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 100% Livstidsrisk Totalbefolkning Befolkning >65 år 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-4 th 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 11% 12% CAD 17% Stroke MI Diabetes 23% 25% 27% Cancer 42% Parkinson's disease 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
Non-adherent days (%) Behaviour (2) Depression decreases medication adherence in diabetes 40 30 Non-depressed Depressed 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/m 2 ) Percent with BMI >30 kg/m 2 (%) 80 70 60 50 40 30 20 10 0 p<0.001 vs none p<0.01 vs none None Minor Major Depression group n=4,225; Adjusted for demographics, medical comorbidity, diabetes severity, diabetes type and duration, treatment type, HbA1c and clinic Katon et al. Diabetes Care 2004; 27 (4): 914 920 15
Kaplan-Meier estimate Depression increases mortality rate in diabetes by two-fold 1.0 Kaplan-Meier survival estimate Non-depressed patients 0.9 Depressed patients 0.8 0 24 48 72 96 120 144 Survival time (weeks) Katon et al. Diabetes Care 2005; 28 (11): 2668 2672 16
Percent mortality (%) Depression associated with increased mortality post MI 25 20 15 Cox model hazard ratio for 6-month mortality associated with depression: 5.74 (95% CI: 4.61 6.87) p=0.0006 Depressed (n=35) 10 5 Non-depressed (n=187) 0 0 1 2 3 4 5 6 Time after MI (months) 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 Event-free survival 1.0 0.9 No depression diagnosis 0.8 0.7 Depression diagnosis 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
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Development of atherosclerotic plaques Fatty streak Normal Lipid rich plaque 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 BLOOD FLOW Aggregated platelets Fibrin Macrophage Tissue factor Adapted from: Falk E et al. Circulation 1995; 92: 657 71. 26
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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 24.7% 7.4% 29.9% Coronary disease 3.3% 3.8% 11.8% 19.2% Peripheral arterial disease *Data from CAPRIE study (n=19,185) 1. Coccheri S. Eur Heart J 1998; 19(suppl): P1268. 29
Survival Peripheral Arterial Disease (PAD) and All- Cause Mortality* 1 1.00 0.75 Normal Subjects 0.50 Asymptomatic LV-PAD Symptomatic LV-PAD 0.25 Severe Symptomatic LV-PAD 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
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G.Walldius, I. Jungner Hjärtinfarktrisk i relation till LDL-C och apo B LDL-C 3.6 mmol/l 3.6 mmol/l C C C C C C C C C apo B apo B CHD risk apo B Large buoyant 0.8 g/l Small dense 1.5 g/l 33
O d d s -R r a t i o ( 9 5 % C I ) 6, 0 5, 0 4, 0 AMORIS: fatal myocardial infarction Adjusted for age, gender TC and TG 3, 0 2, 0 1, 5 1, 0 0, 9 0, 8 1 2 3 4 5 6 7 8 9 1 0 a p o B / a p o A - 1 ( d e c i l e ) M e a n : 0. 4 8 0. 6 1 0. 7 0 0. 7 7 0. 8 4 0. 9 1 1. 0 0 1. 1 0 1. 2 3 1. 5 6 C a s e s : 6 1 7 8 1 2 3 1 4 6 1 5 5 2 3 6 2 6 5 2 9 8 3 7 2 4 7 9 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