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

Zaigham, Suneela LU ; Zhou, Xingwu ; Dencker, Magnus LU ; Frantz, Sophia LU ; Kraen, Morten LU ; Wollmer, Per LU and Malinovschi, Andrei LU (2026) In Clinical Proteomics 23(1).
Abstract

Background: 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. Methods: 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).... (More)

Background: 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. Methods: 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%. Results: 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). Conclusions: 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.

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author
; ; ; ; ; and
organization
publishing date
type
Contribution to journal
publication status
published
subject
in
Clinical Proteomics
volume
23
issue
1
article number
11
publisher
Humana Press
external identifiers
  • scopus:105030997102
  • pmid:41622130
ISSN
1542-6416
DOI
10.1186/s12014-026-09584-6
language
English
LU publication?
yes
additional info
Publisher Copyright: © The Author(s) 2026.
id
0fd5104f-ce04-4ebb-a1d2-e2962eaf34de
date added to LUP
2026-04-16 13:49:28
date last changed
2026-04-17 03:00:06
@article{0fd5104f-ce04-4ebb-a1d2-e2962eaf34de,
  abstract     = {{<p>Background: There are known associations between cardiovascular disease (CVD)-related plasma proteins and spirometry measures. Diffusing capacity for carbon monoxide (D<sub>LCO</sub>) measures gas exchange that can be impaired both by lung and heart diseases. We aimed to study the associations between D<sub>LCO</sub> 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<sub>LCO</sub> 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<sub>1</sub>/VC ratio &lt; 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<sub>LCO</sub>%predicted after full adjustments (GLI reference equations). Eleven of these proteins (Fibroblast growth factor 23 (estimated coefficients, (adjusted p-value)): -0.010 (&lt; 0.001), Matrix metalloproteinase-12; -0.011 (&lt; 0.001), Growth differentiation factor 15: -0.008 (&lt; 0.001), C-C motif chemokine 20: -0.013 (0.006), Interleukin-6: -0.014 (&lt; 0.001), Fatty acid-binding protein, adipocyte − 0.007 (0.001), Urokinase-type plasminogen activator receptor: -0.004 (&lt; 0.001), Interleukin-1 receptor antagonist: -0.008 (&lt; 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<sub>1</sub>/VC &lt; LLN). Conclusions: Several CVD-linked plasma proteins were associated with D<sub>LCO</sub> 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.</p>}},
  author       = {{Zaigham, Suneela and Zhou, Xingwu and Dencker, Magnus and Frantz, Sophia and Kraen, Morten and Wollmer, Per and Malinovschi, Andrei}},
  issn         = {{1542-6416}},
  language     = {{eng}},
  number       = {{1}},
  publisher    = {{Humana Press}},
  series       = {{Clinical Proteomics}},
  title        = {{Diffusing capacity for carbon monoxide is significantly associated with cardiovascular disease-related plasma proteins, independently of obstruction}},
  url          = {{http://dx.doi.org/10.1186/s12014-026-09584-6}},
  doi          = {{10.1186/s12014-026-09584-6}},
  volume       = {{23}},
  year         = {{2026}},
}