Supplementary Material for: Thyroid Hormones within the Normal Range and Cardiac Function in the General Population: The EPIPorto Study

<b><i>Background:</i></b> Hypothyroidism and hyperthyroidism are associated with marked changes in cardiac structure and function. However, the association of thyroid function within the normal range with cardiac structure and function in the general population remains uncertain. <b><i>Methods:</i></b> Eight hundred thirty-five subjects aged ≥45 years from the EPIPorto cohort (evaluation between 2006 and 2008) were cross-sectionally analyzed. We excluded participants with TSH, free T4 (FT4), or free T3 (FT3) outside of the reference range or with self-reported cardiovascular or thyroid disease. Cardiac structure and function were evaluated by echocardiography. We used linear regression models unadjusted and adjusted for sex and age (model 1), and sex, age, BMI, diabetes, hypertension, and smoking (model 2). Nonlinear associations were assessed using restricted cubic splines. <b><i>Results:</i></b> The mean age was 61.5 years (SD 10.5); 61.1% of the patients were women. In the adjusted model 2, heart rate was positively associated with FT3; diastolic blood pressure was positively associated with TSH; LV end-diastolic and end-systolic volumes were inversely associated with TSH, and ejection fraction was nonlinearly associated with FT3, with higher ejection fractions near the limits of the reference range. Left ventricle (LV) posterior wall thickness was nonlinearly associated with FT4 in the adjusted model 1, with a greater thickness near the limits of the reference range. Regarding diastolic function, no significant associations were observed in adjusted models. <b><i>Conclusions:</i></b> Thyroid function within the reference range was associated with heart rate, blood pressure, cardiac structure, and function. Increasing thyroid function (lower TSH, higher FT4, or higher FT3) was associated with a higher heart rate, a lower diastolic blood pressure, and larger LV volumes. LV wall thickness and ejection fraction had a U-shaped association with thyroid hormones.

<b><i>研究背景：</i></b> 甲状腺功能减退症（Hypothyroidism）与甲状腺功能亢进症（Hyperthyroidism）均与心脏结构和功能的显著改变密切相关。然而，在普通人群中，处于正常参考范围内的甲状腺功能与心脏结构和功能之间的关联仍不明确。<b><i>研究方法：</i></b> 本研究对EPIPorto队列（2006年至2008年间完成评估）中835名年龄≥45岁的受试者开展横断面分析。我们排除了促甲状腺激素（TSH）、游离甲状腺素（free T4, FT4）或游离三碘甲状腺原氨酸（free T3, FT3）超出参考范围，或自述患有心血管疾病或甲状腺疾病的参与者。心脏结构与功能通过超声心动图（echocardiography）进行评估。我们采用两类线性回归模型：一类为未校正模型与校正了性别、年龄的模型（模型1），另一类为校正了性别、年龄、体重指数（BMI）、糖尿病、高血压及吸烟状况的模型（模型2）。采用限制性立方样条（restricted cubic splines）评估非线性关联。<b><i>研究结果：</i></b> 受试者平均年龄为61.5岁（标准差为10.5），女性占比61.1%。在校正模型2中，心率与FT3呈正相关；舒张压与TSH呈正相关；左心室（Left ventricle, LV）舒张末期容积与收缩末期容积均与TSH呈负相关；射血分数与FT3呈非线性关联，在参考范围极限附近射血分数更高。在校正模型1中，左心室后壁厚度与FT4呈非线性关联，在参考范围极限附近后壁厚度更大。针对舒张功能而言，在校正模型中未观察到显著关联。<b><i>研究结论：</i></b> 处于参考范围内的甲状腺功能与心率、血压、心脏结构及功能均存在关联。甲状腺功能升高（即TSH降低、FT4升高或FT3升高）与心率增快、舒张压降低以及左心室容积增大相关。左心室壁厚度与射血分数均与甲状腺激素呈U型关联。