Work

Diffusing capacity for carbon monoxide is significantly associated with cardiovascular disease-related plasma proteins, independently of obstruction

Year: 2026

Type: article

Abstract: Background There are known associations between cardiovascular disease (CVD)-related plasma proteins and spirometry measures. Diffusing capacity for carbon monoxide (D LCO ) measures gas exchange that can be impaired both by lung and heart diseases. We aimed to study the associations between D LCO and CVD-linked plasma proteins in a population-based cohort without airflow obstruction. Methods 89 CVD-linked proteins were analysed in 427 individuals who underwent spirometry examination with D LCO measurement. Analyses were adjusted for age, gender, height, weight, smoking status and pack years, plates, storage time and cardiovascular morbidity (carotid plaques, hypertension and cardiac medication). Furthermore, a sensitivity analysis ( n = 362) was carried out after excluding subjects with an FEV 1 /VC ratio < the lower limit of normal (LLN) and steps were taken to ensure a false discovery rate under 5%. Results We found 18 proteins negatively associated with D LCO %predicted after full adjustments (GLI reference equations). Eleven of these proteins (Fibroblast growth factor 23 (estimated coefficients, (adjusted p-value)): -0.010 (< 0.001), Matrix metalloproteinase-12; -0.011 (< 0.001), Growth differentiation factor 15: -0.008 (< 0.001), C-C motif chemokine 20: -0.013 (0.006), Interleukin-6: -0.014 (< 0.001), Fatty acid-binding protein, adipocyte − 0.007 (0.001), Urokinase-type plasminogen activator receptor: -0.004 (< 0.001), Interleukin-1 receptor antagonist: -0.008 (< 0.001), TNF-related apoptosis-inducing ligand receptor 2: -0.005 (0.001), Renin: -0.008 (0.03) and Spondin-1: -0.003 (0.03)) remained significant after further excluding subjects with obstruction on spirometry (FEV 1 /VC < LLN). Conclusions Several CVD-linked plasma proteins were associated with D LCO in subjects without airflow obstruction on spirometry and after adjustments for known cardiovascular morbidity. The likely explanations may be the pro-fibrotic and pro-inflammatory nature of many of the proteins causing changes in gas exchange. These proteins could potentially signal for early disease mechanisms leading to impaired gas exchange.

Source: Clinical Proteomics

DOI: 10.1186/s12014-026-09584-6