Plasma proteins associated with cardiovascular disease in relation to lung function in SCAPIS

Low lung function has been consistently associated with increased cardiovascular disease (CVD) risk, with emerging evidence suggesting a potential causal relationship. However, underlying biological mechanisms remain unclear.

To investigate relationships between CVD-associated plasma proteins and lung function.

We analysed plasma protein profiles in two Swedish population-based cohorts: the Swedish CArdioPulmonary bioImage Study (SCAPIS) (n = 4,982, mean age 57.6 years) as the discovery cohort and the SCAPIS pilot study (n = 1,054, mean age 57.7 years) for replication. Multiple linear regression models were used to assess associations between 92 CVD-associated proteins and z-scores of FEV₁, FVC, and FEV₁/FVC, adjusting for known confounders. P-values were corrected using the Benjamini-Hochberg method (5% FDR). Significantly associated proteins were validated in the replication cohort.

A total of 69 proteins were associated with FEV₁, 57 with FVC, and 9 with FEV₁/FVC. Several inflammatory proteins and adipokines, including leptin, interleukin-6, fatty acid-binding protein (adipocyte), were consistently linked to lower lung function. Leptin had the strongest negative association (FEV₁: β = -0.50, 95 % CI: [-0.69, -0.31], p < 0.001; FVC: β = -0.52, 95 % CI: [-0.68, -0.35], p < 0.001 per-SD increase).

Multiple CVD-associated proteins, mainly reflecting inflammatory and metabolic processes, were associated with reduced FEV₁ and FVC, supporting a link between systemic inflammation, adipokine metabolism and impaired lung function. Leptin had the strongest association, suggesting that its effects on lung function may extend beyond adiposity. Further research is needed to clarify the mechanisms driving these associations and to assess whether these proteins could serve as early biomarkers or intervention targets.