Cardiovascular disease-linked plasma proteins are mainly associated with lung volume

Epidemiological studies have shown that impaired lung function is common and associated with increased risk of cardiovascular disease. Increased levels of several inflammatory and cardiovascular disease-related plasma proteins have been associated with impaired lung function. The aim was to study the association between plasma proteomics and forced expiratory volume in 1 s (FEV₁), forced vital capacity (FVC) and FEV₁/FVC ratio.

We used a discovery and replication approach in two community-based cohorts, EpiHealth and the Malmö Offspring Study (total n=2874), to cross-sectionally study 242 cardiovascular disease- and metabolism-linked proteins in relation to FEV₁, FVC (both % predicted) and FEV₁/FVC ratio. A false discovery rate of 5% was used as the significance threshold in the discovery cohort.

Plasma fatty acid-binding protein 4, interleukin-1 receptor antagonist, interleukin-6 and leptin were negatively associated with FEV₁ and paraoxonase 3 was positively associated therewith. Fatty acid-binding protein 4, fibroblast growth factor 21, interleukin-1 receptor antagonist, interleukin-6 and leptin were negatively associated with FVC and agouti-related protein, insulin-like growth factor-binding protein 2, paraoxonase 3 and receptor for advanced glycation end products were positively associated therewith. No proteins were associated with FEV₁/FVC ratio. A sensitivity analysis in EpiHealth revealed only minor changes after excluding individuals with known cardiovascular disease, diabetes or obesity.

Five proteins were associated with both FEV₁ and FVC. Four proteins associated with only FVC and none with FEV₁/FVC ratio, suggesting associations mainly through lung volume, not airway obstruction. However, additional studies are needed to investigate underlying mechanisms for these findings.