevated depression symptoms predict long-term cardiovascular mortality in patients with atrial fibrillation and heart failure. Circulation 120, 134–140 (2009).
Frasure-Smith, N., Lespérance, F. & Talajic, M. Depression following myocardial infarction. Impact on 6-month survival. JAMA 270, 1819–1825 (1993).
Glassman, A. H., Bigger, J. T. Jr & Gaffney, M. Psychiatric characteristics associated with long-term mortality among 361 patients having an acute coronary syndrome and major depression: seven-year follow-up of SADHART participants. Arch. Gen. Psychiatry 66, 1022–1029 (2009).
Tully, P. J., Baker, R. A., Turnbull, D. & Winefield, H. The role of depression and anxiety symptoms in hospital readmissions after cardiac surgery. J. Behav. Med. 31, 281–290 (2008).
Dao, T. K. et al. Clinical depression, posttraumatic stress disorder, and comorbid depression and posttraumatic stress disorder as risk factors for in-hospital mortality after coronary artery bypass grafting surgery. J. Thorac. Cardiovasc. Surg. 140, 606–610 (2010).
Kendel, F. et al. Predictive relationship between depression and physical functioning after coronary surgery. Arch. Intern. Med. 170, 1717–1721 (2010).
Frasure-Smith, N. & Lespérance, F. Depression and anxiety as predictors of 2-year cardiac events in patients with stable coronary artery disease. Arch. Gen. Psychiatry 65, 62–71 (2010).
Hoen, P. et al. Differential associations between specific depressive symptoms and cardiovascular prognosis in patients with stable coronary heart disease. J. Am. Coll. Cardiol. 56, 838–844 (2010).
Davidson, K. W. et al. Association of anhedonia with recurrent major adverse cardiac events and mortality 1 year after acute coronary syndrome. Arch. Gen. Psychiatry 67, 480–488 (2010).
Leroy, M., Loas, G. & Perez-Diaz, F. Anhedonia as predictor of clinical events after acute coronary syndromes: a 3-year prospective study. Compr. Psychiatry 51, 8–14 (2010).
Druss B. G. et al. Mental disorders and use of cardiovascular procedures after myocardial infaction. JAMA 283, 506–511 (2000).
Gehi, A., Hass, D., Pipkin, S. & Whooley, M. A. Depression and medication adherence in outpatients with coronary heart disease: findings from the Heart and Soul Study. Arch. Intern. Med. 165, 2508–2513 (2005).
Rocha V. Z & Libby P. Obesity, inflammation and atherosclerosis. Nat. Rev. Cardiol. 6, 399–409 (2009).
Currier, M. B & Nemeroff, C. B. Inflammation and mood disorders: proinflammatory cytokines and the pathogenesis of depression. Anti-Inflammatory & Anti-Allergy Agents in Medicinal Chemistry 9, 212–220 (2010).
Raison, C. L., Cowles, M. K. & Miller, A. H. In Textbook of Psychopharmacology 4th Edn (eds Schatzberg, A. F. & Nemeroff, C. B.) 201–220 (American Psychiatric Publishing, Washington DC, 2009).
Raedler, T. J. Inflammatory mechanisms in major depressive disorder. Curr. Opin. Psychiatry 24, 519–525 (2011).
Goldschmidt-Clermont, P. J. Loss of bone marrow-derived vascular progenitor cells leads to inflammation and atherosclerosis. Am. Heart J. 146 (Suppl. 4), S5–S12 (2003).
Goldschmidt-Clermont P. J. & Peterson, E. D. On the memory of a chronic illness. Sci. Aging Knowledge Environ. 45, 8 (2003).
Asahara, T. et al. Isolation of putative progenitor endothelial cells for angiogenesis. Science 275, 964–967 (1997).
Pikhart, H. et al. Depressive symptoms and levels of C-reactive protein: a population-based study. Soc. Psychiatry Psychiatr. Epidemiol. 44, 217–222 (2009).
Elovainio, M. et al. Depression and C-reactive protein: population-based Health 2000 study. Psychosom. Med. 71, 423–430 (2009).
