Stress research over a ten year period what have we learned, trends and future?

Transcription

1 Stress research over a ten year period what have we learned, trends and future? Professor Mika Kivimaki Department of Epidemiology & Public Health University College London, UK

2 Session Outline Stress, stressors and the disease process As a trigger of cardiac event among vulnerable individuals Chronic stress and development of diabetes evidence? Next steps

3 What are the sources of psychological stress? A. Negative thought patterns and emotions 1. Depressive symptoms and syndromes 2. Anxiety symptoms and syndromes 3. Hostility and anger 4. Rumination 5. Resentment 6. Pessimism C. Unsatisfied basic psychological needs 1. Lack of sense of purpose 2. Lack of social connectness 3. Lack of sense of security 4. Lack of autonomy B. Chronic stress 1. Work stress 2. Marital stress and dissatisfaction 3. Social isolation, lack of social support 4. Caregiver strain 5. Trauma or abuse in childhood 6. Perceived injustice D. Lack of rest and relaxation 1. Sleep loss 2. Difficulty in unwinding 3. Time pressure Rozanski. In Hjelmdahl et al. 2012

4 Stress and disease PART 1: CAUSAL MODELS indirect effect Psychological Psychosocial stress factors dire ct e ffect trigger prognostic factor Risk factors x Preclinical disease processes Manifest disease x Complications, Cardiovascular death e.g., obesity, smoking, physical inactivity e.g., atherosclerosis, hyperglycaemia e.g., cardiac event, depressive episode PART 2: ALTERNATIVE EXPLANATIONS confounding, bias, reversed causality Psychological Psychosocial factors stress stress Kivimäki et al. Scand J Work Environ Health 2006

5 Stress as a trigger Major earthquake in Athens in 1981 > an excess of cardiac deaths over the following 3 days Major industrial accidents, wars, terrorist attacks > increase in rates of acute MI/sudden cardiac death Major sport events Risk ratio of death from MI or stroke = 1.4 (95%CI ) among Dutch men aged >45 years on the day on which the Dutch team lost the French under dramatic corcumstances in the 1996 European Cup. 2.7 fold (95%CI ) higher use of emergencies in the Munich region of Germany during the 2006 soccer World Cup on days on which German team played, particularly in the 2h after the start of matches.

6 Steptoe & Kivimaki. Nature Reviews 2012

7 2010 Unemployment rate (%) in Finland Finland EU Unemployment (%) Statistics Finland, Eurostat

8 Short- and long-term associations of downsizing on cardiovascular mortality First 4 years of the follow-up *Adjusted for age, sex, socioeconomic status and type of employment. Next four years of the follow-up Extent of downsizing No Intermediate 4.3 ( ) 1.1 ( ) High 5.1 ( ) 1.4 ( ) Vahtera et al. Br Med J 2004

9 Theoretical models on chronic work stress

10 Karasek 1979 Karasek & Theorell 1990 Job Strain Model

11 Job motivation and job stress models What I put in my work What I get from my work effort reward J. S. Adams: Equity Theory on job motivation 1963 J. Siegrist: Effort Reward Imbalance model 1996

12 Organizational justice theory 3 forms of justice perceptions Distributive justice: fairness of outcomes (equity, equality, and needs) Procedural justice: fairness of the methods or procedures used (decision criteria, voice, control of the process) Relational justice: fairness of the interpersonal treatment received (dignity and respect) Moorman 2001, Greenberg & Cropanzano 2001, Kivimaki et al Arch Intern Med 2005

13 Organisational justice questionnaire items Decisions are well informed, are consistently applied (the rules are applied equally for everyone). Management listens to the concerns of all those affected by the decision, provides opportunities to appeal against or challenge the decision, tries to deal with us in a truthful manner. Elovainio et al Am J Public Health 2002; Kivimäki et al Psychol Med 2003

14 Fairness/justice principle Fundamental human behavior? the brown capuchin monkey (Cebus apella) Brosnan & de Waal. Nature 2003

15 Experiment: Monkeys were tought in pairs to give a token (a white PVC pipe) to the experimenter to receive a food reward (high valued and low valued). The equity test (ET): both partner exchanged token for a low value reward The inequity test (IT): the partner got a high value and the subject a low value reward The effort control test (EC): the partner got a high value reward for free and subject a low value reward The food control test (FC): high value reward shown and low value reward given to the partner Brosnan & de Waal. Nature 2003

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17 Work stress and CHD: Meta analysis of prospective cohort studies published until 2006 Stress model Age and sexadjusted Multiple adjusted** Job strain (10 studies) 1.45 (1.15 to 1.84) 1.11 (0.91 to 1.35) Effort reward imbalance (4) 2.52 (1.63 to 3.90) 2.51 (1.58 to 3.98) Organizational injustice (2) 1.62 (1.24 to 2.13) 1.47 (1.12 to 1.95) *summary estimates **risk factors and potential mediators Kivimäki et al. Scand J Work Environ Health 2006 Updated meta analysis including 15 cohort studies published until 2011 replicated the effect for job strain: Pooled hazard ratio = 1.39! Steptoe & Kivimäki. Nature Reviews 2012

