1. CoRPS Center of Research on Psychology in Somatic diseases Type D personality & haemoglobin in CHF Nina Kupper PhD Aline Pelle PhD Balázs M. Szabó MD PhD Johan Denollet PhD

2. CoRPS Acknowledgment & disclosure Data were collected in two large prospective cohort studies: St. Elisabeth hospital Tilburg (PhD thesis dr. Pelle 2009) TweeSteden hospital (PhD thesis dr. Schiffer 2007) Acknowledge dr. Ramakers (Clinical-Chemistry & Haematology lab) for performing biomedical assays Funding: NWO VICI grant (NWO 453-04-004) and a Dutch Heart Foundation (2003B038) both awarded to Prof.dr. Johan Denollet No conflicts of interest to disclose

3. CoRPS Background Anaemia is a common comorbidity in CHF Related to –chronic kidney dysfunction –increased CHF morbidity and mortality Triggers: –Kidney dysfunction (decrease in erythropoietin levels) –Pro-inflammatory cytokines inhibit haematopoietic proliferation –hemodilution due to the increased plasma volume (preserved kidney) Anemia CHF Chronic kidney dysfunction Casadevall 1995, Anand 2008, Adlbrecht, Kommata et al. 2008

4. CoRPS Background and research question Animal research: psychological stress may promote anaemia –acute psychological stress  decrease blood and bone marrow iron, inhibit erythropoiesis 1 –chronic distress  even lower plasma iron levels 1 Research in humans: depressed mood associated with anaemia in patient populations 2 and community-dwelling elderly pops 3 EPO treatment in CHF: improvement in depressive symptoms 4 Type D (Distressed) personality: increased mortality in CHF 5 1 Teng, Sun et al. 2008; Wei, Zhou et al. 2008 2 Krishnan, Grant et al. 2006 3 Onder, Penninx et al. 2005; Lucca, Tettamanti et al. 2008 4 Kourea, Parissis et al. 2008 Examine the prospective association of Type D personality with haemoglobin levels, while controlling for clinical correlates of CHF. 5 Denollet and Brutsaert 1998 Mechanism?

5. CoRPS Methods: participants & procedure Sample 318 consecutive CHF outpatients (response rate = 77%) Inclusionstable, LVEF≤ 40%; age ≤ 80 years; NYHA-class I-III Exclusionlife-threatening comorbidities; presence of evident cognitive impairments; psychiatric comorbidity (except for mood disorders); insufficient understanding of the Dutch language, or signs of acute infection (blood) Baseline Questionnaire Blood sample 12 months FU Questionnaire Blood sample

6. CoRPS Type D (Distressed) personality Prevalence –Normal population: 13-32.5% –Cardiac patients: 26-53% Construct –Negative affectivity Tendency to experience negative emotions –Sociale inhibition Tendency to suppress emotions in social interaction Denollet. Psychosom Med 2005; 67:89-97 Denollet, Pedersen et al. Eur Heart J 2006;27:171-7 Presence of both NA and SI essential for negative effect on prognosis (RESEARCH Registry) Down in the dumps Feeling blue Angry Worried Bad mood Unhappy Type D Type D ? No!! I do not want to share my emotions with others…

7. CoRPS Methods: blood measures Plasma Hb was used as an indicator of anaemia (K-DOQI guidelines) Anaemia: Hb levels of ≤12g/dL (7.5 mmol/L) for women and <13g/dL (8.1 mmol/L) for men (WHO guidelines) Kidney dysfunction: creatinin was determined and used to calculate GFR (MDRD-equation); GFRcreat <60 mL/min per 1.73m 2 Hb levels (r ic =.51, p<.001) and kidney function (r ic =.85, p<.001) were relatively stable over 1 year

8. CoRPS Results: Type D, Hb levels and anaemia prevalence Inclusion: Hb levels similar for non-Type D and Type D CHF patients (p=.23) 12-mo FU: Hb levels significantly lower in patients with a Type D personality (β= -.14, t=-2.28, p=.02) Inclusion: Prevalence of anaemia (WHO): 15.5% in non- Type Ds and 15.7% in Type D patients 12-mo FU: 17% of non-Type Ds and 28.6% of Type D patients were classified as anaemic

