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 1 A 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.
This proposal addresses the potentially adverse effects of a common medical exposure, excess iodine (via iodinated contrast agents), on thyroid function, cardiovascular outcomes, and mortality in the U.S. Veteran population. These risks are particularly relevant among older Veterans, in whom the adverse health effects of iodine-induced hyperthyroidism and hypothyroidism may further contribute to the high prevalence of underlying cardiac disorders in this population. As there are currently no guidelines for the management of at-risk Veterans receiving iodinated imaging studies, we believe that the findings will be highly clinically relevant and impactful. We expect that these data will be directly influential toward formulating clinical recommendations for the screening and follow up monitoring of Veterans who routinely undergo iodinated radiologic contrast procedures.