Kling, M. A. et al. Sustained low-grade pro-inflammatory state in unmedicated, remitted women with major depressive disorder as evidenced by elevated serum levels of the acute phase proteins C-reactive protein and serum amyloid A. Biol. Psychiatry 62, 309–313 (2007).
Douglas, K. M., Taylor, A. J. & O'Malley, P. G. Relationship between depression and C-reactive protein in a screening population. Psychosom. Med. 66, 679–683 (2004).
Kuo, H. K. et al. Relation of C-reactive protein to stroke, cognitive disorders, and depression in the general population: systematic review and meta-analysis. Lancet Neurol. 4, 371–380 (2005)
Pasco, J. A. et al. Association of high-sensitivity C-reaction protein with de novo major depression. Br. J. Psychiatry 197, 372–377 (2010).
Howren, M. B., Lamkin, D. M. & Suls, J. Associations of depression with C-reactive protein, IL-1, and IL-6: a meta-analysis. Psychosom. Med. 71, 171–186 (2009).
Frasure-Smith, N. et al. Depression, C-reactive protein and two-year major adverse cardiac events in men after acute coronary syndromes. Biol. Psychiatry 62, 302–308 (2007).
Musselman, D. L. et al. Higher than normal plasma interleukin-6 concentrations in cancer patients with depression: preliminary findings. Am. J. Psychiatry. 158, 1252–1257 (2001).
Lindqvist, D. et al. Interleukin-6 is elevated in the cerebrospinal fluid of suicide attempters and related to symptom severity. Biol. Psychiatry 66, 287–292 (2009).
Davidson, K. W. et al. Relation of inflammation to depression and incident coronary heart disease (from the Canadian Nova Scotia Health Survey [NSHS95] Prospective Population Study). Am. J. Cardiol. 103, 755–761 (2009).
Ferketich, A. K., Ferguson, J. P. & Binkley, P. F. Depressive symptoms and inflammation among heart failure patients. Am. Heart J. 150, 132–136 (2005).
Whooley, M. A. et al. Depression and inflammation in patients with coronary heart disease: findings from the Heart and Soul Study. Biol. Psychiatry 62, 314–320 (2007).
Duivis, H. E. et al. Depressive symptoms, health behaviors, and subsequent inflammation in patients with coronary heart disease: prospective findings from the Heart and Soul Study. Am. J. Psychiatry 168, 913–920 (2011).
Morris A. A. et al. Association between depression and inflammation—differences by race and sex. The META-Health Study. Psychosom. Med. 73 462–468 (2011).
Mause, S. F. et al. Platelet microparticles enhance the vasoregenerative potential of angiogenic early outgrowth cells after vascular injury. Circulation 122, 495–506 (2010).
Ross R. Atherosclerosis—an inflammatory disease. N. Engl. J. Med. 340, 115–126 (1999).
Lusis A. J. Atherosclerosis. Nature 407, 233–241 (2000).
Libby, P. Inflammation in atherosclerosis. Nature 420, 868–874 (2002).
Seshiah, P. N. et al. Activated monocytes induce smooth muscle cell death: role of macrophage colony-stimulating factor and cell contact. Circulation 105, 174–180 (2002).
Goldschmidt-Clermont, P. J. et al. Inflammation, stem cells and atherosclerosis genetics. Curr. Opin. Mol. Ther. 12, 712–723 (2010).
Weber, A. A., Köppen, H. O. & Schrör, K. Platelet-derived microparticles stimulate coronary artery smooth muscle cell mitogenesis by a PDGF-independent mechanism. Thromb. Res. 98, 461–466 (2000).
Ando, M. et al. Circulating platelet-derived microparticles with procoagulant activity may be a potential cause of thrombosis in uremic patients. Kidney Int. 5, 1757–1763 (2002).
Markovitz, J. H. & Mathews, K. A. Platelets and coronary heart disease: potential psychophysiologic mechanisms. Psychosom. Med. 53, 643–668 (1991).
