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

心血管疾病（CVD）在撒哈拉以南非洲（SSA）越来越常见。据认为，造成这一负担不断增加的主要原因是寿命延长和重要风险行为的流行，包括不健康饮食、缺乏体育活动以及有害饮酒和吸烟。然而，与此同时，心血管疾病发生在没有这些风险行为的人群中，并且发生在比高收入国家（HIC）常见的更年轻的年龄。心血管疾病的重要生理决定因素，如血压升高，血糖和血脂水平紊乱，通常在生命早期开始，并一直持续到成年。我们的最终目标是确定哪些风险因素以及何时影响这些物理决定因素。了解这一点对于确定何时以及如何进行干预以降低SSA个体发生CVD的风险至关重要。一种可能的解释是，一些SSA人群的早期感染暴露特征，通常与HIC人群不同，影响了CVD的物理决定因素的发展。特别是，我们假设早期感染，特别是蠕虫和疟疾，以及早期营养不良，以低出生体重和微量营养素缺乏为特征，可能在增加心血管疾病发展风险中发挥关键作用。我们还旨在调查以下假设：早期生活的社会经济特征将影响对心血管疾病的了解和认识，以及在成年早期开始重要的风险行为，即不健康的饮食，缺乏体力活动，有害的酒精使用和烟草使用。为了调查这一点，我们的研究将嵌套在恩德培母亲和婴儿研究（EMaBS），乌干达出生队列在2003年开始，其参与者一直随访到今天。从EMaBS参与者那里收集了大量关于生命早期感染、营养不良和生长、社会人口特征和遗传变异的详细数据。我们将补充这些新收集的数据，从EMaBS参与者在21岁。我们将测量心血管疾病的四个主要身体决定因素（血压，血脂水平，血糖和体重指数[BMI]），并比较（1）在幼儿期有许多感染的人和那些没有的人，（2）在幼儿期有生长缺陷的人和那些没有的人，（3）在幼儿期有营养缺乏的人和那些没有的人。如果我们确实发现早期生活暴露会影响21岁时的血压、血脂水平、血糖和BMI，那么我们将进行进一步的重点工作，以评估这些早期生活暴露产生影响的一些潜在方式。例如，这将包括评估生命早期暴露是否会导致代谢组学变化，以及这些变化本身是否与我们的研究结果相关。我们还将收集心血管疾病四个最重要的行为风险因素的信息（不健康的饮食，缺乏身体活动，吸烟，酗酒），描述有多少人已经发展出这些行为，并评估血压，血脂水平，与没有危险行为的人相比，有危险行为的人的血糖和BMI不同。最后，我们将进行访谈和协调讨论小组，以更好地了解参与者对自己心血管疾病风险状况的主观看法，他们对社会，环境和生活方式因素如何影响他们心血管疾病风险的理解，以及他们对年轻人如何减轻未来心血管疾病易感性的看法。我们的研究结果将提供有关生命过程中暴露，何时以及如何，在这种情况下，影响成人CVD易感性，并将深入了解何时以及如何预防干预措施可以应用。我们的研究结果将为SSA心血管疾病的卫生政策提供信息，并为预防干预措施的共同设计和评估奠定基础。

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.