Perfluoroalkyl chemicals and the risk of developing clinical and subclinical CVD

描述（申请人提供）：本提案的总体目的是研究多种族动脉粥样硬化研究（MESA）参与者血清PFC水平与发生冠心病（CHD）、中风、心血管疾病（CVD）、动脉粥样硬化亚临床指标和高血压左心室变化风险之间的前瞻性相关性，MESA是一项大型、多种族、基于人群的研究，一项纵向队列研究，参与者代表美国的男性和女性以及各种种族/族裔群体，包括白人、黑人、西班牙裔和亚裔美国人，并有长达10年的随访数据。我们还将评估当代一般人群样本中美国人PFC暴露的性别和种族/民族差异，并检查PFC与CVD之间的关联是否因性别或种族/民族而异。我们的研究是一项辅助研究，它建立在NIH资助的父梅萨队列研究的现有优势和资源基础上，以高效和具有成本效益的方式解决我们的多个研究目标。在梅萨中，我们已经有了以下数据：1）主要研究结果，包括根据其他成功研究（如NHLBI资助的ARIC研究）改编的标准标准和程序验证的CHD、卒中和CVD事件，动脉粥样硬化的亚临床指标，包括冠状动脉钙（CAC）、腹主动脉钙（AAC）、颈动脉内膜中层厚度（CIMT）、低踝臂指数（ABI），和高血压左心室参数，包括左心室质量、体积和质量与体积（M/V）的比值2）详细的问卷调查、体格检查和关于潜在混杂因素的实验室数据，如吸烟、饮酒、体重指数（BMI）、血压、空腹血糖、血脂、高敏C反应蛋白和若干其他标志物。在目前的研究中，我们提出了一个嵌套在梅萨队列中的病例队列研究，以新测量全氟辛酸（PFOS）、全氟辛烷磺酸（PFOA）、全氟己烷磺酸（PFHxS）、全氟壬酸（PFNA）和其他7种常见检测到的PFC的血清水平，包括全氟庚酸（PFHpA）、全氟癸酸（PFDA）、全氟十一烷酸（PFUnA）、全氟十二烷酸（PFDoA）、全氟辛烷磺酰胺（PFOSA），2-N-乙基全氟辛烷磺酰胺基乙酸（Et-PFOSA-AcOH）和2-（N-甲基-全氟辛烷磺酰胺）乙酸（Me-PFOSA-AcOH），在所有CHD（n=523）和卒中（n=224）事件的基线血清中，病例和n=1000名参与者的种族分层队列随机样本（35%白色，28%黑人，22%西班牙裔和12%中国人）。这项研究设计将使我们能够使用相同的“对照”组检查基线血清PFC水平与多种结局之间的纵向关联，并进行有效的横断面比较（例如，按人种-种族划分的血清PFC水平）。我们的研究意义重大，因为它解决了该领域的一个关键障碍：缺乏纵向研究，探讨PFC暴露与CVD临床和亚临床措施风险之间的关系。 公共卫生相关性：全氟烷基化学品（PFC）在超过98%的美国成年人的血液中可检测到。我们将研究血液PFCs与心血管疾病之间的关系。如果我们发现了这种关联，它间接表明减少PFCs可能在预防这些疾病方面发挥作用。

DESCRIPTION (provided by applicant): The overall aim of this proposal is to study the prospective association between serum levels of PFCs and the risk of developing coronary heart disease (CHD), stroke, cardiovascular disease (CVD), subclinical measures of atherosclerosis and hypertensive left ventricular changes among the participants of the of the Multi-ethnic Study of Atherosclerosis (MESA), a large, multiethnic, population-based, longitudinal cohort study with participants representing both men and women and the various racial/ethnic groups in the US, including whites, blacks, Hispanics, and Asian Americans and with up to 10 years of follow-up data. We will also evaluate gender and racial/ethnic differences in PFC exposure among Americans in this contemporary general population sample and examine if the association between PFCs and CVD vary by gender, or race/ethnicity. Ours is an ancillary study that builds upon the existing strengths and resources of the NIH-funded, parent MESA cohort study to address our multiple study aims in an efficient and cost-effective manner. In the MESA, we already have data on 1) the main study outcomes, including incident CHD, stroke, and CVD validated following standard criteria and procedures adapted from other successful studies such as the NHLBI-funded ARIC study, subclinical measures of atherosclerosis including coronary artery calcium (CAC), abdominal aortic calcium (AAC), carotid intimal-medial thickness (CIMT), low ankle-brachial index (ABI), and hypertensive left ventricular parameters including left ventricular mass, volume and mass to volume (M/V) ratio 2) detailed questionnaire, physical examination, and laboratory data on potential confounding factors such as smoking, alcohol intake, body mass index (BMI), blood pressure, fasting glucose, serum lipids, high sensitivity C-reactive protein, and several other markers. In the current study, we propose a case-cohort study nested within the MESA cohort to newly measure serum levels of perfluorooctanoic acid (PFOS), perfluorooctane sulfonate (PFOA), perfluorohexane sulfonate (PFHxS), perfluorononanoic acid (PFNA), and 7 other commonly detected PFCs, including perfluoroheptanoic acid (PFHpA), perfluorodecanoic acid (PFDA), perfluoroundecanoic acid (PFUnA), perfluorododecanoic acid (PFDoA), perflurooctane sulfanomide (PFOSA), 2-(N-ethyl-perflurooctane sulfonamido) acetic acid (Et-PFOSA-AcOH), and 2-(N-methyl-perflurooctane sulfonamide) acetic acid (Me- PFOSA-AcOH), in the baseline serum of all incident CHD (n=523), and stroke (n=224), cases and a race- stratified cohort random sample of n=1000 participants (35% white, 28% black, 22% Hispanic and 12% Chinese). This study design will allow us to examine the longitudinal associations between baseline serum PFC levels and multiple outcomes using the same "control" group as well as to make valid cross-sectional comparisons (e.g. serum PFC levels by race-ethnicity). Our study is significant because it addresses a critical barrier in the field: the lack of longitudinal studies examining the relationship between PFC exposure and the risk of clinical and subclinical measures of CVD. PUBLIC HEALTH RELEVANCE: Perfluroalkyl chemicals (PFC) are detectable in the blood of >98% of US adults. We will study the association between blood PFCs and cardiovascular disease. If we find an association, it indirectly suggests that reducing PFCs may have a role in preventing these diseases.