Whitehall II Study 30th Anniversary Celebration
Health and vascular ageing
Eric Brunner PhD FFPH
UCL Department of Epidemiology and Public Health
Wednesday 25th November 2015
The Whitehall II study
Scientific value
Medical
Discovery
Public health
Societal
Capacity building
MEDICAL value
Adding blood glucose to the NHS health check
What information does it yield?
Risk assessment for chronic disease is
increasingly integrated
About 10 y ago, DH funded us to
investigate the added value of fasting
glucose in the NHS screening programme
THE SCREENING/PRIMARY CARE TEAM USES: age, gender,
smoking status, family history heart dis., ethnicity, AUDIT, BMI, BP,
physical activity level – and blood cholesterol
Brunner,Shipley,Marmot,Kivimaki,Witte Diab Med 2010
CHD mortality by blood glucose categories
First Whitehall study 33 year follow up
1.6
1.4
Log Hazard Ratio *
1.2
1
0.8
0.6
0.4
0.2
0
3.0
4.0
5.0
6.0
7.0
8.0
9.0
10.0
-0.2
-0.4
Blood Glucose (mmol/l)
Brunner et al Diabetes Care2006
What information does glucose add to screening?
Risk assessment using Framingham Risk Score
Increase in coronary risk per 1% increase in Score
Men
10% (9-12%)
Women
13% (10-17%)
Prediction unchanged when fasting glucose added
IMPROVED DETECTION OF UNDIAGNOSED DIABETES
Risk stratification for CHD unchanged
Brunner,Shipley,Marmot,Kivimaki,Witte Diab Med 2010
5.0
5.2
2 hour
glucose
4.8
4.0
5.0
Fasting
glucose
50
60
70
80
40
50
60
70
80
70
80
4.8
4.6
4.7
5.0
40
4.3
4.4
4.4
4.6
4.5
Pancreatic
Β-cell function
4.2
Insulin
sensitivity
6.0
5.4
7.0
5.6
8.0
Age-trajectories of glycaemic traits in non-diabetic South
Asians and Whites
40
50
60
70
80
40
50
60
Ikehara,Tabak,Akbaraly,Hulman,Kivimaki,Forouhi,Iso,Brunner Diabetologia 2015
DISCOVERY value
Metabolic syndrome by civil service employment grade
Clinic 2, aged 39-63 years
3
P<0.0001
2.5
P<0.0003
OR 2
1.5
1
low
high
0.5
MEN
high
low
WOMEN
Metabolic syndrome case-control study
Autonomic, adrenocortical & inflammation
Controls
n=153
Cases
n=30
SD
diff.
P
Urinary
noradrenaline
177 (151-207)
233 (185-293)
0.45
0.02
Urinary cortisol
6.31 (5.2-7.7)
8.90 (6.6-12)
0.49
0.03
Heart rate variability
42.5 (36-49)
32.3 (24-40)
-0.72
0.006
Serum IL-6
1.10 (09-1.3)
1.90 (1.5-2.4)
0.89
0.001
Cortisol circadian rhythm and longevity
Behavioural predictors
e.g. current smoking, short sleep
Phase 7 baseline. Adjusted for age, sex, grade,
waking time/time of sample collection since waking
Kumari JCEM 2011
Compression of morbidity: the search is on
Guiding principle
Chronic disease can be postponed or prevented by reducing
exposure to vascular risk factors, behaviourally and therapeutically
Mounting evidence that the same is true of physical and cognitive
decline in older people  plasticity of ageing
Fries NEJM 1980
Fries & Crapo 1981
Aortic arteriosclerosis
Pulse wave velocity (Sphygmocor)
5392 men and women aged around 65
lying position after ≥10 min rest
Carotid and femoral pulses and ECG R
wave detection
Path length by fibreglass tape
Gold standard method for arterial
stiffness (Laurent EHJ 2006)
Prospective effect of overweight and obesity on
stiffening of the aorta
1.4
Baseline age 66
FU 4 years later
trend P<0.001
5 year PWV increase (m/s)
1.2
1
0.8
0.6
0.4
0.2
0
<25
25-29.9
BMI
30+
(kg/m2)
Linear mixed model adjusted for age, sex, ethnicity and mean arterial pressure
Brunner et al Hypertension 2015
PUBLIC HEALTH value
Sugar from sweet food/beverages and depression
New depression (GHQ-30)
after 5 y P=0.010
Recurrent depression (CES-D)
after 5 y P=0.025
Odds ratio
1.4
1.4
Men
Men & Women
1.3
1.3
1.2
1.2
1.1
1.1
1.0
1.0
0.9
Ref.
0.8
+30g
sugar
0.9
Ref.
+ 30g
sugar
0.8
Adjustment: energy intake, dietary pattern, tea & coffee consumption
Knuppel, Shipley, Brunner, in preparation
SOCIETAL value
When access to any treatment
is
rationed, wealthier patients better-equipped
SOCIETAL value
to navigate the healthcare system and get around
the restrictions,” - study author Dr Claudia
Cooper (UCL Psychiatry). “…know what to do to
get the diagnosis and treatment that they
want … more confident and assertive in asking
doctors for specific treatments. Observational
studies … understanding inequality
in
treatment” The English National Dementia
Strategy launched in 2009 with a key objective of
reducing treatment inequalities, but the new study
finds no
evidence that this is
being achieved for anti-dementia drugs.
Cooper et al Age & Ageing 2015
Dementia, disability and frailty in later life
Mid-life approaches to delay or prevent onset
NICE guidelines [NG16] October 2015
1. Develop and support population-level initiatives to reduce
risks
2. Integrate dementia risk reduction prevention policies with CVD
etc policies
3. Raise awareness of risks of dementia, disability in general
population and professionals
4. Produce information on reducing the risks of dementia,
disability and frailty
5-8. smoking, physical activity, alcohol, diet
9-15. service delivery
IMPACT-BAM POPULATION PREDICTION model
for CVD, dementia, disability, mortality
• Evidence-based Markov model (ELSA)
• Unique model integrates competing
risks for CVD and dementia
• Annual forecasts: 2016 to 2040
• Built for England & Wales
• IMPACT-BAM is a platform for
simulating impact of change and/or
intervention on occurrence of these
chronic diseases 2015-2040
IMPACT-BAM outputs: prevalence by age and gender for each health
state by calendar year, life expectancy, morbidity-free LE, disabilityfree LE
IMPACT-BAM dashboard, CVD mortality
predictions & dementia prevalence validation 2011
Population over 65 and dementia, 2014 and 2040
England and Wales
18
IMPACT-BAM prediction 2040
16
Dementia prevalence
2014
730,000 (7%)
2040
1,746,000 (11%)
Population / M
14
12
10
8
6
4
2
0
2014
2040
IMPACT-BAM (Better Ageing Model)
Policy layer: forecasting impact of environment/behaviour change on health outcomes
Potential economics layer: cost-benefit analysis of policy options including do-nothing
scenarios
Sara Ahmadi-Abhari
Martin Shipley
Eric Brunner
Maria Guzman-Castillo
Piotr Bandosz
Simon Capewell
Martin O’Flaherty
Capacity building value
UCL Health and Society
9th Summer School : Social Determinants of Health
4th – 8th July 2016
For further information, please email: e.skinner@ucl.ac.uk
http://www.ucl.ac.uk/summer-school-social-determinants-health
Twitter: #UCLSDoH