Musselman, D. L. et al. Exaggerated platelet reactivity in major depression. Am. J. Psychiatry 153, 1313–1317 (1996).
Musselman, D. L. et al. Platelet reactivity in depressed patients treated with paroxetine: preliminary findings. Arch. Gen. Psychiatry 57, 875–882 (2000).
Thiagarajan, P. & Tait, J. F. Binding of annexin V/placental anticoagulant protein I to platelets. Evidence for phosphatidylserine exposure in the procoagulant response of activated platelets. J. Biol. Chem. 265, 17420–17423 (1990).
Morel-Kopp, M. C. et al. The association of depression with platelet activation: evidence for a treatment effect. J. Thromb. Haemost. 7, 573–581 (2009).
Laghrissi-Thode, F., Wagner, W. R., Pollock, B. G., Johnson, P. C. & Finkel, M. S. Elevated platelet factor 4 and β-thromboglobulin plasma levels in depressed patients with ischemic heart disease. Biol. Psychiatry 42, 290–295 (1997).
Parakh, K., Sakhuja, A., Bhat, U. & Zeigelstein, R. C. Platelet function in patients with depression. South. Med. J. 101, 612–617 (2008).
Gehi, A. et al. Depression and platelet activation in outpatients with stable coronary heart disease: findings from the Heart and Soul Study. Psychiatry Res. 175, 200–204 (2010).
Aschbacher, K. et al. Persistent versus transient depressive symptoms in relation to platelet hyperactivation: a longitudinal analysis of dementia caregivers. J. Affect. Disord. 116, 80–87 (2009).
Atar, D. et al. Escitalopram, but not its major metabolites, exhibits antiplatelet activity in humans. J. Clin. Psychopharmacol. 26, 172–177 (2006).
Serebruany, V. L. et al. Platelet/endothelial biomarkers in depressed patients treated with the selective serotonin reuptake inhibitor sertraline after acute coronary events: the Sertraline Antidepressant Heart Attack Randomized Trial (SADHART) Platelet Substudy. Circulation 108, 939–944 (2003).
Serebruany, V. L., Gurbel, P. A. & O'Connor, A. M. Platelet inhibition by sertraline and N-desmethylsertraline: a possible missing link between depression, coronary events, and mortality benefits of selective serotonin reuptake inhibitors. Pharmacol. Res. 43, 453–462 (2001).
D Alderman, C. P., Moritz, C. K. & Ben-Tovim, D. I. Abnormal platelet aggregation associated with fluoxetine therapy. Ann. Pharmacother. 26, 1517–1519 (1992).
van Zyl, L. T. et al. Platelet and endothelial activity in comorbid major depression and coronary artery disease patients treated with citalopram: the Canadian Cardiac Randomized Evaluation of Antidepressant and Psychotherapy Efficacy Trial (CREATE) biomarker sub-study. J. Thromb. Thrombolysis 27, 48–56 (2009).
Tomfohr, L. M., Martin, T. M. & Miller, G. E. Symptoms of depression and impaired endothelial function in healthy adolescent women. J. Behav. Med. 31, 137–143 (2008).
Lavoie, K. L., Pelletier, R., Arsenault, A., Dupuis, J. & Bacon, S. L. Association between clinical depression and endothelial function measured by forearm hyperemic reactivity. Psychosom. Med. 72, 20–26 (2010).
Kim, J. H. et al. Coronary endothelial dysfunction associated with a depressive mood in patients with atypical angina but angiographically normal coronary artery. Int. J. Cardiol. 143, 154–157 (2010).
Cooper, D. C. et al. Depressed mood and flow-mediated dilation: a systematic review and meta-analysis. Psychsom. Med. 73, 360–369 (2011).
Yager, S., Forlenza, M. J. & Miller, G. E. Depression and oxidative damage to lipids. Psychoneuroendocrinology 35, 1356–1362 (2010).
Maes, M. et al. Increased plasma peroxides and serum oxidized low density lipoprotein antibodies in major depression: markers that further explain the higher incidence of neurodegeneration and coronary artery disease. J. Affect. Disord. 125, 287–294 (2010).
