Department of Internal Medicine and Clinical Nutrition, Institute of Medicine at Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden.
Department of Endocrinology, Sahlgrenska University Hospital, Gothenburg, Sweden.
Front Endocrinol (Lausanne). 2022 Jul 8;13:918356. doi: 10.3389/fendo.2022.918356. eCollection 2022.
The aim of the study was to investigate all-cause and disease-specific mortality in a large population-based cohort of oral glucocorticoid (GC) users.
This was a retrospective, matched cohort study. Information on dispensed prescriptions was obtained from the Swedish Prescribed Drug Register. The cause of death was obtained from the Swedish Cause-of-Death Registry. Patients receiving prednisolone ≥5 mg/day (or equivalent dose of other GC) for ≥21 days between 2007-2014 were included. For each patient, one control subject matched for age and sex was included. The study period was divided into 3-month periods and patients were divided into groups according to a defined daily dose (DDD) of GC used per day. The groups were: Non-users (0 DDD per day), low-dose users (>0 but <0.5 DDD per day), medium-dose users (0.5-1.5 DDD per day) and high-dose users (>1.5 DDD per day). Hazard ratios (HRs), unadjusted and adjusted for age, sex and comorbidities, were calculated using a time-dependent Cox proportional hazard model.
Cases (n=223 211) had significantly higher all-cause mortality compared to controls (HR adjusted for age, sex and comorbidities 2.08, 95% confidence interval 2.04 to 2.13). After dividing the cases into subgroups, adjusted HR was 1.31 (1.28 to 1.34) in non-users, 3.64 (3.51 to 3.77) in low-dose users, 5.43 (5.27 to 5.60) in medium-dose users and, 5.12 (4.84 to 5.42) in high-dose users. The highest adjusted hazard ratio was observed in high-dose users for deaths from sepsis 6.71 (5.12 to 8.81) and pulmonary embolism 7.83 (5.71 to 10.74).
Oral GC users have an increased mortality rate compared to the background population, even after adjustment for comorbidities. High-dose users have an increased risk of dying from sepsis, and pulmonary embolism compared to controls. Whether the relationship between GC exposure and the excess mortality is causal remains to be elucidated.
本研究旨在调查大样本基于人群的口服糖皮质激素（GC）使用者的全因死亡率和疾病特异性死亡率。
这是一项回顾性、匹配队列研究。从瑞典处方药物登记处获取处方信息。从瑞典死因登记处获取死亡原因。纳入 2007-2014 年期间每天接受泼尼松龙≥5mg（或其他 GC 的等效剂量）≥21 天的患者。每位患者匹配一名年龄和性别相同的对照者。研究期间分为 3 个月期，并根据每天使用的 GC 定义日剂量（DDD）将患者分为以下几组：非使用者（每天 0 DDD）、低剂量使用者（每天>0 但 <0.5 DDD）、中剂量使用者（每天 0.5-1.5 DDD）和高剂量使用者（每天>1.5 DDD）。使用时间依赖性 Cox 比例风险模型计算未调整和调整年龄、性别和合并症后的危险比（HR）。
病例组（n=223211）的全因死亡率明显高于对照组（调整年龄、性别和合并症后的 HR 2.08，95%置信区间 2.04 至 2.13）。将病例分为亚组后，未使用者的调整 HR 为 1.31（1.28 至 1.34），低剂量使用者为 3.64（3.51 至 3.77），中剂量使用者为 5.43（5.27 至 5.60），高剂量使用者为 5.12（4.84 至 5.42）。高剂量使用者因败血症（6.71，5.12 至 8.81）和肺栓塞（7.83，5.71 至 10.74）导致的死亡调整后危险比最高。
与普通人群相比，口服 GC 使用者的死亡率更高，即使调整了合并症。与对照组相比，高剂量使用者因败血症和肺栓塞导致死亡的风险增加。GC 暴露与超额死亡率之间的关系是否存在因果关系仍有待阐明。
