Mental Depression and Cardiovascular Disease: A Multifaceted, Bidirectional Association

 

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ABSTRACT

The association between cardiovascular disease and mental depression is multifaceted and likely bidirectional. Depressed patients are at significantly higher risk for cardiac morbidity and mortality even in the absence of a diagnosis of major depression, whereas mental depression is nearly 3 times more frequent in patients after an acute myocardial infarction and contributes to a worse prognosis. Therefore, depressed patients might become trapped in a harmful loop, where mental symptoms might be worsened by the synergistic effects of stress and cardiovascular risk factors, and where they are otherwise vulnerable to acute cardiovascular events due to the synergistic effects of mental stress and an underlying atherothrombotic disorder. Although the exact pathway(s) underlying the interplay between depression and cardiovascular disease remains to be elucidated, the mechanisms most often implicated include hormonal variations, metabolic abnormalities, hypercoagulability, increased platelet aggregation, inflammation, and endothelial dysfunction. This article aims to review the biological and clinical links between depression and cardiovascular disease.

REFERENCES

• 1 Murray CJL, Lopez AD The Global Burden of Disease. Boston, MA; Harvard University Press 1996
  Google Scholar
• 2 Kessler R C, Berglund P, Demler O National Comorbidity Survey Replication et al. The epidemiology of major depressive disorder: results from the National Comorbidity Survey Replication (NCS-R).  JAMA. 2003;  289 3095-3105
  CrossrefPubMedGoogle Scholar
• 3 Belmaker R H, Agam G. Major depressive disorder.  N Engl J Med. 2008;  358 55-68
  CrossrefPubMedGoogle Scholar
• 4 American Psychiatric Association .Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, Text Revision: DSM-IV-TR. Washington, DC; American Psychiatric Publishing 2000
  Google Scholar
• 5 National Institute of Mental Health .Older adults and mental health. Bethesda, MD; US Department of Health and Human Services, National Institutes of Health, National Institute of Mental Health 2006 Available at: http://nimh.nih.gov/healthinformation/depoldermenu.cfm Accessed December 2, 2008
  Google Scholar
• 6 Ansorge M S, Hen R, Gingrich J A. Neurodevelopmental origins of depressive disorders.  Curr Opin Pharmacol. 2007;  7 8-17
  CrossrefPubMedGoogle Scholar
• 7 Hayley S, Poulter M O, Merali Z, Anisman H. The pathogenesis of clinical depression: stressor- and cytokine-induced alterations of neuroplasticity.  Neuroscience. 2005;  135 659-678
  CrossrefPubMedGoogle Scholar
• 8 Sowden G L, Huffman J C. The impact of mental illness on cardiac outcomes: a review for the cardiologist.  Int J Cardiol. 2009;  132 30-37
  CrossrefPubMedGoogle Scholar
• 9 Rozanski A, Bairey C N, Krantz D S et al.. Mental stress and the induction of silent myocardial ischemia in patients with coronary artery disease.  N Engl J Med. 1988;  318 1005-1012
  PubMedGoogle Scholar
• 10 Whooley M A, de Jonge P, Vittinghoff E et al.. Depressive symptoms, health behaviors, and risk of cardiovascular events in patients with coronary heart disease.  JAMA. 2008;  300 2379-2388
  Google Scholar
