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

## TL;DR

This study finds that certain blood proteins linked to heart disease are associated with lung gas exchange function, even in people without lung obstruction.

## Contribution

This is the first population-based proteomic study to assess DLCO in relation to cardiovascular disease proteins, independent of lung obstruction.

## Key findings

- 18 CVD-linked plasma proteins were negatively associated with DLCO after adjusting for multiple factors.
- 11 of these proteins remained significant even after excluding individuals with airflow obstruction.
- Many of the significant proteins are involved in pro-fibrotic and pro-inflammatory processes.

## Abstract

There are known associations between cardiovascular disease (CVD)-related plasma proteins and spirometry measures. Diffusing capacity for carbon monoxide (DLCO) measures gas exchange that can be impaired both by lung and heart diseases. We aimed to study the associations between DLCO and CVD-linked plasma proteins in a population-based cohort without airflow obstruction.

89 CVD-linked proteins were analysed in 427 individuals who underwent spirometry examination with DLCO 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 FEV1/VC ratio < the lower limit of normal (LLN) and steps were taken to ensure a false discovery rate under 5%.

We found 18 proteins negatively associated with DLCO%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 (FEV1/VC < LLN).

Several CVD-linked plasma proteins were associated with DLCO 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.

The online version contains supplementary material available at 10.1186/s12014-026-09584-6.

Cardiovascular disease is associated with low lung function. To establish the underlying mechanisms studies have found a link between CVD-associated plasma proteins and FEV1 and FVC but no population-based proteomic studies assessing DLCO have been carried out.We found several CVD-associated plasma proteins related to DLCO, independent of obstruction on spirometry, many of which are linked to profibrotic or proinflammatory processes.The mechanisms of the significant proteins can give us a better understanding of the potential pathophysiological processes that link DLCO to CVD outcomes.

Cardiovascular disease is associated with low lung function. To establish the underlying mechanisms studies have found a link between CVD-associated plasma proteins and FEV1 and FVC but no population-based proteomic studies assessing DLCO have been carried out.

We found several CVD-associated plasma proteins related to DLCO, independent of obstruction on spirometry, many of which are linked to profibrotic or proinflammatory processes.

The mechanisms of the significant proteins can give us a better understanding of the potential pathophysiological processes that link DLCO to CVD outcomes.

The online version contains supplementary material available at 10.1186/s12014-026-09584-6.