Stress research over a ten year period what have we ... · Stress research over a ten year period – what have we learned, trends and ... depressive episode Psychosocial factors
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Stress research over a ten year period –what have we learned, trends and
future?
Professor Mika KivimakiDepartment of Epidemiology & Public Health University
College London, UK
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
What are the sources of psychological stress?
A. Negative thought patterns and emotions1. Depressive symptoms and syndromes2. Anxiety symptoms and syndromes3. Hostility and anger4. Rumination5. Resentment6. Pessimism
C. Unsatisfied basic psychological needs1. Lack of sense of purpose2. Lack of social connectness3. Lack of sense of security4. Lack of autonomy
B. Chronic stress1. Work stress2. Marital stress and dissatisfaction3. Social isolation, lack of social support4. Caregiver strain5. Trauma or abuse in childhood6. Perceived injustice
D. Lack of rest and relaxation1. Sleep loss2. Difficulty in unwinding3. Time pressure
Rozanski . In Hjelmdahl et al. 2012
PART 1:CAUSAL MODELS
Risk factors x
Preclinical disease processes
Cardiovascular death
Manifest disease x
e.g., obesity, smoking, physical inactivity
e.g., atherosclerosis, hyperglycaemia
e.g., cardiac event, depressive episode
Psychosocial factors
indirect effect prognostic factordirect effect trigger
PART 2:ALTERNATIVEEXPLANATIONS Psychosocial
factors stress
confounding, bias, reversed causality
Risk factors x
Preclinical disease processes
Manifest disease x
Complications, death
Psychologicalstress
Psychological stress
Stress and disease
Kivimäki et al. Scand J Work Environ Health 2006
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 1.1‐2.1) among Dutchmen aged >45 years on the day on which the Dutch team lost the Frenchunder dramatic corcumstances in the 1996 European Cup.
2.7‐fold (95%CI 2.3‐3.4) higher use of emergencies in the Munich region of Germany during the 2006 soccer World Cup on days on which Germanteam played, particularly in the 2h after the start of matches.
Unemployment rate (%) in Finland
Statistics Finland, Eurostat
0.0
2.0
4.0
6.0
8.0
10.0
12.0
14.0
16.0
18.0
1980
1982
1984
1986
1988
1990
1992
1994
1996
1998
2000
2002
2004
2006
2008
2010
Une
mpl
oym
ent (
%)
Finland EU-15
Short- and long-term associations of downsizing on cardiovascular mortality
*Adjusted for age, sex, socioeconomic status and type of employment.
First 4 years of the follow-up
Next four years of the follow-up
Extent of downsizingNo 1.0 1.0Intermediate 4.3 (1.3-14.7) 1.1 (0.5-2.1)High 5.1 (1.4-19.3) 1.4 (0.6-3.1)
Vahtera et al. Br Med J 2004
Job motivation and job stressmodels
J. S. Adams: Equity Theory on job motivation 1963
effortreward
J. Siegrist: Effort‐Reward Imbalance model 1996
What I put in my work What I get from my work
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
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
Fairness/justice principle
Fundamental human behavior?
the brown capuchin monkey(Cebus apella)
Brosnan & de Waal. Nature 2003
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
Work stress and CHD: Meta‐analysis of prospective cohort studies published until 2006
Stress model Age‐ and sex‐adjusted
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)
Kivimäki et al. Scand J Work Environ Health 2006
*summary estimates**risk factors and potential mediatorsUpdated 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
• 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. Ann Intern Med 2011
Hard work won't kill you? Well it might actuallyItisoftensaidthat"hardworkwon'tkillyou".
Monday April 4, 2011
Long hours at work may boost heart-attack riskBy Amanda Gardner, Health.com April 4, 2011 -- Updated 2143 GMT (0543 HKT)
UKNEWSHeart risk of long hours
Long hours at work increase heart risk Tue Apr 5, 2011
April 5, 2011
Kivimäki et al. Ann Intern Med 2011
• 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%)
Leading Causes of Death: WHO 2030 scenario
Mathers et al. PLoS Med 2006
According to an American Diabetes Association expert panel, up to 70% of individuals withprediabetes will eventually develop diabetes.
