• Tianyi Huang, Matthew Goodman, Xiaoyu Li, Scott A Sands, Jun Li, Meir J Stampfer, Richa Saxena, Shelley S Tworoger, and Susan Redline.
• 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. Electronic address: tih541@mail.harvard.edu.
• Chest. 2021 Jun 1; 159 (6): 2439-2448.

BackgroundIndividuals with OSA have elevated levels of inflammatory markers, but no prospective study has examined the role of inflammation in the development of OSA.Research QuestionIs C-reactive protein (CRP) prospectively associated with risk of developing OSA?Study Design And MethodsWe 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.ResultsAfter 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/m2 (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).InterpretationHigher 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.Copyright © 2021 American College of Chest Physicians. Published by Elsevier Inc. All rights reserved.

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