Whitehall II Study 30th Anniversary Celebration

Health and vascular ageing

Eric Brunner PhD FFPH UCL Department of 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

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Brunner et al 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 Age-trajectories of glycaemic traits in non-diabetic South Asians and Whites 6 0 . . 5 8 4 0 . . 5 7 Fasting

2 2 hour 0 . . 5 6 glucose glucose 0 0 . . 5 5 8 0 . . 4 4 40 50 60 70 80 40 50 60 70 80 0 7 . . 5 4 6 8 . . 4 4 Insulin Pancreatic 5 . 6 4 . sensitivity 4 Β-cell function 4 . 4 4 . 4 3 . 4 2 . 4 40 50 60 70 80 40 50 60 70 80 Ikehara,Tabak,Akbaraly,Hulman,Kivimaki,Forouhi,Iso,Brunner Diabetologia 2015 DISCOVERY value Metabolic syndrome by civil service employment grade

3 Clinic 2, aged 39-63 years

2.5 P<0.0001 P<0.0003

OR 2

1.5

1 high highlow low MEN WOMEN 0.5 Metabolic syndrome case-control study Autonomic, adrenocortical & inflammation

Controls Cases SD P n=153 n=30 diff.

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 on stiffening of the aorta

1.4 Baseline age 66 trend P<0.001 FU 4 years later 1.2 ) s / 1 m (

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0 <25 25-29.9 30+ BMI (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) Recurrent depression (CES-D) after 5 y P=0.010 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 +30g 0.9 + 30g Ref. sugar Ref. sugar 0.8 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 to navigate the healthcare system and get around the restrictions,” - study author Dr Claudia Cooper (UCL Psychiatry). “…know what to do to SOCIETAL value 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 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, disability- free 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

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Dementia prevalence /

n 10 2014 730,000 (7%) o i t a 2040 1,746,000 (11%) l 8 u p

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4

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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 Maria Guzman-Castillo Martin Shipley Piotr Bandosz Eric Brunner 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: [email protected] http://www.ucl.ac.uk/summer-school-social-determinants-health Twitter: #UCLSDoH