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

热带非洲特征的早期感染和营养暴露如何影响随后的心血管疾病风险？

• 批准号: MR/Y013948/1
• 负责人: Emily Webb
• 金额: $ 144.61万
• 依托单位: London School of Hygiene & Tropical Medicine
• 依托单位国家: 英国
• 项目类别: Research Grant
• 财政年份: 2024
• 资助国家: 英国
• 起止时间: 2024 至 无数据
• 项目状态: 未结题
• 来源: https://gtr.ukri.org/projects?ref=MR%2FY013948%2F1
• 关键词: How; do; early; life; infectious

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.

在撒哈拉以南非洲（SSA）中，心血管疾病（CVD）越来越普遍。人们认为，负担的上升主要是由重要的风险行为的寿命和患病率提高，包括不健康的饮食，缺乏体育锻炼以及有害的酒精使用和烟草使用的驱动。但是，与此同时，没有这些风险行为，并且年轻的人比在高收入国家（HIC）（HIC）中发生的CVD发生。 CVD的重要物理决定因素，例如血压升高，血糖和脂质水平破坏，通常从生命的早期开始，并追踪到成年。我们的最终目标是确定哪些风险因素以及何时影响这些身体决定因素。对此的理解对于识别何时以及如何进行干预以降低SSA个体中CVD发展的风险至关重要。一种可能的解释是，早期的传染性暴露是某些SSA种群的特征，通常与HIC种群不同，会影响CVD的物理决定因素的发展。特别是，我们假设早期生活感染，尤其是蠕虫和疟疾，以及以低出生体重和微量营养素缺乏的特征的早期生活不足，可能在增加CVD发展风险方面起关键作用。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CVD的知识和意识，并在成年初期，即不健康的饮食，缺乏体育锻炼，有害的饮酒和烟草使用的重要风险行为，即不健康的饮食。为了调查这一点，我们的研究将嵌套在乌恩布贝（Entebbe）的母亲和婴儿研究（EMABS）中，这是一个乌干达的出生队列，于2003年启动，其参与者已受到今天的跟进。关于早期感染，营养不良和生长，社会人口统计学特征和遗传变异的大量详细数据已从EMABS参与者中收集。我们将在21年的时间里用来自EMABS参与者的新数据补充这些数据。我们将测量CVD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）（1）早期感染许多感染的人与那些没有感染的人，（2）早期童年患有生长不足的人，而幼年和没有过早期儿童的人，（3）没有营养的人，（3）没有营养的人和那些没有营养的人。如果我们确实发现21岁时会影响BP，脂质水平，葡萄糖和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有效的潜在方式。 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那些没有。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的CVD风险概况的主观看法，他们对他们的社交，环境和生活方式因素如何影响其CVD风险以及对年轻人的看法以及对未来对CVD的未来敏感性的理解，以及他们对CVDS的敏感性的影响，他们对CVD的敏感性将如何在何时及时享受生活方式，并在何时造成生活方式，并在何时造成了临近，并在何时造成了这种临时，并启用了这种临时性，并启用了这种临时性，并启用了这种临时，并启用了这种情况。可以采用干预措施。我们的结果将为SSA中CVD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树立基础。