Air pollutant exposure and progression of subclinical atherosclerosis during the critical transition from childhood to adulthood

项目摘要 心血管疾病(CVD)在全球死亡率和发病率中所占比例最大。当一个 大量证据支持长期接触空气污染在成人心血管疾病中的作用，相对 关于空气污染暴露如何影响亚临床动脉粥样硬化的发展，我们知之甚少。 更年轻的人群。这些致病过程的早期标志物，包括颈动脉内膜-中层 厚度(CIMT)、动脉硬化(CAS)和通过回声测量的动脉壁成分可 洞察疾病起源的不同方面。缺乏重复的纵向研究 年轻人群亚临床动脉粥样硬化指标的表征是该领域的一个主要空白。 目前尚不清楚早期接触空气污染物是否会影响颈动脉病变的进展。 从童年到成年的动脉粥样硬化。我们假设环境和交通相关的空气污染物 暴露可能会影响不良亚临床心血管表型的发展，如下所示 随着儿童成长到成年早期，颈动脉粥样硬化的进展。我们将在内部测试这一假设 南加州儿童健康研究(CHS)，最大和最全面的研究之一 调查空气污染对儿童健康的长期影响。颈动脉超声检查显示 在10岁时对CHS儿童的一部分进行了检查，提供了亚临床动脉粥样硬化的早期测量。AS 这些参与者现在接近成年期早期(~21-23岁)，我们正准备独特地解决 终生接触空气污染是否与动脉粥样硬化标记物的变化有关 从童年到成年早期。使用儿童颈动脉超声图像作为基线测量， 我们建议利用对CHS参与者的持续跟踪来获得亚临床的重复评估 动脉粥样硬化测量(CIMT和CAS)，并计算颈动脉回声(GSM)，这是一种新的动脉指标 根据基线和后续超声图像进行室壁成分分析。我们将评估住宅的影响 环境和交通相关空气污染物对亚临床动脉粥样硬化指标变化的影响 时间，以及在成年早期达到的动脉粥样硬化水平。我们还将评估两国之间的关系 空气污染暴露和心脏代谢功能障碍的生物标志物(血糖、血脂、糖化血红蛋白)，开始 研究早期动脉粥样硬化的潜在机制。这项新颖的研究将填补我们在 随着时间的推移对儿童亚临床动脉粥样硬化的了解，并调查终生空气污染的影响 暴露在疾病进展的早期阶段。

Project Summary Cardiovascular disease (CVD) accounts for the largest proportion of mortality and morbidity worldwide. While a strong body of evidence supports a role for long-term air pollution exposure in CVD among adults, relatively little is known about how air pollution exposures may affect the development of subclinical atherogenesis in younger populations. Early markers of these pathogenic processes, including carotid artery intima-media thickness (CIMT), arterial stiffening (CAS), and arterial wall composition as measured by echogenicity, may provide insight into different facets of the beginnings of disease. The lack of longitudinal studies with repeated characterization of measures of subclinical atherosclerosis in younger populations is a major gap in the field and it is unclear whether early life exposures to air pollutants may impact the progression of carotid atherosclerosis from childhood into adulthood. We hypothesize that ambient and traffic-related air pollutant exposures may influence the development of adverse subclinical cardiovascular phenotypes, indicated by carotid atherosclerosis progression, as children grow into early adulthood. We will test this hypothesis within the Southern California Children's Health Study (CHS), one of the largest and most comprehensive investigations of the long-term effects of air pollution on children's health. Carotid artery ultrasounds were performed on a subset of CHS children at age 10, providing an early measure of subclinical atherosclerosis. As these participants now approach early adulthood (~21-23 years), we are uniquely poised to address the question of whether lifetime air pollution exposures are associated with changes in atherosclerosis markers from childhood into early adulthood. Using childhood carotid artery ultrasound images as a baseline measure, we propose to leverage ongoing follow-up of CHS participants to obtain a repeat assessment of subclinical atherosclerosis measures (CIMT and CAS), and calculate carotid echogenicity (GSM), a novel metric of arterial wall composition, from baseline and follow-up ultrasound images. We will evaluate the effects of residential ambient and traffic-related air pollutants on changes in these measures of subclinical atherosclerosis over time, as well as attained level of atherosclerosis in early adulthood. We will also evaluate the relation between air pollution exposure and biomarkers of cardiometabolic dysfunction (glucose, lipids, HbA1c), to begin to investigate potential mechanisms underlying early atherosclerosis. This novel study will fill a critical gap in our knowledge of subclinical atherosclerosis in children over time and investigate the impact of lifetime air pollution exposure on early phases of disease progression.