Channing Division of Network Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA; Division of Sleep Medicine, Harvard Medical School, Boston, MA.
Division of Sleep and Circadian Disorders, Brigham and Women's Hospital and Harvard Medical School, Boston, MA.
Chest. 2021 Jun;159(6):2439-2448. doi: 10.1016/j.chest.2021.01.060. Epub 2021 Jan 30.
Individuals with OSA have elevated levels of inflammatory markers, but no prospective study has examined the role of inflammation in the development of OSA.
Is C-reactive protein (CRP) prospectively associated with risk of developing OSA?
We followed 1,882 women from the Nurses' Health Study (NHS) (2002-2012), 3,854 women from Nurses' Health Study II (NHSII) (1995-2013), 3,075 men from the Health Professionals Follow-up Study (HPFS) (1996-2012), and 1,919 women and men from the Multi-Ethnic Study of Atherosclerosis (MESA) (2000-2012) who did not have diagnosed OSA at baseline and for whom CRP levels were available. In NHS/NHSII/HPFS, physician-diagnosed OSA was self-reported. In MESA, at-home polysomnography was performed and OSA was identified as an apnea-hypopnea index ≥ 30. Logistic regression was used to estimate the OR for OSA risk according to baseline CRP level, adjusted for multiple inflammation-related factors.
After multivariable adjustment not including BMI, the pooled OR for OSA risk per doubling of baseline CRP level was 1.24 (95% CI, 1.18-1.30). Additional adjustment for BMI substantially attenuated the association (pooled OR, 1.07; 95% CI, 1.01-1.12). The fully adjusted association was consistently stronger in individuals < 55 vs ≥ 55 years of age (P interaction = .01), in individuals with BMI < 25 vs ≥ 25 kg/m (P interaction = .02), and in pre- vs postmenopausal women (P interaction = .002). CRP was more strongly associated with risk of OSA associated with excessive daytime sleepiness, high airway collapsibility, and low arousal threshold (P heterogeneity < .05).
Higher CRP was prospectively associated with increased OSA risk, particularly among younger individuals, underweight/normal-weight individuals, or premenopausal women. The differential associations by OSA phenotype/endotype suggest possible mechanisms through which inflammation operates to modulate OSA risk. Given our reliance on a single CRP level measured a decade before OSA assessment, future studies with repeated CRP measurements are warranted to confirm these prospective associations.
阻塞性睡眠呼吸暂停（OSA）患者的炎症标志物水平升高，但尚无前瞻性研究探讨炎症在 OSA 发展中的作用。
C 反应蛋白（CRP）是否与 OSA 发病风险呈前瞻性相关？
我们随访了来自护士健康研究（NHS）（2002-2012 年）的 1882 名女性、来自护士健康研究 II（NHSII）（1995-2013 年）的 3854 名女性、来自健康专业人员随访研究（HPFS）（1996-2012 年）的 3075 名男性以及来自多民族动脉粥样硬化研究（MESA）（2000-2012 年）的 1919 名女性和男性，这些人在基线时均未被诊断为 OSA，且 CRP 水平可检测。在 NHS/NHSII/HPFS 中，OSA 是通过医生诊断报告的。在 MESA 中，通过家庭多导睡眠图进行检测并将呼吸暂停-低通气指数≥30 作为 OSA 的诊断标准。使用 logistic 回归来估计根据基线 CRP 水平，调整了多种炎症相关因素后，OSA 风险的 OR。
在不包括 BMI 的多变量调整后，每增加一倍 CRP 水平，OSA 风险的合并 OR 为 1.24（95%CI，1.18-1.30）。进一步调整 BMI 后，相关性显著减弱（合并 OR，1.07；95%CI，1.01-1.12）。在年龄<55 岁与≥55 岁的个体（P 交互效应<.01）、BMI<25 与≥25kg/m 的个体（P 交互效应<.02）以及绝经前与绝经后女性（P 交互效应<.002）中，完全调整后的相关性更强。CRP 与日间嗜睡、气道高 collapsibility 和低觉醒阈值相关的 OSA 风险的相关性更强（P 异质性<.05）。
较高的 CRP 水平与 OSA 风险呈前瞻性相关，尤其是在年轻个体、体重不足/正常体重个体或绝经前女性中。根据 OSA 表型/内型的差异相关性，可能存在炎症调节 OSA 风险的机制。鉴于我们依赖于 OSA 评估前十年测量的单次 CRP 水平，需要进一步进行重复 CRP 测量的前瞻性研究来确认这些相关性。