In a Chinese diabetes prevention trial, the 20‐year cumulative incidence of diabetes in controls withimpaired glucose tolerance defined with repeatedOGTTs was even higher (>90%)
Prediabetes ‐‐ a high‐risk status for diabetes
PART 1:CAUSAL MODELS
Risk factors x
Preclinical disease processes
Cardiovascular death
Manifest disease x
e.g., obesity, physical inactivity
e.g., intermediate glycemia/ prediabetes (IFG or IGT)
Psychosocial factors
indirect effect prognostic factoretiological factor trigger
PART 2:ALTERNATIVEEXPLANATIONS Psychosocial
factors stress
confounding, bias, reversed causality
Risk factors x
Preclinical disease processes
Manifest type 2 diabetes x
Complications, death
Psychosocial factors
Psychosocial factors
Psychosocial factors and type 2 diabetes
Phases of the Whitehall II study Phase Dates Type Participants
1 1985-1988 Screening / questionnaire 10,308
2 1989-1990 Questionnaire 8,132
3 1991-1993 Screening / questionnaire 8,815
4 1995-1996 Questionnaire 8,628
5 1997-1999 Screening / questionnaire 7,870
6 2001 Questionnaire 7,355
7 2003-2004 Screening / questionnaire 6,967
8 2006 Questionnaire 7,180
9 2008-2009 Screening / questionnaire 6,755
Questionnaire Clinical examinationDemographic datasocio-economic data (income + work change) retirementwork psychosocial factorsnon-work psychosocial factors (financial insecurity, control at home, family relationships)social engagement
Health behavioursSmoking, alcoholDiet - food frequency, physical activity
CVD & DiabetesDetails of CVD symptoms, investigations & treatment2-h Oral Glucose Tolerance Test (OGTT)
General HealthLongstanding illnessHospital admissionsMedicationsSF-36
Mental healthGHQ (anxiety, depression)CESD depression scaleSF-36, Activities of daily living (ADL), Instrumental ADL
Functioningwalking speed, chair stands, hand grip strengthbalance test, spirometry (peak expiratory vol)weight, height, waist hip ratio, BP
Neuroendocrineheart rate variability hypothalamic-pituitary-adrenal axis measurements (salivary cortisols)
Subclinical CVDECG: Minnesota codes, left ventricular massUltrasound carotid IMT (artery wall thickness) Endothelial function & flow mediated dilation (subset)
Lipidstotal + HDL cholesteroltriglycerides
Carbohydrate metabolismHbA1c, fasting and post load glucose and insulin
Genes50k CHIP, Metabochipserology, CRP, IL-6
Cognitive functionAH4, Mill Hill, memory, verbal fluency, MMSE
Longitudinal association between stress and weight change by baseline BMIThe Whitehall II study
Kivimaki et al. Int J Obesity 2006
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
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
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
Work stress and prediabetes in 1300 Japanese male officeworkers
Nakanishi et al. Occup Environ Med 2001
Work stress and type 2 diabetes in 1300 Japanese male officeworkers
Nakanishi et al. Occup Environ Med 2001
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 stressand diabetes is inconsistent
PART 1:CAUSAL MODELS
Risk factors x
Preclinical disease processes
Cardiovascular death
Manifest disease x
e.g., obesity, physical inactiv ity
e.g., intermediate glycemia/ prediabetes (IFG or IGT)
Psychosocial factors
indirect effect prognostic factoretiological factor trigger
PART 2:ALTERNATIVEEXPLANATIONS Psychosocial
factors stress
confounding, bias, reversed causality
Risk factors x
Preclinical disease processes
Manifest type 2 diabetes x
Complications, death
Perceivedstress
Perceivedstress
Psychosocial factors and type 2 diabetes
Stress
Elevated diabetes risk factors
Metabolic syndrome/ prediabetes
Reduced depression and stress
Effect of stress on diabetesmasked
Time
Masked effect?
Prediabetes reduces risk of depressive symptoms and thus perceived stress?
Golden et al. JAMA 20085200 US men and women aged 45 to 84
Kivimaki et al. Diabetes Care 2009
N = 4228 men and women aged 50‐74
Not strong support for antidepressive effects of prediabetes in Whitehall II
HbA1c and probability of depression: The English Longitudinal Study of Ageing (ELSA)
Hamer et al. Psychosom Med 2010N = 4338, general population, mean age 63 years.
0.00
0.05
0.10
0.15
0.20
0.25
0.30
3 4 5 6 7 8
HbA1c
Pro
babi
lity
of C
ES
D d
epre
ssio
n
Stress
Use of antidepressants
Diabetogenic effects of antidepressants
Effect of stress on diabetesinflated
Time
Inflated effect?
Does antidepressant medication increase the risk of type 2 diabetes?
• The Pharmo database, N = 204,034 (Knol et al. Diabetologia2008)
• 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)
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.
PART 1:CAUSAL MODELS
Risk factors x
Preclinical disease processes
Cardiovascular death
Manifest disease x
e.g., obesity, physical inactiv ity
e.g., intermediate glycemia/ prediabetes (IFG or IGT)
Psychosocial factors
indirect effect prognostic factoretiological factor trigger
PART 2:ALTERNATIVEEXPLANATIONS Psychosocial
factors stress
confounding, bias, reversed causality
Risk factors x
Preclinical disease processes
Manifest type 2 diabetes x
Complications, death
Psychosocial factors
Psychosocial factors
Psychosocial factors and type 2 diabetes
Psychological distress as a predictor of mortality in 11,500 non‐diabetic and diabetic adults
Hamer et al. PsychosomMed 2010
Deaths/N Hazard ratio (95% CI)
Health Surveys for England and Scotland
PART 1:CAUSAL MODELS
Risk factors x
Preclinical disease processes
Cardiov ascular death
Manifest disease x
Physical inactivity(obesity)
Metablolic syndrome
Psychosocial factors
indirect effect prognostic factoretiological factor trigger
PART 2:ALTERNATIVEEXPLANATIONS Psychosocial
factors stress
confounding, bias, reversed causality
Risk factors x
Preclinical disease processes
Manifest type 2 diabetes x
Complications, death
Psychosocial factors
Psychosocial factors
Conclusions based on updated evidence:
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‐basedascertainment 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, riskgroups)‐Randomised controlled trial (‐>reversibility, confounding, bias)‐Instrumental‐regression analyses (‐>subjectivity bias)‐Mechanistic studies (‐>population‐level, chronic stress)
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