HDL cholesterol and chronic lower respiratory disease events in five cohorts

摘要： 慢性下呼吸道疾病(CLRD)是美国第三大致死原因。最多的 慢性阻塞性肺疾病(COPD)、肺气肿、慢性阻塞性肺疾病 支气管炎和哮喘。慢性阻塞性肺疾病死亡和发病的主要原因是病情恶化，但危险因素 人们对病情恶化的认识不足，特别是在老年人、从不吸烟的人和少数群体中。高 密度脂蛋白胆固醇(HDLc)及其亚组分可能与慢性阻塞性肺疾病的发病有关 它们在鞘脂调节和运输中的作用，这与哮喘和 肺气肿。一个队列的初步结果表明，高密度脂蛋白-c和大高密度脂蛋白水平较高 亚组分与更高的CLRD事件发生率和更快的肺功能下降有关。 我们建议对以老年人为主的五个基于NHLBI人群的队列进行分析 成年人测试较高的基线高密度脂蛋白水平和较大的高密度脂蛋白亚组分是否会与高密度脂蛋白含量增加相关 CLRD事件的发生率和肺功能更快的纵向下降独立于标准的社会- 人口统计学和临床风险因素，而小的高密度脂蛋白亚组分将显示相反的情况 联想。我们将进一步研究这些关联是否在由种族/民族定义的不同阶层之间相似， 吸烟状况和年龄组；在CLRD的各个组成部分中都是一致的；在遗传上具有可比性- 根据LIPG rs61755018的基因估计高密度脂蛋白胆固醇。 这些假说的证实将影响未来对有CLRD风险的患者的血脂管理 并建议在高密度脂蛋白-鞘脂途径上的药物开发目标，以防止CLRD事件。

Summary: Chronic lower respiratory disease (CLRD) is the 3rd leading cause of death in the United States (US). The most prevalent components of CLRD are chronic obstructive pulmonary disease (COPD), emphysema, chronic bronchitis and asthma. The primary cause of CLRD mortality and morbidity is exacerbations, yet risk factors for exacerbations are inadequately understood, especially among the elderly, never-smokers and minorities. High density lipoprotein cholesterol (HDL-c) and HDL subfractions may contribute to CLRD pathogenesis due to their roles in sphingolipid regulation and transport, which have been implicated in both asthma and emphysema. Preliminary results from one cohort suggest that higher levels of HDL-c and large HDL subfractions are associated with higher rates of CLRD events and more rapid decline in lung function. We propose to perform analyses across five NHLBI population-based cohorts of predominantly older adults to test if higher baseline HDL-c levels and large HDL subfractions will be associated with increased rates of CLRD events and a more rapid longitudinal decline in lung function independent of standard socio- demographic and clinical risk factors whereas small HDL subfractions will demonstrate the inverse associations. We will further examine if these associations are similar across strata defined by race/ethnicity, smoking status and age group; consistent across components of CLRD; and comparable for genetically- estimated HDL-c based on genotype at LIPG rs61755018. Confirmation of these hypotheses would impact future lipid management for patients at risk for CLRD events and suggest targets for drug development on the HDL-sphinoglipid pathway to prevent CLRD events.