Autoimmune thyroid disease and inflammatory diseases: association with subclinical Atherosclerosis and general and cardiovascular mortality in ELSA-Brasil

Abstract

The main objective of the Longitudinal Study of Adult Health (ELSA-Brasil) is to understand the incidence of Cardiovascular Diseases (CVD) and Diabetes, and the associated risk and protection factors. Although the study includes all classical risk factors for CVD, it also studies the less explored non-classical risk factors in the literature. Among the non-classical risk factors for CVD, the thyroid function was included in a previous thematic project. The new thematic project will study the relationship between chronic inflammatory diseases, thyroid function and cardiovascular disease. The main objective of this postdoctoral project is to evaluate the effect of changes in thyroid function on inflammatory diseases and its influence in the determination of subclinical Atherosclerosis, measured by calcium score (CAC) and carotid intima-media thickness, and fatal and non-fatal cardiovascular events, in addition to all-cause mortality. Other objectives are: 1. evaluate the association of thyroid disease and inflammatory diseases in the long-term survival of patients with inflammatory diseases and thyroid dysfunction; 2. describe the association of thyroid function changes in each of the inflammatory diseases in the project: Rheumatoid Arthritis, disseminated Lupus Erythematosus, Sjögren's Syndrome, Celiac Disease, Vasculitis and Psoriasis; 3. assess the incidence of changes in thyroid function in patients diagnosed with each of the inflammatory diseases, using baseline (2008-2010), 4-year (2012-2014) and 9-year (2017-2019) follow-up data; 4. assess the incidence of inflammatory disease in participants with positive antithyroid peroxidase antibodies and with subclinical thyroid disease at baseline to follow-up. Participants at high risk for inflammatory diseases will be identified using data from questionnaires, annual calls to investigate hospitalizations and cardiovascular events, and the use of medications for the specific treatment of each inflammatory disease and thyroid function data obtained from the waves 1, 2, and 3. The study randomly selected a sample of 1500 participants that are representative of the total study participants (N=15105). This will allow for lower costs associated with greater analysis power. To achieve these goals, the study will use a case-cohort design (in which the comparison group will be chosen from the random sample of the cohort that saved the most biological samples at baseline precisely because of greater future use); and nested case-control design, in which age- and sex-matched controls will be chosen from participants without inflammatory or thyroid disease depending on what is most effective for each analysis. In addition, cross-sectional analyzes may be used for specific purposes. The results will be presented in the form of Poisson regressions in the case of exposures evaluated in data collection waves where the interval between measurements is very similar or by the Cox proportional hazards model when dealing with cardiovascular events or all-cause and cardiovascular mortality. Relative Risk (RR) will be presented without adjustment, adjusted for sociodemographic factors and multivariate adjustment by confounding factors. Survival analysis with Kaplan-Meier curves compared by the log-rank test will be used, in addition with the application of machine learning models in order to identify sociodemographic and clinical variables that are predictive of the prognosis of participants with inflammatory diseases and thyroid dysfunction. (AU)