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.

心血管疾病 (CVD) 在撒哈拉以南非洲 (SSA) 地区越来越常见。人们认为，负担增加的主要原因是寿命的延长和重要危险行为的流行，包括不健康的饮食、缺乏体力活动以及有害的饮酒和吸烟。然而，与此同时，心血管疾病发生在没有这些危险行为的人群中，并且发病年龄比高收入国家 (HIC) 中常见的年龄更小。心血管疾病的重要身体决定因素，例如血压升高、血糖和血脂水平紊乱，通常从生命早期开始，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身体决定因素。了解这一点对于确定我们何时以及如何进行干预以降低 SSA 个体患 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）会影响 CVD 物理决定因素的发展。特别是，我们假设生命早期感染，特别是蠕虫和疟疾，以及以低出生体重和微量营养素缺乏为特征的生命早期营养不良，可能在增加心血管疾病发生风险中发挥关键作用。我们还旨在研究这样的假设：生命早期的社会经济特征将影响对心血管疾病的知识和认识，以及成年早期重要危险行为的开始，即不健康的饮食、缺乏体力活动、有害的饮酒和吸烟。为了对此进行调查，我们的研究将纳入恩德培母婴研究 (EMaBS)，这是一个于 2003 年启动的乌干达出生队列，其参与者一直被跟踪至今。 EMaBS 参与者收集了有关生命早期感染、营养不良和生长、社会人口特征和遗传变异的大量详细数据。我们将用 21 岁时从 EMaBS 参与者新收集的数据来补充这些数据。我们将测量 CVD 的四个主要物理决定因素（血压、血脂水平、血糖和体重指数 [BMI]），并在 (1) 儿童早期多次感染的人和没有感染的人之间进行比较，(2 ) 儿童早期有生长缺陷的人和没有生长缺陷的人，(3) 儿童早期有营养缺乏的人和没有营养缺乏的人。如果我们确实发现生命早期的暴露会影响 21 岁时的血压、血脂水平、血糖和体重指数，那么我们将开展进一步的重点工作，以评估这些生命早期的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可能导致代谢组变化，以及这些变化本身是否与我们的研究结果相关。我们还将收集有关 CVD 的四个最重要的行为风险因素的信息（不健康的饮食、缺乏体力活动、吸烟、酗酒），描述有多少人出现了这些行为，并评估有危险行为的人与没有危险行为的人之间的血压、血脂水平、血糖和体重指数是否存在差异。最后，我们将进行访谈并协调讨论小组，以更好地了解参与者对其自身CVD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CVD风险的理解，以及他们对年轻人如何缓解CVD风险的看法未来对 CVD 的易感性。我们的研究结果将提供重要信息，说明哪些生命全程暴露、何时以及如何影响这种情况下成人 CVD 易感性，并将深入了解何时以及如何应用预防性干预措施。我们的结果将为SSA有关CVD的卫生政策提供信息，并将为预防性干预措施的共同设计和评估奠定基础。