Burg, M. M., Martens, E. J., Collins, D. & Soufer, R. Depression predicts elevated endothelin-1 in patients with coronary artery disease. Psychosom. Med. 73, 2–6 (2011).
Goldschmidt-Clermont, P. J. et al. Atherosclerosis 2005: recent discoveries and novel hypotheses. Circulation 112, 3348–3353 (2005).
Shantsila, E., Watson, T. & Lip, G. Y. Endothelial progenitor cells in cardiovascular disorders. J. Am. Coll. Cardiol. 49, 741–752 (2007).
Karra, R. et al. Molecular evidence for arterial repair in atherosclerosis. Proc. Natl Acad. Sci. USA 102, 16789–16794 (2005).
Rauscher, F. M. et al. Aging, progenitor cell exhaustion, and atherosclerosis. Circulation 108, 457–463 (2003).
Song, X. et al. Will periodic intravenous injections of conditioned bone marrow cells effectively reduce atherosclerosis? Antioxid. Redox Signal. 16, 85–91 (2012).
Dome, P. et al. Circulating endothelial progenitor cells and depression: a possible novel link between heart and soul. Mol. Psychiatry 14, 523–531 (2009).
Cesar, L. et al. An essential role for diet in exercise-mediated protection against dyslipidemia, inflammation and atherosclerosis in ApoE−/− mice. PLoS ONE 6, e17263 (2011).
Lenk, K., Uhlemann, M., Schuler, G. & Adams, V. Role of endothelial progenitor cells in the beneficial effects of physical exercise on atherosclerosis and coronary artery disease. J. Appl. Physiol. 111, 321–328 (2011).
Seals, D. R., Desouza, C. A., Donato, A. J. & Tanaka, H. Habitual exercise and arterial aging. J. Appl. Physiol. 105, 1323–1332 (2008).
Walter, D. H. et al. Statin therapy accelerates reendothelialization: a novel effect involving mobilization and incorporation of bone marrow-derived endothelial progenitor cells. Circulation 105, 3017–3024 (2002).
Li, M. & Losordo, D. W. Statins and the endothelium. Vascul. Pharmacol. 46, 1–9 (2007).
Walter, D. H., Zeiher, A. M. & Dimmeler, S. Effects of statins on endothelium and their contribution to neovascularization by mobilization of endothelial progenitor cells. Coron. Artery Dis. 15, 235–242 (2004).
Jelic, S. et al. Endothelial repair capacity and apoptosis are inversely related in obstructive sleep apnea. Vasc. Health Risk Manag. 5, 909–920 (2009).
Kheirandish-Gozal, L., Bhattacharjee, R., Kim, J., Clair, H. B. & Gozal, D. Endothelial progenitor cells and vascular dysfunction in children with obstructive sleep apnea. Am. J. Respir. Crit. Care Med. 182, 92–97 (2010).
Jelic, S. et al. Inflammation, oxidative stress, and repair capacity of the vascular endothelium in obstructive sleep apnea. Circulation 117, 2270–2278 (2008).
Martin, K., Stanchina, M., Kouttab, N., Harrington, E. O. & Rounds, S. Circulating endothelial cells and endothelial progenitor cells in obstructive sleep apnea. Lung 186, 145–150 (2008).
Chen, H., Yiu, K. H. & Tse, H. F. Relationships between vascular dysfunction, circulating endothelial progenitor cells, and psychological status in healthy subjects. Depress. Anxiety 28, 719–727 (2011).
Kleiger R. E., Miller J. P., Bigger J. T. & Moss A. J. Decreased heart rate variability and its association with increased mortality after myocardial infarction. Am. J. Cardiol. 59, 256–262, (1987).
Carney, R. M. et al. Association of depression with reduced heart rate variability in coronary artery disease. Am. J. Cardiol. 76, 562–564 (1995).
Blasco-Lafarga, C. et al. Linear and nonlinear heart rate dynamics in elderly inpatients. Relations with comorbidity and depression. Medicina (Kaunas) 46, 393–400 (2010).
