Effect of Simvastatin (80 mg) on coronary and abdominal aortic arterial calcium (from the coronary artery calcification treatment with Zocor [CATZ] study)
ABSTRACT We tested the hypothesis that, compared with placebo, simvastatin would reduce the progression of coronary artery calcium (CAC) and abdominal aortic calcium (AAC) levels in participants asymptomatic for vascular disease. Total CAC and AAC were measured with multidetector cardiac computed tomography. Inclusion criteria were a CAC score of >or=50 Agatston units, high-density lipoprotein (HDL) cholesterol level<or=50 mg/dl, low-density lipoprotein (LDL) cholesterol level between 100 and 160 mg/dl, and >or=2 other risk factors. Diabetes and history of vascular disease were exclusion criteria. Participants were randomized to receive 80 mg simvastatin (n=40) or matching placebo (n=40) for 12 months. Lipids were measured at 3-month intervals, and CAC and AAC measurements were repeated at 6 and 12 months. Total cholesterol, triglycerides, and LDL decreased significantly with simvastatin treatment (p<0.0001 for all comparisons, adjusted for baseline levels), whereas lipids remained unchanged for subjects randomized to receive placebo. Total CAC volume increased from baseline in both treatment groups. For subjects in the active treatment group, CAC volume increased by 9%, whereas in the placebo group, plaque volume increased by 5% (p=0.12 for treatment effect). AAC volume also increased in both treatment groups (p=0.15 for treatment effect). In conclusion, simvastatin treatment does not reduce progression of CAC or AAC compared with placebo.
- SourceAvailable from: Stefano Menini[Show abstract] [Hide abstract]
ABSTRACT: Vascular calcification is an unfavorable event in the natural history of atherosclerosis that predicts cardiovascular morbidity and mortality. However, increasing evidence suggests that different calcification patterns are associated with different or even opposite histopathological and clinical features, reflecting the dual relationship between inflammation and calcification. In fact, initial calcium deposition in response to pro-inflammatory stimuli results in the formation of spotty or granular calcification ("microcalcification"), which induces further inflammation. This vicious cycle favors plaque rupture, unless an adaptive response prevails, with blunting of inflammation and survival of vascular smooth muscle cells (VSMCs). VSMCs promote fibrosis and also undergo osteogenic transdifferentiation, with formation of homogeneous or sheet-like calcification ("macrocalcification"), that stabilizes the plaque by serving as a barrier towards inflammation. Unfortunately, little is known about the molecular mechanisms regulating this adaptive response. The advanced glycation/lipoxidation endproducts (AGEs/ALEs) have been shown to promote vascular calcification and atherosclerosis. Recent evidence suggests that two AGE/ALE receptors, RAGE and galectin-3, modulate in divergent ways, not only inflammation, but also vascular osteogenesis, by favoring "microcalcification" and "macrocalcification", respectively. Galectin-3 seems essential for VSMC transdifferentiation into osteoblast-like cells via direct modulation of the WNT-β-catenin signaling, thus driving formation of "macrocalcification", whereas RAGE favors deposition of "microcalcification" by promoting and perpetuating inflammation and by counteracting the osteoblastogenic effect of galectin-3. Further studies are required to understand the molecular mechanisms regulating transition from "microcalcification" to "macrocalcification", thus allowing to design therapeutic strategies which favor this adaptive process, in order to limit the adverse effects of established atherosclerotic calcification. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.Atherosclerosis 12/2014; 238(2):220-230. DOI:10.1016/j.atherosclerosis.2014.12.011 · 3.97 Impact Factor
Conference Paper: Stochastic methods applied to medical image reconstruction[Show abstract] [Hide abstract]
ABSTRACT: Currently used methods of computerized tomographic image reconstruction require a large number of measurements relative to the number of picture elements to be estimated, but employ computationally simple algorithms. However these reconstruction methods do not optimally use the information contained in the measurements. Using a stochastic analysis, the inherent statistical assumptions of some seemingly deterministic reconstruction techniques are examined, and a class of recursive algorithms are developed which use data more efficiently at the price of a small increase in computational complexity per measurement. These algorithms will be useful in cases where the number of measurements are limited by time, cost, geometry, or independence constraints. Examples of reconstructions using state-estimation methods such as square-root, Chandrasekhar, and related algorithms will be discussed.Decision and Control including the 16th Symposium on Adaptive Processes and A Special Symposium on Fuzzy Set Theory and Applications, 1977 IEEE Conference on; 01/1978