A1 Refereed original research article in a scientific journal

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




AuthorsGrote, 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)

Publication year2025

Journal: ERJ Open Research

Article number00707-2025

Volume12

Issue1

eISSN2312-0541

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

Publication's open availability at the time of reportingOpen Access

Publication channel's open availability Open Access publication channel

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

Self-archived copy’s web addresshttps://research.utu.fi/converis/portal/detail/Publication/508526321

Self-archived copy's licenceCC BY NC

Self-archived copy's versionPublisher`s PDF


Abstract
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.


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Funding information in the publication
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