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Tarsus, Turkey

Cabassi A.,University of Parma | Binno S.M.,University of Parma | Tedeschi S.,University of Parma | Ruzicka V.,University of Parma | And 10 more authors.
Circulation Research | Year: 2014

RATIONALE:: Ceruloplasmin antioxidant function is mainly related to its ferroxidase I (FeOxI) activity, which influences iron-dependent oxidative and nitrosative radical species generation. Peroxynitrite, whose production is increased in heart failure (HF), can affect ceruloplasmin antioxidant function through amino acid modification. OBJECTIVE:: We investigated the relationship between FeOxI and ceruloplasmin tyrosine and cysteine modification and explored in a cohort of patients with HF the potential clinical relevance of serum FeOxI. METHODS AND RESULTS:: In patients with chronic HF (n=96, 76±9 years; New York Heart Association class, 2.9±0.8) and age-matched controls (n=35), serum FeOxI, FeOxII, ceruloplasmin, nitrotyrosine-bound ceruloplasmin, B-type natriuretic peptide, norepinephrine, and high-sensitivity C-reactive protein were measured, and the patients were followed up for 24 months. Ceruloplasmin, B-type natriuretic peptide, norepinephrine, and high-sensitivity C-reactive protein were increased in HF versus controls. FeOxI was decreased in HF (-20%) and inversely related to nitrotyrosine-bound ceruloplasmin (r,-0.305; P=0.003). In HF, FeOxI lower tertile had a mortality rate doubled compared with middle-higher tertiles. FeOxI emerged as a mortality predictor (hazard ratio, 2.95; 95% confidence intervals [1.29-6.75]; P=0.011) after adjustment for age, sex, hypertension, smoking, sodium level, estimated glomerular filtration rate, and high-sensitivity C-reactive protein. In experimental settings, peroxynitrite incubation of serum samples and isolated purified ceruloplasmin reduced FeOxI activity while increasing ceruloplasmin tyrosine nitration and cysteine thiol oxidation. Reduced glutathione prevented peroxynitrite-induced FeOxI drop, tyrosine nitration, and cysteine oxidation; flavonoid(-)-epicatechin, which prevented ceruloplasmin tyrosine nitration but not cysteine oxidation, partially impeded peroxynitrite-induced FeOxI drop. CONCLUSIONS:: Reduced activity of serum FeOxI is associated with ceruloplasmin nitration and reduced survival in patients with HF. Both ceruloplasmin tyrosine nitration and cysteine thiol oxidation may be operant in vivo in peroxynitrite-induced FeOxI activity inhibition. © 2014 American Heart Association, Inc.


In this study, we aimed to evaluate whether serum total bilirubin was associated with the severity and morphology of coronary atherosclerotic plaques detected by computed tomography angiography (CTA). The study population consisted of 1,115 patients (55.2 % men) who underwent dual-source 64-slice CTA for the assessment of coronary artery disease (CAD). Coronary arteries were evaluated on 16 segment basis and critical coronary plaque was described as luminal narrowing >50 %, whereas plaque morphology was assessed on per segment basis. Serum bilirubin levels were determined using commercially available assay kits. The critical atherosclerotic lesions were detected in 431/1,115 (38.6 %) subjects by CTA. Serum total bilirubin levels were found to be lower in patients with any coronary plaque (0.62 ± 0.21 vs. 0.70 ± 0.25 mg/dL, p = 0.002). Also bilirubin level was lower in patients with critical stenosis compared to non-critical stenosis (0.57 ± 0.18 vs. 0.70 ± 0.24 mg/dL, p < 0.001). Subjects having primarily noncalcified plaque (NCP) and mixed plaque (MP) have lower bilirubin levels compared to calcified plaque (CP) and normal subjects (0.62 ± 0.20 for NCP and 0.60 ± 0.19 for MP, 0.65 ± 0.26 for CP and 0.71 ± 0.25 for normal subjects, p < 0.001). This independent association was remained for NCP after multinominal regression analysis (OR: 0.76; 95 % CI 0.58-0.88; p < 0.001). Our study demonstrated that serum bilirubin level was significantly associated with the presence, severity and the noncalcified morphology of atherosclerotic plaques detected by CTA. Further prospective clinical studies are needed to clarify the exact physiopathologic and prognostic role of bilirubin in CAD.