Licht, C. M. et al. Association between major depressive disorder and heart rate variability in the Netherlands Study of Depression and Anxiety (NESDA). Arch. Gen. Psychiatry 65, 1358–1367 (2008).
de Jonge, P., Mangano, D. & Whooley, M. A. Differential association of cognitive and somatic depressive symptoms with heart rate variability in patients with stable coronary heart disease: findings from the Heart and Soul Study. Psychosom. Med. 69, 735–739 (2011).
Kemp A. H. et al. Impact of depression and antidepressant treatment on heart rate variability: a review and meta-analysis. Biol. Psychiatry 67, 1067–1074 (2010).
Rondondi, N. et al. Subclinical hypothyroidism and the risk of coronary heart disease and mortality. JAMA 304, 1365–1374 (2010).
Nemeroff, C. B., Simon, J. S., Haggerty, J. J. Jr. & Evans, D. L. Antithyroid antibodies in depressed patients. Am. J. Psychiatry 142, 840–843 (1985).
Gillespie, C. F., Garlow, S. J., Schatzberg, A. F. & Nemeroff, C. B. In Textbook of Psychopharmacology, 4th edn (eds Schatzberg A. & Nemeroff, C. B.) 903–944 (American Psychiatric Publishing, Washington DC, 2009).
Gutman, D. A. & Nemeroff, C. B. in Encyclopedia of Neuroscience (ed. Squire, L. R.). 355–366 (Elsevier, Oxford, England, 2009).
Vogelzangs, N. et al. Urinary cortisol and six-year risk of all-cause and cardiovascular mortality. J. Clin. Endocrinol. Metab. 95, 4959–4964 (2010).
Jokinen, J. & Nordström, P. HPA axis hyperactivity and cardiovascular mortality in mood disorder inpatients. J. Affect. Disord. 116, 88–92 (2009).
Stalder, T., Evans, P. Hucklebridge, F. & Clow, A. Associations between the cortisol awakening response and heart rate variability. Psychoneuroendocrinology 36, 454–462 (2011).
Kullo, I. J. & Cooper, L. T. Early identification of cardiovascular risk using genomics and proteomics. Nat. Rev. Cardiol. 7, 309–317 (2010).
Ordavás, J. M. & Smith, C. E. Epigenetics and cardiovascular disease. Nat. Rev. Cardiol. 7, 510–519 (2010).
de Geus, E. In Depression and Heart Disease (eds Glassman, A. et al.) 57–98 (John Wiley & Sons, Chichester, 2010).
McCaffery, J. M. et al. Genetic predictors of depressive symptoms in cardiac patients. Am. J. Med. Genet. B Neuropsychiatr. Genet. 150B, 381–388 (2009).
López-León, S. et al. Shared genetic factors in the co-occurrence of symptoms of depression and cardiovascular risk factors. J. Affect. Disord. 122, 247–252 (2010).
Yarnell, J. et al. Association of European population levels of thrombotic and inflammatory factors with risk of coronary heart disease: the MONICA Optional Haemostasis Study. Eur. Heart J. 26, 332–342 (2005).
Su, S. et al. Common genes contribute to depressive symptoms and heart rate variability: the Twins Heart Study. Twin Res. Hum. Genet. 13, 1–9 (2010).
Vaccarino, V. et al. Depressive symptoms and heart rate variability: evidence for a shared genetic substrate in a study of twins. Psychosom. Med. 70, 628–636 (2008).
Bozzini, S. et al. Coronary artery disease and depression: possible role of brain-derived neurotrophic factor and serotonin transporter gene polymorphisms. Intl. J. Mol. Med. 24, 813–818 (2009).
Duthie, S. J. Epigenetic modifications and human pathologies: cancer and CVD. Proc. Nutr. Soc. 70, 47–56 (2011).
Bucova, M. in Angina Pectoris Ch. 1 (ed. Piscione, F.) 1–34 (InTech, Rijeka, 2011).
