Long-term prospective associations of PFAS with musculoskeletal and cardiovascular health among older adults

PFAS 与老年人肌肉骨骼和心血管健康的长期前瞻性关联

• 批准号: 10642239
• 负责人: Abby Fleisch
• 金额: $ 58.5万
• 依托单位: HARVARD PILGRIM HEALTH CARE, INC.
• 依托单位国家: 美国
• 财政年份: 2015
• 资助国家: 美国
• 起止时间: 2015-03-01 至 2028-01-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10642239
• 关键词: Address; Adult; Age Years; Aging; Anti-Inflammatory Agents; Attenuated; Behavior; Behavior Therapy; Biological; Biological Assay; Cardiovascular Diseases; Cessation of life; Chemicals; Cholesterol; Cohort Studies; Communities; Congestive Heart Failure; Coronary; Coronary Arteriosclerosis; Data; Diet; Dual-Energy X-Ray Absorptiometry; Elderly; Event; Exercise; Exposure to; Fatty acid glycerol esters; Food; Functional disorder; Funding; Hand; Hand Strength; Health; Hormonal Change; Hormones; Hospitalization; Individual; Industrialization; Inflammatory; Insulin Resistance; Intake; Intervention; Life; Life Style; Longitudinal cohort; Longitudinal cohort study; Manufacturer; Measures; Metabolism; Metformin; Modeling; Modification; Muscle; Musculoskeletal; Myocardial Infarction; National Institute of Environmental Health Sciences; Omega-3 Fatty Acids; Outcome; Outcome Study; Participant; Peripheral; Phase; Physical activity; Placebos; Plasma; Policies; Poly-fluoroalkyl substances; Population; Predisposition; Preventive; Production; Productivity; Public Policy; Randomized; Reporting; Research Priority; Resources; Risk; Risk Reduction; Role; Sample Size; Scanning; Statistical Methods; Statutes and Laws; Strategic Planning; Stroke; Testing; Therapeutic; Unstable angina; Vascularization; Work; abdominal fat; adjudication; age related; arm; bone mass; cardiometabolic risk; cardiovascular disorder risk; cardiovascular health; cardiovascular risk factor; chemical association; cohort; contaminated water; cost; cytokine; developmental toxicity; diabetes prevention program; diabetes risk; dietary; ethnic diversity; follow-up; good diet; grasp; human old age (65+); improved; lifestyle factors; lifestyle intervention; middle age; muscle form; muscle strength; novel; post intervention; prospective; prospective test; racial diversity; randomized trial; reduced muscle mass; water quality

PROJECT ABSTRACT Per- and polyfluoroalkyl substances (PFAS) are persistent “forever chemicals” that contaminate water and food and are detectable in almost every individual in the US. Despite a manufacturer’s voluntary phase-out, efforts to limit production have been incomplete, and there is no US federal legislation to regulate PFAS, in part due to a lack of longitudinal data on policy-relevant health outcomes. In particular, high-quality data are limited from studies among older adults, a population rapidly expanding, and in which altered metabolism, decreased clearance, and hormonal changes may heighten PFAS vulnerability. In our highly productive first funding cycle, we reported associations of higher plasma PFAS with greater insulin resistance, cholesterol, abdominal adiposity, and diabetes risk in midlife. These intermediates presage poorer health in older age, including low muscle mass and strength, low bone mass, and cardiovascular disease (CVD). In this competing renewal R01, we propose to expand our prior work to test our hypothesis that higher and more prolonged exposure to PFAS increases risk for poor musculoskeletal and cardiovascular health in older adults. In addition, we will test a secondary hypothesis that builds on our first funding cycle finding that randomization to an exercise and dietary lifestyle intervention mitigated the effect of PFAS on cardiometabolic risk. We hypothesize that we can identify specific lifestyle factors (e.g., healthier, anti-inflammatory diet higher in omega-3 fatty acids and lower in fat) that will attenuate health effects of PFAS, information important for the growing number of communities identified with high PFAS levels due to contamination and industrial use. We will again leverage the unparalleled resources of the Diabetes Prevention Program (DPP)/Diabetes Prevention Program Outcomes Study (DPPOS), a long-term cohort study nested within a randomized trial. We will leverage the PFAS results from our first funding cycle, perform additional assays to address new hypotheses and increase sample size (n=~1400), and benefit from the study’s wealth of high quality, longitudinal data on covariates, CVD, and aging- relevant outcomes carefully collected over 20 years during critical windows of aging. In Aim 1, we will examine prospective associations of PFAS with muscle strength (e.g., hand grip) and DXA measures of muscle and bone mass. In Aim 2, we will examine prospective associations of PFAS with incident adjudicated CVD events. In Aim 3, a secondary aim, we will examine effect modification of PFAS-outcome associations by study arm and specific lifestyle factors. By examining longitudinal PFAS exposure across midlife and older age and by employing sophisticated statistical methods to examine individual PFAS and PFAS mixtures, we will overcome limitations of the few existing studies of PFAS, musculoskeletal health, and CVD. Our findings will inform PFAS legislation and health guidance for exposed individuals, with implications for musculoskeletal health and cardiovascular risk reduction.

