1. Cardiovascular disease in persons with anxiety or depressive disorders Nicole Vogelzangs 1,2, Adrie Seldenrijk 1,2, Aartjan TF Beekman 1,2, Hein PJ van Hout 1,3, Peter de Jonge 4, Brenda WJH Penninx 1,2 Journal of Affective Disorders, Epub 1 EMGO Institute and Department of 2 Psychiatry, 3 General Practice, VU University Medical Center, Amsterdam, The Netherlands 4 Department of Psychiatry, University Medical Center Groningen, The Netherlands

2. 2030Disease% DALYs* 1Depression9.6% 2Heart disease5.9% 3Alzheimer, dementia5.8% 4Alcohol problems4.7% 5Diabetes4.5% 6Stroke4.5% 7Hearing problems4.1% 8Cancer3.0% 9Arthritis2.9% 10Lung disease2.5% Burden of disease in Western countries * DALYs = disability-adjusted life years = lost life years + lost quality of life WHO: Mathers et al. Plos Medicine 2006

3. Depression as risk factor for CVD General population Proof from systematic reviews Review# studies # 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

4. Review# studies # 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 CVD patients Proof from systematic reviews

5. Relatively unknown Prevalence of CVD in population of depressed and anxious persons Association anxiety disorders and CVD Which characteristics of depression and anxiety are linked with CVD

6. Netherlands Study of Depression and Anxiety www.nesda.nl funded through the mental health program of the Netherlands Organization for Health Research (ZonMW) and matching funds from participating institutes

7. Design Naturalistic cohort study Baseline assessment and follow-up assessments after 1, 2, 4, 6, 8 years Sample Depressed and/or anxious persons (18-65 years) from community, primary care, and outpatient psychiatric clinics (n=2329) and healthy controls (n=652) 2981 persons; 1979 women (66%), 1002 men (34%) Design & Sample NESDA

8. Sample selection Exclusion of – –persons with depressive or anxiety symptoms but no diagnosis (subthreshold symptoms; n=158) – –Persons with self-reported CVD without heart medication (n=16) => 2807

9. Psychopathology CIDI psychiatric interview (DSM-IV) Presence (& subtype), current (1 year) or remitted : – –Depressive disorder (dysthymia, major depressive disorder [MDD; single, recurrent]) – –Anxiety disorder (generalized anxiety disorder, social phobia, panic disorder and/or agoraphobia) Additional subtype specifiers – –Late age of onset (≥ 30 years) – –Atypical symptoms (based on IDS) – –Melancholic symptoms (based on IDS)

10. Clinical characteristics Duration: – –% of time affected of past 48 months, life chart Severity: – –Inventory of Depressive Symptoms (IDS), 0-84 – –Beck Anxiety Inventory (BAI), 0-63 Psychoactive medication: – –Selective serotonin reuptake inhibitor (SSRI) – –Tricyclic antidepressant (TCA) – –Other antidepressant – –Benzodiazepine

11. Cardiovascular disease Stroke and/or coronary heart disease (CHD): – –self-report of stroke supported by use of anticoagulant, antiplatelet, antihypertensive or lipid modifying agent; – –self-report of myocardial infarction or angina pectoris (symptoms) supported by use of beta blocker, nitrate vasodilator, calcium channel blocker, anticoagulant or antiplatelet agent; – –self-report of coronary angioplasty or bypass surgery.

12. Baseline characteristics No CVD (n=2651) CVD (n=156) p Age (years) Women (%) Education (years) Smoking status never smoker (%) former smoker (%) current smoker (%) Alcohol intake < 1 drink/week (%) 1-14 drinks/week (%) > 14 drinks/week (%) Physical activity (MET-min/wk) BMI 41.1 (12.9) 67.7 12.2 (3.3) 28.4 32.3 39.3 32.2 52.1 15.7 3720 (3046) 25.4 (5.0) 54.1 (7.8) 45.5 11.0 (3.2) 18.6 46.2 35.3 37.8 42.3 19.9 3423 (3198) 28.6 (4.8) <.001.001.05.24 <.001

13. Adjusted OR for CVD No depression/anxiety Remitted depression/anxiety Current depression only Current anxiety only Current depression + anxiety 492 544 418 504 849 1.27 0.93 1.96 2.35 REF 0.68-2.37 0.44-1.96 1.06-3.64 1.33-4.20.45.85.03.004 * Adjusted for age, sex, education, smoking, alcohol use, physical activity and BMI NOR*95% CIp No depression Remitted depression Current depression 847 693 1267 1.50 1.59 REF 0.93-2.40 1.02-2.47.10.04 No anxiety Remitted anxiety Current anxiety 1046 408 1353 1.31 2.18 REF 0.74-2.30 1.45-3.28.35 <.001

14. Adjusted OR for stroke and CHD StrokeCHD OR*95%CIpOR*95% CIp No dep/anx Remitted dep/anx Current dep only Current anx only Current dep+anx 0.73 0.53 1.02 1.37 REF 0.24-2.19 0.13-2.18 0.34-3.11 0.49-3.86.57.38.97.55 1.65 1.41 2.70 3.54 REF 0.79-3.43 0.61-3.23 1.31-5.56 1.79-6.98.18.42.007 <.001 * Adjusted for age, sex, education, smoking, alcohol use, physical activity and BMI

15. Current depressive disorder N = 418 Current anxiety disorder N = 504 Current depressive and anxiety disorder N = 848 OR OR* for CHD in persons with a current depressive and/or anxiety disorder * Adjusted for age, sex, education 1.77 2.40

16. Depression and anxiety characteristics and CHD N = 1770OR*95% CIp Type of depressive disorder--- Type of anxiety disorder--- Chronicity--- Severity Depressive symptoms score (IDS) Anxiety symptoms score (BAI) 1.32 1.36 1.05-1.65 1.11-1.66.02.003 Psychoactive medication--- * Per SD increase, adjusted for age, sex, education

17. Conclusions Coronary heart disease is more prevalent among depressed and particularly anxious persons The association of depression with CHD was largely owing to comorbidity with anxiety The highest CHD prevalence was found among those with the most severe anxiety and depressive symptoms

18. Discussion Cross-sectional design – –No effects of symptom duration on CHD risk – –CHD also increased among those with disorder onset before 30 years Anxiety (alone or comorbid to depression) as risk indicator for CHD deserves more attention in research as well as clinical care