• 11 Rosengren A, Hawken S, Ounpuu S INTERHEART investigators et al. Association of psychosocial risk factors with risk of acute myocardial infarction in 11119 cases and 13648 controls from 52 countries (the INTERHEART study): case-control study.  Lancet. 2004;  364 953-962
  Google Scholar
• 12 Anda R, Williamson D, Jones D et al.. Depressed affect, hopelessness, and the risk of ischemic heart disease in a cohort of U.S. adults.  Epidemiology. 1993;  4 285-294
  PubMedGoogle Scholar
• 13 Lichtman J H, Bigger Jr J T, Blumenthal J A American Heart Association Prevention Committee of the Council on Cardiovascular Nursing et al. Depression and coronary heart disease: recommendations for screening, referral, and treatment: a science advisory from the American Heart Association Prevention Committee of the Council on Cardiovascular Nursing, Council on Clinical Cardiology, Council on Epidemiology and Prevention, and Interdisciplinary Council on Quality of Care and Outcomes Research: endorsed by the American Psychiatric Association.  Circulation. 2008;  118 1768-1775
  CrossrefPubMedGoogle Scholar
• 14 Matthews S C, Nelesen R A, Dimsdale J E. Depressive symptoms are associated with increased systemic vascular resistance to stress.  Psychosom Med. 2005;  67 509-513
  CrossrefPubMedGoogle Scholar
• 15 Allen M T, Patterson S M. Hemoconcentration and stress: a review of physiological mechanisms and relevance for cardiovascular disease risk.  Biol Psychol. 1995;  41 1-27
  CrossrefPubMedGoogle Scholar
• 16 Shinagawa M, Otsuka K, Murakami S et al.. Seven-day (24-h) ambulatory blood pressure monitoring, self-reported depression and quality of life scores.  Blood Press Monit. 2002;  7 69-76
  CrossrefPubMedGoogle Scholar
• 17 Hildreth C M, Padley J R, Pilowsky P M, Goodchild A K. Impaired serotonergic regulation of heart rate may underlie reduced baroreflex sensitivity in an animal model of depression.  Am J Physiol Heart Circ Physiol. 2008;  294 H474-H480
  PubMedGoogle Scholar
• 18 Stein P K, Carney R M, Freedland K E et al.. Severe depression is associated with markedly reduced heart rate variability in patients with stable coronary heart disease.  J Psychosom Res. 2000;  48 493-500
  PubMedGoogle Scholar
• 19 Krittayaphong R, Cascio W E, Light K C et al.. Heart rate variability in patients with coronary artery disease: differences in patients with higher and lower depression scores.  Psychosom Med. 1997;  59 231-235
  PubMedGoogle Scholar
• 20 Bigger Jr J T, Fleiss J L, Rolnitzky L M, Steinman R C. Frequency domain measures of heart period variability to assess risk late after myocardial infarction.  J Am Coll Cardiol. 1993;  21 729-736
  PubMedGoogle Scholar
• 21 Sorlie P D, Garcia-Palmieri M R, Costas Jr R, Havlik R J. Hematocrit and risk of coronary heart disease: the Puerto Rico Health Program.  Am Heart J. 1981;  101 456-461
  CrossrefPubMedGoogle Scholar
• 22 Patterson S M, Krantz D S, Gottdiener J S, Hecht G, Vargot S, Goldstein D S. Prothrombotic effects of environmental stress: changes in platelet function, hematocrit, and total plasma protein.  Psychosom Med. 1995;  57 592-599
  PubMedGoogle Scholar
• 23 Lowe G D. Blood rheology in arterial disease.  Clin Sci (Lond). 1986;  71 137-146
  PubMedGoogle Scholar
• 24 Kensey K R. The mechanistic relationships between hemorheological characteristics and cardiovascular disease.  Curr Med Res Opin. 2003;  19 587-596
