Abstract
Background and AimsA 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.MethodsIn 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.ResultsIn 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).ConclusionsWe 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.
Highlights
Cardiorespiratory fitness is a strong and independent predictor of cardiovascular disease (CVD) and all-cause mortality [1,2,3,4,5,6,7,8]
Poor cardiorespiratory fitness has been associated with elevated proinflammatory markers, such as C-reactive protein (CRP) and interleukin-6 (IL-6) [35,36,37,38] and proteins involved in lipid metabolism and atherosclerotic processes [26, 34, 39]
In sex-adjusted linear regression, higher VO2peak normalized for lean mass was associated with lower levels of proteins: fatty-acid binding protein-4 (FABP4), interleukin-6 (IL-6), leptin, cystatin-B (CSTB), interleukin-1 receptor antagonist (IL-1RA), growth differentiation factor-15 (GDF-15), tissue-type plasminogen activator, cathepsin-D (CTSD), hepatocyte growth factor (HGF), e-selectin (SELE), follistatin (FS), fibroblast growth factor-23 (FGF23), tumor necrosis factor ligand superfamily member (TNFSF14); and higher levels of 5 proteins: galanin (GAL), kallikrein-6 (KLK6), heparinbinding EGF-like growth factor (HB-EGF), stem cell factor (SCF), and vascular endothelial growth factor D (VEGF-D), after taking the multiple testing into account using Bonferroni correction (p
Summary
Cardiorespiratory fitness is a strong and independent predictor of cardiovascular disease (CVD) and all-cause mortality [1,2,3,4,5,6,7,8]. Cardiorespiratory fitness has been shown to be a more powerful predictor of CVD compared to traditional risk factors, e.g., hypertension, dyslipidemia, metabolic syndrome, diabetes, smoking, and leisure time physical activity [5, 9, 10]. A strong cardiorespiratory fitness is suggested to have beneficial effects on cardiovascular risk factors such as diabetes [20], hypertension [21, 22], dyslipidemia [23], metabolic syndrome, and obesity [12, 24,25,26,27] These beneficial effects appear independent of weight reduction, as studies have shown reduced risk of CVD and allcause mortality among individuals regardless of weight loss [10, 16, 26, 28, 29]. 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
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Free) 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
