Improving Arterial Wall Characteristics in Patients After Myocardial Infarction with a Very Low Dose of Fluvastatin and Valsartan: A Proof-of-Concept Study.

BACKGROUND We tested the concept of improving arterial wall characteristics by treatment with a very low-dose combination of fluvastatin and valsartan (low-flu/val) in stable, post-myocardial infarction (MI) patients. MATERIAL AND METHODS We enrolled 36 post-MI middle-aged males in the treatment (n=20) or control (n=16) group receiving low-flu/val (10 mg/20 mg) or placebo, respectively. The parameters of endothelial function (flow-mediated dilatation (FMD), reactive hyperemia index), and arterial stiffness (carotid-femoral pulse wave velocity (cf-PWV), local carotid PWV, and beta stiffness coefficient) were measured before and after 30 days of therapy, and 10 weeks later. RESULTS Treatment with low-flu/val improved FMD from 3.1±1.3% to 4.8±1.5% (p<0.001; by 54.8%) and cf-PWV from 7.8±1.1 to 6.7±1.5 m/s (p<0.01; by 14.1%) without affecting either lipids or blood pressure. In the treatment group, FMD and/or cf-PWV significantly improved in 17 patients, but the improvements did not correlate. The benefits obtained were still detectable 10 weeks after complete treatment cessation. No changes were obtained in the control group. No other vascular parameters changed. CONCLUSIONS Low-flu/val added "on top of" optimal therapy substantially improves endothelial function and arterial stiffness in post-MI patients. Since these improved parameters are well-known predictors of future coronary events, such treatment could decrease cardiovascular risk. Further studies are therefore warranted.

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

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), ß-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.