  CrossrefPubMedGoogle Scholar
• 25 Finnerty Jr F A, Buchholz J H, Guillaudeu R L. The blood volumes and plasma protein during levarterenol-induced hypertension.  J Clin Invest. 1958;  37 425-429
  CrossrefPubMedGoogle Scholar
• 26 Cohn J N. Relationship of plasma volume changes to resistance and capacitance vessel effects of sympathomimetic amines and angiotensin in man.  Clin Sci. 1966;  30 267-278
  PubMedGoogle Scholar
• 27 Johanson C E, Donahue J E, Spangenberger A, Stopa E G, Duncan J A, Sharma H S. Atrial natriuretic peptide: its putative role in modulating the choroid plexus-CSF system for intracranial pressure regulation.  Acta Neurochir Suppl. 2006;  96 451-456
  PubMedGoogle Scholar
• 28 Arlt J, Jahn H, Kellner M, Ströhle A, Yassouridis A, Wiedemann K. Modulation of sympathetic activity by corticotropin-releasing hormone and atrial natriuretic peptide.  Neuropeptides. 2003;  37 362-368
  CrossrefPubMedGoogle Scholar
• 29 Maack T. Role of atrial natriuretic factor in volume control.  Kidney Int. 1996;  49 1732-1737
  PubMedGoogle Scholar
• 30 Silver M A. The natriuretic peptide system: kidney and cardiovascular effects.  Curr Opin Nephrol Hypertens. 2006;  15 14-21
  PubMedGoogle Scholar
• 31 Wong M L, Dong C, Esposito K et al.. Elevated stress-hemoconcentration in major depression is normalized by antidepressant treatment: secondary analysis from a randomized, double-blind clinical trial and relevance to cardiovascular disease risk.  PLoS One. 2008;  3 e2350
  CrossrefPubMedGoogle Scholar
• 32 Broadley A JM, Korszun A, Jones C JH, Frenneaux M P. Arterial endothelial function is impaired in treated depression.  Heart. 2002;  88 521-523
  CrossrefPubMedGoogle Scholar
• 33 Sherwood A, Hinderliter A L, Watkins L L, Waugh R A, Blumenthal J A. Impaired endothelial function in coronary heart disease patients with depressive symptomatology.  J Am Coll Cardiol. 2005;  46 656-659
  CrossrefPubMedGoogle Scholar
• 34 Rajagopalan S, Brook R, Rubenfire M, Pitt E, Young E, Pitt B. Abnormal brachial artery flow-mediated vasodilatation in young adults with major depression.  Am J Cardiol. 2001;  88 196-198
  CrossrefPubMedGoogle Scholar
• 35 Rybakowski J K, Wykretowicz A, Heymann-Szlachcinska A, Wysocki H. Impairment of endothelial function in unipolar and bipolar depression.  Biol Psychiatry. 2006;  60 889-891
  CrossrefPubMedGoogle Scholar
• 36 Broadley A J, Korszun A, Abdelaal E et al.. Metyrapone improves endothelial dysfunction in patients with treated depression.  J Am Coll Cardiol. 2006;  48 170-175
  CrossrefPubMedGoogle Scholar
• 37 Wagner J A, Tennen H, Mansoor G A, Abbott G. History of major depressive disorder and endothelial function in postmenopausal women.  Psychosom Med. 2006;  68 80-86
  CrossrefPubMedGoogle Scholar
• 38 Pinto V L, Brunini T M, Ferraz M R, Okinga A, Mendes-Ribeiro A C. Depression and cardiovascular disease: role of nitric oxid.  Cardiovasc Hematol Agents Med Chem. 2008;  6 142-149
  CrossrefPubMedGoogle Scholar
• 39 Arslan A, Uzun M. Does the lower nitric oxide level cause cardiovascular changes in major depressed women?.  Eur Rev Med Pharmacol Sci. 2008;  12 309-313
  PubMedGoogle Scholar
• 40 Chrapko W E, Jurasz P, Radomski M W, Lara N, Archer S L, Le Mellédo J M. Decreased platelet nitric oxide synthase activity and plasma nitric oxide metabolites in major depressive disorder.  Biol Psychiatry. 2004;  56 129-134
