Perfluoroalkyl chemicals and the risk of developing clinical and subclinical CVD

描述（由申请人提供）：本研究的总体目标是在多民族动脉粥样硬化研究（MESA）的参与者中研究血清pfc水平与冠心病（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改变风险之间的前瞻性关联。纵向队列研究，参与者包括男性和女性，以及美国的各种种族/民族群体，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。我们还将评估当代普通人群样本中美国人PFC暴露的性别和种族/民族差异，并检查PFC与心血管疾病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，建立在美国国立卫生研究院资助的现有优势和资源的基础上，父母MESA队列研究以有效和经济的方式解决我们的多重研究目标。在MESA中，我们已经有了1)主要研究结果的数据，包括冠心病、中风和心血管疾病的发生率，这些数据是根据其他成功研究（如nhlbi资助的ARIC研究）的标准标准和程序进行验证的，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-内侧厚度（CIMT）、低踝-肱指数（ABI）和高血压左心室参数包括左心室质量；2)详细的问卷调查、体格检查和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反应蛋白和其他一些标志物。在本研究中，我们提出了一项在MESA队列中嵌套的病例队列研究，以新测量全氟辛酸（PFOS）、全氟辛烷磺酸（PFOA）、全氟己烷磺酸（PFHxS）、全氟十一酸（PFNA）和其他7种常见的全氟化合物的血清水平，包括全氟庚酸（PFHpA）、全氟癸酸（PFDA）、全氟癸酸（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）醋酸（Et-PFOSA-AcOH）和2-（n -甲基-全氟辛烷磺酰胺）醋酸（Me- PFOSA-AcOH），在所有事件冠心病（n=523）和中风（n=224）的基线血清中，病例和种族分层队列随机样本n=1000参与者（35%白人，28%黑人，22%西班牙裔和12%中国人）。本研究设计将允许我们检查基线血清PFC水平与使用相同“对照”组的多个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：缺乏对PFC暴露与CVD临床和亚临床测量风险之间关系的纵向研究。

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.