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

doi:10.1183/23120541.00321-2022

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

ERJ Open Res. 2023 Mar 27;9(2):00321-2022. doi: 10.1183/23120541.00321-2022. eCollection 2023 Mar.

Authors

Andreas Rydell^{1

2

3}, Elisabet Nerpin^{4

5

3}, XingWu Zhou⁴, Lars Lind⁴, Eva Lindberg⁴, Jenny Theorell Haglöw⁴, Tove Fall⁴, Christer Janson⁴, Karin Lisspers⁶, Sölve Elmståhl⁷, Suneela Zaigham^{4

7}, Olle Melander^{7

8}, Peter M Nilsson⁷, Johan Ärnlöv^{1

2

5}, Andrei Malinovschi⁴

Affiliations

¹ Division of Family Medicine and Primary Care, Department of Neurobiology, Care Sciences and Society (NVS), Karolinska Institute, Huddinge, Sweden.
² Region Dalarna, Falun, Sweden.
³ These authors contributed equally.
⁴ Department of Medical Sciences, Uppsala University, Uppsala, Sweden.
⁵ School of Health and Welfare, Dalarna University, Falun, Sweden.
⁶ Department of Public Health and Caring Sciences, Family Medicine and Preventive Medicine, Uppsala University, Uppsala, Sweden.
⁷ Department of Clinical Sciences, Lund University, Malmö, Sweden.
⁸ Skåne University Hospital, Malmö, Sweden.

Abstract

Background: Epidemiological studies have shown that impaired lung function is common and associated with increased risk of cardiovascular disease. 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.