This study aims to evaluate whether remote ischemic preconditioning (RIPC) daily for 28 days reduces the symptoms of intermittent claudication in patients with peripheral artery disease (PAD). The study evaluates the effect of RIPC on patients' total walking distance (TWC), initial claudication distance (ICD), and time to relief of claudication (TRC). In addition, the trial investigates the effect of RIPC on different arterial functional characteristics and low molecular weight metabolites in serum and affected skeletal muscle.

A research hypothesis is that repeated remote ischemic preconditioning (RIPC) daily for 28 days reduces the symptoms of intermittent claudication in patients with peripheral artery disease (PAD).

The investigators plan to conduct a randomized controlled trial. Clinically stable patients with PAD and intermittent claudication are randomly allocated to receive a repeated RIPC or sham for 28 days. An automated device generates RIPC. One cycle of RIPC consists of 4 cycles of 5-min upper limb ischemia followed by 5-min reperfusion (lasting a total of 35 minutes). The participant places the device on his upper arm and presses the "Start "button, starting the intervention. The intervention occurs at rest in the participant's home environment. The first intervention takes place in the research center, where the research assistant teaches the participant how to use the device. In the sham group, a RIPC imitation is performed. The sham device has the same sound and light effects as the active device; the only difference is that the pressure in the cuff does not increase, so ischemia does not occur.

Randomization is performed using blocks. Each block has 2-4 subjects. Subjects are divided according to smoking status (active smoker yes/no) and age (≥ 65 years or < 65 years old). Randomized letters (whether the subject will go into the experimental group or the sham group) are placed in opaque envelopes, which are opened right before the first intervention.

Participants will visit the research center twice. During the first visit, they fill in the VASCUQOL-6 questionnaire to evaluate their symptoms and health-related quality of life. In addition, the investigators collect participants' blood and urine samples, measure their arterial stiffness parameters and assess symptom-free and maximal walking distance on a treadmill. The investigators will take a skeletal muscle biopsy from the first ten participants in each group using a tiny percutaneous needle biopsy (TPNB) technique to measure low molecular weight metabolites in affected skeletal muscle.

These steps are repeated on the second visit (after 28 days of intervention). After data collection is completed, a statistical analysis is performed to evaluate whether RIPC improves participants' maximal walking distance, arterial stiffness, and metabolic parameters.

Inclusion Criteria:

• Peripheral arterial disease, which causes claudication
• Patients who have given written informed consent and are undergoing conservative treatment for claudication (continuous treatment for at least three months)
• Patients with lower limb atherosclerosis Fontaine class IIA or IIB
• The primary limiter of walking is claudication, not any other condition
• Ankle-brachial index (ABI) ≤ 0,9 in symptomatic lower limb

Exclusion Criteria:

• Female gender
• Resting blood pressure > 200 mmHg
• Fontaine class III or IV
• eGFR < 30 ml/min/1,73 m2
• Home oxygen therapy or severe COPD (GOLD 3-4)
• Heart failure NYHA III-IV
• Stable angina pectoris
• Clinically severe COVID-19 infection in the last three months
• History of malignancy (within the last five years)
• Persistent or permanent atrial fibrillation or flutter
• Acute myocardial infarction in the last three months
• Residual signs of cerebral infarction that impede movement
• Significant atherosclerosis of peripheral arteries of the upper limb (symptomatic)
• History of deep vein thrombosis of the upper limb
• Diabetic polyneuropathy
• Under 18 years of age
• Patients who are unable to follow the study regimen