Long-term of Remote Ischemic Preconditioning and Mindfulness in Patients With Hypertension

This was a multicenter, randomized, sham-controlled, 2×2 factorial clinical trial conducted at five hospitals in China. A total of 600 patients with essential hypertension were enrolled between September 2023 and August 2024 and randomly assigned in a 1:1:1:1 ratio to four intervention groups:

1. Control group: sham remote ischemic conditioning (RIC) combined with nature-sound audio.
2. RIC group: active RIC combined with nature-sound audio.
3. Mindfulness group: sham RIC combined with guided mindfulness intervention.
4. Combination group: active RIC combined with guided mindfulness intervention.

Active RIC consisted of three cycles of upper-arm cuff inflation for 6 minutes followed by deflation for 4 minutes, with a total session duration of 30 minutes. Inflation pressure was individualized according to baseline systolic blood pressure using predefined pressure increments. Sham RIC followed the same inflation-deflation schedule with a cuff pressure of 60 mmHg.

The mindfulness intervention consisted of standardized audio-guided mindfulness practice delivered simultaneously with the cuff intervention. The control audio consisted of natural sounds, such as ocean waves, flowing water, and birdsong, without hypertension education or mindfulness instructions. Both interventions were administered twice daily for 12 months.

Home blood pressure was measured repeatedly throughout the study using an automated monitoring system. The primary outcome was the change in pre-intervention home systolic blood pressure from baseline to 12 months. Additional assessments included diastolic blood pressure, longitudinal blood pressure trajectories, blood pressure control and response rates, immediate blood pressure responses, treatment adherence, and adverse events.

Selected circulating biomarkers were also measured in a subset of participants for mechanistic investigations.

The study was designed to assess the independent and combined effects of RIC and mindfulness-based intervention on long-term blood pressure control.

CRIC :Twice daily for 12 months using an automated cuff device. Each 30-minute session consisted of 3 cycles of 6 min inflation (pressure individualized: resting SBP-based increments of +40/+30/+20 mmHg depending on baseline SBP level) followed by 4 min deflation (0 mmHg).

MFT:Twice daily guided audio sessions (synchronized with CRIC timing) emphasizing focused attention on breath and bodily sensations to foster mindful awareness.

Device: CRIC · Behavioral: MFT

Sham CRIC: Identical schedule and device; each cycle used fixed 5 min inflation at 60 mmHg (non-ischemic) followed by 5 min deflation.

MFT: Twice daily guided audio sessions (synchronized with CRIC timing) emphasizing focused attention on breath and bodily sensations to foster mindful awareness.

Behavioral: MFT · Other: sham CRIC

CRIC :Twice daily for 12 months using an automated cuff device. Each 30-minute session consisted of 3 cycles of 6 min inflation (pressure individualized: resting SBP-based increments of +40/+30/+20 mmHg depending on baseline SBP level) followed by 4 min deflation (0 mmHg).

Sham MFT: Twice daily equivalent-duration audio of looped neutral nature sounds (ocean waves, flowing water, birdsong) without mindfulness instructions.

Device: CRIC · Other: sham MFT

Sham CRIC: Identical schedule and device; each cycle used fixed 5 min inflation at 60 mmHg (non-ischemic) followed by 5 min deflation.

Sham MFT: Twice daily equivalent-duration audio of looped neutral nature sounds (ocean waves, flowing water, birdsong) without mindfulness instructions.

Other: sham CRIC · Other: sham MFT

Remote Ischemic Conditioning (CRIC): Twice daily for 12 months using an automated cuff device. Each 30-minute session consisted of 3 cycles of 6 min inflation (pressure individualized: resting SBP-based increments of +40/+30/+20 mmHg depending on baseline SBP level) followed by 4 min deflation (0 mmHg).

Mindfulness-based intervention (MFT) consisted of standardized audio-guided mindfulness practice focusing on breath awareness, bodily sensations, and nonjudgmental present-moment awareness. Each session lasted approximately 30 minutes and was delivered twice daily for 12 months, synchronized with the CRIC or sham CRIC procedure.