  CrossrefPubMedGoogle Scholar
• 41 Chrapko W, Jurasz P, Radomski M W et al.. Alteration of decreased plasma NO metabolites and platelet NO synthase activity by paroxetine in depressed patients.  Neuropsychopharmacology. 2006;  31 1286-1293
  PubMedGoogle Scholar
• 42 Yang E H, Lerman S, Lennon R J, Simari R D, Lerman L O, Lerman A. Relation of depression to coronary endothelial function.  Am J Cardiol. 2007;  99 1134-1136
  CrossrefPubMedGoogle Scholar
• 43 Serebruany V L, Glassman A H, Malinin A I Sertraline AntiDepressant Heart Attack Randomized Trial Study Group 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. 2003;  108 939-944
  CrossrefPubMedGoogle Scholar
• 44 Geiser F, Meier C, Wegener I et al.. Association between anxiety and factors of coagulation and fibrinolysis.  Psychother Psychosom. 2008;  77 377-383
  CrossrefPubMedGoogle Scholar
• 45 Ogston D, McDonald G A, Fullerton H W. The influence of anxiety in tests of blood coagulability and fibrinolytic activity.  Lancet. 1962;  2 521-523
  PubMedGoogle Scholar
• 46 Dreyfuss F. Coagulation time of the blood, level of blood eosinophils and thrombocytes under emotional stress.  J Psychosom Res. 1956;  1 252-257
  CrossrefPubMedGoogle Scholar
• 47 Macht D I. Influence of some drugs and of emotions on blood coagulation.  JAMA. 1952;  148 265-270
  PubMedGoogle Scholar
• 48 Jern C, Eriksson E, Tengborn L, Risberg B, Wadenvik H, Jern S. Changes of plasma coagulation and fibrinolysis in response to mental stress.  Thromb Haemost. 1989;  62 767-771
  PubMedGoogle Scholar
• 49 Davis M C. Oral contraceptive use and hemodynamic, lipid, and fibrinogen responses to smoking and stress in women.  Health Psychol. 1999;  18 122-130
  CrossrefPubMedGoogle Scholar
• 50 Steptoe A, Kunz-Ebrecht S, Owen N et al.. Influence of socioeconomic status and job control on plasma fibrinogen responses to acute mental stress.  Psychosom Med. 2003;  65 137-144
  CrossrefPubMedGoogle Scholar
• 51 Steptoe A, Kunz-Ebrecht S, Rumley A, Lowe G D. Prolonged elevations in haemostatic and rheological responses following psychological stress in low socioeconomic status men and women.  Thromb Haemost. 2003;  89 83-90
  PubMedGoogle Scholar
• 52 Palermo A, Bertalero P, Pizza N, Amelotti R, Libretti A. Decreased fibrinolytic response to adrenergic stimulation in hypertensive patients.  J Hypertens Suppl. 1989;  7 S162-S163
  CrossrefPubMedGoogle Scholar
• 53 von Känel R, Dimsdale J E, Ziegler M G et al.. Effect of acute psychological stress on the hypercoagulable state in subjects (spousal caregivers of patients with Alzheimer's disease) with coronary or cerebrovascular disease and/or systemic hypertension.  Am J Cardiol. 2001;  87 1405-1408
  CrossrefPubMedGoogle Scholar
• 54 von Känel R, Mills P J, Ziegler M G, Dimsdale J E. Effect of beta2-adrenergic receptor functioning and increased norepinephrine on the hypercoagulable state with mental stress.  Am Heart J. 2002;  144 68-72
  CrossrefPubMedGoogle Scholar
• 55 Kudielka B M, Bellingrath S, von Känel R. Circulating fibrinogen but not D-dimer level is associated with vital exhaustion in school teachers.  Stress. 2008;  11 250-258
  CrossrefPubMedGoogle Scholar
• 56 Hou S J, Yen F C, Tsai S J. Is dysfunction of the tissue plasminogen activator (tPA)-plasmin pathway a link between major depression and cardiovascular disease?.  Med Hypotheses. 2009;  72 166-168
