How do early-life infectious and nutritional exposures characteristic of tropical Africa impact subsequent cardiovascular disease risk?

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Cardiovascular diseases (CVDs) are increasingly common in sub-Saharan Africa (SSA). The rising burden is thought to be primarily driven by increased longevity and prevalence of important risk behaviours, including unhealthy diets, lack of physical activity, and harmful alcohol use and tobacco use. However, at the same time, CVDs are occurring in people who do not have these risk behaviours and at a younger age than is often seen in high-income countries (HICs). Important physical determinants of CVDs, such as raised blood pressure, and disrupted blood glucose and lipid levels, often start early in life and track through to adulthood. Our ultimate goal is to ascertain which risk factors, and when, influence these physical determinants. An understanding of this is essential for identifying when, and how, we can intervene to reduce the risk of development of CVDs in individuals in SSA. One possible explanation is that early-life infectious exposures characteristic of some SSA populations and often distinct from HIC populations, influence the development of physical determinants of CVDs. In particular, we hypothesise that early-life infections, particularly worms and malaria, and early-life undernutrition, characterised by low birth weight and micronutrient deficiency, may play a key role in increasing risk of development of CVDs. We also aim to investigate the hypothesis that early-life socio-economic characteristics will influence knowledge and awareness of CVDs and the initiation of important risk behaviours, i.e. unhealthy diet, lack of physical activity, harmful alcohol use and tobacco use, in early adulthood. To investigate this, our study will be nested in the Entebbe Mother and Baby Study (EMaBS), a Ugandan birth cohort initiated in 2003, and whose participants have been followed-up to the present day. A wealth of detailed data on early-life infections, undernutrition and growth, socio-demographic characteristics, and genetic variants have been collected from EMaBS participants. We shall supplement these with newly collected data from EMaBS participants at 21 years. We will measure four main physical determinants of CVDs (blood pressure, blood lipid levels, blood glucose and body mass index [BMI]) and compare these between (1) people who had many infections in early childhood and those who did not, (2) people who had growth deficiency in early childhood and those who did not, (3) people who had nutrient deficiency in early childhood and those who did not. If we do find that early-life exposures influence BP, lipid levels, glucose and BMI at age 21, then we shall conduct further focussed work, to assess some potential ways in which these early-life exposures have an effect. For example, this will include assessment of whether early-life exposures may cause metabolomic changes, and whether these are themselves associated with our study outcomes.We will also collect information on the four most important behavioural risk factors for CVDs (unhealthy diet, lack of physical activity, tobacco use, alcohol misuse), describe how many people have developed these behaviours, and assess whether blood pressure, lipid levels, blood glucose and BMI differ between people with risk behaviours compared to those without. Finally, we will conduct interviews and coordinate discussion groups to better understand participants' subjective perceptions of their own CVD risk profiles, their understanding of how their social, environmental and lifestyle factors may affect their CVD risk, and their views on how young people may mitigate future susceptibility to CVDs.Our findings will provide essential information on which life-course exposures, when and how, influence adult CVD susceptibility in this setting, and will give insight into when and how preventive interventions could be applied. Our results will inform health policy around CVDs in SSA, and will set the basis for co-design and evaluation of preventive interventions.