ORIGINAL ARTICLE   Free access

International Angiology 2018 October;37(5):356-64

DOI: 10.23736/S0392-9590.18.03983-4

Copyright © 2018 EDIZIONI MINERVA MEDICA

lingua: Inglese

Improvement of arterial wall phenotype in subjects at moderate cardiovascular risk induced by very low-dose fluvastatin/valsartan combination: a pilot study

Martina TURK VESELIČ ^{1, 2}, Neža ŽORŽ ¹, Barbara ERŽEN ¹, Petra ŠKERL ³, Srdjan NOVAKOVIĆ ³, Miodrag JANIĆ ¹, Mišo ŠABOVIČ ^{1, 2} ✉

¹ Department of Vascular Diseases, University Medical Centre of Ljubljana, Ljubljana Slovenia; ² Faculty of Medicine, University of Ljubljana, Ljubljana, Slovenia; ³ Department of Molecular Diagnostics, Institute of Oncology Ljubljana, Ljubljana, Slovenia

BACKGROUND: 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. We investigated whether their arterial wall phenotype could be turned to a lower risk direction by low-dose fluvastatin/valsartan combination (low-flu/val).
METHODS: Twenty males at moderate cardiovascular risk (as classified by SCORE) were blindly randomized into the intervention group (N.=10, low-flu/val: 10 mg/20 mg) or control group (N.=10, placebo). At inclusion and after 30 days of treatment, brachial flow-mediated dilatation (FMD), β-stiffness coefficient, carotid pulse wave velocity (c-PWV), carotid-femoral PWV, Reactive Hyperemia 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.
RESULTS: Treatment resulted in improved FMD (from 3% to 4.2%, P=0.008), c-PWV (from 6.7 to 6.2 m/s, P=0.006), hs-CRP (from 5.39 to 3.35 mg/L, P=0.041) and SIRT1 expression (3.34-fold difference, P=0.047). No other vascular, inflammation and genetic parameters changed. The hs-CRP values after intervention correlated significantly with SIRT1 expression. The improved FMD persisted even 10 weeks after treatment discontinuation. The obtained changes were not followed by changes of lipids or blood pressure. Overall, the results revealed improvement in three different, although interrelated preventive arterial wall characteristics.
CONCLUSIONS: This pilot study revealed that intervention with low-flu/val importantly shifts the arterial wall phenotype in a lower risk direction. This improvement could be interpolated into clinical benefits that remain to be further studied.

KEY WORDS: Vascular stiffness - Fluvastatin - Valsartan