  CrossrefPubMedGoogle Scholar
• 57 Eskandari F, Mistry S, Martinez P E POWER (Premenopausal, Odteopenia/Osteoporosis, Women, Alendronate, Depression) Study Group et al. Younger, premenopausal women with major depressive disorder have more abdominal fat and increased serum levels of prothrombotic factors: implications for greater cardiovascular risk.  Metabolism. 2005;  54 918-924
  CrossrefPubMedGoogle Scholar
• 58 Lahlou-Laforet K, Alhenc-Gelas M, Pornin M et al.. Relation of depressive mood to plasminogen activator inhibitor, tissue plasminogen activator, and fibrinogen levels in patients with versus without coronary heart disease.  Am J Cardiol. 2006;  97 1287-1291
  CrossrefPubMedGoogle Scholar
• 59 Duman R S. Synaptic plasticity and mood disorders.  Mol Psychiatry. 2002;  7(Suppl 1) S29-S34
  PubMedGoogle Scholar
• 60 Tsai S J, Hong C J, Liou Y J, Yu Y WY, Chen T J. Plasminogen activator inhibitor-1 gene is associated with major depression and antidepressant treatment response.  Pharmacogenet Genomics. 2008;  18 869-875
  CrossrefPubMedGoogle Scholar
• 61 Nemeroff C B, Musselman D L. Are platelets the link between depression and ischemic heart disease?.  Am Heart J. 2000;  140(4, Suppl) 57-62
  CrossrefPubMedGoogle Scholar
• 62 Musselman D L, Tomer A, Manatunga A K et al.. Exaggerated platelet reactivity in major depression.  Am J Psychiatry. 1996;  153 1212-1217
  PubMedGoogle Scholar
• 63 Berk M, Kirchmann N H, Butkow N. Lithium blocks 45Ca2+ uptake into platelets in bipolar affective disorder and controls.  Clin Neuropharmacol. 1996;  19 48-51
  CrossrefPubMedGoogle Scholar
• 64 Kroll M H, Hellums J D, McIntire L V, Schafer A I, Moake J L. Platelets and shear stress.  Blood. 1996;  88 1525-1541
  PubMedGoogle Scholar
• 65 Markovitz J H, Matthews K A. Platelets and coronary heart disease: potential psychophysiologic mechanisms.  Psychosom Med. 1991;  53 643-668
  PubMedGoogle Scholar
• 66 Laghrissi-Thode F, Wagner W R, Pollock B G, Johnson P C, Finkel M S. Elevated platelet factor 4 and beta-thromboglobulin plasma levels in depressed patients with ischemic heart disease.  Biol Psychiatry. 1997;  42 290-295
  CrossrefPubMedGoogle Scholar
• 67 Shimbo D, Child J, Davidson K et al.. Exaggerated serotonin-mediated platelet reactivity as a possible link in depression and acute coronary syndromes.  Am J Cardiol. 2002;  89 331-333
  CrossrefPubMedGoogle Scholar
• 68 Lett H S, Blumenthal J A, Babyak M A et al.. Depression as a risk factor for coronary artery disease: evidence, mechanisms, and treatment.  Psychosom Med. 2004;  66 305-315
  CrossrefPubMedGoogle Scholar
• 69 Joynt K E, Whellan D J, O'Connor C M. Depression and cardiovascular disease: mechanisms of interaction.  Biol Psychiatry. 2003;  54 248-261
  CrossrefPubMedGoogle Scholar
• 70 Akil H, Haskett R F, Young E A et al.. Multiple HPA profiles in endogenous depression: effect of age and sex on cortisol and beta-endorphin.  Biol Psychiatry. 1993;  33 73-85
  CrossrefPubMedGoogle Scholar
• 71 Lesch K P, Laux G, Schulte H M, Pfüller H, Beckmann H. Corticotropin and cortisol response to human CRH as a probe for HPA system integrity in major depressive disorder.  Psychiatry Res. 1988;  24 25-34
  CrossrefPubMedGoogle Scholar