18 People who worked 11 hours or more a day were 67% more likely to have a heart attack than those who worked shorter hours. When the normal measures that doctors use to assess someone's risk of heart disease were adjusted to take account of this finding (blood pressure, lipids, smoking, diabetes, age & sex), the resulting predictions were far more accurate an improvement of around 5 per cent This is equivalent to around 6,000 of the 125,000 people who suffer heart attacks in the UK each year. Kivimaki et al. AnnInternMed2011

19 Monday April 4, 2011 Hard work won't kill you? Well it might actually It is often said that "hard work won't kill you". Long hours at work may boost heart-attack risk By Amanda Gardner, Health.com April 4, Updated 2143 GMT (0543 HKT) April 5, 2011 UK NEWS Heart risk of long hours Long hours at work increase heart risk Tue Apr 5, 2011 Kivimäki et al. Ann Intern Med 2011

20 A look at evidence Stress diabetes

21 Leading Causes of Death: WHO 2030 scenario High income countries Ischaemic heart disease (15.8%) Cerebrovascular disease (9.0%) Lung cancer (5.1%) Diabetes mellitus (4.8%) COPD (4.1%) Low income countries Ischaemic heart disease (13.4%) HIV/AIDS (13.2%) Cerebrovascular disease (8.2%) COPD (5.5%) Lower respiratory infections (5.1%) Mathers et al. PLoS Med 2006

22 Prediabetes a high risk status for diabetes According to an American Diabetes Association expert panel, up to 70% of individuals with prediabetes will eventually develop diabetes. In a Chinese diabetes prevention trial, the 20 year cumulative incidence of diabetes in controls with impaired glucose tolerance defined with repeated OGTTs was even higher (>90%)

23 Diagnostic criteria for prediabetes Tabak, Kivimaki. Lancet 2012 (in press)

24 Tabak et al. Lancet 2009

25 Tabak, Kivimaki. Lancet 2012 (in press)

26 Psychosocial factors and type 2 diabetes PART 1: CAUSAL MODELS indirect effect Psychosocial factors etiological factor trigger prognostic factor Risk factors x Preclinical disease processes Manifest disease type 2 diabetes x x Complications, Cardiovascular death e.g., obesity, physical inactivity e.g., intermediate glycemia/ prediabetes (IFG or IGT) PART 2: ALTERNATIVE EXPLANATIONS confounding, bias, reversed causality Psychosocial factors factors stress

27 Stress diabetes related risk factors

28 Phases of the Whitehall II study Phase Dates Type Participants Screening / questionnaire 10, Questionnaire 8, Screening / questionnaire 8, Questionnaire 8, Screening / questionnaire 7, Questionnaire 7, Screening / questionnaire 6, Questionnaire 7, Screening / questionnaire 6,755

29 Questionnaire Demographic data socio-economic data (income + work change) retirement work psychosocial factors non-work psychosocial factors (financial insecurity, control at home, family relationships) social engagement Health behaviours Smoking, alcohol Diet - food frequency, physical activity CVD & Diabetes Details of CVD symptoms, investigations & treatment 2-h Oral Glucose Tolerance Test (OGTT) General Health Longstanding illness Hospital admissions Medications SF-36 Mental health GHQ (anxiety, depression) CESD depression scale SF-36, Activities of daily living (ADL), Instrumental ADL Clinical examination Functioning walking speed, chair stands, hand grip strength balance test, spirometry (peak expiratory vol) weight, height, waist hip ratio, BP Neuroendocrine heart rate variability hypothalamic-pituitary-adrenal axis measurements (salivary cortisols) Subclinical CVD ECG: Minnesota codes, left ventricular mass Ultrasound carotid IMT (artery wall thickness) Endothelial function & flow mediated dilation (subset) Lipids total + HDL cholesterol triglycerides Carbohydrate metabolism HbA1c, fasting and post load glucose and insulin Genes 50k CHIP, Metabochip serology, CRP, IL-6 Cognitive function AH4, Mill Hill, memory, verbal fluency, MMSE

30 Chandola et al. Eur Heart J 2008

31 Meta analysis of stress as a predictor of BMI Wardle et al. Obesity 2010

32 Longitudinal association between stress and weight change by baseline BMI The Whitehall II study Kivimaki et al. Int J Obesity 2006

33 IPD Work analysis Nyberg, Kivimaki for IPD Work J Intern Med 2011 [epub ahead of print]

34 Nyberg, Kivimaki for IPD Work J Intern Med 2011 [epub ahead of print]

35 Stress prediabetes

36 Chronic stress and the metabolic syndrome in Whitehall II Chandola et al. BMJ 2006

37 Chronic stress and the metabolic syndrome in Whitehall II *Metabolic syndrome at phase 5. Exposure to stress was assessed at phases 1, 2, 3, 5 (a total of 10 years). Chandola et al. BMJ 2006

38 Chronic stress and the metabolic syndrome in Whitehall II by sex *Metabolic syndrome at phase 5. Exposure to stress was assessed at phases 1, 2, 3, 5. Chandola et al. BMJ 2006

