UNIVERSITY OF CAMBRIDGE Patterns and Predictions: The EPIC-Norfolk study Background General approaches Examples of some current issues: fat, vit D, genetics Kay-Tee Khaw CIPH 25 June 2014

EPIC*-Norfolk population study Aims: to improve health through better understanding of the major determinants health in middle and later life 25,000 men and women 40-79 years from GP age-sex registers in Norfolk, UK Baseline survey 1993-1997 Extensive lifestyle and biologic information Followed up for health endpoints to present * Part of European Prospective Investigation into Cancer: a 10 country collaboration with 450,000 participants http://www.epic-norfolk.org.uk

What influences our risk of health in later life? Disease/disability e.g. stroke, fractures, dementia, cancer functional health e.g. lung function, bone quality, immune function, blood vessel function Physiological risk factors e.g. diet, psychosocial, physical activity, infection, smoking Exposure genetic environmental

Lower blood glucose levels Low levels of inflammation Some simple low cost physiological measures predict subjective and objective health in men and women aged 40-79 years Good lung function Low pulse rate Good bone health Lower blood glucose levels Low levels of inflammation FEV1 and lower hip fracture risk FEV1 and good physical function Moayyeri A JCEM 2009 Myint P Eur Resp J 2005

1 Alcohol >0 <14 units/wk 1 Not inactive Four simple health behaviours and mortality by cause in 20244 men and women aged 40-79 years, EPIC-Norfolk 1993-2007 (multiple endpoints) P<0.001 P<0.0001 P<0.001 1 Non smoker 1 Alcohol >0 <14 units/wk 1 Not inactive 1 Blood vitamin C >50 umol/l (5 servings fruit and vegetable daily) Score 0-4 Equivalent 14 years Adjusted for age, BMI, social class Khaw et al PLOS Medicine 2008

Active compared with inactive equivalent to 7 years in age Physical activity patterns in 1993-1997 predict physical performance* in 2007-8 and in men and women Active compared with inactive equivalent to 7 years in age P<0.01 for trend *timed 5 chair stands adjusted for age and sex

Cognitive function (PAL) by age in men and women EPIC-Norfolk 2006-8 Mean errors Percent scoring Cantab15 Compared to no qualifications, finishing school equivalent to 9 years younger, tertiary education equivalent to 14 years younger cognitive performance [E.g. Delay dementia onset by:- 2 yrs ↓ prevalence by 20% - 5 yrs ↓ prevalence by 50%]

Age and sex adjusted odds ratios for CHD by fatty acid quartile, unadjusted and adjusted for other fatty acids in 2424 CHD cases and 4930 controls, men and women 40-79 years, EPIC Norfolk 1993-2009 Khaw KT et al PLOS Med 2012

Implications Different fatty acids differently related to CHD and overall balance critical Biomarkers of dietary intake/nutritional status and better dietary assessment tools may help clarify associations Future studies need to consider dietary patterns, foods as well as nutrients

Vitamin D and health: (to D or not to D?)

Relative risks* of incident diseases by vitamin D status in 14641 men and women 42-82 years, EPIC Norfolk 1997-2012 3121 4469 2132 563 198 *Adjusted for age, sex, month, body mass index, physical activity, smoking, alcohol, diabetes, Vitamin C, history of cardiovascular disease, history of cancer, social class,& education

Survival between 1997-2012 by baseline 25 OH vitamin D category in men and women, age, sex and month adjusted Public health implications? If everyone increased serum concentrations 20nmol/l (e.g. 1000 IU daily) Estimated theoretical population impact 12% lower mortality p<0.05 1 <30nmol/l 2 30-<90 nmol/l 3 90-<120 nmol/l 4 >=120 nmol /l

Physical activity modifies the relationship between genetic predisposition and body mass index, EPIC-Norfolk Li et al PLOS Med 2010

EPIC-Norfolk: Continuing challenges for population health Disease/disability Better assessment of relevant health outcomes: e.g. quality of life, function, service utilization Better characterisation of physiology and phenotype e.g. gut microbiome Physiological risk factors Better characterisation exposures e.g. diet, physical activity, infection Wider environmental determinants e.g. pollution, social networks genetic environmental Exposure

THANK YOU We are most grateful to all participants, general practitioners and staff in EPIC-Norfolk who have given all their time and effort over the past 20 years Funding support Medical Research Council Cancer Research UK Stroke Association Research Into Ageing British Heart Foundation Academy of Medical Science Department of Health Food Standards Agency EU against Cancer http://www.epic-norfolk.org.uk