Department of Epidemiology, Erasmus Medical Centre, Rotterdam, the Netherlands.
Br J Clin Pharmacol. 2009 Sep;68(3):447-54. doi: 10.1111/j.1365-2125.2009.03474.x.
Thyroid free T4 is associated with QTc-interval prolongation, which is a risk factor for sudden cardiac death (SCD). Hyperthyroidism has been associated with SCD in case reports, but there are no population-based studies confirming this. The aim was to investigate whether use of antithyroid drugs (as a direct cause or as an indicator of poorly controlled hyperthyroidism) is associated with an increased risk of SCD.
We studied the occurrence of SCD in a two-step procedure in two different Dutch populations. First, the prospective population-based Rotterdam Study including 7898 participants (> or =55 years old). Second, we used the Integrated Primary Care Information (IPCI) database, which is a longitudinal general practice research database to see whether we could replicate results from the first study. Drug use at the index date was assessed with prescription information from automated pharmacies (Rotterdam Study) or drug prescriptions from general practices (IPCI). We used a Cox proportional hazards model in a cohort analysis, adjusted for age, gender and use of QTc prolonging drugs (Rotterdam Study) and conditional logistic regression analysis in a case-control analysis, matched for age, gender, practice and calendar time and adjusted for arrhythmia and cerebrovascular ischaemia (IPCI).
In the Rotterdam Study, 375 participants developed SCD during follow-up. Current use of antithyroid drugs was associated with SCD [adjusted hazard ratio 3.9; 95% confidence interval (CI) 1.7, 8.7]. IPCI included 1424 cases with SCD and 14 443 controls. Also in IPCI, current use of antithyroid drugs was associated with SCD (adjusted odds ratio 2.9; 95% CI 1.1, 7.4).
Use of antithyroid drugs was associated with a threefold increased risk of SCD. Although this might be directly caused by antithyroid drug use, it might be more readily explained by underlying poorly controlled hyperthyroidism, since treated patients who developed SCD still had low thyroid-stimulating hormone levels shortly before death.
甲状腺游离 T4 与 QTc 间期延长有关，而 QTc 间期延长是心源性猝死 (SCD) 的一个危险因素。甲状腺功能亢进症与病例报告中的 SCD 有关，但尚无基于人群的研究证实这一点。本研究旨在探讨抗甲状腺药物的使用（直接原因或提示甲状腺功能亢进症控制不佳）是否与 SCD 风险增加有关。
我们在荷兰的两个不同人群中进行了两步法研究来研究 SCD 的发生情况。首先，我们进行了前瞻性的基于人群的鹿特丹研究，该研究纳入了 7898 名参与者（≥55 岁）。其次，我们使用了综合初级保健信息（IPCI）数据库，该数据库是一个纵向的一般实践研究数据库，以验证我们能否复制第一项研究的结果。在索引日期时的药物使用情况是通过自动化药房的处方信息（鹿特丹研究）或一般实践的药物处方（IPCI）来评估的。我们在队列分析中使用了 Cox 比例风险模型，根据年龄、性别和 QTc 延长药物的使用情况进行了调整（鹿特丹研究），在病例对照分析中使用了条件逻辑回归分析，根据年龄、性别、实践和日历时间进行了匹配，并根据心律失常和脑血管缺血进行了调整（IPCI）。
在鹿特丹研究中，375 名参与者在随访期间发生了 SCD。目前使用抗甲状腺药物与 SCD 相关[调整后的危险比 3.9；95%置信区间（CI）1.7，8.7]。IPCI 纳入了 1424 例 SCD 病例和 14443 例对照。在 IPCI 中，目前使用抗甲状腺药物也与 SCD 相关（调整后的比值比 2.9；95%CI 1.1，7.4）。
抗甲状腺药物的使用与 SCD 的风险增加三倍有关。尽管这可能直接由抗甲状腺药物的使用引起，但更可能是由于潜在的甲状腺功能亢进症控制不佳引起的，因为发生 SCD 的治疗患者在死亡前不久仍有较低的促甲状腺激素水平。