项目摘要 全氟烷基物质和多氟烷基物质 (PFAS) 是持久性“永久化学物质”，会污染水和食品 尽管制造商自愿逐步淘汰，但在美国几乎每个人身上都可以检测到。 限制生产的措施尚未完成，并且美国没有联邦立法来监管 PFAS，部分原因是 缺乏与政策相关的健康结果的纵向数据，尤其是高质量数据有限。 针对老年人口的研究，人口迅速膨胀，其中新陈代谢、下降 在我们高效的第一个融资周期中，清除率和荷尔蒙变化可能会加剧 PFAS 的脆弱性。 我们报告了较高的血浆 PFAS 与较高的胰岛素抵抗、胆固醇、腹部 这些中间体预示着老年时的健康状况较差，包括低血压。 肌肉质量和力量、低骨量和心血管疾病 (CVD) 在这个竞争更新 R01 中， 我们建议扩大我们之前的工作来检验我们的假设，即更多和更长时间地接触 PFAS 增加老年人肌肉骨骼和心血管健康状况不佳的风险。 次要假设建立在我们的第一个资助周期的基础上，发现运动和饮食的随机化 生活方式干预减轻了 PFAS 对心脏代谢风险的影响。 特定的生活方式因素（例如，更健康、抗炎饮食、omega-3 脂肪酸含量更高、脂肪含量更低） 这将减轻 PFAS 对健康的影响，这一信息对越来越多的社区很重要 由于污染和工业使用而被确定为高 PFAS 含量，我们将再次利用该产品。 糖尿病预防计划 (DPP)/糖尿病预防计划成果的无与伦比的资源 研究 (DPPOS)，一项随机试验中的长期队列研究，我们将利用 PFAS 结果。 从我们的第一个资助周期开始，进行额外的分析以解决新的假设并增加样本量 (n=~1400)，并受益于该研究丰富的关于协变量、CVD 和衰老的高质量纵向数据 - 在目标 1 中，我们将研究 20 年来在关键衰老窗口期间仔细收集的相关结果。 PFAS 与肌肉力量（例如握力）和 DXA 测量肌肉和肌肉的前瞻性关联 在目标 2 中，我们将研究 PFAS 与已判定的 CVD 事件的前瞻性关联。 在目标 3（次要目标）中，我们将检查研究组对 PFAS 与结果关联的影响修改 通过检查中年和老年时期的 PFAS 暴露情况以及特定的生活方式因素。 采用复杂的统计方法来检查单独的 PFAS 和 PFAS 混合物，我们将克服 现有的少数 PFAS、肌肉骨骼健康和 CVD 研究的局限性，我们的研究结果将为 PFAS 提供信息。 针对暴露个体的立法和健康指导，对肌肉骨骼健康和 降低心血管风险。