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

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.

Association between physical activity, growth differentiation factor 15 and bodyweight in older adults: A longitudinal mediation analysis

“…In accordance with observational data derived from the literature, we found that higher chronic levels in PA were associated with lower GDF‐15 concentrations. These results are consistent with studies demonstrating that resting levels in GDF‐15 are inversely related with both long‐term PA 20 and cardiorespiratory fitness 21 . These findings also support the role of PA in preventing biological aging, because GDF‐15 has been associated with several hallmarks of aging that can be modulated through PA 40 .…”

“…GDF-15 are inversely related with both long-term PA 20 and cardiorespiratory fitness. 21 These findings also support the role of PA in preventing biological aging, because GDF-15 has been associated with several hallmarks of aging that can be modulated through PA. 40 These include telomere attrition, 15 the senescence-associated secretory phenotype (SASP) and mitochondrial dysfunction. In contrast, it has been reported that acute physical exercise 18 and short-term exercise training 19 induce a raise in GDF-15 concentrations, suggesting that PA may exert distinct short-term and long-term effects on GDF-15, as it does on other exerkines such as IL-6, for instance.…”

“…13,14 Besides its role on weight regulation, elevated circulating levels in GDF-15 have also been associated with higher chronological and biological age, 15 higher inflammation 16 and mitochondrial dysfunction. 17 Data on PA demonstrated that an acute bout of exercise, 18 as well as short-period exercise training, 19 induced increases in circulating GDF-15, whereas observational data indicated that higher long-term PA volumes 20 and better cardiorespiratory fitness 21 associate with lower resting GDF-15 levels. Conversely, it has been shown that pharmacologically induced but not exercise-induced increases in circulating GDF-15 suppress food intake, 18 indicating the need for further research on this topic.…”

Physical Inactivity Is Associated With Post-discharge Mortality and Re-hospitalization Risk Among Swedish Heart Failure Patients—The HARVEST-Malmö Study

“…Data from several studies have identified multiple proteins that are associated with HF as well as HF prognosis ( 10 , 11 ). However, while there are data on the association between physical activity and plasma proteins that are associated with cardiovascular disease, they are currently limited in HF populations ( 12 , 13 ). Furthermore, while the role of physical activity as a predictor of mortality and hospitalization has been previously studied, it has oftentimes not specifically studied patients hospitalized for HF.…”