1. Mortality trends in cardiovascular disease in schizophrenia in Sweden Urban Ösby MD, PhD, Senior Consultant Psykiatri Nordöst, Stockholm County Council Department of Clinical Neuroscience, Karolinska Institutet, Stockholm, Sweden urban.osby@sll.se

2. Declaration of interest: Urban Ösby Grant support: Stockholm County Council, NARSAD, Bristol-Myers Squibb, Janssen-Cilag Advisory Board/Consultant: AstraZeneca, Bristol-Myers Squibb, Eli Lilly, Pfizer Speakers Bureau: AstraZeneca, Bristol-Myers Squibb, Eli Lilly, Pfizer

3. Risk factors for cardiovascular disase

4. Lipids Hypertension Age Vascular disease Smoking Obesity Diabetes Diet Family history Sedentary lifestyle Cardiovascular disease: A Multifactorial Condition ENVIRONMENTALENVIRONMENTAL GENETICGENETIC Gender Thrombotic factors

5. FoamCellsFattyStreakIntermediateLesion Atheroma FibrousPlaqueComplicatedLesion/Rupture Endothelial dysfunction Smooth muscle and collagen From first decade From third decade From fourth decade Growth mainly by lipid accumulation Thrombosis, haematoma Adapted from Stary HC et al. Circulation 1995;92:1355-1374. Cardiovascular Timeline

6. Causes of death related to age and sex in Sweden Ref: Socialstyrelsen (1997). Hälso- och sjukvårdsstatistisk årsbok 1997. Socialstyrelsen, Stockholm. L. Wallentin 2000 Inledn./sid 1

7. Infectious Cancer Endocrine Mental Nervous system Cardiovascular Cerebrovascular Respiratory Gastrointestinal Urogenital Accidents Suicide Undet violence All causes Males Females 1510152025 1 510152025 SMR (Observed/Expected) for schizophrenia patients in Stockholm County 1973-95 SMR

8. SMR (Observed/Expected) and Excess deaths (Observed-Expected) for patients with schizophrenia in Stockholm County 1973-95 Ref: Osby U, et al. Mortality and causes of death in schizophrenia in Stockholm county, Sweden. Schizophr Res 2000;45(1-2):21-8.

9. Excess deaths by natural and unnatural causes for schizophrenia patients in Stockholm County 73-95 Men Natural 264 47% Unnatural 296 53% Women Natural 352 62% Unnatural 218 38% Ref: Osby U, et al. Mortality and causes of death in schizophrenia in Stockholm county, Sweden. Schizophr Res 2000;45(1-2):21-8.

10. SMR (O/E) and Excess deaths (O–E) for patients with bipolar disorder in Sweden 1973-95 Ref: Osby U, et al. Excess mortality in bipolar and unipolar disorder in Sweden. Arch Gen Psychiatry 2001;58(9):844-50. Men Women Total Cause of deathObsExpO/EO-EObsExpO/EO-EO/EO-E Cardiovascular5502841.92665231982.63252.2591 Natural causes11856241.956112806122.16682.01229 Suicide3452315.03223271522.431217.7634 Unnatural causes531618.64704673712.743010.2900 All causes17166862.5103017476482.710992.62129

11. SMR (O/E) and Excess deaths (O-E) for patients with unipolar disorder in Sweden 1973-95 Ref: Osby U, et al. Excess mortality in bipolar and unipolar disorder in Sweden. Arch Gen Psychiatry 2001;58(9):844-50. Men Women Total Cause of deathObsExpO/EO-EObsExpO/EO-EO/EO-E Cardiovascular13198711.544814288201.76081.61056 Natural causes274718821.5865361523101.613051.52170 Suicide10525021.010029933726.895623.51958 Unnatural causes13721409.81232128710512.3118210.92414 All causes411920222.02097490224152.024872.04584

12. Mortality in the population in Stockholm County Standardized by the sex- and age distribution of patients with schizophrenia in Stockholm County 1976-95 0 100 200 300 400 500 600 700 800 900 1000 7677787980818283848586878889909192939495 Deaths/100 000 All deaths Natural causes of death Cardiovascular deaths Violent deaths Suicide

13. Mortality trends in Stockholm county 1976-94, all causes of death 0 0.2 0.4 0.6 0.8 1 1.2 1.4 1976197819801982198419861988199019921994 Deaths/100 000 1976 year of reference Patients with schizophrenia* General population** * Controlling for age at first diagnosis and years of follow-up **Standardized by the sex and age distribution of the patients Ref: Osby U, et al. Time trends in schizophrenia mortality in Stockholm county, Sweden: cohort study. Bmj 2000;321(7259):483-4.

14. Deaths/100 000 76-79 period of reference Patients with schizophrenia* General population** * Controlling for age at first diagnosis and years of follow-up **Standardized by the sex and age distribution of the patients Mortality trends in Stockholm county 1976-79 to 1990-95, natural causes of death 0 0.2 0.4 0.6 0.8 1 1.2 1.4 76-7980-8586-8990-95

15. 0 0.2 0.4 0.6 0.8 1 1.2 1.4 76-7980-8586-8990-95 Deaths/100 000 76-79 period of reference Patients with schizophrenia* General population** * Controlling for age at first diagnosis and years of follow-up **Standardized by the sex and age distribution of the patients Mortality trends in Stockholm County 1976-79 to 1990-95, cardiovascular causes of death Ref: Osby U, et al. Time trends in schizophrenia mortality in Stockholm county, Sweden: cohort study. Bmj 2000;321(7259):483-4.

16. Mortality trends in Sweden 1970-2003 adjusted for age Men

17. Mortality trends in Sweden 1970-2003 adjusted for age

18. SMR for schizophrenia in Sweden 1970-2003

19. Time trends for SMR for all causes of death (p<.0001)

20. Time trends for SMR for cardiovascular death (p<.0001)

21. Time trends for SMR for death from coronary heart disease p<.0001)

22. Time trends for SMR for death from myocardial infarction (p<.0001)

27. The Good News We are living longer than ever!