9. CoRPS Results: Multivariate regression Stand. βtp Type D personality-.12-2.16.03 Female sex-.32-5.73<.001 Kidney dysfunction-.26-4.75<.001 NYHA-class-.15-2.61.01 LVEF-.07-1.29.57 Haemoglobin Collinearity statistics: acceptable tolerance, inter-predictor r=-.23 -.17 (low) 25% of variance was explained R 2 due to Type D personality = equal in proportion to the effect of NYHA class Type D personality predicted Hb levels at 12 months follow-up independent from gender, kidney dysfunction & CHF severity

10. CoRPS Conclusion & discussion In CHF patients, Type D personality was independently associated with decreased Hb levels at 12-month follow-up, along with kidney dysfunction, gender, and higher NYHA functional class In line with previous studies on depression/poor QoL & anaemia Results suggest distress may affect cardiac prognosis a.o. by affecting anaemia –targeting haemoglobin in emotionally distressed patients? –In renal failure pt, increasing Hb levels may have deleterious side-effects (e.g. vasoconstriction, venous thrombosis) that may challenge the benefit of anaemia correction in CHF (CREATE, CHOIR, van der Meer, Groenveld et al. 2009 ) Results support recommendation to screen for psychological factors (MacMahon & Lip 2002) –might contribute to the identification of CHF patients at increased risk for adverse health outcomes.

11. CoRPS Limitations No information on iron blood levels or iron intake Although our study design was longitudinal, no final conclusions can be drawn regarding causality CHF patients are characterized by multimorbidity and polypharmacy. This was slightly more pronounced for some biomedical variables, although not significantly, in Type D patients.

12. CoRPS Take home message Type D personality independently predicted decreased Hb levels at 12-month follow-up Important to consider/screen for psychological distress as this does affect somatic health

13. CoRPS Discussion (2) BACK UP SLIDE Potential mechanism: Type D personality Anaemia CHF IL-6 TNF-α IL-6 TNF-α Denollet et al. 2008 Denollet, Kupper et al. 2009 inhibit erythropoietin production in the kidney Inhibit proliferation of bone marrow erythroid progenitor cells

14. CoRPS BACK UP SLIDE descriptives 1 Total (n=312) Type D (n=64) non-Type D (n=248) p Demographics Male sex75.3 (235)71.9 (46)76.2 (189).47 Age (yrs), mean (SD)65.9 (9.9)67.2 (10.4)65.5 (9.8).25 Living without a partner25.6 (80)29.7 (19)24.6 (61).41 Biomedical risk factors BMI (kg/m 2 ) b 27.9 (5.0)28.0 (5.5)27.9 (4.9).89 Smoking22.8 (71)15.6 (10)24.6 (61).13 Hypertension35.6 (111)37.5 (24)35.1 (87).72 Hypercholesterolemia54.8 (171)57.8 (37)54.0 (134).59 Diabetes23.7 (74)26.6 (17)23.0 (57).55 Disease characteristics Ischemic aetiology b 58.1 (180)53.2 (33)59.3 (147).39 LVEF, mean (SD)31.7 (6.7)32.2 (6.3)31.6 (6.8).53 NYHA class III c 31.7 (99)35.9 (23)30.6 (76).42 Time since diagnosis (yrs), mean (SD) b 7.2 (4.5)7.7 (5.2)7.0 (4.2).23

15. CoRPS BACK UP SLIDE descriptives 2 Interventions PCI16.0 (50)15.6 (10)16.1 (40).92 CABG26.9 (84)29.7 (19)26.2 (65).58 Device therapy d 12.5 (39)12.5 (8)12.5 (31).99 Prescribed medications Diuretics e Lisdiuretics only62.2 (194)76.6 (49)58.5 (145).06 Thiazides only3.2 (10)1.6 (1)3.6 (9) Combined6.1 (19)4.7 (3)6.5 (16) Beta-blockers66.5 (206)68.3 (43)66.0 (163).73 ACE-inhibitors71.8 (224)75.0 (48)71.0 (176).52 ARB19.9 (62)21.9 (14)19.4 (48).65 Digoxin25.3 (79)32.8 (21)23.4 (58).12 Calcium-antagonists13.5 (42)25.0 (16)10.5 (26).002 Oral anticoagulants47.4 (148)40.6 (26)49.2 (122).22 Aspirin38.1 (93)40.6 (26)37.5 (93).65 Statins53.5 (167)53.1 (34)53.6 (133).94 Psychotropic medication13.8 (43)18.8 (12)12.5 (31).20