Effect of exercise modality and intensity on endothelial function in patients with cardiovascular disease: a systematic review and network meta-analysis

Abstract

Aims: Endothelial dysfunction is a hallmark of cardiovascular disease (CVD). Exercise effectively improves endothelial function, yet the impact of different modalities and intensities remains unclear. This study evaluated the effect of aerobic (AE), resistance (RE), and combined exercise (CE) on endothelial function measured by flow-mediated dilation (FMD). Methods and results: A systematic review and frequentist network meta-analysis of randomized and non-randomized trials in adults with coronary artery disease or chronic heart failure was conducted. Electronic databases were searched up to April 2025. Interventions were classified as usual care (UC), moderate-intensity AE (MAE), high-intensity interval AE (HIIE), moderate-intensity RE (MRE), high-intensity RE (HRE), moderate-intensity CE (MCE), and high-intensity CE (HCE). Mean differences (MD) with 95% confidence intervals (CI) were used as effect size index, and interventions were ranked using surface under the cumulative ranking curve (SUCRA). Thirty-seven studies (80 groups; n = 6818) were included. Compared with UC, MAE (2.04%; 95% CI: 1.01–3.07), HIIE (3.47%; 95% CI: 2.02–4.92), MCE (2.71%; 95% CI: 0.05–5.36), and HCE (8.25%; 95% CI: 3.18–13.32) significantly improved brachial FMD, whereas MRE did not. HIIE outperformed MAE (1.43%; 95% CI: 0.09–2.78). Although HCE showed the highest surface under the cumulative ranking curve (SUCRA: 98.2%), this relied on a single group. Crucially, sensitivity analyses confirmed HIIE as the most robust high-performing intervention (84.0%) compared with MRE (61.6%) and MCE (61.3%). Conclusion: Exercise significantly enhances endothelial function in patients with CVD. HIIE emerged as the most robust and evidence-based modality, demonstrating superior efficacy over moderate continuous exercise. While high-intensity combined protocols (HCE) show significant theoretical potential, randomized trials are urgently needed to confirm their efficacy. Current evidence supports HIIE as a primary strategy for vascular adaptation in cardiac rehabilitation. - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - Lay summary This network meta-analysis confirms that structured exercise training effectively improves endothelial function in patients with cardiovascular disease. • High-intensity interval training offers the most robust benefits across different ages and conditions, proving superior to moderate-intensity continuous exercise. • A progressive training strategy is recommended to maximize long-term results, starting with moderate exercise for conditioning and advancing to high-intensity or resistance exercise.