INTRODUCTION
Stroke is a major cause of long-term disability worldwide, significantly impacting the quality of life of survivors and placing considerable strain on healthcare systems. Globally, the incidence and prevalence of stroke continue to rise, with the number of stroke cases projected to increase substantially in the coming decades [
1]. While stroke recovery typically peaks within the first six months, evidence indicates that intensive and continuous rehabilitation interventions in the chronic phase can yield additional functional improvements [
2,
3].
Aerobic exercise is a critical component of stroke rehabilitation, aimed at addressing reduced cardiovascular fitness, which is prevalent among stroke survivors due to autonomic dysfunction and reduced physical activity [
4]. Reduced cardiovascular fitness significantly impacts stroke survivors’ physical function and increases the risk of recurrent strokes due to unfavorable lipid profiles, including elevated low-density lipoprotein (LDL), triglycerides (TG), and decreased high-density lipoprotein (HDL) levels [
5].
High-intensity interval training (HIIT) has recently emerged as an effective aerobic training modality that can significantly enhance cardiovascular health, aerobic capacity, and functional mobility compared to traditional moderate-intensity continuous training (MICT). A systematic review and meta-analysis demonstrated that HIIT significantly improved maximal oxygen uptake (VO
2max), walking distance (e.g., 6-Minute Walk Test, 6MWT), and cardiovascular health indicators compared to MICT in stroke patients [
6]. Similarly, another randomized controlled trial indicated greater improvements in aerobic capacity, gait speed, and functional mobility following HIIT compared to moderate-intensity exercise in chronic stroke survivors [
7].
However, MICT remains widely used due to its established efficacy in improving cardiovascular health and mobility outcomes among stroke survivors. Long-term MICT interventions have demonstrated significant benefits, including reduced arterial stiffness, improved lipid profiles, and enhanced quality of life, suggesting their continued relevance in rehabilitation settings [
8].
Despite emerging evidence highlighting the advantages of HIIT, comparative research directly evaluating HIIT and MICT conducted via face-to-face supervised rehabilitation sessions in chronic stroke populations remains limited. Therefore, this study aims to evaluate and directly compare the effectiveness of face-to-face supervised HIIT vs. MICT interventions on cardiovascular function, mobility, and physical activity levels in chronic stroke survivors. The findings from this study will provide critical clinical insights, potentially guiding optimal rehabilitation practices to enhance stroke survivors’ functional outcomes and cardiovascular health.
DISCUSSION
This study rigorously compared the effects of HIIT and MICT on cardiovascular function, gait ability, and hematological variables among chronic stroke survivors, demonstrating clear, differential benefits associated with training intensity. As an effort check at CPX termination, the proportion achieving ≥90% of the age-predicted HRmax was high and comparable between groups, supporting the validity of maximal/near-maximal testing in this sample (
Supplementary Table S4). Session-level ECG analyses showed rapid attainment of the prescribed high-intensity targets and prompt re-entry to ≤60% HRR between intervals, indicating high protocol fidelity and feasibility of HR-targeted HIIT in this cohort (
Supplementary Table S2).
In interpreting these findings, it is pertinent that the program was delivered three times per week for six weeks and evaluated immediately post-intervention. Under our exposure-matched schedule (3 sessions/week×6 weeks), the MICT arm maintained a stable 60%–80% HRmax workload with minimal ≥80% exposure and no prolonged overshoot confirming adherence to a truly moderate prescription yet this stimulus was not associated with a detectable post-intervention improvement in peak cardiorespiratory fitness (VO
2max) in this higher-functioning cohort, whereas a higher relative stimulus with HIIT was observed to improve VO
2max (see
Supplementary Table S3C for MICT intensity distribution;
Supplementary Table S3A for HIIT exposure). Evidence from shorter and longer protocols using a thrice-weekly schedule indicates that clinically meaningful adaptations can emerge within a comparable time window when intensity and task specificity are prioritized. A 4-week, 3×/week preliminary randomized study in ambulatory chronic stroke showed that treadmill-based HIIT yielded moderate-to-very-large between-group effect-size estimates at post-intervention for aerobic capacity and walking outcomes, supporting the capacity of brief high-intensity exposure to initiate central and peripheral cardiopulmonary adaptation [
9]. Complementarily, an 8-week, 3×/week multicenter RCT reported post-intervention improvements in walking distance and balance with treadmill-based HIIT and noted that only executive function (Trail Making Test-B) remained significant at 12-month follow-up, while superiority in peak aerobic capacity over the long term was not sustained together with our results, this pattern suggests that the most prominent cardiopulmonary effects of HIIT emerge early and require continued training for persistence [
10,
14]. From a mechanistic perspective, interval prescriptions at high relative intensity accelerate stroke-volume augmentation, endothelial adaptation, and skeletal-muscle mitochondrial remodeling with a modest weekly time dose, providing a rationale for robust effects over six weeks at three sessions per week [
15,
16]. Positioned against higher-dose comparators, a 24-week randomized trial contrasting MICT (five days/week) with a HIIT-based regimen demonstrated greater improvements in VO
2peak with HIIT while walking-distance gains were similar between groups, underscoring that intensity is the primary driver of cardiorespiratory fitness, whereas endurance-type walking performance may converge over time [
12]. These dose duration timing considerations were explicitly accounted for when aligning the present findings with prior literature (our assessment: post-6 weeks; comparators: post-4 weeks and post-8 weeks with an additional 12-month follow-up) [
9,
10,
14].
