Transcript Models of the Life course

An ESRC Research Centre
ESRC International Centre for Life Course
Studies in Society and Health
http://www.ucl.ac.uk/icls
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Epidemiological Approach to the
Life course
Integrating social, psychological
and biological
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Life course approach in epidemiology• Investigates long term effects on chronic disease
risk and ageing of physical and social hazards
during gestation, childhood, adolescence, young
adulthood and later adult life
• Integrates biological and psychosocial pathways
• Understands the natural history and
physiological trajectory of normal biological
systems
Kuh & Ben Shlomo 1997, 2004
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Fetal origins hypothesis and
programming
“the process whereby a stimulus or
insult during critical periods of
development has lasting or lifelong
effects on the structure or function of
organs, tissues and body systems”
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The Fetal Origins or “Barker” Hypothesis
•
Pioneered by David Barker in the
early 1990s
–
•
•
Part 1: Impaired fetal growth causes
adult disease
Part 2: “Thrifty phenotype” impaired fetal growth permanently
changes the body’s structure and
physiology
–
–
•
From: Keith M Godfrey and David JP Barker
Fetal nutrition and adult disease
Am J Clin Nutr 2000 71: 1344S-1352S.
Painstaking development of
historical birth cohort studies in
England
Adaptive for compromised nutrition
Maladaptive for over-nutrition
Potential mechanisms include blood
pressure, fibrinogen concentration &
glucose tolerance
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A bit of biology: i. blood pressure
• Diastolic = when the heart is at rest
• Systolic = When the heart contracts to
push blood around the body
• Normal diastolic = 80 mm mercury
• Normal systolic = 120 mm mercury
(mercury level in sphygmomanometer, a
kind of thermometer).
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Blood pressure ii.
• SBP is more responsive to stress
• DBP is influenced by longer term factors
• High BP can damage blood vessels, and
cause clots that block them
• Blockage in vessel that feeds heart muscle
can cause heart attack
• Blockage in brain can cause stroke.
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Biology 2: Insulin (i)
• Insulin vital to transfer fats and sugars
from blood to feed muscles
• Insulin produced in the pancreas
• Pancreas develops during “critical period”
of gestation
• Less developed pancreas >> too little
insulin >> diabetes
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Insulin (ii)
• If too much sugar stays in blood =
diabetes
• If too much fat stays in blood =
“atheroma”, porridgy slush sticks to blood
vessel walls
• Increased risk of heart disease
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Insulin resistance: metabolic syndrome
• Even if the pancreas produces normal
amounts of insulin, the cells may “resist”
transfer of sugars & fats to muscle
• Not very well understood but e.g. if you
take cortisone for asthma you are at
higher risk.
• So too much cortisol may be a cause
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The “HPA Axis”
(hypothalamic-pituitary-adrenal)
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Linking it together …
• Stress signal to brain
• Brain signal to adrenal gland boosts
cortisol secretion
• Cortisol keeps sugars in blood, raises
heart rate and BP “Fight or Flight”
• Temporary response is useful but chronic
stress > insulin resistance
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Life course effect
• When adrenal gland has produced enough
cortisol, receptors in the brain lower the
level to pre-threat
• Some research indicates that early life
stress prevents this adjustment from
happening
• Cortisol stays too high
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• Research on rats by Meaney et al
• Rats whose mothers showed them more
care (licking) developed plenty of cortisol
receptors during critical period of
development
• Rats with less affectionate mothers had
fewer cortisol receptors
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Birth Weight and Hypertension
165
160
155
Systolic Pressure (mmHg)
170
Barker Hypothesis:
<=5.5
5.6-6.5
6.6-7.5
Birthweight (lbs)
7.6-8.5
>8.5
Law 1993
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Birth Weight and Insulin Resistance Syndrome
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Odds ratio adjusted for BMI
16
14
12
10
8
6
4
2
0
<5.5
5.6-6.5
6.6-7.5
7.6-8.5
Birthweight (lbs)
8.6-9.5
>9.5
Barker 1993
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Evidence from studies with better follow-up
Risk of non-fatal cardiovascular disease
• Nurses’ Health Study:
– Study cohort = 121,700
women followed since 1976
– Sample cohort = 70,297
(58%), excluded were
women who did not provide
retrospective information on
birthweight
– Effect most pronounced at
extremes of birthweight
• Confirmed in Scandinavian
birth cohorts with > 97%
follow-up, able to look at
fetal growth rates
Source: Rich-Edwards et al BMJ 1997
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Epidemiologists’ explanation
• Developmental Origins of Adult Disease
• “DOHAD”
• Holds that health problems arise when
gestation takes place in “poor”
circumstances but adult life is “rich”
• Irony: if your parents were poor you will be
healthier if poor yourself.
