Metal Exposure and Early Cardiovascular Risk in Adult E-Cigarette Users

项目摘要 尽管对电子烟的毒性和健康影响的了解有限，但电子烟的使用 在以前吸烟者和从未吸烟的年轻人中增加。越来越多的证据表明， 电子烟气雾剂含有相对高水平的有毒金属，包括铅和镍， 在心血管（CV）疾病中发挥作用的证据。本提案的目的是评估（1） 电子烟使用与金属暴露的关联，（2）电子烟使用与冠状动脉钙化的关联 和其他相关途径（内皮细胞健康，血压和炎症），和（3）潜在的 电子烟金属的作用来解释，至少部分地，电子烟的CV效应。在初步研究中，我们发现 所产生的气溶胶中的金属水平与来自以下装置的分配器的电子液体相比有所增加： 每日电子烟使用者，表明加热线圈是金属暴露的来源。电子烟气溶胶中的金属， 此外，与金属生物标志物水平呈正相关。我们将对男性进行纵向研究 以及来自纽约市的18至50岁的不同种族/民族背景的妇女（130人从不吸烟 吸烟者或电子烟使用者（对照组），130名从不吸烟的电子烟使用者，130名吸烟的电子烟使用者， 前吸烟者和130名目前吸烟的电子烟使用者，并在一年内对每位参与者进行3次评估。 1.5-一年期间（第1、9和18个月）。为进行暴露评估，我们会收集电子烟使用及使用的资料 来自调查问卷和每4周一次的移动的评估（第3、6、12、15个月）的模式，来自的气溶胶样本 参与者的电子烟设备和尿液和血液样本来测量金属。对于结果评估，我们 将在基线时使用心脏CT扫描测量冠状动脉钙化（CAC）， 加权钙评分（SWCS）。SWCS提供了一种有效的、连续的CAC测量方法，适用于 量化动脉粥样硬化的程度而没有阈值。每次访视时，还将测量内皮细胞 使用EndoPAT 2000装置和内皮细胞通过内皮依赖性动脉血管舒张实现健康- 衍生的微粒（EMP）（内皮细胞损伤的标志物）、血压和 炎症（C-反应蛋白和白细胞介素-6）。我们将估计金属生物标志物和CV 将电子烟使用者与非使用者进行比较的风险以及电子烟使用模式（例如，器械类型，抽吸次数， 每周消耗的电子液体、线圈类型）。在正式的中介分析中，我们将评估电子商务的关联性， 吸烟与CV措施占金属的中介作用。拟议的纵向研究 利用跨学科的专业知识来表征CV疾病，评估金属，招募 电子烟使用者的检查和烟草监管科学的一般领域，以填补 了解使用电子烟可能产生的长期影响，并帮助为电子烟监管行动提供信息。

PROJECT SUMMARY Despite limited knowledge about their toxicity and health effects, the use of electronic cigarettes (e-cigs) has increased among former smokers and young adults who have never smoked. Increasing evidence shows that e-cig aerosol contains relatively high levels of toxic metals, including lead and nickel, metals with strong evidence for a role in cardiovascular (CV) disease. The objective of this proposal is to evaluate (1) the association of e-cig use with metal exposure, (2) the association of e-cig use with coronary artery calcification and other relevant pathways (endothelial cell health, blood pressure and inflammation), and (3) the potential role of e-cig metals to explain, at least in part, the CV effects of e-cigs. In preliminary studies, we found marked increases in metal levels in the generated aerosol compared to e-liquid from the dispenser from devices of daily e-cig users, demonstrating that the heating coil is a source of metal exposure. Metals in e-cig aerosols, moreover, were positively associated with metal biomarker levels. We will conduct a longitudinal study of men and women 18 to 50 years of age of diverse race/ethnic backgrounds from New York City (130 never tobacco smokers or e-cig users (controls), 130 e-cig users who are never tobacco smokers, 130 e-cig users who are former smokers, and 130 e-cig users who are current smokers and evaluate each participant 3 times over a 1.5-year period (month 1, 9, and 18). For exposure assessment, we will collect data on e-cig use and use patterns from a questionnaire and 4-weekly mobile assessments (month 3, 6, 12, 15), an aerosol sample from the participants' e-cig device and urine and blood samples to measure metals. For outcome assessment, we will measure coronary artery calcification (CAC) using cardiac CT-scan at baseline estimating the spatially weighted calcium score (SWCS). The SWCS provides a valid, continuous measure of CAC suitable for quantifying the extent of atherosclerosis without a threshold. At each visit will also measure endothelial cell health through endothelium-dependent arterial vasodilation using EndoPAT2000 device and endothelial cells- derived microparticles (EMPs) (a marker of endothelial cell injury), blood pressure, and biomarkers of inflammation (C-reactive protein and interleukin-6). We will estimate differences in metal biomarkers and in CV risk comparing e-cig users to non-users and by e-cigarette use patterns (e.g., type of device, number of puffs, e-liquid consumed per week, type of coil). In a formal mediation analysis, we will assess the association of e- cig use with the CV measures accounting for the mediating role of metals. The proposed longitudinal study utilizes interdisciplinary expertise in the characterization of CV disease, assessment of metals, the recruitment and examination of e-cig users, and the general field of tobacco regulatory science, to fill a critical gap in the knowledge about the possible long-term effects of e-cig use and to help inform e-cig regulatory action.