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 每种和多氟烷基物质（PFA）是持续的“永远的化学物质”，污染了水和食物 并且在美国几乎每个人都可以检测到。尽管制造商自愿淘汰，但努力 限制生产是不完整的，没有美国联邦立法来规范PFA，部分原因是 缺乏有关与政策相关的健康结果的纵向数据。特别是，高质量数据受到限制 老年人的研究，人口迅速扩展，新陈代谢改变了 清除和马匹变化可能会增加PFA的脆弱性。在我们高效的第一筹周期中， 我们报道了较高的血浆PFA与更大的胰岛素耐药性，胆固醇，腹部的关联 肥胖和中年糖尿病风险。这些中间体预示年龄较大的健康状况较差，包括低 肌肉质量和力量，低骨量和心血管疾病（CVD）。在这个竞争的更新R01中， 我们建议扩大我们的先前工作，以检验我们的假设，即较高和更长的PFA暴露 老年人增加了肌肉骨骼和心血管健康不良的风险。此外，我们将测试 次要假设是基于我们的第一个融资周期，发现随机化的运动和饮食 生活方式干预减轻了PFA对心脏代谢风险的影响。我们假设我们可以识别 特定的生活方式因素（例如，欧米茄3脂肪酸更健康，抗炎饮食较高，脂肪较低） 这将减轻PFA的健康影响，信息对越来越多的社区重要 由于污染和工业用途而被确定为高PFA水平。我们将再次利用 糖尿病预防计划（DPP）/糖尿病预防计划的无与伦比资源 研究（DPPO），一项嵌套在随机试验中的长期队列研究。我们将利用PFAS结果 从我们的第一个资金周期开始，请执行其他测定法以解决新的假设并增加样本量 （n = 〜1400），并受益于该研究的高质量丰富，关于协变量，CVD和衰老的纵向数据 在关键的衰老窗口期间，经过20年的仔细收集的相关结果。在AIM 1中，我们将检查 PFA与肌肉力量（例如，手握）和DXA肌肉和DXA的预期关联 骨骼质量。在AIM 2中，我们将检查PFA与事件调整后的CVD事件的潜在关联。 在AIM 3中，一个次要目标，我们将通过研究部门检查PFAS结果关联的效果修改 和特定的生活方式因素。通过检查中年和老年的纵向PFA暴露以及 采用复杂的统计方法检查单个PFA和PFA混合物，我们将克服 PFA，肌肉骨骼健康和CVD的少数现有研究的局限性。我们的发现将通知PFA 对暴露个人的立法和健康指导，对肌肉骨骼健康有影响 心血管风险降低。