Our results revealed significant improvements in cardiovascular parameters, particularly VO
2max and HRmax, within the HG. The short time to 80%/90% HRmax during 1-minute intervals and the consistent 4-minute recovery to ≤60% HRR suggest that intensity dosing was delivered as intended while preserving recovery capacity, a pattern that aligns with established HR on/off kinetics and supports the translatability of HR-guided interval prescriptions to post-stroke rehabilitation. The observed enhancement in VO
2max is consistent with previous studies emphasizing HIIT’s superior capacity for augmenting cardiovascular fitness through central and peripheral adaptations such as increased stroke volume, mitochondrial density, and endothelial function [
15,
17]. Additionally, a considerable effect size underscores the marked physiological response elicited by high-intensity training modalities, reinforcing the robust cardiovascular benefit of HIIT in chronic stroke populations.
In contrast to HG, the MG showed only minimal and non-significant changes in VO
2max and HRmax after six weeks of thrice-weekly training. This likely reflects the limited training dose, as moderate-intensity continuous exercise generally produces measurable cardiovascular adaptations only after longer (≥12 weeks) and more frequent (≥5 sessions per week) protocols [
9,
12]. In addition, our participants were relatively high-functioning chronic stroke survivors (FAC≥4, BBS≥41), leaving little margin for further improvement in aerobic capacity within such a short timeframe. Taken together, these factors explain the absence of significant VO
2max improvement in the MG. Nevertheless, previous research has shown that MICT can yield cardiovascular benefits when applied over longer durations and higher frequencies, suggesting that the lack of effect here reflects the limited intervention dose and participant characteristics rather than an inherent inefficacy of MICT. Fidelity analyses further confirmed that participants performed the training as prescribed: thresholds of ≥60%/≥70%/≥80% HRmax were typically reached within minutes of session onset and then maintained predominantly within the 60%–80% band, with minimal exposure above 80% HRmax (
Supplementary Table S3); groupwise background-care dose (setting, sessions per week, and minutes per session) is summarized in
Supplementary Table S1. This pattern indicates that MICT provided a stable and controlled aerobic workload, with high target adherence and minimal overshoot, even though it did not elicit significant cardiovascular improvements within the short study period.
The principal finding of this trial is that HIIT produced substantially greater improvements in cardiovascular fitness compared with MICT. The HG demonstrated marked gains in VO2max and HRmax, and importantly, also showed a significant reduction in heart rate while walking, suggesting improved cardiovascular efficiency during submaximal functional activity. By contrast, changes in the MG were negligible. These results emphasize that short-term, thrice-weekly HIIT is sufficient to produce measurable cardiovascular adaptations, whereas MICT may require longer duration and higher frequency to achieve comparable benefits.
Functional mobility assessments revealed pronounced improvements in gait parameters, including the 10MWT, TUG, and 6MWT, notably superior within the HG. The significant reductions in time observed in the 10MWT and TUG, and improved endurance reflected by enhanced 6MWT performance, align with findings by Gjellesvik et al. [
10] and Lau and Mak [
18], highlighting that HIIT promotes muscular adaptations crucial for improved neuromuscular coordination and endurance. These adaptations are instrumental in translating enhanced physiological capacity into tangible functional improvements, critical for daily life activities in chronic stroke survivors.
