Endothelial dysfunction is a hallmark of cardiovascular disease (CVD) and plays a central role in vascular inflammation, thrombosis, and impaired vasodilation. A study led by researchers from Miguel Hernández University of Elche (UMH) and the Alicante Institute for Health and Biomedical Research (ISABIAL) identifies high-intensity interval exercise (HIIE) as the most robust and evidence-based strategy to improve endothelial function in patients with CVD.
The findings, published in the European Journal of Preventive Cardiology, are based on a systematic review and network meta-analysis of 37 studies that included 6,818 adult patients with coronary artery disease or chronic heart failure. The analysis compared different exercise modalities and intensities, including moderate-intensity aerobic exercise (MAE), high-intensity interval exercise (HIIE), resistance exercise (RE), and combined training programs.
Exercise intensity matters
All exercise modalities—except moderate-intensity resistance exercise alone—improved endothelial function compared with usual care. However, the magnitude of improvement varied significantly depending on exercise intensity and structure.
High-intensity interval exercise emerged as the most consistent and effective intervention. Compared with moderate continuous aerobic exercise, HIIE produced greater improvements in flow-mediated dilation (FMD), the gold-standard non-invasive measure of endothelial function.
"HIIE appears as the most robust option based on current evidence," explains UMH professor José Manuel Sarabia, co-leader of the study. "It consistently outperforms moderate-intensity continuous exercise in improving vascular function."
This exercise modality alternates short bursts of high-intensity effort with recovery periods. This pattern generates repeated fluctuations in blood flow and shear stress—the frictional force exerted by blood on vessel walls—which are key stimuli for endothelial adaptation.
Increased shear stress enhances nitric oxide (NO) bioavailability, a critical mediator of vasodilation and vascular health. These mechanisms explain why higher-intensity exercise produces stronger endothelial responses than moderate continuous training.
The analysis also suggests that longer high-intensity intervals may be more effective than shorter ones, though further head-to-head studies are needed to confirm this.
Combined high-intensity training programs (aerobic plus resistance exercise) showed the largest estimated effects on endothelial function. However, these results were based on limited evidence from a single intervention group and should be interpreted cautiously.
Moderate-intensity aerobic exercise also improved vascular function, though to a lesser extent. In contrast, resistance training alone did not show significant effects, possibly due to shorter intervention durations and limited available data.
Clinical implications for cardiac rehabilitation
Cardiovascular diseases remain the leading cause of death worldwide. Improving endothelial function is associated with reduced cardiovascular risk and better clinical outcomes.
"These findings help refine exercise prescriptions in cardiac rehabilitation," says Laura Fuertes Kenneally, cardiologist at Alicante General University Hospital and first author of the study. "They support moving toward more personalized and effective training programs."
The results suggest that HIIE could be integrated as a primary or complementary strategy within cardiac rehabilitation programs, provided it is performed under appropriate clinical supervision.
The study also highlights that exercise-induced improvements were specific to endothelial function, with no significant changes observed in endothelium-independent vasodilation. This indicates that adaptations occur primarily at the endothelial level rather than in vascular smooth muscle.
Beyond identifying the most effective modality, the study underscores that not all forms of exercise produce the same physiological benefits. Intensity, structure, and individual patient characteristics play a decisive role in vascular adaptation.
The authors emphasize the need for further high-quality randomized trials to confirm the potential of combined high-intensity programs and to better understand how factors such as age, disease type, and supervision influence outcomes.
