Environmental heavy metals and risk of ischemic heart disease and stroke in the Brazilian Longitudinal Study of Adult Health (ELSA-Brasil)

项目摘要 环境退化和暴露于重金属（个人往往无法控制）可能会导致 对心血管疾病（CVD）的发展有直接影响，心血管疾病已成为最重要的疾病之一。 全球个人和人口健康的紧迫克星。最近的研究提供了挑衅性的 有证据表明，环境暴露于重金属与糖尿病和高血压风险增加有关， 是心血管疾病的高危因素。相比之下，前瞻性队列研究表明，较高水平的饮食和 血清必需微量金属与较低CVD风险直接相关， 通过减轻有毒金属对心血管系统的影响而具有潜在的益处。但很少 研究直接和全面地调查了多种金属的暴露，特别是它们的联合效应 影响CVD风险（包括中风）。正在进行的巴西成人健康纵向研究（葡萄牙语， “Estudo Longitudinal de Sau 'de do Adulto”，ELSA-巴西），这是南苏丹建立的唯一一项大型前瞻性研究。 美国专门调查心脏代谢健康的风险因素，代表了一个独特的资源研究 多种金属暴露及其与膳食微量元素的相互作用对心血管疾病风险的影响。在 基线时，在圣保罗的ELSA-巴西中心，4，428名无心血管疾病的参与者完成了1）体格检查; 2)临床实验室检查; 3）面对面访谈; 4）收集血液和尿液样本; 5）CT 检查以量化冠状动脉钙（CAC）评分。迄今为止，共有466例CVD事件（约150例卒中） 在10年随访中，在ELSA-巴西队列中对病例进行了裁定。在当前的应用目标中， 为了进行调查，我们将利用这些特殊的资源以及大量的时间和精力投入， ELSA-Brasil研究人员在过去十年中以最具成本效益和及时的方式进行调查， 金属在CVD发展中的作用。具体地，本申请旨在利用这种正在进行的 前瞻性队列研究不仅确定重金属暴露是否会增加CAC评分和CVD 风险，但也确定了必要金属的最佳身体水平，可以减轻有毒金属的CVD风险。 如果存在拮抗作用，并且可以减少有毒金属影响的必需金属的最佳体内水平是 证实，这项工作将导致简单，安全，易于获得，可接受和高度负担得起的营养 这将在全球范围内具有临床和公共卫生意义。

PROJECT SUMMARY Environmental degradation and exposure to heavy metals (over which individuals often have little control) may have a direct impact on cardiovascular diseases (CVD) development, which have become one of the most pressing nemesis for individual- and population-health globally. Recent studies have provided provocative evidence linking environmental exposure to heavy metals to increased risk of diabetes and hypertension, which are strong CVD risk factors. In contrast, prospective cohort studies have shown that higher levels of dietary and serum essential trace metals are directly associated with lower CVD risk and that supplementation of which may have potential benefits by mitigating the effects of toxic metals on the cardiovascular system. However, very few studies have directly and comprehensively investigated exposure to multiple metals particularly their joint effects on affecting CVD risk (including stroke). The ongoing Brazilian Longitudinal Study of Adult Health (in Portuguese, ‘Estudo Longitudinal de Sau´ de do Adulto’, ELSA-Brasil), the only large prospective study established in South America to specifically investigate risk factors for cardiometabolic health, represents a unique resource to study the roles of multiple metal exposures and their interactions with dietary trace elements in affecting CVD risk. At baseline, 4,428 CVD-free participants at the ELSA-Brasil site in Sao Paulo completed 1) physical examinations; 2) clinical laboratory tests; 3) in-person interviews; 4) collections of blood and urine samples; and 5) a CT examination to quantify coronary artery calcium (CAC) score. To date, a total of 466 incident CVD (~150 stroke) cases have been adjudicated in the ELSA-Brasil cohort in the 10-year follow up. ln the current application aims to investigate, we will leverage these exceptional resources and the substantial investment of time and effort by ELSA-Brasil study investigators over the past ten years to investigate, in a most cost-efficient and timely manner, the roles of metals playing in CVD development. Specifically, the current application aims to utilize this ongoing prospective cohort study to not only determine whether heavy metal exposures increase CAC score and CVD risk, but also identify the optimal body levels of essential metals that could mitigate CVD risk from toxic metals. If antagonistic effects exist and optimal body levels of essential metals that could reduce toxic metal impacts are confirmed, this work would lead to simple, safe, readily-available, acceptable and highly-affordable nutritional intervention for CVD prevention that will have both clinical and public health significance worldwide.