Karolinska Severe Asthma Center, Department of Respiratory Medicine and Allergy, Karolinska University Hospital, Stockholm, Sweden; Division of Lung and Airway Research, Institute of Environmental Medicine, Karolinska Institutet, and Center for Molecular Medicine, Stockholm, Sweden; Lung Laboratory, Centre for Molecular Medicine, Karolinska University Hospital, Stockholm, Sweden.
Region Västra Götaland, Sahlgrenska University Hospital, Department of Clinical Physiology, Gothenburg, Sweden; Department of Clinical Physiology, Karolinska University Hospital, and Karolinska Institutet, Stockholm, Sweden.
Section of Occupational and Environmental Medicine, School of Public Health and Community Medicine, Institute of Medicine, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden.
Department of Clinical Sciences Lund, Respiratory Medicine, Allergology and Palliative Medicine, Lund university, Lund, Sweden.
Department of Clinical Physiology, and Department of Health, Medicine, and Caring Sciences, Linköping University, Linköping, Sweden; CMIV, Centre of Medical Image Science and Visualization, Linköping University, Linköping, Sweden.
Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine.
Centre for Sleep and Vigilance Disorders, Department of Internal Medicine and Clinical Nutrition, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden; Sleep Disorders Centre, Pulmonary Medicine, Sahlgrenska University Hospital, Gothenburg, Sweden.
Region Västra Götaland, Sahlgrenska University Hospital, Department of Clinical Genetics and Genomics, Gothenburg, Sweden; Department of Molecular and Clinical Medicine, Institute of Medicine, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden.
Department of Clinical Sciences, Lund University and Department of Cardiology, Skåne University Hospital, Malmö, Sweden.
Department of Medical Sciences, Respiratory, Allergy and Sleep Research, Uppsala University, Uppsala, Sweden.
Department of Health, Medicine and Caring Sciences and Department of Clinical Physiology and Wallenberg Centre for Molecular Medicine, Linköping University, Linköping, Sweden.
Department of Medical Sciences, Respiratory, Allergy and Sleep Research, Uppsala University, Uppsala, Sweden.
Division of Lung and Airway Research, Institute of Environmental Medicine, Karolinska Institutet, and Center for Molecular Medicine, Stockholm, Sweden; Karolinska Severe COPD Center, Department of Respiratory Medicine and Allergy, Karolinska University Hospital, Stockholm, Sweden.
Department of Medical Sciences, Respiratory, Allergy and Sleep Research, Uppsala University, Uppsala, Sweden.
Department of Health, Medicine and Caring Sciences, Linköping University, Linköping, Sweden; Department of Respiratory Medicine in Linköping, Linköping University, Linköping, Sweden.
Division of Immunology and Respiratory Medicine, Department of Medicine, Karolinska Institutet, Solna, Stockholm, Sweden; Department of Respiratory Medicine and Allergy, Karolinska University Hospital, Stockholm, Sweden.
Department of Clinical Sciences Lund, Respiratory Medicine, Allergology and Palliative Medicine, Lund university, Lund, Sweden.
COPD Center, Department of Internal Medicine and Clinical Nutrition, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden.
Department of Medical Sciences, Clinical Physiology, Uppsala University, Uppsala, Sweden.
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. R
ESULTS: 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 FEV1 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.
Elsevier, 2025. Vol. 249, article id 108463