Association between Cardiorespiratory Fitness and Circulating Proteins in 50-Year-Old Swedish Men and Women: a Cross-Sectional Study

Malin Enarsson; Tobias Feldreich; Liisa Byberg; Christoph Nowak; Lars Lind; Johan Ärnlöv

doi:10.1186/s40798-021-00343-5

Association between Cardiorespiratory Fitness and Circulating Proteins in 50-Year-Old Swedish Men and Women: a Cross-Sectional Study

Sports Med Open. 2021 Jul 26;7(1):52. doi: 10.1186/s40798-021-00343-5.

Authors

Malin Enarsson¹, Tobias Feldreich², Liisa Byberg³, Christoph Nowak⁴, Lars Lind⁵, Johan Ärnlöv^{6

7}

Affiliations

¹ Center for Clinical Research Dalarna, Uppsala University, Region Dalarna, Nissers väg 3, 79182, Falun, Sweden.
² School of Health and Social Studies, Dalarna University, 79188, Falun, Sweden.
³ Department of Surgical Sciences, Orthopedics, Uppsala University, Dag Hammarskjölds väg 14, B 75185, Uppsala, Sweden.
⁴ Division of Family Medicine and Primary Care, Department of Neurobiology, Care Sciences and Society (NVS), Karolinska Institutet, Alfred Nobels Allé 23, 14183, Huddinge, SE, Sweden.
⁵ Department of Medical Sciences, Uppsala University, Dag Hammarskölds väg 10B, 75237, Uppsala, Sweden.
⁶ School of Health and Social Studies, Dalarna University, 79188, Falun, Sweden. johan.arnlov@ki.se.
⁷ Division of Family Medicine and Primary Care, Department of Neurobiology, Care Sciences and Society (NVS), Karolinska Institutet, Alfred Nobels Allé 23, 14183, Huddinge, SE, Sweden. johan.arnlov@ki.se.

Abstract

Background and aims: A strong cardiorespiratory fitness is suggested to have beneficial effects on cardiovascular risk; the exact mechanisms underlying the cardioprotective effects of fitness remain uncertain. Our aim was to investigate associations between cardiorespiratory fitness and multiple plasma proteins, in order to obtain insights about physiological pathways associated with the effects of exercise on cardiovascular health.

Methods: In the Prospective investigation of Obesity, Energy and Metabolism (POEM) study (n=444 adults aged 50 years, 50% women), cardiorespiratory fitness was measured by a maximal exercise test on bicycle ergometer with gas exchange (VO₂peak) normalized for body lean mass (dual-energy X-ray absorptiometry (DXA)). We measured 82 cardiovascular proteins associated with cardiovascular pathology and inflammation in plasma samples with a proximity extension assay.

Results: In sex-adjusted linear regression, VO₂peak was associated with 18 proteins after Bonferroni correction for multiple testing (p<0.0006). Following additional adjustment for fat mass (DXA), fasting glucose (mmol/L), low-density lipoprotein (LDL, mmol/L), smoking status, waist/hip ratio, blood pressure (mmHg), education level, and lpnr (lab sequence number), higher VO₂peak was significantly associated with lower levels of 6 proteins: fatty-acid binding protein-4 (FABP4), interleukin-6 (IL-6), leptin, cystatin-B (CSTB), interleukin-1 receptor antagonist (IL-1RA), and growth differentiation factor 15 (GDF-15), and higher levels of 3 proteins: galanin, kallikrein-6 (KLK6), and heparin-binding EGF-like growth factor (HB-EGF), at nominal p-values (p<0.05).

Conclusions: We identified multiple novel associations between cardiorespiratory fitness and plasma proteins involved in several atherosclerotic processes and key cellular mechanisms such as inflammation, energy homeostasis, and protease activity, which shed new light on how exercise asserts its beneficial effects on cardiovascular health. Our findings encourage additional studies in order to understand the underlying causal mechanisms for these associations.

Keywords: Biomarkers; Cardiorespiratory fitness; Proteomics.