Abstract

Introduction: An auto-immune process strongly determines subclinical thyroid disorders generating a high grade of inflammation. However, the evidence from epidemiologic studies of the association between subclinical thyroid disorders with coronary heart disease has not been reported as mediated or moderated by a traditional inflammatory marker such as the high-sensitivity C-Reactive Protein. Recently, another inflammatory marker that reflects protein glycosylation in acute-phase reactant proteins - GlycA was associated with coronary heart disease events. Hypothesis: The association of GlycA, a more comprehensive biomarker of inflammation, with subclinical hypothyroidism, and subclinical hyperthyroidism, should explain some mechanisms of the association subclinical thyroid disorders and coronary heart disease. Methods: We tested this hypothesis among 5060 men and women aged 35 to 74 years-old enrolled in the Brazilian Longitudinal Study of Adult Health (ELSA-Brasil) at baseline. Subclinical thyroid disorders were defined as thyroid-stimulating hormone (TSH) >4 IU/ml (subclinical hypothyroidism) and TSH <0.4 IU/ml (subclinical hyperthyroidism) with normal free-thyroxine levels. The variable of exposure was GlycA measured in serum by proton nuclear magnetic resonance (1H NMR) spectroscopy at (LabCorp, Raleigh, NC). We excluded participants who reported previous cardiovascular disease, use of lipid-lowering agents or drugs that interfere with thyroid function. The cross-sectional relationship between GlycA and subclinical hyperthyroidism and subclinical thyroid was evaluated separately by linear regression models using the category of the subjects with euthyroidism as the reference. Both crude unadjusted and adjusted (age, sex, race, education, smoking, alcohol use, physical activity body-mass index, hypertension, diabetes, smoking, alcohol use, and physical activity data are presented Results: After exclusions, we analyzed 47 individuals with subclinical hyperthyroidism (mean age 53.1 (±9.4) years; 61.7% women), 258 with subclinical hypothyroidism (mean age 52.3 (±8.9); 58.1% of women) and 3,642 participants with normal thyroid function (mean age: 50.1 (±8.6); 52% of women). Crude linear regression models showed no significant association between GlycA and subclinical hyperthyroidism (Beta-coefficient [B], 15.77; P = 0.10) or subclinical hypothyroidism (B, 3.60; P=0.39). Results remained nonsignificant after multivariate adjustment for subclinical hyperthyroidism (B, 12.96; P=0.15) and subclinical hypothyroidism (B, 0.44; (P=0.91). Conclusions: There is no association between subclinical thyroid disorders and GlycA. Other presumptive inflammatory pathways should be contemplated in further studies addressing the link between subclinical thyroid disorders and coronary heart disease.

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