(3S-5S-6E)-7-[3-(4-fluorophenyl)-1-(propan-2-yl)-1H-indol-2-yl]-3-5-dihydroxyhept-6-enoic-acid and Dilatation--Pathologic

Early arterial wall changes are already present in the apparently healthy, middle-aged population and continuously progress with age. The aim of our study was to investigate whether 30 days low-dose fluvastatin treatment could improve and reverse these arterial changes that are primarily associated with ageing, in otherwise healthy middle-aged males.. In a double blind, randomized study, 50 middle-aged males received either placebo or fluvastatin (10mg) for 30 days. Brachial artery flow-mediated dilation (FMD), pulse wave velocity (PWV) and β-stiffness of the common carotid artery were measured on the 1st, 14th and 30th day of the study using an Aloka instrument by integrated eTracking.. In 77% of subjects, impaired endothelial function was revealed at inclusion in the study. All the parameters were improved already after 14 days, and after 30 days of treatment FMD improved by 91.5 ± 15.6%, while PWV and β-stiffness improved by 6.2 ± 1.1% and 10.7 ± 1.5%, respectively (all P<0.001). After therapy discontinuation, the beneficial effects progressively decreased, but were still detectable after 5 months. During the study the lipid profile remained unchanged, thus the beneficial effects obtained were attributed to the pleiotropic effects of fluvastatin.. We found that subtherapeutic low-dose fluvastatin (10mg daily; 30 days) considerably improves and reverses early functional and morphological arterial wall impairments that are present in apparently healthy, middle-aged males. It might be supposed that such a new and original approach could be valuable in cardiovascular prevention.

Topics: Adult; Aging; Blood Flow Velocity; Brachial Artery; Carotid Artery, Common; Dilatation, Pathologic; Fatty Acids, Monounsaturated; Fluvastatin; Humans; Indoles; Male; Middle Aged; Pilot Projects; Placebos; Pulsatile Flow; Ultrasonography; Vascular Resistance

Short-term administration of 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitors, statins, has been shown to attenuate ischemia-reperfusion injury. However, the effects of long-term administration of statins on left ventricular (LV) remodeling and failure after myocardial infarction remain unknown.. Mice were subjected to coronary artery ligation and were treated for 4 weeks with vehicle or fluvastatin (10 mg/kg per day PO). Fluvastatin increased survival (61% versus 86%; P<0.05) without affecting the infarct size (52+/-2% versus 49+/-3%; P=NS). Fluvastatin not only attenuated LV dilatation but also decreased LV end-diastolic pressure and lung weight. Furthermore, it reduced cardiac myocyte hypertrophy and interstitial fibrosis of the noninfarcted LV and also improved LV ejection performance. LV matrix metalloproteinase (MMP)-2 and MMP-13 were increased in myocardial infarction, which was attenuated in fluvastatin-treated mice.. Fluvastatin increased survival in a murine model of postinfarct heart failure, which was associated with the amelioration of LV structural remodeling and contractile failure. Moreover, these effects were associated with the attenuation of increased MMP activity. Thus, long-term treatment with fluvastatin might be beneficial also in patients with heart failure and might improve their long-term survival.

Topics: Administration, Oral; Animals; Blotting, Western; Body Weight; Dilatation, Pathologic; Disease Models, Animal; Echocardiography; Fatty Acids, Monounsaturated; Fluvastatin; Heart Failure; Hemodynamics; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Indoles; Lung; Male; Matrix Metalloproteinases; Mice; Myocardial Infarction; Myocardium; Nitric Oxide Synthase; Nitric Oxide Synthase Type II; Nitric Oxide Synthase Type III; Organ Size; Peptidyl-Dipeptidase A; Survival Rate; Ventricular Function, Left; Ventricular Remodeling