Mercury, Arsenic, and Carotid Atherosclerosis

描述（由申请人提供）：背景：长期暴露于低浓度汞或砷的心血管后果尚不清楚。在一些（但不是全部）研究中，汞与心血管风险有关，其与动脉粥样硬化进展的关系尚不确定。高砷暴露是血管疾病的确定原因，但低浓度的影响，更典型的暴露在美国人口中，基本上是未知的。由于鱼类摄入是一般人群甲基汞暴露的主要来源，也是有机砷化合物的主要来源，这些化合物的影响可能与鱼类中具有心脏保护作用的n-3脂肪酸相混淆。目的：在1989- 1999年随访的一组个体中，研究汞和砷暴露与颈动脉内膜-中膜厚度（IMT）（亚临床动脉粥样硬化的标志）的关系。假设：脚趾甲中汞或砷的暴露与基线颈动脉IMT及其10年随访进展有关。这些关联独立于已知的冠状动脉危险因素和血浆磷脂长链n-3脂肪酸（鱼油摄入量的生物标志物）。背景：2085名年龄在45岁及以上的男性和女性，马里兰州华盛顿县居民，同时参加CLUE II队列（收集脚趾甲）和ARIC或CHS队列（测量IMT和心血管危险因素）。设计和测量：前瞻性纵向研究基线汞和砷水平与颈动脉IMT进展的关系超过10年。用仪器中子活化法测定趾甲汞和砷，用毛细管气相色谱法测定血浆n-3脂肪酸。颈动脉IMT已通过b超测量。统计分析计划：将使用纵向数据分析方法来模拟IMT的进展。重要的统计问题将是控制重复IMT测量中的测量误差，控制心血管危险因素对IMT进展的影响，以及评估汞或砷和n-3脂肪酸的联合效应。相关性：确认汞或砷在动脉粥样硬化中的作用可能会影响目前的环境和饮食公共卫生建议。

DESCRIPTION (provided by applicant): Background: The cardiovascular consequences of long-term exposure to low concentrations of mercury or arsenic are insufficiently understood. Mercury has been linked to cardiovascular risk in some, but not all, studies, and its association with the progression of atherosclerosis is uncertain. High arsenic exposure is an established cause of vascular disease, but the effect of low concentrations, more typical of the exposure of the US population, is essentially unknown. Since fish intake is the main source of methylmercury exposure in the general population, and a major source of organic arsenic compounds, the effects of these compounds may be confounded by the cardioprotective n-3 fatty acids in fish. Objective: To investigate the association of mercury and arsenic exposure with carotid intima-media thickness (IMT), a marker of subclinical atherosclerosis, in a cohort of individuals followed during 1989-99. Hypothesis: Exposure to mercury or arsenic, as determined in toenails, are associated with baseline carotid IMT and with its progression over 10 years follow-up. These associations are independent of established coronary risk factors and of plasma phospholipid long-chain n-3 fatty acids, a biomarker of fish oil intake. Setting: Cohort of 2,085 men and women, aged 45 years and older and residents in Washington County, MD, who participated simultaneously in the CLUE II cohort (that collected toenail clippings) and either in ARIC or in the CHS cohorts (that measured IMT and cardiovascular risk factors). Design and measurements: Prospective longitudinal study of the association of baseline mercury and arsenic levels with carotid IMT progression over 10 years. Toenail mercury and arsenic will be measured by instrumental neutron activation analysis, and plasma n-3 fatty acids by capillary gas chromatography. Carotid IMT has already been measured by B-mode ultrasound. Statistical analysis plan: Longitudinal data analysis methods will be used to model IMT progression. Important statistical issues will be the control of measurement error in repeated IMT measurements, the control of the effect of cardiovascular risk factors on IMT progression, and the evaluation of the joint effect of mercury or arsenic and n-3 fatty acids. Relevance: Confirmation of the role of mercury or arsenic on atherogenesis could impact current environmental and dietary public health recommendations.