Turk Veselič Martina, Žorž Neža, Eržen Barbara, Škerl Petra, Novaković Srdjan, Janić Miodrag, Šabovič Mišo
Department of Vascular Diseases, University Medical Centre of Ljubljana, Ljubljana Slovenia.
Faculty of Medicine, University of Ljubljana, Ljubljana, Slovenia.
Int Angiol. 2018 Oct;37(5):356-364. doi: 10.23736/S0392-9590.18.03983-4. Epub 2018 Jun 27.
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).
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.
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.
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.
患心血管事件的最大群体是心血管风险中等的受试者。然而，针对该群体尚无有效且安全的预防性治疗方法。我们研究了低剂量氟伐他汀/缬沙坦联合用药（低氟/缬）是否能使他们的动脉壁表型转向风险更低的方向。
20名心血管风险中等的男性（根据SCORE分类）被随机分为干预组（n = 10，低氟/缬：10毫克/20毫克）或对照组（n = 10，安慰剂）。在纳入研究时和治疗30天后，随访肱动脉血流介导的舒张功能（FMD）、β-硬度系数、颈动脉脉搏波速度（c-PWV）、颈股PWV、反应性充血指数、高敏C反应蛋白（hs-CRP）、白细胞介素6、血管细胞黏附分子1、总抗氧化状态以及几种保护基因（SIRT1、mTOR、NF-κB1、NFE2L2、PRKAA1）的表达。
治疗使FMD改善（从3%提高到4.2%，P = 0.008）、c-PWV改善（从6.7降至6.2米/秒，P = 0.006）、hs-CRP改善（从5.39降至3.35毫克/升，P = 0.041）以及SIRT1表达改善（差异为3.34倍，P = 0.047）。其他血管、炎症和基因参数未发生变化。干预后的hs-CRP值与SIRT1表达显著相关。即使在停药10周后，改善的FMD仍持续存在。所获得的变化并未伴随血脂或血压的改变。总体而言，结果显示三种不同但相互关联的预防性动脉壁特征得到了改善。
这项初步研究表明，低氟/缬干预能显著使动脉壁表型朝着风险更低的方向转变。这种改善可能转化为临床益处，有待进一步研究。
