What type of study is this?

This is a Cross-Sectional Study study (also classified as: Quantitative Study).

September 12, 2025Open Access

Dose-response relationship between Obstructive Sleep Apnoea severity and C-reactive protein levels: Data from the European Sleep Apnoea Database

LGLudger GroteSahlgrenska University Hospital HGHaralampos GouverisJohannes Gutenberg University Mainz LLLea LethuillierInserm

Key Points

A dose-response relationship exists between OSA severity and C-reactive protein levels, showcasing a clear increase with higher severity.
CRP levels showed significant differences across OSA severity categories, with a median of 3.7 mg·L −1 for severe cases (AHI ≥30/h).
Inverse probability weighted regression adjustment within a linear mixed-effects model examined the associations while controlling for multiple covariates.
Findings support elevated CRP as a marker for systemic inflammation linked to cardiovascular risks in patients with OSA.

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 multi-centre 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 (interquartile range: 44; 62) years, median Apnoea-hypopnoea index (AHI) 22.1 9; 44.9 events·h −1 ) were included. CRP (median 3.0 1.2; 5.1 mg·L −1 ) increased in a dose-response fashion across OSA severity categories (2.0 1.0;4.0 for AHI<5/h; 2.5 1.0; 5.0 for AHI 5≤15/h); 2.9 1.2; 5.0 for AHI 15-<30/h; and 3.7 1.8; 6.4 mg·L −1 for AHI ≥30/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 (BMI ≥35 kg·m −2 ) had among other comorbidities the strongest independent effect on CRP levels with 2.7 (95% CI 2.45; 2.90) mg·L −1 . 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 if elevated CRP could serve as a prognostic marker for subsequent cardiovascular events in OSA.

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