長時間睡眠與心血管疾病及全死因風險：動脈粥樣硬化標記物在臺灣社區型世代研究中的中介角色

Abstract

背景介紹：本研究探討不同睡眠時長和總死亡及心血管疾病死亡風險的關聯性，並進一步考慮動脈粥狀硬化標記物的中介角色，釐清異常睡眠時長是否會透過動脈粥狀硬化標記物間接影響死亡風險，以找出生物學的路徑。 方法：本研究為長期追蹤的世代研究，使用臺灣金山社區心血管疾病世代追蹤資料，排除資料不全者以及患有心血管疾病的受試者後，共納入3,305名受試者。透過結構式問卷蒐集人口學資料及習慣性睡眠時長，並抽取血液樣本檢測生化指標。睡眠時長分為三組，分別為短時間睡眠(≤6小時)、正常睡眠時間(7–8小時)和長時間睡眠(≥9小時)。利用Cox比例風險模型探討睡眠時長和全死因及心血管疾病死亡的關聯，並利用限制性立方曲線模型(Restricted Cubic Spline model)來判斷此關聯是否呈現非線性，更進一步利用因果中介分析來評估潛在的中介因子。 結果：經過中位數30.8年的追蹤期間下，調整潛在的干擾因子後，長時間睡眠相較於正常睡眠有顯著較高的全死因風險(調整後的HR: 1.17, 95% CI: 1.01, 1.35)，而短時間睡眠則未達顯著差異。長時間睡眠與心血管疾病死亡則未達顯著相關(調整後的HR: 1.18, 95% CI: 0.89, 1.56)。在年齡、性別、身體質量指數、高血壓和糖尿病分層分析皆未發現顯著交互作用。因果中介分析發現，收縮壓作為長時間睡眠和全死因之間的潛在中介因子，在基準測量和追蹤期間的間接效應分別為1.05 (95% CI: 1.02, 1.08)和1.03 (95% CI: 1.00, 1.06)。 結論：本研究發現較長的睡眠時間會增加全死因風險，此風險部分可由收縮壓所中介。

Introduction: The study investigated the association between sleep duration and the risks of all-cause and cardiovascular diseases death, and elucidated the mediating role of atherosclerotic markers in these associations to identify potential biological pathways. Methods: We used data from the Chin-Shan Community Cardiovascular Cohort in Taiwan, a prospective study. After excluding individuals with incomplete data and those with cardiovascular diseases, 3,305 participants were included. Demographic data and habitual sleep duration were collected through structured questionnaires, and blood samples were obtained to assess biomarkers. Participants were classified into three sleep duration groups as short (≤6 hours), normal (7–8 hours), and long (≥9 hours). Cox proportional hazard models and restricted cubic splines assessed the associations and non-linear trends. Causal mediation analysis was performed to identify potential mediators. Results: During a median of 30.8 years of follow-up, after adjusting for potential confounding factors, long sleep duration was significantly associated with increased risks of all-cause mortality (adjusted hazard ratio: 1.17, 95% confidence interval: 1.01, 1.35), while short sleep duration showed no significant difference. Long sleep duration was not significantly associated with cardiovascular mortality (adjusted hazard ratio: 1.18, 95% confidence interval: 0.89, 1.56). Short sleep duration showed no significant association with either outcome. No significant interactions were found in subgroup analyses by age, sex, body mass index, hypertension, and diabetes. Systolic blood pressure was identified as a potential mediator between long sleep duration and all-cause mortality, with indirect effects of 1.05 (95% confidence interval: 1.02, 1.08) at baseline and 1.03 during follow-up (95% confidence interval: 1.00, 1.06). Conclusions: This study found that longer sleep duration increases the risk of all-cause mortality, which may be partially mediated by systolic blood pressure.