• 72 Carney R M, Freedland K E, Miller G E, Jaffe A S. Depression as a risk factor for cardiac mortality and morbidity: a review of potential mechanisms.  J Psychosom Res. 2002;  53 897-902
  CrossrefPubMedGoogle Scholar
• 73 Leonard B E. The immune system, depression and the action of antidepressants.  Prog Neuropsychopharmacol Biol Psychiatry. 2001;  25 767-780
  CrossrefPubMedGoogle Scholar
• 74 Douglas K M, Taylor A J, O'Malley P G. Relationship between depression and C-reactive protein in a screening population.  Psychosom Med. 2004;  66 679-683
  CrossrefPubMedGoogle Scholar
• 75 Musselman D L, Marzec U M, Manatunga A et al.. Platelet reactivity in depressed patients treated with paroxetine: preliminary findings.  Arch Gen Psychiatry. 2000;  57 875-882
  CrossrefPubMedGoogle Scholar
• 76 Dentino A N, Pieper C F, Rao M K et al.. Association of interleukin-6 and other biologic variables with depression in older people living in the community.  J Am Geriatr Soc. 1999;  47 6-11
  PubMedGoogle Scholar
• 77 Maes M, Bosmans E, De Jongh R, Kenis G, Vandoolaeghe E, Neels H. Increased serum IL-6 and IL-1 receptor antagonist concentrations in major depression and treatment resistant depression.  Cytokine. 1997;  9 853-858
  CrossrefPubMedGoogle Scholar
• 78 Gotthardt U, Schweiger U, Fahrenberg J, Lauer C J, Holsboer F, Heuser I. Cortisol, ACTH, and cardiovascular response to a cognitive challenge paradigm in aging and depression.  Am J Physiol. 1995;  268(4 Pt 2) R865-R873
  PubMedGoogle Scholar
• 79 Kop W J, Gottdiener J S, Tangen C M et al.. Inflammation and coagulation factors in persons >65 years of age with symptoms of depression but without evidence of myocardial ischemia.  Am J Cardiol. 2002;  89 419-424
  CrossrefPubMedGoogle Scholar
• 80 Christensen N J. Adrenergic mechanisms in selected diseases: arterial hypertension, duodenal ulcer, primary depressive illness, malignant tumors, and ketotic hypoglycemia.  Metabolism. 1980;  29(11, Suppl 1) 1190-1197
  CrossrefPubMedGoogle Scholar
• 81 Louis W J, Doyle A E, Anavekar S N. Plasma noradrenaline concentration and blood pressure in essential hypertension, phaeochromocytoma and depression.  Clin Sci Mol Med Suppl. 1975;  2 239s-242s
  PubMedGoogle Scholar
• 82 Sheline Y I, Freedland K E, Carney R M. How safe are serotonin reuptake inhibitors for depression in patients with coronary heart disease?.  Am J Med. 1997;  102 54-59
  CrossrefPubMedGoogle Scholar
• 83 Januzzi Jr J L, Stern T A, Pasternak R C, DeSanctis R W. The influence of anxiety and depression on outcomes of patients with coronary artery disease.  Arch Intern Med. 2000;  160 1913-1921
  CrossrefPubMedGoogle Scholar
• 84 Jiang W, Krishnan R R, O'Connor C M. Depression and heart disease: evidence of a link, and its therapeutic implications.  CNS Drugs. 2002;  16 111-127
  PubMedGoogle Scholar
• 85 Kubzansky L D, Kawachi I. Going to the heart of the matter: do negative emotions cause coronary heart disease?.  J Psychosom Res. 2000;  48 323-337
  CrossrefPubMedGoogle Scholar
• 86 Rozanski A, Blumenthal J A, Kaplan J. Impact of psychological factors on the pathogenesis of cardiovascular disease and implications for therapy.  Circulation. 1999;  99 2192-2217
  CrossrefPubMedGoogle Scholar
• 87 Rivelli S, Jiang W. Depression and ischemic heart disease: what have we learned from clinical trials?.  Curr Opin Cardiol. 2007;  22 286-291
