Thomas Kjellström F. d. överläkare, Docent internmedicin och endokrinologi Helsingborgs lasarett 10 oktober 2014 1 F Folksjukdom Prevalens över 2 % 2 VÄRLDENS VANLIGASTE SJUKDOMAR ÅR 2020 (enligt WHO) • 1. KARDIOVASKULÄRA SJUKDOMAR • 2. DEPRESSION • 3. ÖVRIGA 3 Depression – en folksjukdom Prevalens Livstidsrisk 100% Befolkning >65 år Totalbefolkning 90 80 30 20 10 Ref. WHO 1974, Sartorius 1974 Hagnell et al. Psychol Med.1982;12(2):279-289 4 Diabetes och depression Typ 1 diabetes har cirka DIABETES OCH DEPRESSION 16 % depression. Typ 2 diabetes har cirka 17 % depression. Icke-diabetiker hälften. 5 Depression – god prognos vid rätt hjälp Förekomst av depression i befolkningen (3-5%) Exempel: 100 individer 70% söker inte hjälp 30% söker hjälp i primärvården eller psykiatrin Ex: 30 individer 60% får: - fel diagnos - rätt diagnos, men fel behandling - rätt behandling, men farmaka i för låg dos eller under för kort period 40% får rätt behandling Ex: 12 individer 20% oförbättrade 80% blir bra Ex: 10 Ref Bodlund O. Läkartidningen, vol 97, nr 11 2000 6 Diagnos klassifikationssystem • DSM-IV - • Diagnostic and Statistical Manual of mental disorder-4th edition Utarbetad av APA (American Psychiatric Association) ICD-10 International Classification of Diseases and Related Health Problems Utarbetad av WHO (World Health Organisation) 7 PATIENT HEALTH QUESTIONNAIRE (PHQ 2 ELLER 9) 1. Little interest or pleasure in doing things? 2. Feeling down, depressed, or hopeless? 8 Diagnoskriterier för egentlig depression DSM-IV A Minst fem av följande symtom under minst två veckor – minst ett av symtomen (1) eller (2) måste föreligga: (1) nedstämdhet (2) minskat intresse, minskad glädje (3) viktnedgång alt viktuppgång minskad alt ökad aptit (4) sömnstörning (5) psykomotorisk hämning alt agitation (6) svaghetskänsla alt brist på energi (7) känslor av värdelöshet, skuldkänslor (8) minskad tanke – eller koncentrations-förmåga (9) tankar på döden, självmordstankar 9 Remission är viktigt Att inte uppnå remission kan innebära: • • • • Minskad livskvalitet Minskad arbetsförmåga Ökad risk för återfall - remission (återfallsfrekvens 24%) - respons (återfallsfrekvens 74%) Ökad risk för suicid Ref. Keller MB et al 2002;17:265-271 10 Prevalence of major depression in chronic medical illness Alzheimer's disease HIV CAD Stroke MI Diabetes Cancer Parkinson's disease 11% 12% 17% 23% 25% 27% 42% 51% NHDS, NAMCS, NHAMCS. Sutor et al. Mayo Clin Proc 1998; 73 (4): 329–337; Jiang et al. CNS Drugs 2002; 16 (2):111–127 11 VID KLINISK DEPRESSION FÖRÄNDRAS FYSIOLOGIN PÅ MÅNGA SÄTT (ex.) • Aktivering av nervsystemet (sympatikus + , parasympatikus -) • Immunologiska förändringar • Rytmrubbningar i hjärtat • Trombocytfunktionen • Endotelfunktionen 12 Behaviour (1) Depression decreases adherence to medical regimens • Adversely influences expectations and benefits of treatment efficacy • Increases withdrawal and social isolation • Reduces cognitive (executive) functioning and memory • Influences dietary choices and reduces motivation to exercise and follow self-management regimens • e.g. checking blood glucose DiMatteo et al. Arch Intern Med 2000; 160 (14): 2101–2107 13 Behaviour (2) Depression decreases medication adherence in diabetes Non-adherent days (%) 40 Non-depressed Depressed 30 20 10 0 Oral hypoglycaemic Lipid lowering meds ACE inhibitors Lin et al. Diabetes Care 2004; 27 (9): 2154–2160 14 Risk factors (2) Depression and increased BMI (>30 kg/m2) 80 p<0.001 vs none Percent with BMI >30 kg/m2 (%) 70 p<0.01 vs none 60 50 40 30 20 10 0 None Minor Depression group n=4,225; Adjusted for demographics, medical comorbidity, diabetes severity, diabetes type and duration, treatment type, HbA1c and clinic Major Katon et al. Diabetes Care 2004; 27 (4): 914–920 15 Depression