Effects of combined administration of low dose atorvastatin and vitamin E on inflammatory markers and endothelial function in patients with heart failure.
ABSTRACT Heart failure has been associated with impaired endothelial function, increased inflammatory process and elevated oxidative stress status. Both statins and vitamin E separately improve endothelial function in patients with hypercholesterolemia and/or advanced atherosclerosis.
To evaluate the effect of atorvastatin alone or in combination with vitamin E on endothelial function and serum levels of interleukin-6 (IL-6), tumor necrosis factor alpha (TNF-alpha) and vascular cells adhesion molecule (sVCAM-1) in patients with ischemic heart failure.
Thirty-eight male patients with ischemic cardiomyopathy were randomly divided into three groups and received either atorvastatin 10 mg/day (n = 14), a combination of atorvastatin 10 mg/day plus vitamin E 400 IU/day (n = 12), or no statin or antioxidant treatment (n=12, controls) for 4 weeks. Forearm blood flow (FBF) was measured using venous occlusion strain-gauge plethysmography. Forearm vasodilatory response to reactive hyperemia (RH%) or to nitrate (NTG%) was defined as the percent change of FBF from rest to the maximum flow during reactive hyperemia or after nitrate administration, respectively.
RH% was significantly improved in both the atorvastatin-treated (p < 0.01) and atorvastatin plus vitamin E groups (p < 0.05), but the increase was significantly higher in the atorvastatin-treated group (p < 0.05). Serum levels of IL-6, TNF-alpha and sVCAM-1 were decreased in the atorvastatin-treated group (p < 0.05 for all), but remained unaffected in the other two groups (p = NS for all).
Low dose atorvastatin treatment improves endothelial function and reduces the expression of proinflammatory cytokines and adhesion molecules in patients with ischemic heart failure, an effect partly depressed by vitamin E.
Article: Evaluating oxidative stress in human cardiovascular disease: methodological aspects and considerations.[show abstract] [hide abstract]
ABSTRACT: Oxidative stress is a key feature in atherogenesis, since reactive oxygen species (ROS) are involved in all stages of the disease, from endothelial dysfunction to atheromatic plaque formation and rupture. It is therefore important to identify reliable biomarkers allowing us to monitor vascular oxidative stress status. These may lead to improved understanding of disease pathogenesis and development of new therapeutic strategies. Measurement of circulating biomarkers of oxidative stress is challenging, since circulation usually behaves as a separate compartment to the individual structures of the vascular wall. However, measurement of stable products released by the reaction of ROS and vascular/circulating molecular structures is a particularly popular approach. Serum lipid hydroperoxides, plasma malondialdehyde or urine F2-isoprostanes are widely used and have a prognostic value in cardiovascular disease. Quantification of oxidative stress at a tissue level is much more accurate. Various chemiluminescence and high performance liquid chromatography assays have been developed over the last few years, and some of them are extremely accurate and specific. Electron spin resonance spectroscopy and micro-electrode assays able to detect ROS directly are also widely used. In conclusion, measurement of circulating biomarkers of oxidative stress is valuable, and some of them appear to have predictive value in cardiovascular disease. However, these biomarkers do not necessarily reflect intravascular oxidative stress and therefore cannot be used as therapeutic targets or markers to monitor pharmacological treatments in clinical settings. Measurement of vascular oxidative stress status is still the only reliable way to evaluate the involvement of oxidative stress in atherogenesis.Current Medicinal Chemistry 04/2012; 19(16):2504-20. · 4.86 Impact Factor
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ABSTRACT: Statins possess immunomodulatory properties and have been proposed for reducing morbidity during an influenza pandemic. We sought to evaluate the effect of statins on hospitalizations and deaths related to seasonal influenza outbreaks. We conducted a population-based cohort study over 10 influenza seasons (1996 to 2006) using linked administrative databases in Ontario, Canada. We identified all adults older than 65 years who had received an influenza vaccination prior to the start of influenza season and distinguished those also prescribed statins (23%) from those not also prescribed statins (77%). Propensity-based matching, which accounted for each individual's likelihood of receiving a statin, yielded a final cohort of 2,240,638 patients, exactly half of whom received statins. Statins were associated with small protective effects against pneumonia hospitalization (odds ratio [OR] 0.92; 95% CI 0.89-0.95), 30-day pneumonia mortality (0.84; 95% CI 0.77-0.91), and all-cause mortality (0.87; 95% CI 0.84-0.89). These protective effects attenuated substantially after multivariate adjustment and when we excluded multiple observations for each individual, declined over time, differed across propensity score quintiles and risk groups, and were unchanged during post-influenza season periods. The main limitations of this study were the observational study design, the non-specific outcomes, and the lack of information on medications while hospitalized. Statin use is associated with a statistically significant but minimal protective effect against influenza morbidity that can easily be attributed to residual confounding. Public health officials and clinicians should focus on other measures to reduce morbidity and mortality from the next influenza pandemic.PLoS ONE 01/2009; 4(11):e8087. · 4.09 Impact Factor
Article: Management of bisphosphonate-associated osteonecrosis: pentoxifylline and tocopherol in addition to antimicrobial therapy. An initial case series.[show abstract] [hide abstract]
ABSTRACT: Studies of the use of pentoxifylline and α-tocopherol in osteoradionecrosis of the jaw have suggested their efficacy in this condition. We report an initial case series of pentoxifylline and α-tocopherol for patients with bisphosphonate-associated osteonecrosis (BON). Six cases referred for management of BON were provided pentoxifylline and α-tocopherol in addition to antimicrobial therapy, and followed for a mean of 10 months. A 74% decrease in area of bony exposure and symptom control was achieved in these cases. Pentoxifylline with α-tocopherol may represent a strategy for management of BON. Controlled trials in cases of BON appear warranted.Oral surgery, oral medicine, oral pathology, oral radiology, and endodontics 11/2010; 110(5):593-6. · 1.50 Impact Factor