阻塞性睡眠呼吸暂停早期机体损伤机制及相关标志物研究

Relevant study have confirmed that severe OSA without treatment will increase the risk of cardiovascular diseases and all-cause death, Several researches and the SAVE study in which we participated earlier found that CPAP therapy was not significantly related with cardiovascular events or deaths. We suppose that early intervention is effective, especially for mild OSA patients. However, our earlier investigation shown that up to 67.4% patients with mild OSA were not treated and the reason may be related to the lack of stronger basis for intervention. Besides, some evidences suggest that mild OSA is not independent from cardiovascular diseases, and it may be represented an intermediate step of causing severe pathological damage, but its mechanism is unclear. However, using PSG to diagnosis OSA only can base on AHI and it fail to reflect the early damage and markers of OSA from ECG and EEG data. This study is aiming at mild OSA, using the dynamic ECG technology mining the ECG data in PSG to explore the heart rate variability and to measured left ventricular function by using two-dimensional speckle tracking technology. We analyze the changes of EEG and EEG energy in PSG and explore its relationship with the impaired cognitive function of mild OSA. To explore the early cardiovascular and cerebrovascular injury of OSA which we can’t figure out by using conventional methods. This subject will help us to clarify the early damage mechanism and related markers of OSA and provide a scientific evidence for mild OSA intervention.

研究证实不治疗的重度OSA增加心脑血管风险和全因死亡。我们前期参与完成的SAVE研究及多项研究发现CPAP治疗与心血管事件或死亡没有显著相关，可能与干预时机有关。我们假设早期干预有效，特别是对轻度OSA，但前期调查发现高达67.4%轻度OSA患者不治疗，与缺乏有力干预依据有关。有证据认为轻度OSA并不独立于心脑血管疾病，可能代表造成严重病理损害的一个中间步骤，但其机制不清楚。PSG诊断OSA仅依据AHI，未能从ECG和EEG数据中反应出OSA早期的机体损伤及标志物。本课题针对轻度OSA，用动态心电分析技术挖掘PSG的ECG数据探索其夜间心律变异性和二维斑点追踪技术测量左心室功能，分析PSG脑电频谱和脑电能量以找出轻度OSA睡眠脑电与认知受损的关系。探索常规方法反应不出的OSA早期心脑血管损伤。这一课题将有助于阐明OSA早期损伤机制及相关标志物，为轻度OSA干预提供科学依据。

轻度OSA患者临床需不需要治疗，什么样的临床标准或标志物能反应OSA特别是早期OSA的机体损伤而作为治疗依据尚不清楚。我们团队使用动态心电分析技术挖掘PSG的ECG数据探索其夜间心律变异性和二维斑点追踪技术测量左心室功能，分析PSG脑电功率谱，揭示了不伴心律失常的OSA患者PSG的心率变异性（HRV）发生异常改变，SDNN指数、 LF/HF随着睡眠呼吸疾病严重程度增加而升高。提示了OSA患者早期心脏节律异常，可能是OSA患者发生心律失常的早期病理损伤标志。此外，还发现未合并心血管疾病的 OSA 患者可在常规心脏彩超及核磁共振扫描检查上出现心脏结构及功能指标的异常改变。功能指标的改变可能较结构指标更早出现。即使是轻度OSA也存在早期心脏损伤并出现相关指标的异常改变，且随着疾病进展，这些损伤可逐渐加重。PSG睡眠脑电分析发现OSA患者的脑电的微观结构与正常人相比存在差异，额区β功率可能是反映OSA患者疾病严重程度的早期神经生理标志物。总体上，我们的研究结果揭示了未出现合并症的OSA早期即存在机体结构或功能上的损伤，即使是轻度OSA，提示OSA需要在未出现合并症前进行及时干预。并提示需对常规的临床检查数据进行深入挖掘，以为OSA早期机体损伤及早期干预提供依据。