ABC | Volume 112, Nº6, June 2019

759 Original Article Rajão et al Subclinical thyroid dysfunction and arrhythmias Arq Bras Cardiol. 2019; 112(6):758-766 SCHypoTh and cardiac arrhythmias. Weak evidence, mostly in the form of case reports, suggests that SCHypoTh can lead to bradyarrhythmias, including sinus bradycardia and atrioventricular blocks, atrial arrhythmias, prolonged QTi, and severe ventricular arrhythmias. 19,20 Most of the related studies have focused on older adults. The aim of the present study was to investigate whether STD was associated with cardiac arrhythmias in a cohort of middle-aged and older adults in the baseline of the Longitudinal Study of Adult Health (ELSA–Brasil), the largest cohort of a Brazilian adult population to date. Methods Study population The present investigation is a subproject of ELSA–Brasil, in which the baseline cohort comprised 15,105 civil servants aged 35–74 years from six Brazilian cities, who were enrolled between August 2008 and December 2010. The majority of participants were young adults (78% aged < 60 years), with 54% female. The ELSA–Brasil protocol conforms to the ethical guidelines of the 1975 Declaration of Helsinki and was approved by the research ethics committees at all six centers. All participants provided a written informed consent. 21 Participants were excluded if they were using any drugs that could interfere with TSH or free thyroxine (FT4) laboratory assays (levodopa, carbidopa, metoclopramide, haloperidol, valproic acid, propranolol, heparin, prazosin, rifampicin, carbamazepine, primidone, phenytoin, and furosemide). 22 Participants with serum TSH and FT4 alterations indicating clinical thyroid dysfunction, including those with normal serum FT4 levels and TSH > 20 μU/mL, or if they were using levothyroxine or antithyroid agents (thiamazole or propylthiouracil) were excluded. All participants who did not present exclusion criteria were included. Study protocol Standardized interviews were conducted with participants at their workplaces and at the research center. Clinical examinations and laboratory tests were performed according to standardized protocols developed for the study. Participants were instructed to present all medical prescriptions and medications they had used in the preceding month. 21 Skin color was self-reported. Anthropometric parameters, including height and weight, were measured using standardized techniques and materials. Resting heart rate (HR) and blood pressure (BP) were measured three times, with the mean values for the second and third measurements considered for analysis. 23 Standard 12-lead resting electrocardiograms (ECGs) were recorded and analyzed according to theMinnesota code criteria 24 using a digital device (Atria 6100, Burdick, Cardiac Science Corporation, Bothel, WA, USA) with automated readings of HR; duration, range, and axes of P, QRS, and T waves; QT intervals, and QTc (Bazett’s correction). The ECG tracings were analyzed at the ECG Reading Center of ELSA‑Brasil in Minas Gerais. In total, 11,795 ECGs were available for analysis. Blood samples were collected after an overnight fast. Participants were instructed to reschedule their appointment at the research center if they had a fever or developed any acute disease symptoms. All laboratory analyses were centralized in a single research center (University of São Paulo). 25 The quality and management of data collection and storage were ensured through training sessions, certifications, and renewal of certifications of the interviewers and technicians in charge of the clinical examinations and laboratory tests of the study protocol. 21 The methods, reagents, and equipment used in the assays conducted at the central laboratory were as follows: 1) TSH: immunoenzymatic bead-based technique, Siemens reagent L2KTS2, analytical sensitivity of 0.004 mU/L, conducted for all participants; 2) FT4: immunoenzymatic bead-based technique, analytical sensitivity of 0.3 ng/dL, only for those patients with abnormal TSH levels (both the TSH and FT4 assays were performed using a Siemens IMMULITE 2000 Immunoassay System ® – Siemens Healthcare Diagnostics, Deerfield, IL, USA); 3) Total cholesterol: enzymatic colorimetric method, Siemens reagent (code 99301390); 4) Triglycerides: enzymatic colorimetric method with glycerol phosphate peroxidase according to Trinder; 5) HDL cholesterol: homogeneous enzymatic colorimetric method without precipitation; 6) LDL cholesterol: Friedewald equation for triglycerides < 400 mg/dL; otherwise, measured directly using a homogeneous enzymatic colorimetric assay without precipitation; 7) Serum blood sugar: enzymatic hexokinase method; 8) Hemoglobin A1C: high-pressure liquid chromatography (HPLC), Bio-Rad D-10 Hemoglobin A1c Program (Bio-Rad Laboratories, Inc., Hercules, CA, USA). All biochemical tests were analyzed using the ADVIA 1200 Chemistry System (Siemens Healthcare Diagnostics, Deerfield, IL, USA); and 9) Chagas disease serology: ELISA method using a solid-phase microplate (CHAGATEST, Wiener Laboratorios S.A.I.C., Rosario, Argentina). 25 Definition of cases Participants were allocated into one of three groups: euthyroidism (TSH= 0.4–4.0 μU/mL), SCHypoTh (TSH> 4.0 and ≤ 20 μU/mL with FT4 = 0.8–1.9 ng/dL), and SCHyperTh (TSH < 0.4 μU/mL and FT4 = 0.8–1.9 ng/dL). = Abnormalities on ECG were categorized into rhythm disorders (AF and flutter: Minnesota codes 8.3.1, 8.3.2, 8.3.3, 8.3.4; supraventricular extrasystoles (SVES): 8.1.1; ventricular extrasystoles (VES): 8.1.2; persistent supraventricular rhythm: 8.4.1) and blocks or conduction disorders (complete right and left bundle branch block: 7.2.1, 7.2.2, 7.1.1, 7.1.2; incomplete right and left bundle branch block: 7.3 and 7.6; nonspecific intraventricular block: 7.4, and atrioventricular blocks: 6.1; 6,2,1; 6.2.2; 6.2.3; 6.3). The presence of long QTi (> 115%) and low QRS complex voltage (9.1) was also investigated. 24, 26 Abnormalities on heart ratemeasured by clinical examination were classified as bradycardia (HR < 60 or < 50 beats per minute [bpm]) and tachycardia (HR > 100 or >110 bpm). Diabetes mellitus was defined by abnormal laboratory findings according to American Diabetes Association criteria (fasting blood glucose ≥ 126 mg/dL, blood glucose levels two