39 Evidence of an association between stress and diabetes risk factors (physical inactivity and obesity) stress and prediabetic conditions, such as the metabolic syndrome The association between stress and diabetes should therefore be plausible, but does the evidence to date confirm this? Stress diabetes

40 Work stress and type 2 diabetes in 2600 Japanese men Kawakami et al. JECH 1999

41 Work stress and prediabetes in 1300 Japanese male office workers Nakanishi et al. Occup Environ Med 2001

42 Work stress and type 2 diabetes in 1300 Japanese male office workers Nakanishi et al. Occup Environ Med 2001

43 Nurses Health Study, USA Kroenke et al. Am J Epidemiol 2007

44 Nurses Health Study, USA Kroenke et al. Am J Epidemiol 2007

45 *BUT in men 1.07 (95% CI )! Heraclides et al. Diabetes Care 2009

46 Despite evidence of the association between stress and diabetes risk factors (physical inactivity and obesity) stress and prediabetic conditions, such as the metabolic syndrome The evidence of an association between stress and diabetes is inconsistent

47 Psychosocial factors and type 2 diabetes PART 1: CAUSAL MODELS indirect effect Psychosocial Perceived stress factors etiological factor trigger prognostic factor Risk Risk factors x Preclinical disease processes Manifest disease type 2 diabetes x x Complications, Cardiovascular death e.g., obesity, physical inactiv ity e.g., intermediate glycemia/ prediabetes (IFG or IGT) PART 2: ALTERNATIVE EXPLANATIONS confounding, bias, reversed causality Psychosocial Pe rceived factors stress stress

48 Masked effect? Stress Elevated diabetes risk factors Metabolic syndrome/ prediabetes Time Reduced depression and stress Effect of stress on diabetes masked

49 Prediabetes reduces risk of depressive symptoms and thus perceived stress? 5200 US men and womenaged45 to 84 Golden et al. JAMA 2008

50 Not strong support for antidepressive effects of prediabetes in Whitehall II N = 4228 men and womenaged50 74 Kivimaki et al. Diabetes Care 2009

51 A linear association in 4300 US Veterans at mean age 39 Gale et al. Biol Psychiatry 2010

52 HbA1c and probability of depression: The English Longitudinal Study of Ageing (ELSA) 0.30 Probability of CESD depression HbA1c N = 4338, general population, mean age 63 years. Hamer et al. Psychosom Med 2010

53 A linear association in >1 Million Korean adults Batty et al. JECH 2012 epub

54 Inflated effect? Stress Use of antidepressants Time Diabetogenic effects of antidepressants Effect of stress on diabetes inflated

55 Does antidepressant medication increase the risk of type 2 diabetes? The Pharmo database, N = 204,034 (Knol et al. Diabetologia 2008) The UK General Practice Research Database Study, N = 11,206 (Andersohn et al. Am J Psychiatry 2009) The Diabetes Prevention Program Trial, N = 3187 (Rubin et al. Diabetes Care 2008 and 2010) The Finnish Public Sector study, N = 5085 (Kivimaki et al. Diabetes Care 2010)

56 Detection bias The notion that people under the care of a physician for depression are more likely to have other hidden health problems (such as diabetes) diagnosed, compared with their untreated counterparts who have less regular contact with medical services.

57 Detection bias? Kivimaki et al. Biol Psychiatry 2011

58 Antidepressant use not related to changes in glycaemia Kivimaki et al. Biol Psychiatry 2011

59 Psychosocial factors and type 2 diabetes PART 1: CAUSAL MODELS indirect effect Psychosocial factors etiological factor trigger prognostic factor Risk factors x Preclinical disease processes Manifest disease type 2 diabetes x x Complications, Cardiovascular death e.g., obesity, physical inactiv ity e.g., intermediate glycemia/ prediabetes (IFG or IGT) PART 2: ALTERNATIVE EXPLANATIONS confounding, bias, reversed causality Psychosocial factors factors stress

60 Psychological distress as a predictor of mortality in 11,500 non diabetic and diabetic adults Deaths/N Hazard ratio (95% CI) Health Surveys for England and Scotland Hamer et al. Psychosom Med 2010

61 Conclusions based on updated evidence: PART 1: CAUSAL MODELS indirect effect Psychosocial factors etiological factor trigger prognostic factor Risk Risk factors x Preclinical disease processes Manifest disease type 2 diabetes x x Complications, Cardiovascular death Physical inactivity (obesity) Metablolic syndrome PART 2: ALTERNATIVE EXPLANATIONS confounding, bias, reversed causality Psychosocial factors factors stress

62 Conclusions Association with depression repeatedly shown and likely to be true with CHD established, but might be imprecise due to publication bias and reverse causation bias with diabetes inconsistent, but few well powered studies with OGTT based ascertainment of diabetes available with stroke uncertain, but studies on triggering rare with cancer unclear Next steps to strengthen evidence: Individual level meta analysis ( >reverse causation, publication bias, risk groups) Randomisedcontrolledtrial ( >reversibility, confounding, bias) Instrumental regression analyses ( >subjectivity bias) Mechanistic studies ( >population level, chronic stress)