Dong, C., Yoon, W. & Goldschmidt-Clermont P. J. DNA methylation and atherosclerosis. J. Nutr. 132 (Suppl. 8), 2406S–2409S (2002).
Meaney, M. J. & Ferguson-Smith A. C. Epigenetic regulation of the neural transcriptome: the meaning of the marks. Nat. Neurosci. 13, 1313–1318 (2010).
Feinberg, A. P. Epigenomics reveals a functional genome anatomy and a new approach to common disease. Nat. Biotechnol. 28, 1049–1052 (2010).
Dong M. et al. Insights into causal pathways for ischemic heart disease: adverse childhood experiences study. Circulation 110, 1761–1766 (2004).
Feinberg, A. P. & Irizarry, R A. Evolution in health and medicine Sackler colloquium: stochastic epigenetic variation as a driving force of development, evolutionary adaptation, and disease. Proc. Natl Acad. Sci. USA 107 (Suppl. 1), 1757–1764 (2010).
Goldschmidt-Clermont, P. J., Dong, C., West, M. & Seo, D. M. Of cardiovascular illness and diversity of biological response. Trends Cardiovasc. Med. 18, 194–197 (2008).
Fuster, V., Lois, F. & Franco, M. Early identification of atherosclerotic disease by noninvasive imaging. Nat. Rev. Cardiol. 7, 327–333 (2010).
de Couto, G., Ouzounian, M. & Liu, P. P. Early detection of myocardial dysfunction and heart failure. Nat. Rev. Cardiol. 7, 334–344 (2010).
Choudhury, R. P. & Fisher, E. A. Molecular imaging in atherosclerosis, thrombosis and vascular inflammation. Arterioscler. Thromb. Vasc. Biol. 29, 983–991 (2009).
Hamer, M., Kivimaki, M., Lahiri, A., Marmot, M. G. & Steptoe, A. Persistent cognitive depressive symptoms are associated with coronary artery calcification. Atherosclerosis 210, 209–213 (2010).
Vural, M., Satiroglu, O., Akbas, B., Goksel, I. & Karabay, O. Coronary artery disease in association with depression or anxiety among patients undergoing angiography to investigate chest pain. Tex. Heart Inst. J. 36, 17–23 (2009).
Kabir, A. A. et al. Association between depression and intima–media thickness of carotid bulb in asymptomatic young adults. Am. J. Med. 122, 1151.e1–1151.e8 (2009).
Paranthaman, R. et al. Vascular function in older adults with depressive disorder. Biol. Psychiatry 68, 133–139 (2010).
Smoller, J. W. et al. Antidepressant use and risk of incident cardiovascular morbidity and mortality among postmenopausal women in the Women's Health Initiative study. Arch. Intern. Med. 169, 2128–2139 (2009).
Dowlati, Y., Herrmann, N., Swardfager, W. L., Reim, E. K. & Lanctot, K. L. Efficacy and tolerability of antidepressants for treatment of depression in coronary artery disease: a meta-analysis. Can. J. Psychiatry 55, 91–99 (2010).
Gottlieb, S. S. et al. A double-blind placebo-controlled pilot study of controlled-release paroxetine on depression and quality of life in chronic heart failure. Am. Heart J. 153, 868–873 (2007).
O'Connor, C. M. et al. Safety and efficacy of sertraline for depression in patients with heart failure: results of the SADHART-CHF (Sertraline Against Depression and Heart Disease in Chronic Heart Failure) trial. J. Am. Coll. Cardiol. 56, 692–699 (2010).
Berkman, L. F. et al. 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 (2003).
Taylor, C. B. et al. Effects of antidepressant medication on morbidity and mortality in depressed patients after myocardial infarction. Arch. Gen. Psychiatry 62, 792–798 (2005).
Honig, A. et al. Treatment of post-myocardial infarction depressive disorder: a randomized, placebo-controlled trial with mirtazapine. Psychosom. Med. 69, 606–613 (2007).
de Jonge, P. et al. Nonresponse to treatment for depression following myocardial infarction: association with subsequent cardiac events. Am. J. Psychiatry 164, 1371–1378 (2007).
