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Cardiovascular disease-linked plasma proteins are mainly associated with lung volume

Andreas Rydell, Elisabet Nerpin, XingWu Zhou, Lars Lind, Eva Lindberg, Jenny Theorell Haglöw, Tove Fall, Christer Janson, Karin Lisspers, Sölve Elmståhl, Suneela Zaigham, Olle Melander, Peter M Nilsson, Johan Ärnlöv, Andrei Malinovschi
ERJ Open Research 2023; DOI: 10.1183/23120541.00321-2022
Andreas Rydell
1Division of Family Medicine and Primary Care, Department of Neurobiology, Care Sciences and Society (NVS), Karolinska Institute, Huddinge, Sweden
2Region Dalarna, Falun, Sweden
8Shared first authorship
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  • For correspondence: ene@du.se
Elisabet Nerpin
3Department of Medical Sciences, Uppsala University, Uppsala, Sweden
4School of Health and Welfare, Dalarna University, Falun, Sweden
8Shared first authorship
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  • ORCID record for Elisabet Nerpin
  • For correspondence: ene@du.se
XingWu Zhou
3Department of Medical Sciences, Uppsala University, Uppsala, Sweden
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Lars Lind
3Department of Medical Sciences, Uppsala University, Uppsala, Sweden
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Eva Lindberg
3Department of Medical Sciences, Uppsala University, Uppsala, Sweden
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Jenny Theorell Haglöw
3Department of Medical Sciences, Uppsala University, Uppsala, Sweden
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Tove Fall
3Department of Medical Sciences, Uppsala University, Uppsala, Sweden
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Christer Janson
3Department of Medical Sciences, Uppsala University, Uppsala, Sweden
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Karin Lisspers
5Department of Public Health and Caring Sciences, Family Medicine and Preventive Medicine, Uppsala University, Uppsala, Sweden
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Sölve Elmståhl
6Department of Clinical Sciences, Lund University, Malmö, Sweden
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Suneela Zaigham
6Department of Clinical Sciences, Lund University, Malmö, Sweden
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Olle Melander
6Department of Clinical Sciences, Lund University, Malmö, Sweden
7Skåne University Hospital, Malmö, Sweden
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Peter M Nilsson
6Department of Clinical Sciences, Lund University, Malmö, Sweden
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Johan Ärnlöv
1Division of Family Medicine and Primary Care, Department of Neurobiology, Care Sciences and Society (NVS), Karolinska Institute, Huddinge, Sweden
2Region Dalarna, Falun, Sweden
4School of Health and Welfare, Dalarna University, Falun, Sweden
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Andrei Malinovschi
3Department of Medical Sciences, Uppsala University, Uppsala, Sweden
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Abstract

Background Impaired lung function is common and associated with increased risk of cardiovascular disease in epidemiological studies. Increased levels of several inflammatory and cardiovascular disease-related plasma proteins have been associated with impaired lung function. The aim was to study the association between plasma proteomics and forced expiratory volume in 1 s (FEV1), forced vital capacity (FVC) and FEV1/FVC ratio.

Methods We used a discovery and replication approach in two community-based cohorts, EpiHealth and the Malmö Offspring Study (total n=2874), to cross-sectionally study 242 cardiovascular disease- and metabolism-linked proteins in relation to FEV1, FVC (both %predicted) and FEV1/FVC ratio. A false discovery rate of 5% was used as the significance threshold in the discovery cohort.

Results Plasma fatty acid-binding protein 4, interleukin-1 receptor antagonist, interleukin-6 and leptin were negatively associated with FEV1 and paraoxonase 3 was positively associated therewith. Fatty acid-binding protein 4, fibroblast growth factor 21, interleukin-1 receptor antagonist, interleukin-6 and leptin were negatively associated with FVC and agouti-related protein, insulin-like growth factor-binding protein 2, paraoxonase 3 and receptor for advanced glycation end products were positively associated therewith. No proteins were associated with FEV1/FVC ratio. A sensitivity analysis in EpiHealth revealed only minor changes after excluding individuals with known cardiovascular disease, diabetes, or obesity.

Conclusions Five proteins were associated with both FEV1 and FVC. Four proteins associated with only FVC and none with FEV1/FVC ratio, suggesting associations mainly through lung volume, not airway obstruction. However, additional studies are needed to investigate underlying mechanisms for these findings.

Footnotes

This manuscript has recently been accepted for publication in the ERJ Open Research. It is published here in its accepted form prior to copyediting and typesetting by our production team. After these production processes are complete and the authors have approved the resulting proofs, the article will move to the latest issue of the ERJOR online. Please open or download the PDF to view this article.

Conflicts of interest: A. Rydell has received lecturing fees from AstraZeneca.

Conflicts of interest: Karin Lisspers has received lecturing fees from AstraZeneca, Novartis and Boehringer Ingelheim; and payments for advisory board membership from AstraZeneca, Boehringer Ingelheim and GlaxoSmithKline.

Conflicts of interest: S. Zaigham has received a research grant from Magnus Bergvalls Stiftelse.

Conflicts of interest: P.M. Nilsson has received lecturing fees from Novartis, Novo Nordisk, Amgen and Boehringer Ingelheim.

Conflicts of interest: J. Ärnlöv has received lecturing fees from AstraZeneca and Novartis and served on advisory boards for AstraZeneca and Boehringer Ingelheim on subjects unrelated to this study.

This is a PDF-only article. Please click on the PDF link above to read it.

  • Received June 30, 2022.
  • Accepted December 4, 2022.
  • Copyright ©The authors 2023
http://creativecommons.org/licenses/by-nc/4.0/

This version is distributed under the terms of the Creative Commons Attribution Non-Commercial Licence 4.0. For commercial reproduction rights and permissions contact permissions{at}ersnet.org

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Cardiovascular disease-linked plasma proteins are mainly associated with lung volume
Andreas Rydell, Elisabet Nerpin, XingWu Zhou, Lars Lind, Eva Lindberg, Jenny Theorell Haglöw, Tove Fall, Christer Janson, Karin Lisspers, Sölve Elmståhl, Suneela Zaigham, Olle Melander, Peter M Nilsson, Johan Ärnlöv, Andrei Malinovschi
ERJ Open Research Jan 2023, 00321-2022; DOI: 10.1183/23120541.00321-2022

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Cardiovascular disease-linked plasma proteins are mainly associated with lung volume
Andreas Rydell, Elisabet Nerpin, XingWu Zhou, Lars Lind, Eva Lindberg, Jenny Theorell Haglöw, Tove Fall, Christer Janson, Karin Lisspers, Sölve Elmståhl, Suneela Zaigham, Olle Melander, Peter M Nilsson, Johan Ärnlöv, Andrei Malinovschi
ERJ Open Research Jan 2023, 00321-2022; DOI: 10.1183/23120541.00321-2022
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