1. Depression and cardiovascular disease an epidemiological perspective Nicole Vogelzangs Psychiatry / EMGO institute, VU University Medical Center

2. 2030Disease% DALYs* 1Depression9.6% 2Heart disease5.9% 3Alzheimer, dementia5.8% 4Alcohol problems4.7% 5Diabetes4.5% 6Stroke4.5% 7Hearing problems4.1% 8Cancer3.0% 9Artrosis2.9% 10Lung disease2.5% Disease burden in western countries: WHO * DALYs = disability-adjusted life years = lost life years + loss of quality of life WHO: Mathers et al. Plos Medicine 2006

3. Disease Burden* in the Netherlands: RIVM * in life years lived in health (RIVM, Nationaal Kompas Volksgezondheid) 1Heart disease 2Anxiety disorders 3Stroke 4Depression 5Lung disease 6Diabetes 7Lung cancer 8Alcohol dependence 9Artrosis 10Dementia

4. Depression and cardiovascular disease cluster: Heart patient:  depression Depression patient:  cardiovascular disease

5. Prevalence of depression in heart disease Longitudinal Aging Study Amsterdam, n=2847, 55-85 years old % minor major minor major depression depression 12.0 17.8 2.6 1.6 p<.001 No heart disease n=2397 Heart disease n=450 Penninx et al. Arch Gen Psychiatry 2001

6. Depression and cardiovascular disease Cause or effect? Cardiovascular disease Depression Depression Cardiovascular disease

7. When the head follows the heart …… prospective evidence Cardiovascular disease Depression

8. CVD as risk factor for depression After myocardial infarcton or stroke: – –Prevalene of depression is increased (60-100%) compared to general population – –Approximately half are new cases

9. Mast et al. Biol Psychiatry in press 2008 ConditionOdds Ratio 95%CI Coronary heart disease 1.76*1.15-2.68 Myocardial infarction 2.70*1.00-7.25 Angina complaints 1.74*1.21-2.52 Claudication score 1.66*1.10-2.50 Heart failure1.260.43-3.67 Periferal artery disease1.810.87-3.78 Risk of onset of depressive symptoms CVD  depressive symptoms (CES-D>15) after 2 years? Health ABC study, n= 1796, 70-79 years old, no depression on T0

10. When the heart follows the head …… prospective evidence Depression Cardiovascular disease

11. Frasure-Smith et al. JAMA 1993 6-month mortality: Nondepressed: 3% Depressed (MDD): 17% HR= 5.74 (4.61-6.87) After adjustment for disease severity: HR= 4.29 (3.14-5.44) Depression predicts death after myocardial infarction

12. ReviewNumber of studies Number of persons RR Barth, 20042011 0182.24 Van Melle, 2004166 3672.59 Nicholson, 20063417 8421.80 Barth et al. Psychosom Med 2004 Van Melle et al. Psychosom Med 2004 Nicholson et al. Eur Heart J 2006 Depression and CVD prognosis in CVD patients Evidence from systematic reviews

13. Meta-analysis: depression predicts prognosis in heart patients Nicholson et al. Eur Heart J 2006

14. Does effect of depression only exist in heart patients? Heart disease: DepressionDeath by heart disease ? No heart disease: DepressionDeath by heart disease ? = ?

15. no minor major no minor major depression depression No heart disease Heart disease n=2397 n=450 Depression and 4-year cardiovascular mortality Longitudinal Aging Study Amsterdam, n=2847, 55-85 year Death per 1000 person years Penninx et al. Arch Gen Psychiatry 2001

16. 5.1 10.5 3.4 3.8 1.6 Risk of cardiovascular mortality baseline CVD no minor depression major Depression and 4-year cardiovascular mortality Longitudinal Aging Study Amsterdam, n=2847 Penninx et al. Arch Gen Psychiatry 2001 no baseline CVD

17. Depression as risk factor for CVD in general population: Evidence from systematic reviews ReviewNumber of studies Number of persons RR Rugulies, 20021136 5491.64 Wulsin, 20031028 7371.64 Nicholson, 200621124 5091.81 Van der Kooy, 200728±80 0001.60 Rugulies Am J Prev Med 2002 Wulsin & Singal Psychosom Med 2003 Nicholson et al. Eur Heart J 2006 Van der Kooy et al. Int J Geriatr Psychiatry 2007

