1. Psychosocial Interventions prolong lives in women with Coronary Artery Disease –trial evidence Kristina Orth-Gomér, MD, PhD Karolinska institutet, Stockholm ESC Congress Barcelona September 1st, 2014

2. Women´s hearts 1.Women die from heart disease as often as men 2.Women get heart disease ten years later than men 3.Younger women with CHD – worse prognosis than men

3. Psychosocial risk factors verified and supported by ”European Guidelines of cardiovascular disease prevention” (European Heart J 2003) Low SES Stress Lack of social support Depression Anxiety Hostility

4. Behavioral model in cardiovascular disease

6. Progression of atherosclerosis by Marital & Work Stress Mean Segment Diameter Change (mm) Wang, Theorell, Orth Gomer, et al, 2004

8. Progression of atherosclerosis by Exhaustion Zimmermann-Viehoff, Orth-Gomér K et al, Psychosomatic Medicine (2013)

9. FemCorRisk findings psychosocial predictors of CHD in women - Low education, low occupation, low SES Wamala et al Am J Public Health,1999.,316-321 - Marital Stress Orth-Gomér et al, JAMA 2000, 3008-3014 - Job stress Wamala et al,Soc Sci Med 2000, 481 – 489 - Poor sleep quality Leineweber et al J Psychosom Res 2003 - Social isolation Horsten et al Eur Heart J 2000, 21, 1072-1081 - Depression Horsten et al Eur Heart J 2000, 1072 - 1081, Zimmerman et al Eur J cardiovascular Prev, 2009 - Vital exhaustion Zimmerman, Orth-Gomér et al, Psychsom Med 2013

10. In 2003 ESC Guidelines summarized ….Evidence for Psychosocial Factors In 2004 Interheart estimated Psychosocial Factors to contribute 1/3 of etiologic fraction

11. Psychosocial stress Cognitive behavior therapy to reduce stress - Randomized Controlled Trials : ENRICHD multicenter US men, women patients (n=3000)neg / pos substudy SWITCHD Stockholm women patients pos SUPRIM Uppsala patients pos

12. RCT´s in coronary heart disease since 2003 Endpoints depressive cardiac events mortality symptoms Therapy __________________________________________________________________________ SAD HEART Antidepressants + - - CREATE Interpersonal therapy - - - and antidepressants Long term follow up: ENRICHD CBT - - - SWICHD CBT - - + SUPRIM CBT - + - _________________________________________________________________________ (Linden, Psychosomatic Medicine 2013)

13. ENRICHD – Effects of CBT to mortality and MI Writing Committee for the ENRICHD investigators, JAMA 2003;289:3106-16 OR 1.01 (0.86 – 1.08)

14. ENRICHD - secondary analysis: differential effects by gender and ethnicity Schneiderman et al., Psychosom Med 2004;66:475-83 white men: cardiac death, non fatal MI OR 0.46 - 0.87, p=.004

15. Objective To examine whether stress reduction may improve prognosis in patients with CHD Orth-Gom é r,K, Schneiderman,N,Wang H, et al Circulation, Quality & Outcome, 2009

16. Study group 237 Stockholm women < 75 years, mean age 62 Hospitalized for acute myocardial infarction or cardiological intervention Randomized to CBT + regular care/ regular cardiologcal care Adding CBT to regular care may reduce recurrent events?

17. Cognitive behavioral group based Stress reduction - based on Type A intervention in San Fransisco, modified for Swedish women - twenty 2-hour sessions, 4-6 patients/group session 1-10 weekly, session 11-20 monthly - delivered by cardiology research nurses with special interest and training in behavioral/psychosocial medicine - education, discussions, and home assignments.

18. Stress reduction balancing work and family demands solving interpersonal conflicts, male/female role conflicts Counteracting -stress - depression - isolation - low self-esteem

19. Changes in Daily stress behaviour in intervention and controlgroup (p< 0.0001) treatment time interaction p<.0001

20. Heading

21. Clinical predictors of mortality in women with CHD

22. Behavioral change in survivors Interv Controls p __________________________________________ Quit smoking 38% 43% ns Improved diet 88% 78% ns Increased exercise 40% 47% ns __________________________________________

23. Behavioral change in survivors Interv. Controls p Improved sleep 23% 5% Worsened sleep 13% 27% Sleep quality (1-4) 2.5(1.0) 2.1(1.2) p=.05

24. the group was a life line was allowed to dwell on heart disease felt comparisonship felt support Worried less felt social cohesion developed more patience could talk about things one don’t really want to talk about learnt not to get hurt not afraid any more increased self esteem courage to say no stonger psyche become aware become more egocentered not as angy as previously enjoys life more courage to talk in the group has fewer obligations

25. Heading Mortality by statin use and CBT

26. Psychophysiological Pathways Autonomic Cardiac Imbalance - Decreased Heart Rate Variability, Increased Heart Rate Neuroendocrine/metabolic pathways -Dyslipidemia, Insuline Resistance, Metabolic syndrome Prothrombotic/inflammatory pathways - Fibrinogen, Von Willebrand, Factor VII, PAI - I, hs CRP…..

27. Conclusions Prognosis of the heart disease improved by adding CBT to usual care Mechanisms -stress reduction - unhealthy habits improved -autonomic dysfunction improved -better adherence to cardiologic treatment

29. Conclusion in women with CHD… harmful marital stress worsened prognosis marital stress accelerated coronary atherosclerosis progression protective cognitive behavioral intervention reduced all cause mortality a happy marriage - deceleration of coronary atherosclerosis

30. Thank you for listening