Background: The improvement of arterial wall characteristics in groups of patients after myocardial infarction (MI) and subjects at moderate cardiovascular risk leads to better cardiovascular prognosis. We explored whether in these groups the preventive arterial wall phenotype could be attained with low-dose combination of fluvastatin and valsartan (low-flu/val).
Methods: The randomized double-blind study was conducted. 36 post-MI middle-aged males were enrolled in the intervention group (n=20) or control group (n=16). Further on, 20 middle-aged males at moderate cardiovascular risk (as classified by SCORE) were also enrolled in the intervention group (n=10) or control group (n=10). The intervention group was receiving low-dose combination of fluvastatin (10 mg) and valsartan (20 mg), and the control group was receiving placebo for 30 days. At inclusion, after 30 days of treatment, and 10 weeks after treatment completion brachial flow-mediated dilatation (FMD), β-stiffness coefficient, carotid and carotid-femoral pulse wave velocity (c-PWV and cf-PWV), reactive hyperaemia index, intima media thickness, high-sensitivity C-reactive protein (hs-CRP), interleukin 6, vascular cell adhesion molecule 1 (VCAM-1), total antioxidant status and expression of protective genes (SIRT1, MTOR, NFKB1, NFE2L2, PRKAA1) were followed.
Results: In post-MI patients the low-flu/val treatment improved FMD (from 3.1 % to 4.8%, p<0.001), cf-PWV (from 7.8 to 6.7 m/s, p<0.01), VCAM-1 (from 772.0 to 745.4 ng/ml, p<0.05) and SIRT1 expression (1.69-fold difference, p<0.05). In subjects at moderate cardiovascular risk the flu/val treatment resulted in improved FMD (from 3.0% to 4.2%, p<0.01), c-PWV (from 6.7 to 6.2 m/s, p<0.01), hs-CRP (from 5.39 to 3.35 mg/l, p<0.05) and SIRT1 expression (3.34-fold difference, p<0.05). The obtained improvements were not followed by changes of blood pressure or lipid levels. No other vascular, inflammation, oxidative and genetic parameters changed. No changes were obtained in the control group. The improved FMD persisted even 10 weeks after treatment cessation.
Conclusions: The study confirmed that the short-term intervention with low-flu/val importantly shifts the arterial wall phenotype in a preventive direction, improving three different, although interrelated preventive levels of arterial wall characteristics: vascular, inflammatory and genetic. These improvements of endothelial function, arterial stiffness, markers of inflammation and expression of SIRT1 could be interpolated into clinical benefits enabled by cardiovascular risk reduction what warrants further research.
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