C-reactive protein and risk of obstructive sleep apnea in four US cohorts.

Individuals with obstructive sleep apnea (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 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, clinician-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 odds ratio (OR) for OSA risk according to baseline CRP level, adjusted for multiple inflammation-related factors.
After multivariable adjustment not including BMI, the pooled OR (95% CI) for OSA risk per doubling of baseline CRP level was 1.24 (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 years versus ≥55 years (p-interaction=0.01), in individuals with BMI<25 kg/m versus ≥25 kg/m (p-interaction=0.02) and in premenopausal versus postmenopausal women (p-interaction=0.002). CRP was more strongly associated with risk of OSA associated with excessive daytime sleepiness, high airway collapsibility and low arousal threshold (p-heterogeneity<0.05).
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.