ABC | Volume 112, Nº6, June 2019

763 Original Article Rajão et al Subclinical thyroid dysfunction and arrhythmias Arq Bras Cardiol. 2019; 112(6):758-766 Table 5 – Comparison between Previous Studies and ELSA-Brasil Results, 2008-2010 Consistent Findings Cross-Sectional Analysis: Study/Author Population Design/enrollment TSH level (µU/mL) Ascertainment of Events Results Cappola 2006 (Cardiovascular Health Study, USA) 3,233 elderly people (mean age 72.7 years) Population-based prospective cohort study 0.45 – 4.5 ECG No difference in AF prevalence between SCHyperTh and euthyroidism groups (8.5% vs. 5.2%. p > 0.05) Longitudinal analysis: Nanchen 2012 (PROSPER Trial, Netherlands, Scotland and Ireland) 5,316 elderly people (mean age 75 years) prospective cohort study; outpatients of centers study 0.45 - 4.5 ECG No difference in AF incidence between SCHypoTh, SCHyperTh and euthyroidism groups in 3.5 years follow-up DISCORDANT FINDINGS Cross-sectional analysis Auer 2001 (Austria) 23,838 patients (median 67.9 years old) Cross-sectional Patients admitted in a hospital 0.4 – 4.0 ECG Higher AF prevalence in SCHyperTh (12.7% vs. 2.3%. OR adjusted 2.8 CI95% 1.3-5.8) Gammage 2007 (England) 5,860 elderly people (median 72 years old) Cross-sectional; Primary care service 0.4 – 5.5 ECG Higher AF prevalence in SCHyperTh (9.5% vs. 4.7%. OR adjusted 1.89 CI95% 1.01-3.57) Vadiveloo 2011 (TEARS, Scotland) 2,004 cases (mean age 66.5 years) and 10,111 controls Retrospective; Tayside health registry 0.4 - 4.0 ECG/ Holter Higher arrhythmia frequency in SCHyperTh (2.7% vs. 1.4%. p < 0.001) TSH: thyroid-stimulating hormone; ECG: electrocardiogram; SCHyperTh: subclinical hyperthyroidism; SCHypoTh: subclinical hypothyroidism; AF: atrial fibrillation. Most longitudinal studies, 9,12,17,33-35 but not all, 36 have found AF to be associated with SCHyperTh. However, that association differs between cross-sectional studies. Interestingly, no participant with SCHyperTh in the present study manifested AF/atrial flutter. In line with this study, Cappola et al.showed no association between AF and STD at the baseline assessment of a community cohort of 2,639 older adults (mean age, 72.7 years). 9 In contrast, Auer et al. reviewed the data of 23,838 individuals admitted to a hospital in Austria and found a prevalence rate of 12.7% for AF among the 613 patients (mean age, 67.9 years) with SCHyperTh (adjusted OR, 2.8; 95% CI 1.3-5.8), but the tests were not performed at a single laboratory. 15 In a study by Gammage et al., the prevalence of AF was 9.5% among individuals with SCHyperTh in a cohort of 5,860 primary care patients with a median age of 72 years (adjusted OR, 1.89; 95% CI 1.01-3.57), however, the TSH levels adopted to define euthyroidism were higher (5.5 μU/mL). 16 The prevalence of extrasystoles in the present study was also low (0.66% for SVES and 0.13% for VES), compared to the prevalence of VES in the HCHS/SOL study (0.98% in men and 0.53% in women). 29 In general, the prevalence rates of the other arrhythmias were similar to those found in the aforementioned studies. No association was noted between SVES or VES and STD, and no differences were detected in HR means between the groups in the present study. Vadiveloo et al. demonstrated in baseline data a greater prevalence of arrhythmias among the participants with SCHyperTh (2.7% vs. 1.4%, p < 0.001), although there was a higher frequency of preexisting cardiovascular disease in their cohort. 17 In the present study, higher FT4 medians were identified in participants with tachycardia, albeit still within the normal range, which could be explained by the physiological effect of the thyroid hormone on cardiac chronotropism. 37 Gammage et al. found similar results, with a positive and direct correlation between FT4 levels and a tachyarrhythmia (AF) in their cross‑sectional study. 16 Surprisingly, higher TSH medians were also associated with tachycardia after adjustment for potential confounding factors, but the probable mechanism for this association is unknown. It can be speculated that STD may result in greater electrocardiographic repercussions only in specific populations with more severe comorbidities. In the ELSA population, a lower median age (51 years) and the smaller prevalence of comorbidities than in the populations recruited in cardiology or emergency services, can explain the discrepancies in relation to previous studies, which may also be due to the different TSH thresholds used to define SCHypoTh (4.5 to 5.5 μU/mL vs. 4.0 μU/mL). 9,12,16 The findings of the most relevant studies reporting concordant or discordant results with those of the present study are summarized in Table 5.