Interestingly, MICT also showed beneficial effects on functional mobility, although smaller compared to HIIT. The consistent yet modest improvements in gait speed and mobility observed in the MG corroborate evidence suggesting its utility in scenarios requiring gentler physiological adjustments and gradual improvements in functional capacity [
9].
Hematological analysis showed small but statistically significant within-arm improvements in LDL, HDL, and TG in the HG at six weeks, without a group×time interaction; all lipid samples were obtained after a standardized 12-hour fast with identical procedures, and lipid-lowering medications were neither used at entry nor changed during the intervention (see Methods and Participants). A single aerobic session lowers very low density lipoprotein triglycerides (VLDL-TG) the next day and for up to ~2–3 days by increasing plasma clearance and (in some cohorts) modestly reducing hepatic secretion demonstrated directly with human stable-isotope tracer kinetics [
19]. When this stimulus is repeated three times per week, these 24–72 hour windows overlap and accumulate, so TG fall first, with smaller, slower shifts in LDL/HDL emerging over several weeks [
19]. Over weeks, interval training can also reduce hepatic VLDL-TG secretion rate in humans [
20], and exercise transiently up-regulates skeletal-muscle lipoprotein-lipase, which accelerates removal of triglyceride-rich lipoproteins and reinforces the early fall in TG when bouts are repeated [
21]. In these data, HIIT sessions consistently reached the prescribed high-relative-intensity bouts with recovery between bouts (
Supplementary Tables S2,
S3), whereas the dose-matched MICT arm was kept predominantly in the 60%–80% HRmax band with minimal ≥80% exposure (
Supplementary Table S3C); consequently, a small but detectable within-HIIT improvement at six weeks is physiologically coherent under medication-neutral, conditions, while MICT shows no detectable change over the same horizon.
This study has several limitations that warrant consideration. First, the six-week intervention period precludes firm conclusions about durability; longer follow-up (e.g., ≥3–6 months) is needed to clarify maintenance of effects. Second, participants were treated in both inpatient and outpatient settings, and a subset of outpatients received additional conventional therapy at other institutions. Inpatients (HIIT: 11, MICT: 8) typically completed the three supervised study sessions per week plus two routine 60-minute sessions, whereas most outpatients (HIIT: 4, MICT: 6) attended only the three study sessions, with a small number receiving extra sessions elsewhere (1–2 sessions/week). To limit bias, the intervention was defined a priori as the protocolized sessions only, and any outside-institution therapy was prospectively logged and treated as non-exposure. Importantly, descriptive summaries in
Supplementary Table S1 indicate no material between-group difference in background rehabilitation dose, and participants did not change care setting during the intervention. Nonetheless, unmeasured co-interventions cannot be completely excluded. Beyond these internal-validity considerations, generalizability is bounded to higher-functioning, ambulatory chronic stroke survivors; applicability to lower-functioning or non-ambulatory populations requires dedicated evaluation. Given the high intensity involved, HIIT may pose risks for patients with significant cardiovascular comorbidities or severely impaired physical function. Therefore, careful patient screening and risk assessment are imperative when translating HIIT protocols to clinical practice. Future studies should explore the feasibility, safety, and specific strategies for adapting HIIT across a broader spectrum of stroke severity and clinical settings to enhance applicability. Finally, two measurement/analysis constraints warrant mention: time-to-target and exposure metrics were derived post hoc from session ECGs and summarized descriptively (not prespecified outcomes), and mechanical speed/workload was not standardized across treadmill and cycle sessions because prescription was HR-based; accordingly, emphasis was placed on modality-agnostic, HR-derived attainment and recovery metrics.
In conclusion, this study provides robust evidence advocating for HIIT as a highly effective rehabilitation strategy for improving cardiovascular fitness, gait performance, and metabolic profiles in chronic stroke survivors. It also reinforces the continuing relevance of MICT, particularly for patients who require more gradual physiological adaptations, underscoring the necessity of individualized rehabilitation approaches based on patient-specific functional capacities and goals.
Conclusion
In higher-functioning chronic stroke survivors, HIIT was superior to MICT for cardiovascular fitness and functional mobility under a matched exposure, while lipid changes occurred within the HIIT arm only without between-group differences. These results support incorporating HIIT for appropriately selected higher-functioning patients and highlight the need to evaluate applicability in lower-functioning cohorts. Future studies should investigate long-term effects and optimal implementation strategies of HIIT for sustained stroke rehabilitation outcomes.