biomarkers in large scale observational studies: the ... · pdf filehaemos tasis, inflammatory...
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Biomarkers in social studies: the examples of Whitehall II and the
English Longitudinal Study of Ageing (ELSA)
Meena Kumari
UCL
30th April, 2010
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What is a biomarker?
A biomarker is a characteristic that is objectively measured and evaluated as an indicator of normal biological processes, pathogenic processes and pharmacologic responses to a therapeutic intervention
Biomarkers working group, NIH. 2001
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Why collect biomarkers in social surveys?
• Understanding the pathways by which social circumstances influence health– Understanding causality
• Sub-clinical disease• Clinical ‘iceberg’
• Contribution to the research: data sharing and consortia
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Pathways between social position and health: the example of Whitehall II
HEALTH BEHAVIOURS
SOCIAL POSITION
INITIAL PATHO-PHYSIOLOGICAL RESPONSE TO STRESSORS
CORONARY HEART DISEASE DIABETES
Genes Early Life
METABOLIC SYNDROME, HAEMOSTASIS, INFLAMMATORY MARKERS
PSYCHOSOCIAL WORK
FACTORS
PSYCHOLOGIAL
RESPONSE
SUB-CLINICAL DISEASE
SOCIAL ENVIRONMENT
Medical care
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Pathways between social position and health: the example of Whitehall II: biomarkers
HEALTH BEHAVIOURS
SOCIAL POSITION
INITIAL PATHO-PHYSIOLOGICAL RESPONSE TO STRESSORS
Heart rate variability; cortisol
CORONARY HEART DISEASE DIABETES
Genes Early Life
METABOLIC SYNDROME, LIPIDS, HAEMOSTASIS, INFLAMMATORY MARKERS Blood pressure; glucose; cholesterol; HDL,
LDL, Fibrinogen; factor VII, C-reactive protein; interleukin-6; von willebrand factor; Lp(a)
PSYCHOSOCIAL WORK
FACTORS
PSYCHOLOGIAL
RESPONSE
SUB-CLINICAL DISEASE
Intima-media thickness
SOCIAL ENVIRONMENT
Medical care
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Biomaker Associated with social position in Whitehall II?
Metabolic markers
Waist circumference yes
Body mass index Yes (in women)
Blood pressure Yes
Glucose No
Lipids
Triglycerides Yes
HDL-cholesterol Yes
LDL-cholesterol No
Total cholesterol No
Inflammatory markers
C-reactive protein Yes
Interleukin-6 Yes
Haemostatic markers
fibrinogen Yes
Factor VII No
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Pathways between social position and health: example of haemostasis
• Haemostasis: clotting
– Fibrinogen
• Made in the liver
• Acute phase protein, activated by inflammatory markers – associated with adiposity thro’ these markers
• Associated with smoking behaviour
– Factor VII
• Made in liver
• body mass index (direct association), plasma lipids (especially triglycerides ) and diabetes
• Associated with dietary fat intake
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P<0.0001
From Marmot et al., Diabetologia 2008
Association of Factor VII and fibrinogen with
Civil service employment grade in the Whitehall II study
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• Fibrinogen associated with social position, factor VII not associated.
– Haemostasis not important per se
– Other pathways might be important
• inflammatory markers
– Further supported when examining additional inflammatory markers; C-reactive protein and interleukins
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Sub-clinical disease
• Clinical ‘iceberg’
– Contribution of undiagnosed disease to public health burden
– Variations in the association of social factors with diagnosed vs undiagnosed disease
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Sub-clinical disease: association of diagnosed and undiagnosed diabetes with wealth in ELSA
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Measures common across Whitehall II and ELSA
‘reported’ ‘objective’
Cardiovascular
Doctor diagnosed disease Blood pressure, AnthropometryLipids, glucose/ HBA1c, CRP, fibrinogen,
Rose Angina
Edinburgh Claudication
Non cardiovascular
Diagnosed disease
MRC respiratory questionnaire Lung function
Functioning
Activities of daily living Hand grip strength, balance, walking speedInstrumental ADLs
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Utility of objective data: contribution of ‘our studies’ to
meta-analyses
• Biomarkers: Whitehall II and ELSA currently contributing to 5 meta-analyses to look at cardiovascular outcomes (fibrinogen, CRP, vWF, triglycerides, Lp(a))
• Genetic studies: Whitehall II and ELSA currently contributing to 30 consortia. Examples include Vitamin D, glucose, hand grip strength
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conclusions
• Metabolic and inflammatory markers mediate social differences in cardiovascular disease
• Emerging public health concerns also point to the importance of measurement of these biomarkers
• New risk factors are addressed through both biomarker and genetic studies