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: 9774865
• 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/9774865
• 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; Diagnostic radiologic examination; 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; mortality; novel; prospective; 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.

研究建议将检查过多的碘暴露之间的关联（来自碘 放射对比剂）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，这反过来很重要 用于总体新陈代谢（调节氧气消耗和蛋白质的作用，碳水化合物，脂质和 使用维生素），并对情绪，认知，心脏，肌肉和骨骼产生影响。 在美国成年人中，碘的建议饮食津贴（RDA）为150 mcg/天。接触 碘水平过多会诱导甲状腺激素不足或由于两个公认的 甲状腺学的生理原理：未能摆脱急性Wolff-Chaikoff效应和Jod- 基础现象分别。放射性碘化对比剂的碘含量可以达到 碘的碘比美国RDA高了几千倍。在易感人群中，甲状腺功能障碍 （甲状腺功能亢进或甲状腺功能减退症）即使仅一次暴露于富含碘的物质后也会产生。 甲状腺激素对于多种心脏参数很重要，包括收缩收缩，心输出量， 预加载，冠状动脉血管生成，冠状动脉血管抗性，血管张力和心脏 肥大。甲状腺功能亢进和甲状腺功能减退症都与充血性心力衰竭有关 （CHF），与甲状腺功能低下的个体相比，（CHF），心血管死亡率和全因死亡率；甲状腺功能亢进是 另外，房颤的危险因素（AF）。目前在退伍军人或美国一般人口中 在常规施用冠状动脉造影的碘对比度之后，没有临床指南， 计算机断层扫描，瘘管图，囊肿图，定性图和其他碘化成像研究。 该提案的假设是过多的碘暴露（通过碘对比介质 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 （AF，CHF，心血管死亡率）以及在甲状腺中的资深人口中的总体死亡率 功能障碍可能会增加心脏疾病的潜在风险。具体目的1a和1b将是案例 - 控制研究以确定碘化射线照相对比暴露对血清甲状腺的影响 功能障碍，AF，CHF，心血管死亡率和退伍军人的全因死亡率 VA公司数据仓库数据库。将使用混合效果条件逻辑回归模型 估计碘化对比媒体的OR和95％CI在公开和亚临界事件上暴露于事件 甲状腺功能亢进和甲状腺功能减退症，AF和CHF，并针对重要的协变量进行调整，其中包括 相关合并症和血清CRP，IL-1和IL-6浓度。考克斯比例危害回归 模型将用于检查碘暴露对心血管死亡率和全因的影响 死亡。特定的目标2将是前瞻性注射的座龙理主体，他们接受选修课 西洛杉矶VA医疗中心的冠状动脉血管造影。该项目将确定重要风险 甲状腺退伍军人中甲状腺功能障碍，AF和CHF的发育因素 从冠状动脉造影中获得碘负荷。受试者将用血清纵向遵循 甲状腺功能测试，心电图和经胸膜超声心动图36个月。混合效果 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的时间的预测指标，AF， 和瑞士法郎。由于退伍军人可能有对碘引起的甲状腺功能障碍的独特风险和敏感性，我们 认为这些研究是需要和及时的，并且将对临床有很高的相关性和影响力 该人群的护理指南。