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The aim of the prospective, randomized, placebo-controlled Tyrolean Aortic Stenosis Study (TASS) was to characterize the natural history and risk factors and their possible modulation by new-onset atorvastatin treatment (20 mg/day vs placebo) in patients with asymptomatic calcified aortic stenosis. Forty-seven patients without previous lipid-lowering therapy or indications for it according to guidelines at study entry were randomized to atorvastatin treatment or placebo and prospectively followed for a mean study period of 2.3 +/- 1.2 years. Patients' prognoses were worse than expected, with 24 (51%) experiencing major adverse clinical events, in most cases the new onset of symptoms followed by aortic valve replacement. In multivariate regression analysis, independent risk factors for worse clinical outcomes were aortic valve calcification, as assessed by multidetector computed tomography, and plasma levels of C-reactive protein. In univariate analysis, mean systolic pressure gradient or an increased N-terminal-pro-B-type natriuretic peptide plasma level allowed the prediction of major adverse clinical events as well, whereas concomitant coronary calcification, age, and the initiation of atorvastatin treatment had no significant prognostic implication. As shown in a subgroup of 35 patients (19 randomly assigned to atorvastatin and 16 to placebo), annular progression in aortic valve calcification and hemodynamic deterioration were similar in both treatment groups. In conclusion, TASS could demonstrate a poor clinical outcome in patients with asymptomatic calcified aortic stenosis which can be predicted by new risk factors such as strong AVC or increased plasma levels of CRP or NT-proBNP. The study does not support the concept that treatment with a HMG-CoA reductase inhibitor (20 mg atorvastatin once daily) halts the progression of calcified aortic stenosis.

Background: Endothelial dysfunction, detectable by an impaired flow-mediated vasodilation (FMD) of the brachial artery, has been shown to be associated with increased levels of circulating proinflammatory markers. Therapeutic interventions such as lipid-lowering with statins increase FMD and decrease inflammatory markers, like soluble (s) E-selectin, soluble intercellular adhesion molecule-1 (sICAM-1) or high-sensitivity Creactive protein (hsCRP). The effect of atorvastatin therapy on both FMD and inflammatory markers in patients with stable coronary artery disease (CAD) has not been investigated., Methods: Thirty hypercholesterolemic patients with angiographically documented stable coronary artery disease (CAD) were randomized to placebo or atorvastatin (20 mg/d) for 3 months. FMD was assessed using highresolution ultrasound (13 MHz, Acuson Sequoia, C256). High-sensitivity CRP was measured with Latex agglutination assay, sE-selectin and sICAM-1 were determined with ELISA., Results: Baseline characteristics were not different between groups. FMD improved in patients on atorvastatin (6.7+/-3.8% to 8.5+/-4.4%; p<0.01), but remained unchanged in placebo-treated patients (8.2+/-3.3% to 8.9+/-5.1%; p=NS). Atorvastatin treatment was associated with decreases of sICAM-1 (from 274.2+/-92.2 to 197.9+/-70.0 ng/ml; p<0.01) and hsCRP (from 0.57+/-0.45 to 0.18+/-0.15 mg/dl; p<0.01), whereas placebo treatment had no effect on these markers. sE-selectin levels were not influenced by either treatment. No correlations were found between changes in FMD, lipids and inflammatory markers., Conclusions: Treatment with atorvastatin leads to an improvement in endothelial function and a reduction in inflammatory markers in patients with stable CAD. The lack of correlation between changes in FMD and inflammatory markers may support the concept of pleiotropic effects of statins in humans.