Mindfulness-based intervention (MFT) consisted of standardized audio-guided mindfulness practice focusing on breath awareness, bodily sensations, and nonjudgmental present-moment awareness. Each session lasted approximately 30 minutes and was delivered twice daily for 12 months, synchronized with the CRIC or sham CRIC procedure.

The control audio consisted of standardized recordings of natural sounds, including ocean waves, flowing water, and birdsong, without mindfulness instructions, breathing exercises, or hypertension-related health education. Each audio session lasted approximately 30 minutes and was delivered twice daily for 12 months, synchronized with the CRIC or sham CRIC procedure.

Plazo: Baseline (screening days -7 to -1) and Month 12 (days 335-364 after randomization)

Change in mean pre-intervention home systolic blood pressure (SBP) from screening baseline to the 12-month endpoint window. Home blood pressure was measured twice daily using an automated device. Three measurements were obtained before each intervention session; the first reading was excluded, and the mean of the remaining two readings was used. The 12-month endpoint was calculated as the mean of valid pre-intervention SBP measurements during days 335-364 after randomization. Participants with at least 20 valid measurement sessions during this window were included in the primary endpoint analysis. The outcome was expressed in mmHg.

Plazo: Baseline (screening days -7 to -1) and Month 12 (days 335-364)

Change in mean pre-intervention home diastolic blood pressure (DBP) from screening baseline to the 12-month endpoint window. Home blood pressure was measured twice daily using an automated device. Three measurements were obtained before each intervention session; the first reading was discarded, and the mean of the remaining two readings was used. The 12-month endpoint was calculated as the mean of valid pre-intervention DBP measurements during days 335-364 after randomization. Changes were expressed in mmHg.

Plazo: Baseline and Days 30, 90, 180, and 270 after randomization

Changes in mean pre-intervention home systolic blood pressure (SBP) from screening baseline at multiple follow-up time points. Home SBP was measured twice daily using an automated device, with the mean of the second and third pre-intervention readings used for each session. Window-mean SBP values were calculated around days 30, 90, 180, and 270 after randomization to characterize the longitudinal blood pressure response to the assigned interventions. Changes were expressed in mmHg.

Plazo: Baseline and Month 12 (days 335-364)

Proportion of participants achieving a reduction of at least 5 mmHg in mean pre-intervention home systolic blood pressure from screening baseline to the 12-month endpoint window (days 335-364 after randomization). The response rate was calculated as the number of participants meeting this threshold divided by the number of participants with evaluable endpoint data, expressed as a percentage.

Plazo: Month 12 (days 335-364)

Proportion of participants achieving home blood pressure control, defined as a mean pre-intervention home systolic blood pressure below 135 mmHg and a mean pre-intervention home diastolic blood pressure below 85 mmHg during the 12-month endpoint window (days 335-364 after randomization). Blood pressure control rates were expressed as percentages among participants with evaluable endpoint data.

Plazo: Month 12 (days 335-364)

Proportion of participants achieving home blood pressure control using a less stringent threshold, defined as a mean pre-intervention home systolic blood pressure below 140 mmHg and a mean pre-intervention home diastolic blood pressure below 90 mmHg during the 12-month endpoint window (days 335-364 after randomization). Blood pressure control rates were expressed as percentages among participants with evaluable endpoint data.

Plazo: Throughout the 12-month intervention period

The immediate blood pressure response was assessed as the difference between post-intervention and pre-intervention home systolic blood pressure within each treatment session. Three consecutive blood pressure measurements were obtained before and after each session, with the first reading excluded and the mean of the remaining two readings used for each time point. The participant-level mean of post-intervention minus pre-intervention SBP differences was calculated across available sessions. Between-group comparisons relative to the double-sham control group were used to estimate the net immediate intervention effect, expressed in mmHg.

Long-term of Remote Ischemic Preconditioning and Mindfulness in Patients With Hypertension