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Associations between physical activity and CVD-related metabolomic and proteomic biomarkers

Ekblom, Örjan ; Björkbacka, Harry LU orcid ; Börjesson, Mats ; Ekblom-Bak, Elin ; Blomberg, Anders ; Caidahl, Kenneth ; Ehrenborg, Ewa ; Engström, Gunnar LU ; Engvall, Jan and Erlinge, David LU orcid , et al. (2025) In PLOS ONE 20(6 June).
Abstract

Aim Habitual physical activity (PA) affects metabolism and homeostasis in various tissues and organs. However, detailed knowledge of associations between PA and cardiovascular disease (CVD) risk markers is limited. We sought to identify associations between accelerometer-assessed PA classes and 183 proteomic and 154 metabolomic CVD-related biomarkers. Method We utilized cross-sectional data from the main SCAPIS cohort (n = 4647, median age: 57.5 yrs, 50.5% female) as a discovery sample and the SCAPIS pilot cohort (n = 910, median age: 57.5 yrs, 50.3% female) as a validation sample. PA was assessed via hip-worn accelerometers, while plasma concentrations of proteomic biomarkers were measured using Olink CVD II and III panels. Metabolomic... (More)

Aim Habitual physical activity (PA) affects metabolism and homeostasis in various tissues and organs. However, detailed knowledge of associations between PA and cardiovascular disease (CVD) risk markers is limited. We sought to identify associations between accelerometer-assessed PA classes and 183 proteomic and 154 metabolomic CVD-related biomarkers. Method We utilized cross-sectional data from the main SCAPIS cohort (n = 4647, median age: 57.5 yrs, 50.5% female) as a discovery sample and the SCAPIS pilot cohort (n = 910, median age: 57.5 yrs, 50.3% female) as a validation sample. PA was assessed via hip-worn accelerometers, while plasma concentrations of proteomic biomarkers were measured using Olink CVD II and III panels. Metabolomic markers were assessed using the Nightingale NMR platform. We evaluated associations between four PA classes (moderate-to-vigorous PA [MVPA], low-intensity PA [LIPA], sedentary [SED], and prolonged SED [prolSED]) and biomarkers, controlling for potential confounders and applying a false discovery rate of 5% using multiple linear regressions. Results A total of eighty-five metabolomic markers and forty-three proteomic markers were validated and found to be significantly associated with one or more PA classes. LIPA and SED markers demonstrated significant mirroring or opposing relations to biomarkers, while prolSED mainly shared relations with SED. Notably, HDL species were predominantly negatively associated with SED, whereas LDL species were positively associated with SED and negatively associated with MVPA. Among the proteomic markers, eighteen were uniquely associated with MVPA (among those Interleukin – 6 [IL6] and Growth/differentiation factor 15 [GDF15] both negatively related), seven with SED (among those Metalloproteinase inhibitor 4 [TIMP4] and Tumor necrosis factor receptor 2 [TNFR2], both positively related), and eight were related to both SED/prolSED (among those Lipoprotein lipase [LPL] negatively related to SED and leptin [LEP] positively related to SED) and MVPA (with LPL positively related to MVPA and LEP negatively related to MVPA). Conclusion Our findings suggest the existence of specific associations between PA classes and metabolomic and cardiovascular protein biomarkers in a middle-aged population. Beyond validation of previous results, we identified new associations. This multitude of connections between PA and CVD-related markers may help elucidate the previously observed relationship between PA and CVD. The identified cross-sectional associations could inform the design of future experimental studies, serving as important outcome measures.

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organization
publishing date
type
Contribution to journal
publication status
published
subject
in
PLOS ONE
volume
20
issue
6 June
article number
e0325720
publisher
Public Library of Science (PLoS)
external identifiers
  • pmid:40498722
  • scopus:105007909310
ISSN
1932-6203
DOI
10.1371/journal.pone.0325720
language
English
LU publication?
yes
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Publisher Copyright: © 2025 Ekblom et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
id
dc3c3c28-b418-4cb6-8e8b-5805acb313db
date added to LUP
2025-12-17 14:10:03
date last changed
2025-12-18 06:36:52
@article{dc3c3c28-b418-4cb6-8e8b-5805acb313db,
  abstract     = {{<p>Aim Habitual physical activity (PA) affects metabolism and homeostasis in various tissues and organs. However, detailed knowledge of associations between PA and cardiovascular disease (CVD) risk markers is limited. We sought to identify associations between accelerometer-assessed PA classes and 183 proteomic and 154 metabolomic CVD-related biomarkers. Method We utilized cross-sectional data from the main SCAPIS cohort (n = 4647, median age: 57.5 yrs, 50.5% female) as a discovery sample and the SCAPIS pilot cohort (n = 910, median age: 57.5 yrs, 50.3% female) as a validation sample. PA was assessed via hip-worn accelerometers, while plasma concentrations of proteomic biomarkers were measured using Olink CVD II and III panels. Metabolomic markers were assessed using the Nightingale NMR platform. We evaluated associations between four PA classes (moderate-to-vigorous PA [MVPA], low-intensity PA [LIPA], sedentary [SED], and prolonged SED [prolSED]) and biomarkers, controlling for potential confounders and applying a false discovery rate of 5% using multiple linear regressions. Results A total of eighty-five metabolomic markers and forty-three proteomic markers were validated and found to be significantly associated with one or more PA classes. LIPA and SED markers demonstrated significant mirroring or opposing relations to biomarkers, while prolSED mainly shared relations with SED. Notably, HDL species were predominantly negatively associated with SED, whereas LDL species were positively associated with SED and negatively associated with MVPA. Among the proteomic markers, eighteen were uniquely associated with MVPA (among those Interleukin – 6 [IL6] and Growth/differentiation factor 15 [GDF15] both negatively related), seven with SED (among those Metalloproteinase inhibitor 4 [TIMP4] and Tumor necrosis factor receptor 2 [TNFR2], both positively related), and eight were related to both SED/prolSED (among those Lipoprotein lipase [LPL] negatively related to SED and leptin [LEP] positively related to SED) and MVPA (with LPL positively related to MVPA and LEP negatively related to MVPA). Conclusion Our findings suggest the existence of specific associations between PA classes and metabolomic and cardiovascular protein biomarkers in a middle-aged population. Beyond validation of previous results, we identified new associations. This multitude of connections between PA and CVD-related markers may help elucidate the previously observed relationship between PA and CVD. The identified cross-sectional associations could inform the design of future experimental studies, serving as important outcome measures.</p>}},
  author       = {{Ekblom, Örjan and Björkbacka, Harry and Börjesson, Mats and Ekblom-Bak, Elin and Blomberg, Anders and Caidahl, Kenneth and Ehrenborg, Ewa and Engström, Gunnar and Engvall, Jan and Erlinge, David and Fall, Tove and Gigante, Bruna and Gummesson, Anders and Jernberg, Tomas and Lind, Lars and Molnar, David and Oldgren, Jonas and Rawshani, Aidin and Sundström, Johan and Söderberg, Stefan and Wennberg, Patrik and Östgren, Carl Johan}},
  issn         = {{1932-6203}},
  language     = {{eng}},
  number       = {{6 June}},
  publisher    = {{Public Library of Science (PLoS)}},
  series       = {{PLOS ONE}},
  title        = {{Associations between physical activity and CVD-related metabolomic and proteomic biomarkers}},
  url          = {{http://dx.doi.org/10.1371/journal.pone.0325720}},
  doi          = {{10.1371/journal.pone.0325720}},
  volume       = {{20}},
  year         = {{2025}},
}