  CrossrefPubMedGoogle Scholar
• 88 Perlmutter J B, Frishman W H, Feinstein R E. Major depression as a risk factor for cardiovascular disease: therapeutic implications.  Heart Dis. 2000;  2 75-82
  PubMedGoogle Scholar
• 89 O'connor C M, Gurbel P A, Serebruany V L. Depression and ischemic heart disease.  Am Heart J. 2000;  140(4, Suppl) 63-69
  CrossrefPubMedGoogle Scholar
• 90 Zellweger M J, Osterwalder R H, Langewitz W, Pfisterer M E. Coronary artery disease and depression.  Eur Heart J. 2004;  25 3-9
  CrossrefPubMedGoogle Scholar
• 91 Ford D E, Mead L A, Chang P P, Cooper-Patrick L, Wang N Y, Klag M J. Depression is a risk factor for coronary artery disease in men: the precursors study.  Arch Intern Med. 1998;  158 1422-1426
  PubMedGoogle Scholar
• 92 Penninx B W, Beekman A T, Honig A et al.. Depression and cardiac mortality: results from a community-based longitudinal study.  Arch Gen Psychiatry. 2001;  58 221-227
  PubMedGoogle Scholar
• 93 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. 2007;  62 25-32
  CrossrefPubMedGoogle Scholar
• 94 Ferketich A K, Schwartzbaum J A, Frid D J, Moeschberger M L. Depression as an antecedent to heart disease among women and men in the NHANES I study. National Health and Nutrition Examination Survey.  Arch Intern Med. 2000;  160 1261-1268
  PubMedGoogle Scholar
• 95 Rutledge T, Reis S E, Olson M B et al.. Depression symptom severity and reported treatment history in the prediction of cardiac risk in women with suspected myocardial ischemia: The NHLBI-sponsored WISE study.  Arch Gen Psychiatry. 2006;  63 874-880
  CrossrefPubMedGoogle Scholar
• 96 Penninx B W, Guralnik J M, Mendes de Leon C F et al.. Cardiovascular events and mortality in newly and chronically depressed persons >70 years of age.  Am J Cardiol. 1998;  81 988-994
  CrossrefPubMedGoogle Scholar
• 97 Almeida O P, Flicker L, Norman P et al.. Association of cardiovascular risk factors and disease with depression in later life.  Am J Geriatr Psychiatry. 2007;  15 506-513
  CrossrefPubMedGoogle Scholar
• 98 Van der Kooy K, van Hout H, Marwijk H, Marten H, Stehouwer C, Beekman A. Depression and the risk for cardiovascular diseases: systematic review and meta analysis.  Int J Geriatr Psychiatry. 2007;  22 613-626
  CrossrefPubMedGoogle Scholar
• 99 Wulsin L R, Singal B M. Do depressive symptoms increase the risk for the onset of coronary disease? A systematic quantitative review.  Psychosom Med. 2003;  65 201-210
  Google Scholar
• 100 Rutledge T, Reis V A, Linke S E, Greenberg B H, Mills P J. Depression in heart failure: a meta-analytic review of prevalence, intervention effects, and associations with clinical outcomes.  J Am Coll Cardiol. 2006;  48 1527-1537
  CrossrefPubMedGoogle Scholar
• 101 Carney R M, Freedland K E, Sheps D S. Depression is a risk factor for mortality in coronary heart disease.  Psychosom Med. 2004;  66 799-801
  CrossrefPubMedGoogle Scholar
• 102 Shimbo D, Davidson K W, Haas D C, Fuster V, Badimon J J. Negative impact of depression on outcomes in patients with coronary artery disease: mechanisms, treatment considerations, and future directions.  J Thromb Haemost. 2005;  3 897-908
  CrossrefPubMedGoogle Scholar
• 103 Parissis J T, Fountoulaki K, Filippatos G, Adamopoulos S, Paraskevaidis I, Kremastinos D. Depression in coronary artery disease: novel pathophysiologic mechanisms and therapeutic implications.  Int J Cardiol. 2007;  116 153-160