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What happens when gestation ‘predicts’ a deprived
environment but real life gives you a more plentiful one?
Source: Gluckman Am J Hum Biol 2007
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Uterine environment as predictor of mature environment
Fetus A was gestated in deprived circumstances, fetus B in more adequate
circumstances
Source: Gluckman Am J Hum Biol 2007
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Sociological explanations
• Social Reproduction
• Tendency for similarity in social &
economic circumstances over time
• Needed cohort studies to see this more
clearly
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Continuities in social adversity
• We know that birth weight is lower in children
born into more socio-economically adverse
circumstances
• Original studies do not adjust for a life-course
measure of disadvantage, only for e.g. social
class in late adulthood.
• What happens when you look at longitudinal
measures?
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% with 3+ instances
Instances of housing inadequacy by
weight at birth: 1958 British Birth Cohort
30
25
20
15
136+
125-135
115-124
106-115
Birth weight
<=105
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Birth weight and housing across childhood
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Birth weight and financial hardship to 23 years
NCDS men
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Birth weight and social class at 42.
Biological or social?
oz
Birthweight and social class at age 42:
NCDS men
123
122
121
120
119
118
117
116
115
I Prof essional
II Managerialtechnical
IIINM Skilled
non-manual
IIIM Skilled
manual
IV Partly skilled
V Unskilled
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Accumulation versus fetal programming
Source: Nederhof & Schmidt Physiol.& Behavior 2012
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Childhood social factors and adult health
• Most life-course research at present
focuses on this
• Parental social class is most often used
• Various measures in adulthood
– Blood pressure
– Metabolic syndrome
– Mortality
• Less about intervening processes
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Early research on social position in
the life course
• Social position in early life may have long term
consequences
• Why should this be?
• Does social position in early life increase the
likelihood of risk exposures?
• First look at whether social position in childhood
seems to be related to health measures in adult
and later life
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Social Class: English Registrar-General’s schema
• I – Professional
• II – Managerial
I/II
Non-manual
• III Non-Manual – Clerical, sales
• III Manual – Skilled manual, crafts
• IV – Semi skilled manual
• V – Non-skilled manual
Manual
IV/V
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Relative rates of mortality by father’s social class:
men in West of Scotland aged 35-64 in 1970-73
Source: Davey Smith et al BMJ 1998; 316: 1631-5
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Mortality in adults aged 26-54 years by social class of their father during
their childhood: 1946 Birth Cohort Study
Source: Kuh et al. BMJ 2002; 325: 1076-80
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Do influences of social position
“add up”?
• If there seem to be influences of childhood
and earlier adulthood social position, how
can we combine these?
• Early studies just added them up!
• “Accumulated socio-economic
disadvantage”
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What if you add up the number of times in a less
advantaged social class?
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Childhood social class and biomarkers at age 45. Men &
women, NCDS.
Adj sex & adult class
More disadvantage=higher
level of biomarker
SD scores per 1-unit increase
0.08
0.06
0.04
0.02
0
-0.02
-0.04
-0.06
-0.08
More disadvantage=lower level of biomarker
Social class ‘scored’ 1 (high) to 6 (low): higher value = more disadvantaged
Source: Power et al IJE 2007
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Social class at birth and inflammatory markers
3.5
130
3
128
126
2.5
124
Fibrinogen
gm/litre
122
CRP mg/litre
2
1.5
120
vWF UI/deci
1
118
0.5
116
0
114
Class 1
Class 2
Class 3
social class
Source: Tabassum et al AJE 2008
Class 4
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Inflammatory markers at age 45 by cumulative (birth, age 23 and age 42)
life time social class score
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Source: Tabassum et al AJE
2008
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“Accumulated social class”
• Far more powerful than class at any one
time
• BUT: there is more than one way to have
a score of “2”.
