IODINE EXCESS, THYROID DYSFUNCTION, CARDIOVASCULAR OUTCOMES, AND MORTALITY AMONG U.S. VETERANS

这项研究计划将检查过量碘暴露（来自碘化的 放射性造影剂）和碘诱导的甲状腺功能障碍、心血管结局和死亡率 在退伍军人中。碘是甲状腺激素产生所需的微量营养素，这反过来又很重要 对于整体代谢（氧消耗的调节和蛋白质、碳水化合物、脂质和 维生素的使用），并对情绪，认知，心脏，肌肉和骨骼有影响。 在美国成年人中，碘的推荐膳食供给量（RDA）为150 mcg/天。暴露于 过量的碘会导致甲状腺激素分泌不足或过多，这是由于两个公认的原因， 甲状腺学中的生理学原理：未能逃避急性Wolff-Chaikoff效应，以及Jod- Basedow现象。放射性碘化造影剂的碘含量可高达 比美国碘的RDA高几千倍。在易感个体中，甲状腺功能障碍 甲状腺功能亢进症或甲状腺功能减退症（hypothyroidism），即使只接触一次富碘物质也会导致。 甲状腺激素对几个心脏参数很重要，包括收缩期收缩，心输出量， 前负荷、冠状动脉血管生成、冠状动脉血管阻力、血管张力和心脏 肥厚甲状腺功能亢进和甲状腺功能减退都与充血性心力衰竭有关 (CHF)与甲状腺功能正常的个体相比， 此外，心房颤动（AF）的风险因素。目前在退伍军人或一般美国人口中， 在冠状动脉血管造影中常规给予碘化造影剂后没有临床指南， 计算机断层扫描、瘘管造影、膀胱造影、静脉造影和其他碘化成像研究。 该建议的假设是过量碘暴露（通过碘化造影剂） 给药）与碘诱导的甲状腺功能障碍、不良临床心血管结局 (AF，CHF，心血管死亡率）和退伍军人人群的总死亡率，其中甲状腺 功能障碍可能增加潜在心脏疾病的风险。具体目标1A和1B将是案例- 对照研究，以确定碘化放射造影剂暴露对血清甲状腺激素的影响。 根据健康记录， VA公司数据仓库数据库。将使用混合效应条件logistic回归模型 估计碘化造影剂暴露在显性和亚临床事件中的OR和95% CI 甲状腺功能亢进症和甲状腺功能减退症、AF和CHF，并针对重要协变量进行校正，包括 相关合并症和血清CRP、IL-1和IL-6浓度。考克斯比例风险回归 模型将用于检查碘暴露对心血管死亡率和全因死亡率的影响。 mortality. SPECIFIC AIM 2将是一个前瞻性入组的甲状腺功能正常受试者队列， 在西洛杉矶退伍军人医疗中心做冠状动脉造影。该项目将确定重要的风险 甲状腺功能正常的退伍军人中发生血清甲状腺功能障碍、AF和CHF的因素 接受了冠状动脉造影的碘负荷。将对受试者进行纵向随访， 甲状腺功能检查、心电图和经胸超声心动图，持续36个月。混合效应 纵向模型将用于描述研究期间血清甲状腺功能试验的变化 期将使用考克斯回归模型评估至发生甲状腺功能障碍、AF、 的CHF。由于退伍军人可能有独特的风险和易感性碘诱导的甲状腺功能障碍，我们 我相信这些研究是必要的和及时的，将是高度相关的和有影响力的，以告知临床 在这个人群中的护理指南。

The research proposal will examine the associations between excess iodine exposure (from iodinated radiologic contrast agents) and iodine-induced thyroid dysfunction, cardiovascular outcomes, and mortality among Veterans. Iodine is a micronutrient required for thyroid hormone production, which in turn is important for overall metabolism (regulation of oxygen consumption and actions of protein, carbohydrate, lipid, and vitamin use) and has effects on mood, cognition, the heart, muscle, and bone. In U.S. adults, the recommended dietary allowance (RDA) of iodine is 150 mcg/day. Exposure to excessive levels of iodine can induce thyroid hormone under- or overproduction due to two well-established physiologic principles in thyroidology: the failure to escape from the acute Wolff-Chaikoff effect, and the Jod- Basedow phenomenon, respectively. The iodine content of radiologic iodinated contrast agents can be up to several thousand-fold higher than the U.S. RDA for iodine. In susceptible individuals, thyroid dysfunction (hyperthyroidism or hypothyroidism) can result even after only a single exposure to an iodine-rich substance. Thyroid hormone is important for several cardiac parameters, including systolic contraction, cardiac output, preload, coronary arteriolar angiogenesis, coronary vascular resistance, vascular tone, and cardiac hypertrophy. Both hyperthyroidism and hypothyroidism have been associated with congestive heart failure (CHF), cardiovascular mortality, and all-cause mortality, compared to euthyroid individuals; hyperthyroidism is additionally a risk factor for atrial fibrillation (AF). Currently in Veterans or the general U.S. population, there are no clinical guidelines following the routine administration of iodinated contrast from coronary angiograms, computed tomography scans, fistulograms, cystograms, venograms, and other iodinated imaging studies. The hypotheses of this proposal are that excess iodine exposure (via iodinated contrast media administration) is associated with iodine-induced thyroid dysfunction, adverse clinical cardiovascular outcomes (AF, CHF, cardiovascular mortality), and overall mortality in the Veteran population, in whom thyroid dysfunction may augment the risks of underlying cardiac disorders. SPECIFIC AIMS 1A and 1B will be case- control studues to determine the effects of iodinated radiographic contrast exposure on serum thyroid dysfunction, AF, CHF, cardiovascular mortality, and all-cause mortality among Veterans from health records in the VA Corporate Data Warehouse database. Mixed effects conditional logistic regression models will be used to estimate the OR and 95% CI of iodinated contrast media exposure on incident overt and subclinical hyperthyroidism and hypothyroidism, AF, and CHF, and adjusted for important covariates which will include relevant comorbidities and serum CRP, IL-1, and IL-6 concentrations. Cox proportional hazard regression models will be used to examine the effect of iodine exposure on cardiovascular mortality and all-cause mortality. SPECIFIC AIM 2 will be a prospectively-enrolled cohort of euthyroid subjects who undergo elective coronary angiography at the West Los Angeles VA Medical Center. This project will determine important risks factors for the development of incident serum thyroid dysfunction, AF, and CHF among euthyroid Veterans who receive an iodine load from coronary angiography. Subjects will be followed longitudinally with serum thyroid function tests, electrocardiograms, and transthoracic echocardiograms for 36 months. Mixed effects longitudinal models will be used to characterize changes in serum thyroid function tests during the study period. Cox regression models will be used to assess predictors of the time to incident thyroid dysfunction, AF, and CHF. As Veterans may have unique risks of and susceptibility to iodine-induced thyroid dysfunction, we believe these studies are needed and timely, and will be highly relevant and impactful toward informing clinical care guidelines in this population.