The Long-term Effect of Remote Ischemic Conditioning on Main Organs in ASVCD Patients With Very High Risks

• remote ischemic conditioning (Device): 5 cycles of cuff inflation for 5 minutes and deflation for 5 minutes to the bilateral upper limbs to 200 mmHg

Primary outcomes

• Incidence of Composite Endpoint Events [1 year]: including cardiovascular events, stroke, vascular death, and deterioration of renal function.

Secondary outcomes

• Number of participants with no-fatal cardiovascular events [1 year]
• Number of participants with no-fatal stroke [1 year]
• Number of participants with no-fatal deterioration of renal function [1 year]
• Change of renal function [1 year]: renal function was meausred by serum urea nitrogen and creatinine
• Change of blood pressure [1 year]
• Changes in serological indicators such as blood glucose, blood lipids, and glycated hemoglobin (HbA1c) [1 year]: Changes in the following serological indicators will be assessed and reported as separate outcome measures: Blood glucose (in mmol/L or mg/dL) Blood lipids \[specify component, e.g., LDL-C, in mmol/L or mg/dL\] Glycated hemoglobin (HbA1c) (in %)
• Number of participants with new onset diabetes [1 year]
• Occurence of vascular death [1 year]
• Barthel Index (BI) scores [1 year]: BI ranges from 0-100, higher scores meaning a better outcome.
• Death due to all causes [1 year]

Other outcomes

• Changes in cerebral small vessel disease burden (CSVD) [1 year]: The total CSVD score is calculated by the following four neuroimaging features on MRI: lacunes, white matter hyperintensities, cerebral microbleeds and perivascular spaces (PVS). The score ranges from 0-4, with high score meaning heavier burden.
• Changes in cognitive function measured by MoCA and MMSE [1 year]: The Montreal Cognitive Assessment (MoCA) (score range: 0-30) and The Mini-Mental State Examination (MMSE) (score range: 0-30), with higher score meaning better cognitive function
• Depressive symptoms measured by the Patient Health Questionnaire-9 (PHQ-9) [1 year]: range from 0-27, higher score meaning worse symptoms
• Anxiety symptoms measured by the Generalized Anxiety Disorder-7 (GAD-7) [1 year]: range from 0-21, higher score meaning worse symptoms
• Changes in cerebral autoregulation [1 year]: cerebral autoregulation is measured by using TCD and Transfer Function Analysis

Sex: All, ages: 40 Years to any

Inclusion Criteria:

* Age over 40 years
* Two or more prior major ASCVD events; OR one documented major ASCVD event with two or more of the following risk factors
* signed informed consent

Note： Definition of Major ASCVD Events:

A. Acute coronary syndrome within the past year. B. History of myocardial infarction (not part of a new acute coronary syndrome episode).

C. Ischemic stroke or history of ischemic stroke. D. Symptomatic peripheral artery disease, defined as intermittent claudication with an ankle-brachial index (ABI) < 0.85, or prior limb revascularization or amputation.

Risk factors:

1. Age ≥65 y
2. Heterozygous familial hypercholesterolemia
3. History of prior coronary artery bypass surgery or percutaneous coronary intervention outside of the major
4. ASCVD event(s)
5. Diabetes mellitus
6. Hypertension
7. CKD (eGFR 15-59 mL/min/1.73 m2)
8. Current smoking
9. Persistently elevated LDL-C (LDL-C ≥100 mg/dL \[≥2.6 mmol/L\]) despite maximally tolerated statin therapy and ezetimibe
10. History of congestive HF

Exclusion Criteria:

* Presence of severe neurological deficit (mRS score ≥ 3)
* Uncontrolled severe hypertension (systolic blood pressure > 180 mmHg or diastolic blood pressure > 110 mmHg despite medication)
* Subclavian artery stenosis ≥ 50% or presence of subclavian steal syndrome
* Severe hematological disorders or significant coagulation abnormalities
* Contraindications to remote ischemic conditioning, such as severe soft tissue injury, fracture, or vascular injury in the upper limbs, or peripheral vascular disease in the distal upper limbs
* Severe comorbid conditions with a life expectancy of less than 1 year
* Participation in another clinical trial within the past 3 months or ongoing participation
* Any other circumstances deemed by the investigator as unsuitable for participation in this clinical study.