18. Meta-analysis on depression and CVD in general population Van der Kooy et al. Int J Ger Psychiatr 2007 MDD: RR= 2.54 (2.07-3.10) Depressive symptoms: RR= 1.39 (1.26-1.54)

19. Other somatic consequences of depression: Evidence from systematic reviews ReviewNumber of studies Evidence Mortality Wulsin 1999 n=21 +, RR=1.9 Cuijpers 2002 n=25 +, RR=1.8 Diabetes Knol 2006 n=9 +, RR=1.4 Stroke-n=7+ Hypertension-n=7+/- Cancer-n=4 -, -/+

20. Depression Heart disease

22. Mechanisms for depression  CVD

23. association = causality Unhealthy life style Decreased (self)care Poorer psychosocial profile Pathofysiologic association ≠ causality Depression = (early) sign of (severity of) disease depression Third factor cardiovascular disease

25. Unhealthy life style Controls n=524 Remitted MDD n=774 Current MDD n=1075 p Physical activity -low -moderate -high 12.8% 37.2% 50.0% 15.2% 37.3% 47.5% 21.1% 36.3% 42.6%.001 Alcohol dependence 1.4%5.2%9.1% <.001 Smoking26.5%39.5%45.2%<.001 Body Mass Index25.125.625.9.01

26. Decreased (self) care Depressive patients: Poorer adherence to life style advice Less therapy compliant receive less adequate (somatic) care DiMatteo et al. Arch Int Med 2000: meta- analyse: Depressed persons are 3 times less compliant to therapy than nondepressed persons

27. Poorer psychosocial profile Depressive patients: Less support from close contacts Lower social economical situation Less adequate coping

28. Depression Cardiovascular disease Metabolic changes, atherosclerosis Biological black box

29. Depression Cardiovascular disease Metabolic changes, atherosclerosis inflammation autonomic HPA-axis nervous system

30. Vascular depression The ‘vascular depression hypothesis’: “vascular damage in the brain might predispose, precipitate or perpetuate depression in the elderly” Alexopoulos et al. Arch Gen Psychiatry 1997

31. Mechanisms for depression  CVD association = causality Unhealthy life style Decreased (self)care Poorer psychosocial profile Pathofysiologic association ≠ causality Depression = (early) sign of (severity of) disease depression Third factor cardiovascular disease

32. (Early) disease signs : “reverse causality” Depressive symptoms are first signs of a preclinical disease status Time Preclinical disease status Depressive symptoms Clinical CVD diagnosis Depressive symptoms reflect severity of somatic disease ‘somatic depression’

33. “pseudo association” Depression Cardiovascular disease Genetics Other disease processes + physiology SES

34. Depression Cardiovascular disease

35. Depression Cardiovascular disease Psycho-social ‘third factor’ -ses -GENES -physiology metabolic disturbances: e.g. glucose, inflammation, atherosclerosis Pathophysiology (self) careLife style

36. Depression and cardiovascular disease are reciprocal and longitudinally linked Evidence mostly from studies in the elderly  possibly specific for ‘late-onset’ depression ? Causal explanation through pathophysiology, behavior and psychosocial mechanisms. Alternatively via ‘third factor’ and underlying disease (severity) Take-home message

39. Farmacological intervention SADHART Sertraline Antidepressant Heart Attack Randomized Trial 369 patients admitted with MI or unstable angina and MDD (DSM-IV) Randomized intervention (24 weeks) : – –Sertraline – –placebo Glassman et al. JAMA 2002

40. Farmacological intervention SADHART - Sertraline can be used safely in heart patients (no effect op heart measures) Sertraline is effective in this population Results Glassman et al. JAMA 2002

41. Farmacological intervention SADHART - Non-significant decrease in number of new cardiovascular events Non-significant decrease in number of new cardiovascular events Results Glassman et al. JAMA 2002

42. Psychological intervention ENRICHD - Enhancing Recovery in Coronary Heart Disease patients 2481 patients admitted with MI (958 major, 811 minor, 66 dysthymia, 647 no social support) Randomized intervention (max. 6 mnd) : – –1243 cognitive behavioral therapy – –1238 usual care Methods Berkman et al. JAMA 2003

43. Psychological intervention ENRICHD - Results Significant less depressive symptoms after 6 months Berkman et al. JAMA 2003

44. Psychological intervention ENRICHD - Results No change in mortality or non-fatal cardiovascular events Berkman et al. JAMA 2003

45. No evidence yet that depression treatment improves CVD prognosis Take-home message