2025

Shoghli, Mohammadreza; Sinisalo, Juha; Lokki, A. Inkeri; Lääperi, Mitja; Lokki, Marja Liisa; Hilvo, Mika; Jylhä, Antti; Tuomilehto, Jaakko; Laaksonen, Reijo

<p>Background: Ceramides (Cers) and phosphatidylcholines (PCs) are potential lipid biomarkers in obstructive pulmonary disease (COPD). Even though they are linked to inflammation and lipid dysregulation, little is known about how these factors affect the prevalence and incidence of COPD in population-based cohorts. This study investigates these associations, addressing knowledge gaps regarding the interplay of Cers, PCs, and COPD risk, focusing on sex-specific differences and smoking. Methods: This observational study analysed data from the population-based FINRISK 2002 cohort, with 7,722 participants for prevalence and 7,662 for incidence analyses. Logistic regression models were used to assess associations between lipid biomarkers and prevalent COPD, while Cox regression models were applied for incident COPD. CERT1 and CERT2 (Cardiovascular Event Risk Test 1 and 2) are lipid-based scores derived from ceramide (Cer) ratios that estimate cardiovascular risk; in this study, they were used to examine their association with COPD. Kaplan-Meier curves were used to evaluate the impact of CERT scores on COPD risk, stratified by smoking status. Results: Elevated CERT1 and CERT2 scores were associated with both prevalent and incident COPD. For CERT1, the association with prevalent COPD was significant (univariable OR = 1.81, 95% CI: 1.41–2.33, p = &lt; 0.001), as was the association with incident COPD (univariable HR = 1.33, 95% CI: 1.16–1.53, p = &lt; 0.001). CERT2 was also significantly associated with prevalent COPD (adjusted OR = 1.57, 95% CI: 1.15–2.16, p = 0.005) and with incident COPD (univariable HR = 1.53, 95% CI: 1.32–1.77, p = &lt; 0.001). PC species (14:0/22:6) was significantly associated with a lower risk of incident COPD (adjusted HR = 0.85, 95% CI: 0.73–0.98, p = 0.023). The Cer(d18:1/18:0)/PC (14:0/22:6) ratio was associated with both prevalent COPD (adjusted OR = 1.37, 95% CI: 1.01–1.86, p = 0.041) and incident COPD (HR = 1.24, 95% CI: 1.07–1.44, p = 0.004). Smokers had an elevated risk of COPD with increasing CERT scores. Conclusion: These findings support the role of lipid biomarkers, particularly Cers and CERT scores, in improving COPD risk prediction and management, with potential implications for targeted interventions in smokers.</p>