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

Zaigham, Suneela LU ; Liv, Per ; Chorell, Elin ; Behndig, Annelie ; Bossios, Apostolos ; Caidahl, Kenneth ; Olin, Anna Carin ; Egesten, Arne LU ; Engvall, Jan and Eriksson Ström, Jonas , et al. (2025) In Respiratory Medicine 249.
Abstract

Background: 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. Aim: To investigate relationships between CVD-associated plasma proteins and lung function. Methods: 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... (More)

Background: 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. Aim: To investigate relationships between CVD-associated plasma proteins and lung function. Methods: 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. Results: 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). Conclusions: Multiple CVD-associated proteins, mainly reflecting inflammatory and metabolic processes, were associated with reduced FEV1and 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.

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organization
publishing date
type
Contribution to journal
publication status
published
subject
in
Respiratory Medicine
volume
249
article number
108463
publisher
Elsevier
external identifiers
  • pmid:41183685
  • scopus:105022411954
ISSN
0954-6111
DOI
10.1016/j.rmed.2025.108463
language
English
LU publication?
yes
additional info
Publisher Copyright: © 2025 The Authors. Published by Elsevier Ltd. This is an open access article under the CC BY license. http://creativecommons.org/licenses/by/4.0/
id
eb000354-7e58-4120-9881-92c9d5f673e7
date added to LUP
2026-01-22 14:59:33
date last changed
2026-01-23 02:25:00
@article{eb000354-7e58-4120-9881-92c9d5f673e7,
  abstract     = {{<p>Background: 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. Aim: To investigate relationships between CVD-associated plasma proteins and lung function. Methods: 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 FEV<sub>1</sub>, FVC, and FEV<sub>1</sub>/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. Results: A total of 69 proteins were associated with FEV<sub>1</sub>, 57 with FVC, and 9 with FEV<sub>1</sub>/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 (FEV<sub>1</sub>: β = −0.50, 95 % CI: [-0.69, −0.31], p &lt; 0.001; FVC: β = −0.52, 95 % CI: [-0.68, −0.35], p &lt; 0.001 per-SD increase). Conclusions: Multiple CVD-associated proteins, mainly reflecting inflammatory and metabolic processes, were associated with reduced FEV<sub>1</sub>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.</p>}},
  author       = {{Zaigham, Suneela and Liv, Per and Chorell, Elin and Behndig, Annelie and Bossios, Apostolos and Caidahl, Kenneth and Olin, Anna Carin and Egesten, Arne and Engvall, Jan and Eriksson Ström, Jonas and Frølich, Andreas and Grote, Ludger and Gummesson, Anders and Hamrefors, Viktor and Janson, Christer and Kylhammar, David and Lindberg, Eva and Lindén, Anders and Ljunggren, Mirjam and Persson, Hans Lennart and Sköld, Magnus and Tufvesson, Ellen and Vanfleteren, Lowie egw and Malinovschi, Andrei and Blomberg, Anders}},
  issn         = {{0954-6111}},
  language     = {{eng}},
  month        = {{11}},
  publisher    = {{Elsevier}},
  series       = {{Respiratory Medicine}},
  title        = {{Plasma proteins associated with cardiovascular disease in relation to lung function in SCAPIS}},
  url          = {{http://dx.doi.org/10.1016/j.rmed.2025.108463}},
  doi          = {{10.1016/j.rmed.2025.108463}},
  volume       = {{249}},
  year         = {{2025}},
}