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

该研究提案将研究过量碘暴露(从加碘)之间的关系 放射学造影剂)和碘引起的甲状腺功能障碍、心血管结果和死亡率 在退伍军人中。碘是一种微量营养素，是产生甲状腺激素所必需的，这反过来又很重要。 对于整体新陈代谢(调节氧耗和蛋白质、碳水化合物、脂肪和 维生素的使用)，对情绪、认知、心脏、肌肉和骨骼有影响。 在美国成年人中，推荐的膳食碘摄入量(RDA)为150微克/天。暴露于 过量的碘可导致甲状腺激素分泌不足或过剩，这是由于两种公认的 甲状腺生理学原理：未能逃脱急性Wolff-Chaikoff效应，以及Jod-Chaikoff 基影现象。放射性碘对比剂的碘含量可达 碘含量比美国的RDA高出几千倍。在易感人群中，甲状腺功能障碍 即使只接触了一种富碘物质，也可能导致甲亢(甲亢或甲减)。 甲状腺激素对一些心脏参数很重要，包括收缩、心输出量、 前负荷、冠状动脉小动脉血管生成、冠状动脉血管阻力、血管张力和心脏 肥大。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)、心血管死亡率和全因死亡率，与甲状腺功能正常的人相比；甲亢是 此外，房颤(房颤)的危险因素。目前在退伍军人或普通美国人中， 在常规进行冠状动脉造影术的碘化造影剂后，没有临床指南， 计算机断层扫描、瘘管造影术、膀胱造影术、静脉造影术和其他碘化成像研究。 这项提议的假设是过量的碘暴露(通过碘化造影剂 )与碘引起的甲状腺功能障碍、不良的临床心血管后果有关 (房颤、心力衰竭、心血管死亡率)，以及退伍军人人群的总体死亡率，其中甲状腺 功能障碍可能会增加潜在心脏疾病的风险。具体目标1A和1B将是案例- 放射性造影剂碘暴露对血清甲状腺影响的对照研究 年健康记录中退伍军人的功能障碍、房颤、充血性心力衰竭、心血管死亡率和全因死亡率 退伍军人事务部数据仓库数据库。将使用混合效应条件Logistic回归模型 显性和亚临床事件中碘化造影剂暴露的OR值和95%可信区间的估计 甲亢和甲减、房颤和充血性心力衰竭，并对重要的协变量进行了调整，其中包括 相关合并症及血清CRP、IL-1、IL-6浓度。Cox比例风险回归 模型将被用来检验碘暴露对心血管死亡率和所有原因的影响 死亡率。特定的AIM 2将是一组预期登记的甲状腺功能正常受试者，这些受试者将接受选择性治疗 西洛杉矶退伍军人医疗中心的冠状动脉造影术。这个项目将决定重大风险 甲状腺功能正常退伍军人中发生血清甲状腺功能障碍、房颤和心力衰竭的因素 接受冠状动脉造影术的碘负荷。受试者将被纵向追踪血清 甲状腺功能检查、心电图和经胸超声心动图检查36个月。混合效果 纵向模型将被用来描述研究期间血清甲状腺功能测试的变化。 句号。COX回归模型将用于评估甲状腺功能障碍、房颤、 和瑞士法郎。由于退伍军人可能有独特的碘致甲状腺功能障碍的风险和易感性，我们 相信这些研究是必要的和及时的，并将高度相关和影响告知临床 这一人群的护理指南。

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.