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

美国退伍军人的碘过量、甲状腺功能障碍、心血管结果和死亡率

• 批准号: 10417002
• 负责人: Angela Mei-Tin Leung
• 金额: --
• 依托单位: VA GREATER LOS ANGELES HEALTHCARE SYSTEM
• 依托单位国家: 美国
• 财政年份: 2020
• 资助国家: 美国
• 起止时间: 2020-01-01 至 2023-12-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10417002
• 关键词: Acute; Address; Adult; Adverse effects; Angiography; Atrial Fibrillation; Biological; Biological Markers; Blood Vessels; C-reactive protein; Carbohydrates; Cardiac; Cardiac Output; Cardiovascular system; Caring; Clinical; Clinical Research; Cognition; Congestive Heart Failure; Contrast Media; Coronary; Coronary Angiography; Data; Databases; Development; Dose; Echocardiography; Electrocardiogram; Enrollment; Exposure to; Failure; Functional disorder; Guidelines; Health; Heart Diseases; Heart Hypertrophy; High Prevalence; Hyperthyroidism; Hypothyroidism; Incidence; Individual; Inflammatory; Influentials; Intake; Interleukin-1; Interleukin-6; Iodine; Lipids; Literature; Logistic Regressions; Los Angeles; Mediating; Mediation; Mediator of activation protein; Medical; Medical center; Metabolism; Micronutrients; Modeling; Modification; Monitor; Moods; Myocardium; Nested Case-Control Study; Outcome; Oxygen Consumption; Patient Care; Patients; Physiological; Population; Predisposition; Procedures; Production; Proteins; Radiology Specialty; Recommendation; Recommended Dietary Allowance; Recording of previous events; Regulation; Research Proposals; Risk; Risk Estimate; Risk Factors; Sampling; Scanning; Schedule; Serum; Subgroup; System; Testing; Thyroid Diseases; Thyroid Function Tests; Thyroid Gland; Thyroid Hormones; Thyroid Nodule; Time; Vascular resistance; Veterans; Vitamins; X-Ray Computed Tomography; angiogenesis; base; bone; case control; clinical care; clinical development; clinically relevant; cohort; comorbidity; data warehouse; density; epidemiologic data; follow-up; hazard; health record; high risk; imaging study; interest; military veteran; mortality; novel; prospective; radiological imaging; screening guidelines

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.

该研究计划将研究过量碘暴露（来自碘化物）之间的关联。 放射造影剂）和碘引起的甲状腺功能障碍、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 整体代谢（调节耗氧量以及蛋白质、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。 美国成年人的碘推荐膳食摄入量 (RDA) 为 150 微克/天。接触 碘含量过高会导致甲状腺激素分泌不足或过多，原因有两种： 甲状腺学的生理原理：未能摆脱急性沃尔夫-柴科夫效应和乔德- 分别为巴杜现象。放射性碘造影剂的碘含量可高达 比美国建议碘摄入量高出数千倍。在易感人群中，甲状腺功能障碍 即使仅接触一次富含碘的物质，也可能导致（甲状腺功能亢进或甲状腺功能减退）。 甲状腺激素对多种心脏参数很重要，包括收缩期收缩、心输出量、 前负荷、冠状动脉血管生成、冠状血管阻力、血管张力和心脏 肥大。甲状腺功能亢进症和甲状腺功能减退症都与充血性心力衰竭有关 与甲状腺功能正常的个体相比，（CHF）、心血管死亡率和全因死亡率；甲状腺功能亢进症是 另外，它也是心房颤动 (AF) 的危险因素。目前在退伍军人或普通美国人中， 冠状动脉造影中常规使用碘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、静脉造影和其他碘成像研究。 该提案的假设是过量的碘暴露（通过含碘造影剂） 给药）与碘引起的甲状腺功能障碍、不良临床心血管结局有关 （房颤、慢性心力衰竭、心血管死亡率）以及退伍军人群体的总体死亡率，其中甲状腺疾病 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- 确定碘放射造影剂暴露对血清甲状腺影响的对照研究 退伍军人健康记录中的功能障碍、房颤、心力衰竭、心血管死亡率和全因死亡率 VA 公司数据仓库数据库。将使用混合效应条件逻辑回归模型 估计碘造影剂暴露对事件明显和亚临床的 OR 和 95% CI 甲状腺功能亢进症和甲状腺功能减退症、房颤和慢性心力衰竭，并针对重要的协变量进行了调整，其中包括 相关合并症和血清 CRP、IL-1 和 IL-6 浓度。 Cox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 死亡。具体目标 2 将是一个前瞻性招募的甲状腺功能正常受试者队列，这些受试者接受选择性 在西洛杉矶退伍军人医疗中心进行冠状动脉造影。该项目将确定重大风险 甲状腺功能正常的退伍军人中发生血清甲状腺功能障碍、房颤和慢性心力衰竭的因素 通过冠状动脉造影接受碘负荷的人。将用血清对受试者进行纵向跟踪 甲状腺功能检查、心电图和经胸超声心动图 36 个月。混合效应 纵向模型将用于表征研究期间血清甲状腺功能测试的变化 时期。 Cox 回归模型将用于评估甲状腺功能障碍、房颤、 和瑞士法郎。由于退伍军人可能具有碘引起的甲状腺功能障碍的独特风险和易感性，我们 相信这些研究是必要且及时的，并且对于为临床提供信息具有高度相关性和影响力 该人群的护理指南。