increases mortality rate in diabetes by two-fold Kaplan-Meier survival estimate Kaplan-Meier estimate 1.0 Non-depressed patients Depressed patients 0.9 0.8 0 24 48 72 96 Survival time (weeks) 120 144 Katon et al. Diabetes Care 2005; 28 (11): 2668–2672 16 Depression associated with increased mortality post MI 25 Cox model hazard ratio for 6-month mortality associated with depression: 5.74 (95% CI: 4.61–6.87) p=0.0006 Percent mortality (%) 20 Depressed (n=35) 15 10 Non-depressed (n=187) 5 0 0 1 2 3 4 Time after MI (months) 5 6 Frasure-Smith et al. JAMA 1993; 270: 1819–1825 17 SSRIs heal a SADHART Patients treated with sertraline had 22% fewer adverse cardiac events, 60% fewer deaths Sertraline Placebo Heart rate 65/64 65/66 PR (ms) 167/167 172/173 VT 20/14 21/23 SDNN (ms) 100/104 109/103 Deaths 2 5 JAMA 2002 18 Depression after coronary artery disease is associated with heart failure 1.0 Event-free survival No depression diagnosis 0.9 0.8 Depression diagnosis 0.7 0.6 0.5 0 1,000 2,000 3,000 4,000 5,000 Days to heart failure admission May et al. J Am Coll Cardiol 2009; 53 (16): 1440–1447 19 Post-stroke depression (PSD) • Depression is one of the most frequent co-morbid psychiatric disorders in stroke patients • About 40% of patients with stroke will develop depression during the first 2 years after the acute event • PSD peaks within 3–6 months after the stroke Starkstein et al. Expert Opinion 2008; 9: 1291–1298 20 M-PRO-05-LIP-046-CSB The Cytokine Theory of Depression Depression – en inflammatorisk sjukdom som svar på kronisk psykisk stress 21 22 Development of atherosclerotic plaques Fatty streak Lipid rich plaque Normal Foam cells Fibrous cap Complex plaque Lipid core Thrombus 23 Preventing atherosclerotic progression 24 Atherosclerosis Involves More Than Just Lipids 25 Plaque Disruption Leading to Atherothrombosis Formation Aggregated platelets BLOOD FLOW Fibrin Macrophage Tissue factor Adapted from: Falk E et al. Circulation 1995; 92: 657–71. 26 27 Most MIs Arise From Smaller Stenosis % Stenosis Falk et al: Circulation 1995; 92:657-671 28 Manifestations of Atherothrombosis are Commonly Found in More than One Arterial Bed in an Individual Patient*1 Cerebrovascular disease Coronary disease 7.4% 24.7% 29.9% 3.3% 11.8% 3.8% 19.2% Peripheral arterial disease *Data from CAPRIE study (n=19,185) 1. Coccheri S. Eur Heart J 1998; 19(suppl): P1268. 29 Peripheral Arterial Disease (PAD) and AllCause Mortality*1 1.00 Normal Subjects Survival 0.75 Asymptomatic LV-PAD† 0.50 Symptomatic LV-PAD† Severe Symptomatic LV-PAD† 0.25 0.00 0 2 4 6 8 10 12 Year *Kaplan-Meier survival curves based on mortality from all-causes †Large-vessel PAD 1. Criqui MH. Vasc Med 2001; 6(suppl 1): 3–7. 30 Statins and Stroke •No clear relationship between cholesterol and the incidence of total stroke •An unexpected finding: some statin trials showed reductions in the risk for stroke even in patients taking aspirin 31 32 © G.Walldius, I. Jungner Hjärtinfarktrisk i relation till LDL-C och apo B LDL-C 3.6 mmol/L C C C 3.6 mmol/L C C C C C C apo B apo B Large buoyant apo B CHD risk 0.8 g/L † Small dense 1.5 g/L †† 33 AMORIS: fatal myocardial infarction 6,0 5,0 Adjusted for age, gender TC and TG O d d s -R r a t io ( 9 5 % C I) 4,0 3,0 2,0 1,5 1,0 0,9 0,8 1 2 3 4 5 6 7 8 9 10 a p o B / a p o A - 1 ( d e c ile ) M e a n: 0.48 0 .6 1 0.70 0.77 0 .8 4 0 .9 1 1 .0 0 1.10 1 .2 3 1 .5 6 Cases: 61 78 123 146 155 236 265 298 372 479 34 Look AHEAD trial • Long-term effects of a lifestyle intervention on weight and cardiovascular risk factors in individuals with type 2 diabetes. • Arch Intern Med 2010; 170; 1566-75. • 5145 individer. 4 år. Intervention och kontrollgrupp. • -6.15% i vikt, HbA1c -0.36%, systoliskt bltr – 5.33, diast bltr – 2.92 och lipider bättre. 35