RT Journal Article SR Electronic T1 Cardiovascular disease-linked plasma proteins are mainly associated with lung volume JF ERJ Open Research JO erjor FD European Respiratory Society SP 00321-2022 DO 10.1183/23120541.00321-2022 A1 Andreas Rydell A1 Elisabet Nerpin A1 XingWu Zhou A1 Lars Lind A1 Eva Lindberg A1 Jenny Theorell Haglöw A1 Tove Fall A1 Christer Janson A1 Karin Lisspers A1 Sölve Elmståhl A1 Suneela Zaigham A1 Olle Melander A1 Peter M Nilsson A1 Johan Ärnlöv A1 Andrei Malinovschi YR 2023 UL http://openres.ersjournals.com/content/early/2022/12/08/23120541.00321-2022.abstract AB 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.FootnotesThis 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.