Preventive Arterial Wall Phenotype and Low-dose Fluvastatin/Valsartan Combination

Study Overview
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Brief Summary
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The study was designed to test whether short-term treatment with a very low-dose combination of fluvastatin and valsartan could induce improvement of endothelial function, arterial stiffness, vascular inflammation, oxidative stress and expression of protective genes in subjects with moderate cardiovascular risk.

Detailed Description
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The largest population that suffers from cardiovascular events are subjects at moderate cardiovascular risk. However, no effective and safe preventive treatment is available for this population. This study aimed to investigate whether their arterial wall phenotype could be turned to a preventive direction by low-dose fluvastatin/valsartan combination (low-flu/val). Twenty males at moderate cardiovascular risk (as classified by SCORE) were blindly randomised into the intervention group (n=10, low-flu/val: 10 mg/20mg) or control group (n=10, placebo). At inclusion and after 30 days of treatment, brachial flow-mediated dilatation (FMD), beta stiffness coefficient, carotid pulse wave velocity (c-PWV), carotid-femoral PWV, reactive hyperaemia index, high-sensitivity C-reactive protein (hs-CRP), interleukin 6, vascular cell adhesion molecule 1, total antioxidant status and expression of several protective genes (SIRT1, mTOR, NF-κB1, NFE2L2, PRKAA1) were followed.

Official Title
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Preventive Arterial Wall Phenotype in Subjects at Moderate Cardiovascular Risk Induced by Very Low-dose Fluvastatin/Valsartan Combination: a Pilot Study

Conditions
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Atherosclerosis

Intervention / Treatment
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* Drug: fluvastatin 10 mg and valsartan 20 mg
* Drug: placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: moderate cardiovascular risk according to Systematic Coronary Risk Estimation (SCORE) risk charts of the European Society of Cardiology males aged between 40 and 55 years Exclusion Criteria: diabetes mellitus manifest peripheral artery disease or carotid artery disease acute infection chronic diseases present therapy with fluvastatin and/or valsartan

Ages Eligible for Study
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Minimum Age: 40 Years
Maximum Age: 55 Years

Sexes Eligible for Study
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Male

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: intervention group<br>received fluvastatin 10 mg and valsartan 20 mg (low-flu/val) for 30 days | Drug: fluvastatin 10 mg and valsartan 20 mg<br> <br> * Other names: low-flu/val;|
| Placebo Comparator: control group<br>received placebo for 30 days | Drug: placebo<br> <br> |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| brachial flow-mediated dilatation (FMD) | FMD measured by ultrasound on right brachial artery (as result of reactive hyperaemia) | 30 days | 
| reactive hyperaemia index (RHI) | RHI measured by Endopat device | 30 days | 
| beta stiffness coefficient | assessed by ultrasound employing e-Tracking on right common carotid artery | 30 days | 
| carotid pulse wave velocity (c-PWV) | assessed by ultrasound employing e-Tracking on right common carotid artery | 30 days | 
| carotid-femoral PWV (cf-PWV) | cf-PWV measured by Sphygmocor device | 30 days | 
| high-sensitivity C-reactive protein (hs-CRP) | inflammatory marker | 30 days | 
| interleukin 6 (IL-6) | inflammatory marker | 30 days | 
| vascular cell adhesion molecule 1 (VCAM1) | inflammatory marker | 30 days | 
| total antioxidant status (TAS) | marker of oxidative stress | 30 days | 
| gene SIRT1 | Hs01009006_m1 | 30 days | 
| gene mTOR | Hs00234522_m1 | 30 days | 
| gene NF-kB1 | Hs00765730_m1 | 30 days | 
| gene Nrf2/NFE2L2 | Hs00975961_g1 | 30 days | 
| gene AMPK/PRKAA1 | Hs01562315_m1 | 30 days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| brachial flow-mediated dilatation (FMD) | FMD measured by ultrasound on right brachial artery (as result of reactive hyperaemia) | 10 weeks after treatment completion | 
| reactive hyperaemia index (RHI) | RHI measured by Endopat device | 10 weeks after treatment completion | 
| beta stiffness coefficient | assessed by ultrasound employing e-Tracking on right common carotid artery | 10 weeks after treatment completion | 
| carotid pulse wave velocity (c-PWV) | assessed by ultrasound employing e-Tracking on right common carotid artery | 10 weeks after treatment completion | 
| carotid-femoral PWV (cf-PWV) | cf-PWV measured by Sphygmocor device | 10 weeks after treatment completion | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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arterial stiffness, endothelial dysfunction, fluvastatin, valsartan, inflammatory markers, oxidative stress, SIRT1