LDL-c Level Variability and Trained Immunity

Study Overview
=================
Brief Summary
-----------------
Statin treatment significantly reduces the incidence of cardiovascular events. However, cholesterol variability is associated with the risk of adverse events such as mortality, myocardial infarction, and stroke. The previous research found that the inflammatory activity of peripheral blood mononuclear cells in mice fed with intermittent high-fat diet was significantly increased, and the cholesterol variability had an impact on the trained immunity of peripheral blood mononuclear cells, thus aggravating the atherosclerosis in mice. We plan to compare the differences in serum LDL-C levels after intermittent atorvastatin treatment and continuous atorvastatin treatment, and investigate the impact of this difference on the trained immunity of peripheral blood mononuclear cells.

Official Title
-----------------
Continuous Atorvastatin Therapy Compared With Intermittent Atorvastatin Therapy for the Effect of LDL-c Level Variability and the Regulation of Trained Immunity

Conditions
-----------------
Cholesterol Variability, Trained Immunity

Intervention / Treatment
-----------------
* Drug: Atorvastatin


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Voluntarily participate, understand and sign an informed consent form; Age ≥ 18 years old, male or postmenopausal female (defined as amenorrhea over 2 years with relevant clinical characteristics, such as age over 55 years old or menopausal cardiovascular symptoms such as hot flashes, night sweats, palpitations, etc.). Women with hysterectomy and/or bilateral oophorectomy may also be considered for inclusion in the group; Commit to complying with research procedures and cooperate in the implementation of the entire process of research; 4、LDL-c>3.4mmol/L Exclusion Criteria: Previous cardiovascular history; Statins should not be discontinued in high-risk groups for cardiovascular events; Any known organ dysfunction; Intolerance to statins; Pregnant women, lactating women, or women of childbearing age who do not use effective contraception; Participating in other clinical trials; Unable to follow the study procedure.

Ages Eligible for Study
-----------------
Minimum Age: 18 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
Accepts Healthy Volunteers

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Atorvastatin<br> | Drug: Atorvastatin<br>* Patients are treated with atorvastatin for 2 weeks (40 mg/day), atorvastatin free for 2 weeks, atorvastatin treatment for 2 weeks, atorvastatin free for 2 weeks, a 4-week washout period (no treatment), and atorvastatin treatment for the last 4 weeks.<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Changes in LDL-C levels between baseline and atorvastatin treatment cycles | in the phase of atorvastatin intermittent treatment and continuous treatment | 16 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| PBMCs subgroup percentage and activation status | in the phase of atorvastatin intermittent treatment and continuous treatment | 16 weeks | 
| PBMCs secreting cytokines | in the phase of atorvastatin intermittent treatment and continuous treatment | 16 weeks | 
| Differences in gene expression of PBMCs | in the phase of atorvastatin intermittent treatment and continuous treatment | 16 weeks | 
| The levels of hs-CRP, IL-6, IL-18, and sVCAM-1 | in the phase of atorvastatin intermittent treatment and continuous treatment | 16 weeks |