  CrossrefPubMedGoogle Scholar
• 104 Frasure-Smith N, Lespérance F, Talajic M. Depression following myocardial infarction. Impact on 6-month survival.  JAMA. 1993;  270 1819-1825
  CrossrefPubMedGoogle Scholar
• 105 Frasure-Smith N, Lespérance F, Talajic M. Depression and 18-month prognosis after myocardial infarction.  Circulation. 1995;  91 999-1005
  PubMedGoogle Scholar
• 106 Horsten M, Mittleman M A, Wamala S P, Schenck-Gustafsson K, Orth-Gomér K. Depressive symptoms and lack of social integration in relation to prognosis of CHD in middle-aged women. The Stockholm Female Coronary Risk Study.  Eur Heart J. 2000;  21 1072-1080
  Google Scholar
• 107 de Jonge P, Spijkerman T A, van den Brink R H, Ormel J. Depression after myocardial infarction is a risk factor for declining health related quality of life and increased disability and cardiac complaints at 12 months.  Heart. 2006;  92 32-39
  CrossrefPubMedGoogle Scholar
• 108 van Melle J P, de Jonge P, Spijkerman T A et al.. Prognostic association of depression following myocardial infarction with mortality and cardiovascular events: a meta-analysis.  Psychosom Med. 2004;  66 814-822
  CrossrefPubMedGoogle Scholar
• 109 Barth 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;  66 802-813
  Google Scholar
• 110 Dokras A. Cardiovascular disease risk factors in polycystic ovary syndrome.  Semin Reprod Med. 2008;  26 39-44
  Article in Thieme ConnectPubMedGoogle Scholar
• 111 Mina A, Favaloro E J, Koutts J. Hemostatic dysfunction associated with endocrine disorders as a major risk factor and cause of human morbidity and mortality: a comprehensive meta-review.  Semin Thromb Hemost. 2007;  33 798-809
  Article in Thieme ConnectPubMedGoogle Scholar
• 112 Hollinrake E, Abreu A, Maifeld M, Van Voorhis B J, Dokras A. Increased risk of depressive disorders in women with polycystic ovary syndrome.  Fertil Steril. 2007;  87 1369-1376
  CrossrefPubMedGoogle Scholar
• 113 Kerchner A, Lester W, Stuart S P, Dokras A. Risk of depression and other mental health disorders in women with polycystic ovary syndrome: a longitudinal study.  Fertil Steril. 2009;  91 207-212
  CrossrefPubMedGoogle Scholar
• 114 Hirshkowitz M. The clinical consequences of obstructive sleep apnea and associated excessive sleepiness.  J Fam Pract. 2008;  57(8, Suppl) S9-S16
  PubMedGoogle Scholar
• 115 Dawson B, Taylor J, Favaloro E J. Potential benefits of improved protein intake in older people.  Nutrition Dietetics. 2008;  65 151-156
  CrossrefPubMedGoogle Scholar
• 116 Brand-Miller J, Dickinson S, Barclay A, Allman-Farinelli M. Glycemic index, glycemic load and thrombogenesis.  Semin Thromb Hemost. 2009;  35 111-118
  Article in Thieme ConnectPubMedGoogle Scholar
• 117 Singh N A, Stavrinos T M, Scarbek Y, Galambos G, Liber C, Fiatarone Singh M A. A randomized controlled trial of high versus low intensity weight training versus general practitioner care for clinical depression in older adults.  J Gerontol A Biol Sci Med Sci. 2005;  60 768-776
  CrossrefPubMedGoogle Scholar

Prof. Giuseppe LippiM.D. 

Sezione di Chimica Clinica, Dipartimento di Scienze Morfologico-Biomediche, Ospedale Policlinico G.B. Rossi

Piazzale Scuro, 10, 37134 – Verona, Italy

Email: giuseppe.lippi@univr.it