HDL cholesterol and chronic lower respiratory disease events in five cohorts

描述（由申请人提供）：慢性下呼吸道疾病（CLRD）是美国（US）的第三大死亡原因。CLRD最常见的组成部分是慢性阻塞性肺病（COPD）、肺气肿、慢性支气管炎和哮喘。CLRD死亡和发病的主要原因是病情加重，但对病情加重的风险因素了解不足，尤其是在老年人、从不吸烟者和少数民族中。高密度脂蛋白胆固醇（HDL-c）和HDL亚组分可能有助于CLRD的发病机制，因为它们在鞘脂调节和转运中的作用，这与哮喘和肺气肿有关。一个队列的初步结果表明，高密度脂蛋白-c和大的高密度脂蛋白亚组分水平与CLRD事件的发生率较高和肺功能下降更快相关。 我们建议在5个以NHLBI人群为基础的队列（主要是老年人）中进行分析，以检验较高的基线HDL-c水平和较大的HDL亚组分是否与CLRD事件发生率增加和肺功能更快速的纵向下降相关，而与标准的社会人口统计学和临床风险因素无关，而较小的HDL亚组分将显示相反的相关性。我们将进一步检查这些相关性在按人种/种族、吸烟状态和年龄组定义的分层中是否相似;在CLRD的各个组成部分中是否一致;以及基于LIPG rs61755018基因型的遗传学估计的HDL-c是否相当。 这些假设的证实将影响未来CLRD事件风险患者的脂质管理，并建议HDL-鞘脂途径药物开发的目标，以预防CLRD事件。

DESCRIPTION (provided by applicant): 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 sub-fractions 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 sub-fractions 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 sub-fractions 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 sub-fractions 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.