4月23日在线发表于《内科学文献》(Archives of Internal Medicine)的一项研究显示，内源性亚临床甲状腺功能亢进可增加冠心病死亡、全因死亡和房颤风险。瑞士洛桑大学非卧床护理和社区医学系的Tinh-Hai Collet医生及其合作者报告，在促甲状腺素水平最低(<0.10 mIU/L)的患者中，风险增高最为显著(Arch. Intern. Med. 2012 April 23 [doi:10.1001/archinternmed.2012.402])。

　　长期以来，研究者一直怀疑亚临床甲状腺功能亢进与不良心血管效应之间存在关联，但前瞻性队列研究和研究水平的Meta分析得出的结论相互矛盾。

　　Collet医生及其同事针对这一问题，进行了一项患者水平的Meta分析，假设评估来自大型队列研究的受试者数据可能解决这一问题。研究者纳入了文献检索得出的所有报告基线促甲状腺素和游离甲状腺素水平(包括甲状腺功能正常的对照组)并对冠心病和死亡结局进行特定追踪的10个前瞻性纵向队列。排除使用第一代促甲状腺素分析的研究，因为这种检测对于亚临床甲状腺功能亢进的敏感性不足。10个队列共包括52，674例患者，中位年龄为59岁。中位随访时间为8.8年，总共随访501,922患者-年。其中共有2,188例患者 (4.2%)存在内源性亚临床甲状腺功能亢进。

　　结果显示，随访期间共有8,527例患者死亡，其中包括1,896例冠心病死亡、3,653起冠心病事件和785例偶发房颤。相对于甲状腺功能正常的对照患者，亚临床甲状腺功能亢进患者全因死亡的总危险比(HR)为1.24，冠心病死亡HR为1.29，冠心病事件HR为1.21，偶发房颤HR为1.68。在促甲状腺素水平极低的患者中，冠心病死亡和房颤发生率均显著较高，而其他预后指标无相似变化。当根据患者年龄或既往是否有心血管疾病病史对数据进行分析时，风险增高无实质变化。在敏感性分析中结果亦无变化，即使校正体重指数和降脂或降压药物的使用之后，结果仍保持一致。但亚临床甲状腺功能亢进患者的癌症死亡和卒中死亡风险并不高于对照患者。

　　研究者总结认为，基于受试者个体数据，亚临床甲状腺功能亢进确实与总死亡和冠心病死亡风险增高相关。

　　该研究由瑞士国家科学基金会资助。研究者报告无相关利益冲突。

原文阅读：

BY MARY ANN MOON

Elsevier Global Medical News

　　Breaking News

　　Endogenous subclinical hyperthyroidism increased the risks of coronary heart disease mortality, total mortality, and atrial fibrillation, a study published online April 23 in the Archives of Internal Medicine has shown.

　　The excess risk was most pronounced in patients who had the lowest thyrotropin levels – below 0.10 mIU/L – said Dr. Tinh-Hai Collet of the department of ambulatory care and community medicine, University of Lausanne (Switzerland), and associates (Arch. Intern. Med. 2012 April 23 [doi:10.1001/archinternmed.2012.402]).

　　Researchers have long suspected an association between subclinical hyperthyroidism and adverse cardiovascular effects, but prospective cohort studies and study-level meta-analyses alike have reached conflicting conclusions about such a link.

　　Dr. Collet and colleagues conducted a patient-level meta-analysis of the issue, reasoning that examining individual participant data from large cohort studies might resolve the question.

　　The researchers included all 10 prospective longitudinal cohorts in the literature that reported baseline thyrotropin and free thyroxine levels, included euthyroid control groups, and specifically tracked coronary heart disease (CHD) and mortality outcomes. They excluded studies that used first-generation thyrotropin assays, because those tests are not sensitive enough to detect subclinical hyperthyroidism reliably.

　　The 10 cohorts comprised 52,674 patients with a median age of 59 years. The median follow-up was 8.8 years, and the total follow-up was 501,922 person-years. A total of 2,188 (4.2%) of those patients had endogenous subclinical hyperthyroidism.

　　Overall, 8,527 patients died during follow-up. There were 1,896 CHD deaths, 3,653 CHD events, and 785 cases of incident atrial fibrillation (AF).

　　For patients with subclinical hyperthyroidism, the overall hazard ratio compared with euthyroid control patients for all-cause mortality was 1.24, for CHD mortality was 1.29, for CHD events was 1.21, and for incident AF was 1.68.

　　Both CHD mortality and AF rates – but not the other outcomes – were significantly higher among patients with the very lowest thyrotropin levels, the investigators said.

　　Those increased risks did not change materially when the data were analyzed according to patient age or the presence of preexisting cardiovascular disease. The results also remained the same in sensitivity analyses, even after the data were adjusted to account for body mass index and the use of lipid-lowering or antihypertensive medication.

　　In contrast, cancer mortality and stroke mortality were no higher in patients with subclinical hyperthyroidism than in control patients.

　　“Our results, based on individual participant data, demonstrate that there is indeed an increased risk of total and CHD mortality associated with subclinical hyperthyroidism,” Dr. Collet and associates said.

　　Their findings support recent guidelines stating that the treatment of subclinical hyperthyroidism “should be strongly considered” in all patients aged 65 and older whose thyrotropin level is lower than 0.10 mIU/L.

　　The study could not address whether such therapy decreases the elevated risk of death, CHD events, or AF, the authors said, and no large randomized controlled trial has yet attempted to do so. Such a trial would be “challenging” to perform because of the low prevalence of subclinical hyperthyroidism in the general population, they added.

　　The Swiss National Science Foundation supported the study. The investigators reported no relevant financial conflicts of interest.

（责任编辑：颜子力）