The Sleep Apnea-Specific Pulse-Rate Response Predicts Cardiovascular Morbidity and Mortality
The Sleep Apnea-Specific Pulse-Rate Response Predicts Cardiovascular Morbidity and Mortality
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DOI：
10.1164/rccm.202010-3900oc
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发表时间：
2021-06-15
影响因子：
24.7
通讯作者：
Wellman, Andrew
中科院分区：
文献类型：
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作者：
Azarbarzin, Ali;Sands, Scott A.;Wellman, Andrew
理论基础：随机对照试验一直无法检测到在未选定的阻塞性睡眠呼吸暂停(OSA)患者中持续气道正压对心血管的益处。我们假设有害的心血管结果集中在对呼吸暂停和低呼吸综合征(Delta HR)有高脉率反应的患者子组中。方法：我们测量了MESA(动脉粥样硬化多民族研究)(N=1,395)和SHHS(睡眠心脏健康研究)(N=4,575)的Delta HR。MESA数据被用来确定Delta HR和亚临床心血管生物标记物之间的功能形式，而初步分析在SHHS的纵向数据中测试Delta HR与非致命性或致命性心血管疾病(CVD)和全因死亡率的关联。测量和主要结果：在MESA中，亚临床CVD生物标记物(冠状动脉钙、NT-proBNP[N-末端前激素BNP]和Framingham风险评分)与Delta HR之间观察到U型关系；值得注意的是，与Delta HR中值(第25-75百分位数)相比，Delta HR高(上四分位)与生物标记物得分高相关。在SIMS中，与中值Delta HR相比，Delta HR高的个体患非致命性或致命性心血管疾病和全因死亡的风险增加(非致命性调整危险比[95%可信区间(CI)]，1.60[1.28-2.00]；致命调整危险性比[95%CI]，1.68[1.22-2.30]；全因调整危险性比[95%CI]，1.29[1.07-1.55])。与Delta HR升高相关的风险在那些有大量低氧负担的人中尤其高(非致命性，1.93[1.36-2.73]；致命性，3.50[2.15-5.71]；全原因，1.84[1.40-2.40])，并且仅在不嗜睡的个体中观察到。结论：OSA患者Delta HR升高，心血管并发症和死亡率的风险增加。这项研究确定了OSA的一个预后生物标志物，该标志物似乎对未来临床试验的风险分层和患者选择有用。
Rationale: Randomized controlled trials have been unable to detect a cardiovascular benefit of continuous positive airway pressure in unselected patients with obstructive sleep apnea (OSA). We hypothesize that deleterious cardiovascular outcomes are concentrated in a subgroup of patients with a heightened pulse-rate response to apneas and hypopneas (Delta HR).Methods: We measured the Delta HR in the MESA (Multi-Ethnic Study of Atherosclerosis) (N = 1,395) and the SHHS (Sleep Heart Health Study) (N= 4,575). MESA data were used to determine the functional form of the association between the Delta HR and subclinical cardiovascular biomarkers, whereas primary analyses tested the association of the Delta HR with nonfatal or fatal cardiovascular disease (CVD) and all-cause mortality in longitudinal data from the SHHS.Measurements and Main Results: In the MESA, U-shaped relationships were observed between subclinical CVD biomarkers (coronary artery calcium, NT-proBNP [N-terminal prohormone BNP], and Framingham risk score) and the Delta HR; notably, a high Delta HR (upper quartile) was associated with elevated biomarker scores compared with a midrange Delta HR (25th-75th centiles). In the SIMS, individuals with a high Delta HR compared with a midrange Delta HR were at increased risk of nonfatal or fatal CVD and all-cause mortality (nonfatal adjusted hazard ratio [95% confidence interval (CI)], 1.60 [1.28-2.00]; fatal adjusted hazard ratio [95% CI], 1.68 [1.22-2.30]; allcause adjusted hazard ratio [95% CI], 1.29 [1.07-1.55]). The risk associated with a high Delta HR was particularly high in those with a substantial hypoxic burden (nonfatal, 1.93 [1.36-2.73]; fatal, 3.50 [2.15-5.71]; all-cause, 1.84 [1.40-2.40]) and was exclusively observed in nonsleepy individuals.Conclusions: Individuals with OSA who demonstrate an elevated Delta HR are at increased risk of cardiovascular morbidity and mortality. This study identifies a prognostic biomarker for OSA that appears useful for risk stratification and patient selection for future clinical trials.