Division of Sleep and Circadian Disorders, Brigham and Women's Hospital and Harvard Medical School, Harvard University, Boston, Massachusetts.
Sleep Disorders Center, University of Manitoba, Winnipeg, Manitoba, Canada; and.
Am J Respir Crit Care Med. 2021 Jun 15;203(12):1546-1555. doi: 10.1164/rccm.202010-3900OC.
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 (ΔHR). We measured the ΔHR in the MESA (Multi-Ethnic Study of Atherosclerosis) ( = 1,395) and the SHHS (Sleep Heart Health Study) ( = 4,575). MESA data were used to determine the functional form of the association between the ΔHR and subclinical cardiovascular biomarkers, whereas primary analyses tested the association of the ΔHR with nonfatal or fatal cardiovascular disease (CVD) and all-cause mortality in longitudinal data from the SHHS. 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 ΔHR; notably, a high ΔHR (upper quartile) was associated with elevated biomarker scores compared with a midrange ΔHR (25th-75th centiles). In the SHHS, individuals with a high ΔHR compared with a midrange ΔHR 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]; all-cause adjusted hazard ratio [95% CI], 1.29 [1.07-1.55]). The risk associated with a high ΔHR 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. Individuals with OSA who demonstrate an elevated ΔHR 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.
随机对照试验未能发现持续气道正压通气对未经选择的阻塞性睡眠呼吸暂停（OSA）患者的心血管益处。我们假设有害的心血管结果集中在对呼吸暂停和低通气（ΔHR）反应增强的亚组患者中。我们在 MESA（多民族动脉粥样硬化研究）（ = 1395）和 SHHS（睡眠心脏健康研究）（ = 4575）中测量了ΔHR。MESA 数据用于确定ΔHR与亚临床心血管生物标志物之间关联的函数形式，而主要分析则测试了 SHHS 纵向数据中ΔHR与非致命性或致命性心血管疾病（CVD）和全因死亡率的关联。在 MESA 中，亚临床 CVD 生物标志物（冠状动脉钙、NT-proBNP[N 末端前体脑钠肽]和弗雷明汉风险评分）与ΔHR 之间观察到 U 形关系；值得注意的是，与中范围ΔHR（25 至 75 百分位）相比，高ΔHR（上四分位数）与升高的生物标志物评分相关。在 SHHS 中，与中范围ΔHR 相比，高ΔHR 的个体发生非致命性或致命性 CVD 和全因死亡率的风险增加（非致命性校正风险比[95%置信区间（CI）]，1.60[1.28-2.00]；致命性校正风险比[95%CI]，1.68[1.22-2.30]；全因校正风险比[95%CI]，1.29[1.07-1.55]）。在缺氧负担较大的患者中（非致命性，1.93[1.36-2.73]；致命性，3.50[2.15-5.71]；全因，1.84[1.40-2.40]），与高ΔHR 相关的风险特别高，并且仅在非嗜睡个体中观察到。表现出升高的ΔHR 的 OSA 患者发生心血管发病率和死亡率的风险增加。这项研究确定了 OSA 的预后生物标志物，似乎对未来临床试验的风险分层和患者选择有用。
