Impact of Aerobic Exercise on Endothelial Function and Other Cardiovascular Disease Markers in Health and Disease: A Systematic Review and Meta-analysis with Meta-regression of Randomized Controlled Trials

Background Aerobic exercise (AE) has long been recognized as a potent stimulus for improving various cardiovascular disease (CVD)-related markers. Although several meta-analyses have focused on some of these markers, no meta-analysis or meta-regression has comprehensively evaluated the influence of multiple CVD-related markers on endothelial function, assessed by brachial-artery flow-mediated dilation ( ba FMD). Methods This meta-analysis and meta-regression included randomized controlled trials investigating the effect of AE on ba FMD. The primary outcome was pre- to post-intervention changes in ba FMD. Secondary outcomes included endothelial blood biomarkers, hemodynamic measurements, cardiorespiratory fitness, body composition, glucose metabolism, and lipid profile. Pre- to post-intervention changes were summarized using a randomeffects model. Meta-regression analyses were performed to explore whether changes in secondary outcomes moderated changes in ba FMD. Results Seventy-two studies comprising 3357 participants were included. AE significantly improved ba FMD (mean difference = 2.35%, p < 0.001), corresponding to an estimated 24% reduction in CVD risk. Significant improvements were observed across multiple CVD-related markers. Meta-regression revealed that changes in body weight and body fat ( β = − 4.021 and − 1.721), systolic and diastolic blood pressure ( β = − 0.525 and − 0.484), maximal oxygen uptake ( β = 0.656), and insulin levels ( β = 0.381) significantly moderated ba FMD improvements. Conclusions AE elicits robust improvements in endothelial function and a wide range of CVD-related markers. This is the first meta-analysis to integrate these outcomes through meta-regression, demonstrating that exercise induced enhancements in body composition, cardiorespiratory fitness, blood pressure and insulin regulation collectively contribute to endothelial adaptations. These findings provide new mechanistic insights into the vascular benefits of AE and reinforce its role as a potent nonpharmacological strategy for CVD prevention and vascular health optimization. The protocol was prospectively registered in the Open Science Framework online registry (DOI: https://doi.org/10.17605/OSF.IO/E4QYD ).