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
Authors: 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
Publisher: European Respiratory Society (ERS)
Publication year: 2025
Journal: ERJ Open Research
Article number: 00707-2025
Volume: 12
Issue: 1
eISSN: 2312-0541
DOI: https://doi.org/10.1183/23120541.00707-2025
Publication's open availability at the time of reporting: Open 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 address: https://research.utu.fi/converis/portal/detail/Publication/508526321
Self-archived copy's licence: CC BY NC
Self-archived copy's version: Publisher`s PDF
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.
MethodsThis 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.
Results18 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).
ConclusionsOur 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).