Project 5: Cardiovascular Assessment ofthe Effects of Tobacco and Nicot p341-385

吸烟仍然是心血管疾病(CVD)的主要原因。相比之下， 其他常用烟草产品(无烟烟草)和新烟草的心血管风险 对产品(电子烟)的了解不足。FDA将需要关于 这些产品的心血管安全性，为他们的监管决策提供信息。虽然长期的临床结果 调查烟草产品的心血管风险的研究将是最佳的，因为它们需要太长的时间来 提供FDA现在需要的数据。血管内皮细胞功能紊乱(血管内皮细胞内层 动脉在调节血管功能方面起着重要作用)，在自主神经的激活中起着重要作用 神经系统和炎症增加、氧化应激和血栓形成(凝血)的倾向是关键 在心血管疾病进展中的机制，并提供有用和有效的心血管疾病风险的生物标志物。这些 生物标志物构成了我们评估烟草产品使用和二手产品的心血管疾病风险的模型的基础 暴露在烟雾中。我们将对受试者进行受控的短期暴露，以测试以下产品 提供广泛的尼古丁、微粒和其他心血管毒素浓度，以确定如何 这些与烟草使用相关的成分会对心血管风险产生不利影响。具体地说，我们将1) 确定尼古丁和燃烧产物对活动性心脏病风险的相对贡献 吸烟；2)确定哪些心血管风险生物标志物会受到低剂量吸烟的影响 二手烟的浓度；3)决定使用无烟烟草的心血管风险；以及4) 确定电子烟的心血管风险以及尼古丁和尼古丁各自的贡献 电子烟蒸气。通过量化和比较4种不同烟草的即时效果 心血管系统上的产品。项目5将验证一个敏感而实用的生理学专家小组 以及预测心血管疾病的分子生物标志物，将在上市前的人类中发挥重要作用 烟草产品的检测。 C 相关性(请参阅说明)： 我们的研究将提供烟草和尼古丁传递的个别关键成分的信息 产品，即尼古丁、颗粒物和其他心血管毒素，会影响心血管风险，如果 无烟烟草和电子烟会增加心血管风险。最终，我们的生物标记物模型将作为 FDA在监督传统烟草、新烟草和新兴烟草时的心血管安全筛查 产品。

Cigarette smoking continues to be a major cause of cardiovascular disease (CVD). In contrast, the cardiovascular risks of other tobacco products in common use (smokeless tobacco) and new tobacco products (e-cigarettes) are not adequately understood. The FDA will need information about the cardiovascular safety of these products to inform their regulatory decisions. While long-term clinical outcome studies that investigate the cardiovascular risks of tobacco products would be optimal, they take too long to provide the data that the FDA needs now. Disturbances in the function of vascular endothelium (the lining of arteries, which plays an important role in regulating vascular function), in the activation ofthe autonomic nervous system and increased inflammation, oxidative stress and propensity to thrombosis (clotting) are key mechanisms in the progression of CVD and provide useful and validated biomarkers of CVD risk. These biomarkers form the basis for our model to assess the CVD risks of tobacco product use and secondhand smoke exposure. We will conduct controlled, short-term exposures of human subjects to test products that provide a wide range of nicotine, particle and other cardiovascular toxin concentrations to determine how these components associated with tobacco use adversely affect cardiovascular risk. Specifically, we will 1) determine the relative contributions of nicotine and combustion products to the cardiovascular risk of active cigarette smoking; 2) determine which cardiovascular risk biomarkers are affected by exposure to low concentrations of secondhand smoke; 3) determine the cardiovascular risk of smokeless tobacco use; and 4) determine the cardiovascular risk of electronic cigarettes and the respective contributions of nicotine and electronic cigarette vapor. By quantifying and comparing the immediate effects of 4 different kinds of tobacco products on the cardiovascular system. Project 5 will validate a sensitive and practical panel of physiological and molecular biomarkers that predict cardiovascular disease and will be of great use in premarket human testing of tobacco products. C RELEVANCE (See instructions): Our research will provide information as to how individual key components of tobacco and nicotine delivery products, i.e. nicotine, particulate matter, and other cardiovascular toxins, affect cardiovascular risk and if smokeless tobacco and e-cigarettes pose cardiovascular risks. Ultimately, our biomarker model will serve as a cardiovascular safety screen for the FDA in its oversight of conventional, new, and emerging tobacco products.