Dose–response relationship between obstructive sleep apnoea severity and C-reactive protein levels: data from the European Sleep Apnoea Database




Grote, Ludger; Gouveris, Haralampos; Lethuillier, Lea; Verbraecken, Johan; Basoglu, Ozen K.; Schiza, Sophia; Ludka, Ondrej; Ryan, Silke; Joppa, Pavol; Fanfulla, Francesco; Mihaicuta, Stefan; Saaresranta, Tarja; Sliwinski, Pawel; Hedner, Jan; Pepin, Jean Louis; Bailly, Sebastien; ESADA Study Group

PublisherEuropean Respiratory Society (ERS)

2025

 ERJ Open Research

00707-2025

12

1

2312-0541

DOIhttps://doi.org/10.1183/23120541.00707-2025

https://doi.org/10.1183/23120541.00707-2025

https://research.utu.fi/converis/portal/detail/Publication/508526321



Introduction

Obstructive sleep apnoea (OSA) characterised by intermittent hypoxia promotes systemic inflammation. This study evaluated the association between OSA severity and circulating C-reactive protein (CRP) levels as marker of systemic inflammation in a pan-European patient cohort.

Methods

This cross-sectional analysis of the multicentre European Sleep Apnoea Database (ESADA) cohort used inverse probability weighted regression adjustment for multiple covariates within a linear mixed-effects model (LMEM) to test the independent association between OSA severity and CRP levels. Covariates included anthropometrics and comorbidities. Study centre and year of analysis accounted for methodological variability in CRP analysis.

Results

18 445 subjects (71% male, median age 53 years (interquartile range 44–62), median apnoea–hypopnoea index (AHI) 22.1 events per h (9–44.9)) were included. CRP (median 3.0 mg·L−1 (1.2–5.1)) increased in a dose–response fashion across OSA severity categories (2.0 (1.0–4.0) for AHI <5 events per h; 2.5 (1.0–5.0) for AHI 5–<15 events per h); 2.9 (1.2–5.0) for AHI 15–<30 events per h; and 3.7 mg·L−1 (1.8–6.4) for AHI ≥30 events per h; p<0.001, respectively). In the final LMEM model, AHI remained an independent predictor of CRP concentration (p<0.001). Other significant predictors of CRP were age and female sex. Obesity (body mass index ≥35 kg·m−2) had, among other comorbidities, the strongest independent effect on CRP levels with 2.7 mg·L−1 (95% CI 2.45–2.90).

Conclusions

Our results showed a consistent and robust dose–response relationship between OSA severity and systemic inflammation independent of usual confounders. The combination of OSA and obesity amplified the association. Future studies should address whether elevated CRP could serve as a prognostic marker for subsequent cardiovascular events in OSA.


The ESADA network was supported by the European Union COST action B26 (2005–2009). In addition, the European Respiratory Society (ERS) has funded ESADA as a Clinical Research Collaboration (2015–ongoing). The ResMed Foundation and the Philips Respironics Foundation have provided unrestricted seeding grants for establishment of the database in 2007 and 2011. 24 ESADA centres participate in the EU Horizon 2020-funded Sleep Revolution project (965417).


Last updated on 26/01/2026 11:40:55 AM