Clinical trial NCT03393377: Preventive Arterial Wall Phenotype and Low-dose Fluvastatin/Valsartan Combination
Official title: Preventive Arterial Wall Phenotype in Subjects at Moderate Cardiovascular Risk Induced by Very Low-dose Fluvastatin/Valsartan Combination: a Pilot Study
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Atherosclerosis
Keywords: arterial stiffness
endothelial dysfunction
fluvastatin
valsartan
inflammatory markers
oxidative stress
SIRT1
Lead sponsor: University Medical Centre Ljubljana
Sponsor class: OTHER
First posted: 2018-01-08
Enrollment: 20
Sex: MALE
Minimum age (years): 40
Maximum age (years): 55
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: PREVENTION

Brief summary: 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: 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.

Eligibility criteria: 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

Primary outcomes:
measure: brachial flow-mediated dilatation (FMD)
timeFrame: 30 days
measure: reactive hyperaemia index (RHI)
timeFrame: 30 days
measure: beta stiffness coefficient
timeFrame: 30 days
measure: carotid pulse wave velocity (c-PWV)
timeFrame: 30 days
measure: carotid-femoral PWV (cf-PWV)
timeFrame: 30 days
measure: high-sensitivity C-reactive protein (hs-CRP)
timeFrame: 30 days
measure: interleukin 6 (IL-6)
timeFrame: 30 days
measure: vascular cell adhesion molecule 1 (VCAM1)
timeFrame: 30 days
measure: total antioxidant status (TAS)
timeFrame: 30 days
measure: gene SIRT1
timeFrame: 30 days
measure: gene mTOR
timeFrame: 30 days
measure: gene NF-kB1
timeFrame: 30 days
measure: gene Nrf2/NFE2L2
timeFrame: 30 days
measure: gene AMPK/PRKAA1
timeFrame: 30 days
Secondary outcomes:
measure: brachial flow-mediated dilatation (FMD)
timeFrame: 10 weeks after treatment completion
measure: reactive hyperaemia index (RHI)
timeFrame: 10 weeks after treatment completion
measure: beta stiffness coefficient
timeFrame: 10 weeks after treatment completion
measure: carotid pulse wave velocity (c-PWV)
timeFrame: 10 weeks after treatment completion
measure: carotid-femoral PWV (cf-PWV)
timeFrame: 10 weeks after treatment completion
Other outcomes:
Locations:
Study officials:
References:
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