Thombs, B. D. et al. Depression screening and patient outcomes in cardiovascular care: a systematic review. JAMA 300, 2161–2171 (2008).
Hansen, B. H. et al. Effects of escitalopram in prevention of depression in patients with acute coronary syndrome (DECARD). J. Psychosom. Res. 72, 11–16 (2012).
Davidson, K. W. et al. Enhanced depression care for patients with acute coronary syndrome and persistent depressive symptoms: coronary psychosocial evaluation studies randomized controlled trial. Arch. Intern. Med. 170, 600–608 (2010).
Gulliksson, M. et al. Randomized controlled trial of cognitive behavioral therapy vs standard treatment to prevent recurrent cardiovascular events in patients with coronary heart disease: Secondary Prevention in Uppsala Primary Health Care project (SUPRIM). Arch. Intern. Med. 171, 134–140 (2011).
Lespérance, F. et al. Effects of citalopram and interpersonal psychotherapy on depression in patients with coronary artery disease: the Canadian Cardiac Randomized Evaluation of Antidepressant and Psychotherapy Efficacy (CREATE) trial. JAMA 297, 367–379 (2007).
Van Zyl, L. T. et al. Platelet and endothelial activity in comorbid major depression and coronary artery disease patients treated with citalopram: the Canadian Cardiac Randomized Evaluation of Antidepressant and Psychotherapy Efficacy Trial (CREATE) biomarker sub-study. J. Thromb. Thrombolysis 27, 48–56 (2009).
Santangelo, A. et al. Use of specific serotonin reuptake inhibitors (SSRIs) (sertraline or citalopram) in the treatment of depression reduces the cardiovascular risk in the elderly: evidence from a Sicilian population >80 years recovered in the assisted sanitary residences (RSA). Arch. Gerontol. Geriatr. 48, 350–352 (2009).
Pollock, B. G., Laghrissi-Thode, F. & Wagner, W. R. Evaluation of platelet activation in depressed patients with ischemic heart disease after paroxetine or nortriptyline treatment. J. Clin. Psychopharmacol. 20, 137–140 (2000).
Pizzi, C. et al. 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 (2009).
Paslakis, G. et al. Treatment with paroxetine, but not amitriptyline, lowers levels of lipoprotein (a) in patients with major depression. J. Psychopharmacol. 25, 1344–1346 (2011).
Taylor, C. B. et al. Does improving mood in depressed patients alter factors that may affect cardiovascular disease risk? J. Psychiatr. Res. 43, 1246–1252 (2009).
P. J. Goldschmidt-Clermont's research is supported by grants from the National Cancer Institute and NIH (R01CA136387). C B. Nemeroff's research is supported by grants from the NIH (NIMH MH-078775, MH-094759, and NIDA DA-031201).
C B. Nemeroff has acted as a consultant for Roche, Shire, SK Pharma, Takeda, Lilly, and Xhale and is a stockholder of CeNeRx BioPharma, NovaDel Pharma, PharmaNeuroBoost, Revaax, and Xhale. He is also a member of the scientific advisory boards for the American Foundation for Suicide Prevention, Anxiety and Depression Association of America, BioPharma, CeNeRx, National Alliance for Research on Schizophrenia and Depression, PharmaNeuroBoost, Skyland Trail, and Xhale. He is currently, or has served in the past 2 years, on the board of directors of the American Foundation for Suicide Prevention, Gratitude America, the Anxiety and Depression Association of America, NovaDel Pharma, and Skyland Trail. P. J. Goldschmidt-Clermont is a shareholder and board member of Health Management Associates, Mednax and OPKO Health, Inc, and a stockholder and scientific advisory board member for Synecor.
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Nemeroff, C., Goldschmidt-Clermont, P. Heartache and heartbreak—the link between depression and cardiovascular disease. Nat Rev Cardiol 9, 526–539 (2012). https://doi.org/10.1038/nrcardio.2012.91
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