HDL cholesterol and chronic lower respiratory disease events in five cohorts

五个队列中的高密度脂蛋白胆固醇和慢性下呼吸道疾病事件

• 批准号: 8624969
• 负责人: R Graham BARR
• 金额: $ 11.42万
• 依托单位: COLUMBIA UNIVERSITY HEALTH SCIENCES
• 依托单位国家: 美国
• 财政年份: 2013
• 资助国家: 美国
• 起止时间: 2013-09-15 至 2015-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8624969
• 关键词: Adult; Allergens; Animal Model; Apolipoproteins; Apoptotic; Asthma; Atherosclerosis; Attenuated; Biological; Bronchitis; Candidate Disease Gene; Cause of Death; Centers for Disease Control and Prevention (U.S.); Ceramides; Cessation of life; Chronic; Chronic Bronchitis; Chronic Obstructive Airway Disease; Data; Development; Elderly; Ethnic Origin; Event; Future; General Population; Genetic Variation; Genotype; High Density Lipoprotein Cholesterol; High Density Lipoproteins; Hospitalization; Human; Link; Lipids; Lipoproteins; Literature; Lung; Lung diseases; Minority; Modeling; Morbidity - disease rate; Mus; National Heart, Lung, and Blood Institute; Obstruction; Pathogenesis; Pathway interactions; Patients; Persons; Pulmonary Emphysema; Race; Reflux; Regulation; Resources; Respiratory physiology; Risk; Risk Factors; Role; Sampling; Smoker; Smoking; Smoking History; Smoking Status; Sphingolipids; Spirometry; Stomach; Structure of parenchyma of lung; Symptoms; Testing; United States; Work; World Health Organization; X-Ray Computed Tomography; administrative database; age group; airway inflammation; airway remodeling; base; cigarette smoking; clinical risk; cohort; drug development; follow-up; innovation; mortality; never smoker; non-smoker; novel; particle; population based; prevent; public health relevance; sphingosine 1-phosphate; young adult

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.

总结： 慢性下呼吸道疾病（CLRD）是美国（US）的第三大死亡原因。最 CLRD的普遍组分是慢性阻塞性肺疾病（COPD）、肺气肿、慢性阻塞性肺疾病（COPD）、慢性阻塞性肺疾病（CLRD）、慢性阻塞性肺疾病（CLRD 支气管炎和哮喘。CLRD死亡率和发病率的主要原因是病情加重，但 对病情加重的认识不足，特别是在老年人、从不吸烟者和少数群体中。高 密度脂蛋白胆固醇（HDL-c）和HDL亚组分可能有助于CLRD发病机制， 它们在鞘脂调节和转运中的作用，这与哮喘和 肺气肿一个队列的初步结果表明，高水平的HDL-c和大HDL 亚组分与CLRD事件发生率较高和肺功能下降较快相关。 我们建议在五个以NHLBI人群为基础的队列中进行分析，这些队列主要是老年人。 成年人，以测试是否较高的基线HDL-c水平和大的HDL亚组分将与增加 CLRD事件的发生率和肺功能更快速的纵向下降，与标准社会因素无关， 人口统计学和临床风险因素，而小HDL亚组分将证明相反 协会.我们将进一步研究这些关联在由种族/民族定义的分层中是否相似， 吸烟状况和年龄组; CLRD的各个组成部分一致;遗传学方面具有可比性- 基于LIPG rs61755018基因型估计的HDL-c。 这些假设的证实将影响未来CLRD风险患者的血脂管理 事件，并为HDL-鞘脂途径的药物开发提供了靶点，以预防CLRD事件。