• Does the timing of being in a
disadvantaged social class matter?
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Figure 2 Age standardised mortality rates (with 95% confidence intervals) per 100 000 person
years for all cause mortality by adult and childhood social class in period 1991-98, men aged 3034 in 1990. N-M, non-manual; M, manual. The width of the bar is directly proportional to the size
of the group it refers to.
Pensola, T H et al. J Epidemiol Community Health 2003;57:745-751
Copyright ©2003 BMJ Publishing Group Ltd.
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Getting beyond crude measures of
social position
• Social position measures (class, status,
income) are not risk factors
• Must work through links to biologically
plausible exposures
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Accumulated adversities and
unhealthy behaviour
Life course precursors of smoking in women 18-49,
GB
80
70
60
50
40
30
20
10
0
No quals
+ low skilled job + social
housing
Smokers
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+ benefits
none of these
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Example: From early psychosocial adversity
to heart disease
• Maternal separation is associated with
diurnal cortisol secretion
• Cortisol secretion pattern is associated
with cardiovascular disease at older ages
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Emotional environment in childhood, diurnal cortisol
response and cardiovascular disease in older people
Maternal separation
Cortisol diurnal response
Cardiovascular disease
Source: Kumari et al Psychol Med under revision
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Maternal separation and decrease in cortisol level during the day
Men and women: Whitehall II
Less healthy
Coeff.
More healthy
Sharper slope is healthier
Source: Kumari et al Psychol Med 2012
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Source: Kumari et al J Clin Endocrinol Metab 2011; 96(5): 1478-85
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Accumulation is not the only life
course model
• Accumulation: risk should increase
steadily as dose of hazard increases
• Critical period: risk should be the same in
all those exposed in the critical period
regardless of other events
• Pathway: a factor only increases health
risk if it leads on to another exposure.
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SHEEP Study
• Stockholm Heart Epidemiology Program
• Case-control study
• Cases = 1st MI events in Swedish
citizens aged 45-70 years in Stockholm
1992-3. N=2246
• Controls = healthy population study
base. N=3206
• This sample aged 53-70
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Life course social class and risk of heart disease
Social class
N times manual
Odds Ratio
Age of exposure
OR for
accumulated
score
All non manual
0
1 (ref)
Never
1
M, NM, NM
1
1.1
Childhood
NM, M, NM
1
2.1
25
NM, NM, M
1
2.0
55
M,M,NM
2
1.5
Childhood, 25
M, NM, M
2
1.7
Childhood, 55
NM, M, M
2
1.7
25, 55
M,M,M
3
3
All ages
ICLS
}
1.2
}
1.6
2
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Frequency of different social trajectories
Socio-economic trajectory
% OF SAMPLE
NM-NM-NM
30.2
N-M N-M M
0.3
N-M M N-M
4.1
N-M M M
4.9
M N-M N-M
24.3
M N-M M
0.8
M M N-M
15.1
MMM
20.4
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“Social Structure”
• The last slide gives a good example of
what is meant by “social structure”.
• Note that half of the 8 possible trajectories
have very few people in them.
• Movement between classes is not random
over time.
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Weakness of “C, A, P” life-course
models approach
• Very helpful at the beginning, helped to
organise people’s thoughts
• But not ‘theoretical’
• In reality many complex mixtures
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• Next steps: frame hypotheses that are
socially and biologically plausible
• At each life stage:
– Material
– Psychosocial
– Biological
Influences on the processes PLUS
● Consequences of earlier influences.
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Health in the life course
• How to combine
– Social processes
– Physiological processes
• Needs to be guided by theories from both
biological and social sciences
• Additional data is great but not sufficient