High free thyroxine levels are associated with QTc prolongation in males

The literature on the effect of excess thyroid hormone on ventricular repolarization is controversial. To study whether free thyroxine (T(4)) and TSH are associated with QTc prolongation we conducted population-based cohort study. This study was conducted as part of the Rotterdam Study and included 365 men and 574 women aged 55 years and older with an electrocardiogram, who were randomly sampled for the assessment of thyroid status (free T(4)/TSH) at baseline, after exclusion of participants with hypothyroidism, use of antithyroid drugs, thyroid hormones or digoxin, left ventricular hypertrophy, and left and right bundle branch block. Endpoints were the length of the QTc interval and risk of borderline QTc prolongation. The associations were examined by means of linear and logistic regression analysis, adjusted for age and gender, diabetes mellitus, myocardial infarction, hypertension, and heart failure. Overall, there was no significant association between TSH and QTc interval (0.8 ms (95% confidence interval (CI) -3.5, 5.2) in the first quintile compared with the fifth quintile). Subjects in the fifth quintile of free T(4) did not have an increased QTc interval (3.2 ms (95% CI -1.1, 7.6)); stratification on gender showed an increment of 10.9 ms (95% CI 3.4, 18.3) in the fifth quintile in men and 1.1 ms (95% CI -4.2, 6.3) in the fifth quintile of free T(4) in women. When compared with subjects in the first quintile, male subjects in the fifth quintile of free T(4) had a significantly increased risk of a borderline QTc interval and QTc prolongation (odds ratio 2.40 (95% CI 1.20, 4.80)). High levels of free T(4) are associated with substantial QTc prolongation in men of up to 10 ms. The fact that free T(4) is also associated with a significantly increased risk of borderline and prolonged QTc values with its risk of sudden cardiac death, endorses the clinical importance of our findings.