Atherosclerosis
Conditions
Keywords
arterial stiffness, endothelial dysfunction, fluvastatin, valsartan, inflammatory markers, oxidative stress, SIRT1
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.
Interventions
DRUGfluvastatin 10 mg and valsartan 20 mg
DRUGplacebo
Sponsors
University Medical Centre Ljubljana
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
PREVENTION
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
MALE
Age
40 Years to 55 Years
Healthy volunteers
Yes
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| gene AMPK/PRKAA1 | 30 days | Hs01562315\_m1 |
| total antioxidant status (TAS) | 30 days | marker of oxidative stress |
| gene SIRT1 | 30 days | Hs01009006\_m1 |
| gene mTOR | 30 days | Hs00234522\_m1 |
| gene NF-kB1 | 30 days | Hs00765730\_m1 |
| gene Nrf2/NFE2L2 | 30 days | Hs00975961\_g1 |
| brachial flow-mediated dilatation (FMD) | 30 days | FMD measured by ultrasound on right brachial artery (as result of reactive hyperaemia) |
| reactive hyperaemia index (RHI) | 30 days | RHI measured by Endopat device |
| beta stiffness coefficient | 30 days | assessed by ultrasound employing e-Tracking on right common carotid artery |
| carotid pulse wave velocity (c-PWV) | 30 days | assessed by ultrasound employing e-Tracking on right common carotid artery |
| carotid-femoral PWV (cf-PWV) | 30 days | cf-PWV measured by Sphygmocor device |
| high-sensitivity C-reactive protein (hs-CRP) | 30 days | inflammatory marker |
| interleukin 6 (IL-6) | 30 days | inflammatory marker |
| vascular cell adhesion molecule 1 (VCAM1) | 30 days | inflammatory marker |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| reactive hyperaemia index (RHI) | 10 weeks after treatment completion | RHI measured by Endopat device |
| beta stiffness coefficient | 10 weeks after treatment completion | assessed by ultrasound employing e-Tracking on right common carotid artery |
| carotid pulse wave velocity (c-PWV) | 10 weeks after treatment completion | assessed by ultrasound employing e-Tracking on right common carotid artery |
| carotid-femoral PWV (cf-PWV) | 10 weeks after treatment completion | cf-PWV measured by Sphygmocor device |
| brachial flow-mediated dilatation (FMD) | 10 weeks after treatment completion | FMD measured by ultrasound on right brachial artery (as result of reactive hyperaemia) |
Outcome results
None listed