Successful long-term management of spasticity in patients with multiple sclerosis using a software application (APP): A pilot study.

BACKGROUND: Spasticity is a very common syndrome in patients with multiple sclerosis (pwMS), but available treatments lead to sufficient symptom control only in one third. OBJECTIVE: To investigate the impact of an individualized training program on improving spasticity in a prospective pilot trial in pwMS suffering from moderate spasticity (defined as ≥ 4 on a normative rating scale; NRS). METHODS: PwMS were familiarized with predefined exercises targeting spasticity while undergoing inpatient rehabilitation (IR). After IR, 20 pwMS were 1:1 randomized either to a newly designed APP-based home therapy program providing suitable exercises on a daily basis or to a paper-based home therapy program for 3 months. At month 3, all patients received the APP-based home program for another 3 months. Degree of spasticity was rated on the NRS. RESULTS: Undergoing inpatient rehabilitation for a mean of 32 days led to a significant reduction in spasticity in pwMS (p = 0.00). Further self-training with the APP-based home program for 3 months led to 1.2 lower mean NRS as compared to training with the conventional paper-based program (p = 0.09). Spasticity was found to be on low levels again in both groups after 6 months. CONCLUSION: In pwMS, an individually tailored anti-spasticity program delivered by a software APP is a feasible tool for increasing long-term adherence to self-training thereby positively impacting spasticity in pwMS.

Primary percutaneous intervention of ST-elevation myocardial infarction in Austria: Results from the Austrian acute PCI registry 2005-2007.

BACKGROUND: Primary percutaneous coronary intervention (PPCI) has become the preferred reperfusion strategy in ST-elevation myocardial infarction (STEMI). Implementation of networks of care and registries providing continuous quality assessment are key components for optimal management in patients with STEMI. AIM: To analyze procedural success and in-hospital outcome of interventional therapy of STEMI in Austria. METHODS: We evaluated a total number of 4016 consecutive STEMI patients registered in the first three years after implementation of the Austrian acute PCI registry in January 2005. RESULTS: The rate of PPCI as an indication for acute coronary intervention increased from 83.5% in 2005 to 92.4% in 2007 (P < 0.0001). During this period the median door-to-balloon time decreased from 60.0 (40.0-90.0) min to 53.0 (30.0-80.0) min (P = 0.012). The percentage of patients receiving adequate adjunctive antithrombotic therapy with ASA/heparin and clopidogrel significantly increased (78.8-85.1% and 67.8-90.3%, respectively; P < 0.001). Overall in-hospital mortality was 9.6% in rescue PCI, 6.4% in facilitated PCI and 5.1% in PPCI. On multivariate analysis, cardiogenic shock (OR: 20.21, 95% CI: 12.21-33.44, P < 0.001), resuscitation (OR: 2.62, 95% CI: 1.47-4.69, P = 0.01), age (OR: 1.04, 95% CI: 1.02-1.06, P < 0.001) and angiographic success (OR: 5.93, 95% CI: 3.33-10.57, P < 0.001) were independent predictors of in-hospital death. CONCLUSION: Continuous nationwide efforts to establish regional networks for STEMI treatment in the years 2005-2007 led to a decrease in door-to-balloon time, improved adjunctive antithrombotic therapy and an in-hospital mortality of 5%. Results of interventional STEMI treatment in Austria are in accordance with current guidelines and with other contemporary registries.

Prognosis and risk factors in patients with asymptomatic aortic stenosis and their modulation by atorvastatin (20 mg).

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.

Effect of atorvastatin on peripheral endothelial function and systemic inflammatory markers in patients with stable coronary artery disease.

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.

Effect of atorvastatin on circulating proinflammatory T-lymphocyte subsets and soluble CD40 ligand in patients with stable coronary artery disease--a randomized, placebo-controlled study.

BACKGROUND: Coronary atherosclerosis includes an activation of circulating T lymphocytes. Statins exert anti-inflammatory effects beyond lipid lowering. Whether these properties influence systemic T lymphocytes is unclear. METHODS: To investigate the effect of atorvastatin on circulating T-lymphocyte subsets producing proinflammatory and anti-inflammatory cytokines (interferon gamma [IFN-gamma(+)], interleukin 2 [IL-2(+)], IL-4(+), and IL-10(+)) and on the T-cell-activating soluble CD40 ligand (sCD40L), 30 hypercholesterolemic patients with angiographically documented stable coronary artery disease (CAD) were randomized to placebo or atorvastatin (20 mg/d) for 3 months. Eight healthy volunteers served as controls. Levels of peripheral cytokine-producing CD4+ and CD8+ T cells and their CD28- subsets were determined by FACS. Serum soluble CD40L was measured with ELISA. RESULTS: IL-2(+) T lymphocytes and sCD40L levels were higher in patients with CAD compared with controls, whereas IFN-gamma(+) and anti-inflammatory IL-4(+) and IL-10(+) T lymphocytes were similar. Levels of IL-2(+), IFN-gamma(+), IL-4(+), and IL-10(+) T-cell subsets as well as CD28- T lymphocytes were neither changed by atorvastatin nor by placebo, whereas sCD40L was lowered only in atorvastatin-treated patients (P < .01). CONCLUSION: Circulating IL-2(+) T lymphocytes are increased in patients with stable CAD reflecting an activation of the global immune system, but are not influenced by atorvastatin therapy. The elevated levels of platelet-derived T-lymphocyte-stimulating sCD40L are decreased by atorvastatin probably reflecting an atheroprotective effect. Hence, sCD40L may be an additional biomarker to be considered when evaluating the treatment effects of statins in patients with stable CAD.

Atorvastatin decreases vascular endothelial growth factor in patients with coronary artery disease.

OBJECTIVES: The aim of this study was to test a possible influence of atorvastatin on the production of vascular endothelial growth factor (VEGF) in patients with coronary artery disease (CAD) and in vitro. BACKGROUND: Vascular endothelial growth factor is suggested to be involved in the growth of atherosclerotic plaque by inducing its neovascularization. Hepatic hydroxymethyl glutaryl-coenzyme A reductase inhibitors (statins) are known to have atheroprotective effects beyond lipid lowering. METHODS: Blood was collected from 14 male hypercholesterolemic patients with angiographically confirmed CAD at baseline and after two months of atorvastatin therapy (20 mg/d) and from eight male control patients. In an ex vivo assay, human coronary artery smooth muscle cells (HCASMC) were incubated with the patient plasma collected before and after atorvastatin therapy. To test the direct effect of atorvastatin on VEGF synthesis in vitro, HCASMC were treated with atorvastatin (1, 3 and 10 microM). The VEGF concentration was measured by enzyme-linked immunosorbent assay. RESULTS: Atorvastatin therapy reduced VEGF plasma levels in CAD patients (from 31.1 +/- 6.1 to 19.0 +/- 3.6 pg/ml; p < 0.05). The VEGF plasma concentration tended to be higher in CAD patients before treatment compared to control patients (31.1 +/- 6.1 vs. 23.4 +/- 3.6 pg/ml; p = NS). Plasma collected before therapy induced significantly more VEGF in HCASMC compared to the plasma collected after treatment and compared to control cells. In vitro, atorvastatin decreased both the basal and the interleukin-1beta-induced VEGF release in HCASMC. CONCLUSIONS: These data suggest that atorvastatin may lower the plasma level of VEGF in CAD patients, which could represent a novel beneficial effect of this and perhaps other statins.