Perfluoroalkyl chemicals and the risk of developing clinical and subclinical CVD

描述(由申请人提供)：这项建议的总体目标是研究血清PFC水平与发展为冠心病(CHD)、中风、心血管疾病(CVD)的风险之间的预期相关性，研究人群中动脉粥样硬化和高血压左心室变化的亚临床指标，这是一项多种族的动脉粥样硬化研究(MESA)，这是一项大型、多种族、基于人群的纵向队列研究，参与者包括男性和女性以及美国不同种族/民族，包括白人、黑人、西班牙裔和亚裔美国人，并拥有长达10年的随访数据。我们还将在当代总体人群样本中评估美国人在PFC暴露方面的性别和种族/民族差异，并检查PFC和心血管疾病之间的联系是否因性别或种族/民族而异。我们的研究是一项辅助性研究，建立在NIH资助的家长MESA队列研究的现有优势和资源的基础上，以高效和成本效益的方式解决我们的多重研究目标。在MESA，我们已经有了关于1)主要研究结果的数据，包括：1)主要研究结果，包括根据标准和程序从其他成功的研究，如NHLBI资助的ARIC研究，动脉粥样硬化的亚临床测量包括冠状动脉钙(CAC)，腹主动脉钙(AAC)，颈动脉内膜-中层厚度(CIMT)，低踝臂指数(ABI)，以及高血压左心室参数包括左心室质量，容量和质量/体积比(M/V)2)详细的问卷调查，体检，以及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、超敏C反应蛋白和其他几个标记物。在目前的研究中，我们提出了一项嵌套在MESA队列中的病例队列研究，以新测量血清中全氟辛酸(PFOS)、全氟辛烷磺酸盐(PFOA)、全氟己烷磺酸(PFHxS)、全氟农酸(PFNA)以及其他7种常见的PFC的水平，包括全氟庚酸(PFHpA)、全氟十一酸(PFDA)、全氟十一酸(PFUnA)、全氟碘酸(PFDoA)、全氟辛烷磺胺(PFOSA)、2-(N-乙基-全氟辛磺酰胺)(ET-PFOSA-ACoH)和2-(N-甲基-全氟辛烷磺酸)在所有发生的冠心病(n=523)和中风(n=224)的基线血清中，病例和按种族分层的队列随机抽样n=1000人(白人35%，黑人28%，西班牙裔22%，中国人12%)。这项研究设计将使我们能够使用相同的“对照”组来检验基线血清PFC水平和多种结果之间的纵向关联，并进行有效的横断面比较(例如，按种族-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：缺乏检查PFC暴露与心血管疾病临床和亚临床测量风险之间关系的纵向研究。 与公共健康相关：98%的美国成年人的血液中可检测到全氟烷基化合物(PFC)。我们将研究全血PFC与心血管疾病之间的关系。如果我们发现了关联，这间接地表明减少PFC可能在预防这些疾病方面起到了作用。

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.