Background. 1) Current research has shown that atherosclerosis starts early in life. The social patterning of coronary heart disease (CHD) in adulthood is also likely to start early in life. However, knowledge of the social patterning of the pre-clinical phases of CHD (endothelial function) and its early life determinants in childhood is scarce. 2) The role of passive smoking, a potential exposure linked to the early social patterning of disease, on CHD aetiology is controversial. Applying the principle of Mendelian randomisation will allow me to investigate whether there is a link between exposure to passive smoking in childhood and measures of early-life atherosclerosis.

Objectives.

1. To systematically review the current evidence regarding social patterning of CHD exposures and pre-clinical disease indicators occurring in early life.

2. To describe the social patterning of endothelial function in childhood.

3. To describe the social patterning of CHD risk factors in early life.

4. To investigate how the social patterning of potential CHD early-life risk factors contributes to the social patterning of endothelial function in childhood.

5. To investigate whether candidate genetic polymorphisms associated with slower detoxification of tobacco smoke are associated with endothelial dysfunction among children exposed to environmental tobacco smoke.

Methods.

Systematic reviews will establish the strongest candidate factors in early life contributing to the development of atherosclerosis and social inequalities in adulthood (Objective 1).

TheAvon Longitudinal Study of Parents and Children (ALSPAC) is a unique prospective cohort study set up to investigate the health and development of children. Vascular function measures are available from at least 6,000 children and include flow mediated dilation, arterial distensibility and pulse wave velocity. DNA for genotyping was obtained from 10,232 children. Early life CHD risk factors and detailed childhood socioeconomic circumstances data are available.This will allow establishing which exposures are likely to initiate and contribute to the social patterning of CHD risk (Objectives 2 to 4).

Polymorphisms in candidate genes related to detoxification of tobacco smoke and their association with endothelial dysfunction will be assessed in the ALSPAC cohort (Objective 5).

Scientific opportunity. The ALSPAC cohort offers a unique opportunity to answer scientific questions regarding the early life determinants of disease andseveral funders have given program support to this cohort. The analyses, proposed here for the first time, will enhance the scientific return from this investment.

Public health importance This proposal will inform interventions for public health policy by identifying the early life factors that may contribute to the adult social patterning of CHD risk. In addition, it will provide evidence regarding a potential link between passive smoking and vascular dysfunction.