1. CoRPS Center of Research on Psychology in Somatic diseases Inflammation, Mediation and Type D personality Multiple inflammatory biomarkers as mediators between Type D personality and course of 18 month health status in patients with heart failure. Brain Behav Immun 2011;Sep 29 Paula Mommersteeg, PhD

2. CoRPS Contributors Aline Pelle PhD, CoRPS, Tilburg University Christian Ramakers PhD, Clinical Chemistry and Hematology Laboratory, St. Elisabeth Hospital, Tilburg Balázs M. Szabó MD PhD, Department of Cardiology, St. Elisabeth Hospital, Tilburg, Johan Denollet PhD, CoRPS, Tilburg University Nina Kupper PhD, CoRPS, Tilburg University Project on patients with Heart Failure

3. CoRPS What ? Type D personality Inflammation Health status

4. CoRPS Type D personality Distressed Negative affectivity Social inhibition Prevalence 13-25% Stable construct Denollet, J. (2005). Psychosom Med, 67(1), 89-97 Denollet et al (2010). Circ Cardiovasc Qual Outcomes, 3(5), 546-557

5. CoRPS Meta-analysis – Cardiac mortality, MI, MACE

6. CoRPS Meta-analysis – …Health status Denollet et al (2010). Circ Cardiovasc Qual Outcomes, 3(5), 546-557

7. CoRPS Health status – poor prognosis

8. CoRPS Inflammation and health status?

9. CoRPS Health status, inflammation & prognosis

10. CoRPS Type D, health status, inflammation How ?

11. CoRPS How ? Type D personality Inflammation Health status Mediation!

12. CoRPS Health status Type D Personality A. Total effect B. Mediation Inflammation Type D personality c ab c’ Mediation

13. CoRPS Mediation - challenge Many ingredients –Type D personality: subscales negative affectivity (NA) and social inhibition (SI) -Multiple inflammatory variables: IL-6, hsCRP, TNFα, sTNFr1, sTNFr2 -Health status: physical, mental and disease specific -Multiple outcome assessment: health status at 0, 6, 12 and 18 months -Optimal use of these ingredients

14. CoRPS Multiple Mediation Figure 1. Model 1 Model 2 Preacher, K. J. and A. F. Hayes (2008). Behavior research methods 40(3): 879-91.

15. NA SI Type D HS baseline (intercept ) HS change (slope) HS 0 months HS 6 months HS 12 months HS 18 months CiCi CsCs 1 1 1 1 0 1 2 3 A. Model 1 B. Model 2 ** * NA SI Type D HS baseline (intercept ) HS change (slope) HS 0 months HS 6 months HS 12 months HS 18 months Ci’Ci’ Cs’Cs’ 1 1 1 1 0 1 2 3 ** * IL-6 CRP TNF-α sTNFr1 sTNFr2 a IL-6 a CRP a TNF a r1 a r2 bi IL-6 bi CRP bi TNF bi r1 bi r2 bs IL-6 bs CRP bs TNF bs r1 bs r2

16. CoRPS What did we find?

17. CoRPS C-pathways; intercept and slope

18. CoRPS C-pathways; intercept and slope

19. CoRPS C’pathways; intercept

20. CoRPS C’pathways; slope

21. CoRPS The model showed that Type D was associated with –poor health status –deterioration of mental health status over time –increased levels of TNFα and sTNFr2 Increased inflammatory variables were associated with –poor baseline health status and change in health status

22. CoRPS …was there mediation?

23. CoRPS Mediation ? Physical health status: –Intercept/baseline (Zi = 0.573, pi = 0.283) : No –Slope/ change (Zs = 1.948, ps = 0.026) : Yes Mental health status: –Intercept/baseline (Zi = 0.977, p i = 0.164) : No –Slope/ change (Zs = 1.525, ps = 0.064) : Possibly Disease specific health status: –Intercept/baseline (Zi = 0.591, pi = 0.277): No –Slope/ change (Zs = 1.131, ps = 0.129) : Not likely

24. CoRPS Mediation ? The association between Type D personality and health status in patients with heart failure is NOT LIKELY mediated by multiple inflammatory biomarkers –Strongest case for physical health status But: group didn’t show a lot of change over time Sample size was restricted (N= 228 max) M-plus is better at analysing a complex model like this What about depression or anxiety?

25. CoRPS Take home message Multiple mediation analysis: innovative –Use in other fields with multiple assessments Type D personality is associated with poor health status Inflammatory factors are associated with poor health status …. …but they are not likely to mediate this association

26. CoRPS Mommersteeg et al. “Type D personality and course of health status over 18 months in outpatients with heart failure: multiple mediating inflammatory biomarkers.” Brain Behav Immun 2011;Sep 29. [Epub ahead of print].

27. CoRPS Correlations

28. CoRPS C-path; Type D – Health status

29. CoRPS a-path; Type D - Inflammation

30. CoRPS b-path; inflammation – health status

31. CoRPS Are they associated? Correlation