Kosmas C.E.,Mount Sinai Hospital | Dejesus E.,Bronx Lebanon Hospital Center | Rosario D.,Cardiology Clinic | Vittorio T.J.,Advanced Cardiac Therapeutics
Clinical Medicine Insights: Cardiology | Year: 2016

The atheroprotective role of high-density lipoprotein cholesterol (HDL-C) in cardiovascular disease has been unequivocally established, and epidemiological data have clearly demonstrated a strong inverse relationship between HDL-C levels and the risk of cardiovascular events, which is independent of the low-density lipoprotein cholesterol (LDL-C) levels. Thus, it would be logical to hypothesize that raising HDL-C might potentially lead to a reduction of cardiovascular risk. Cholesteryl ester transfer protein (CETP) promotes the transfer of cholesteryl esters from HDL to very low-density lipoprotein and LDL. Therefore, CETP inhibition raises HDL-C levels and decreases LDL-C levels. The first trials with CETP inhibitors failed to show a reduction in cardiovascular events. However, newer CETP inhibitors with more favorable effects on lipids are presently being tested in clinical trials with the hope that their use may lead to a reduction in cardiovascular risk. This review aims to provide the current evidence regarding CETP inhibition, as well as the clinical and scientific data pertaining to the new CETP inhibitors in development. © The authors, publisher and licensee Libertas Academica Limited.


Bozbas S.S.,Baskent University | Bozbas H.,Cardiology Clinic
World Journal of Gastroenterology | Year: 2016

Pulmonary vascular disorders including portopulmonary hypertension (PoPHT) are among the common complications of liver disease and are prognostically significant. Survival is very low without medical treatment and liver transplantation. With advances in medical therapy for elevated pulmonary artery pressure (PAP) and liver transplant surgery, survival of patients with PoPHT and advanced liver disease is significantly improved. Because of the prognostic significance of PoPHT and the limited donor pool, a comprehensive preoperative cardio-pulmonary assessment is of great importance in cirrhotic patients prior to transplant surgery. Therefore, a detailed transthoracic Doppler echocardiographic examination must be an essential component of this evaluation. Patients with mild PoPHT can safely undergo liver transplant surgery. In cases of moderate to severe PoPHT, right heart catheterization (RHC) should be performed. In patients with moderate to severe PoPHT on RHC (mean PAP 35-45 mmHg), vasodilator therapy should be attempted. Liver transplantation should be encouraged in cases that demonstrate a positive response. Bridging therapy with specific pulmonary arterial hypertension treatment agents should be considered until the transplant surgery and should be continued during the peri-and post-operative periods as needed. © The Author(s) 2016.


Cojocaru L.,Ovidius University | Rusali A.C.,Ovidius University | Suta C.,Ovidius University | Radulescu A.M.,Cardiology Clinic | And 2 more authors.
Autoimmune Diseases | Year: 2013

The pleiotropic effects of statins, especially the anti-inflammatory and immunomodulatory ones, indicate that their therapeutic potential might extend beyond cholesterol lowering and cardiovascular disease to other inflammatory disorders such as rheumatoid arthritis. Therefore, we undertook a prospective cohort study to evaluate the efficacy and safety of simvastatin used for inflammation control in patients with rheumatoid arthritis. One hundred patients with active rheumatoid arthritis divided into two equal groups (the study one who received 20 mg/day of simvastatin in addition to prior DMARDs and the control one) were followed up over six months during three study visits. The results of the study support the fact that simvastatin at a dose of 20 mg/day has a low anti-inflammatory effect in patients with rheumatoid arthritis with a good safety profile. © 2013 Lucia Cojocaru et al.

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