阻塞性睡眠呼吸暂停患者心血管死亡的危险因素

文献信息

中文摘要

研究目的： 阻塞性睡眠呼吸暂停（OSA）与心血管死亡增加相关，但OSA特异性参数与经典心血管代谢危险因素的相对贡献仍不明确。
方法： 我们开展了一项回顾性队列研究，纳入连续转诊至三级睡眠中心接受诊断性多导睡眠监测的4,368名成人，随访长达20年。主要结局为通过国家死亡登记链接确定的心血管特异性死亡。分析整合了病因特异性Cox回归、Fine-Gray亚分布风险模型以及随机生存森林（RSF）竞争风险模型（1000棵树；70/30训练-测试划分）。基于Gower距离的层次聚类对RSF预测的累积发生率进行聚类，以识别患者表型。
结果： 在中位随访8.6年（四分位距6.7-12.5）期间，发生335例心血管死亡。心力衰竭（30.4%）、慢性缺血性心脏病（14.0%）和急性心肌梗死（11.6%）是主要原因。独立预测因素为年龄（风险比1.08，95%置信区间1.07-1.10，每岁）、男性（1.68，1.29-2.18）、当前吸烟（1.68，1.30-2.15）、高血压（1.73，1.29-2.33）、心房颤动（2.16，1.56-2.98）、既往心肌梗死（1.71，1.25-2.35）和糖尿病（1.37，1.06-1.76）。夜间血氧饱和度下降在多变量调整后失去显著性。在呼吸暂停低通气指数≥15次/小时的患者中，良好的持续气道正压通气（CPAP）反应与较低的心血管死亡相关（0.72，0.55-0.96）。RSF的C指数为0.80。六种表型的心血管死亡率为2.9%至14.4%。
结论： OSA中的心血管死亡主要由经典心血管代谢危险因素驱动，而非夜间低氧负荷或CPAP反应。应优先考虑针对合并症的预防，而表型感知的分层可能识别出需要加强心血管监测的亚组。

英文摘要

STUDY OBJECTIVES: Obstructive sleep apnea (OSA) is associated with increased cardiovascular mortality, but the relative contributions of OSA-specific parameters versus classical cardiometabolic risk factors remain poorly defined.
METHODS: We conducted a retrospective cohort study of 4,368 consecutive adults referred for diagnostic polysomnography at a tertiary sleep center and followed for up to 20 years. The primary outcome was cause-specific cardiovascular mortality ascertained by national death registry linkage. Analyses integrated cause-specific Cox regression, Fine-Gray subdistribution hazard models, and a random survival forest (RSF) competing-risk model (1000 trees; 70/30 train-test split). Gower-distance-based hierarchical clustering of RSF-predicted cumulative incidence identified patient phenotypes.
RESULTS: Over a median follow-up of 8.6 years (interquartile range 6.7-12.5), 335 cardiovascular deaths occurred. Heart failure (30.4%), chronic ischemic heart disease (14.0%), and acute myocardial infarction (11.6%) were the leading causes. Independent predictors were age (hazard ratio 1.08, 95% confidence interval 1.07-1.10, per year), male sex (1.68, 1.29-2.18), active smoking (1.68, 1.30-2.15), hypertension (1.73, 1.29-2.33), atrial fibrillation (2.16, 1.56-2.98), prior myocardial infarction (1.71, 1.25-2.35), and diabetes (1.37, 1.06-1.76). Nocturnal desaturation lost significance after multivariable adjustment. Among patients with an apnea-hypopnea index ≥15 events/h, a good continuous positive airway pressure (CPAP) response was associated with lower cardiovascular mortality (0.72, 0.55-0.96). The RSF C-index was 0.80. Six phenotypes showed cardiovascular mortality of 2.9% to 14.4%.
CONCLUSIONS: Cardiovascular mortality in OSA was driven predominantly by classical cardiometabolic risk factors rather than by nocturnal hypoxemic burden or CPAP response. Comorbidity-targeted prevention should be prioritized, and phenotype-aware stratification may identify subgroups warranting intensified cardiovascular surveillance.