Maciej Banach

ETC-1002: A future option for lipid disorders?

ETC-1002 is a new investigational low density lipoprotein cholesterol (LDL-C)-lowering agent (Esperion Therapeutics, Inc.). ETC-1002 is a dicarboxylic acid derivative with a novel mechanism of action targeting two hepatic enzymes--adenosine triphosphate-citrate lyase (ACL) and adenosine monophosphate-activated protein kinase (AMPK), inhibiting sterol and fatty acid synthesis and promoting mitochondrial long-chain fatty acid oxidation. This agent is currently in phase II clinical research. Available data report that ETC-1002 significantly decreased LDL-C levels (up to 32%) in both patients with normal and elevated baseline levels of triglycerides. Such beneficial effect is superior to currently approved non-statin lipid lowering agents. The levels of apolipoprotein B (apoB) and non-high density lipoprotein cholesterol (non-HDL-C) were also reduced with beneficial effect on other cardiometabolic factors such as inflammatory markers, blood pressure and body weight. Although, the safety and tolerability of ETC-1002 needs to be confirmed in ongoing and future, larger studies, this agent has, so far, been generally safe and well tolerated. This novel, oral, once-daily, small molecule may lead to effective LDL-C lowering treatment in hypercholesterolaemic subjects who are statin intolerant or as add-on therapy in those who are unable to reach the LDL-C goals despite being on statin therapy. This agent might not only exert lipid-lowering related benefits, but also favourable cardiometabolic effects.

Natriuretic Peptides in Septic Patients

The natriuretic peptide family is comprised of atrial natriuretic peptide (ANP), brain natriuretic peptide (BNP), C-type natriuretic peptide (CNP), dendroaspis natriuretic peptide - DNP and urodilatin. They play a role in the diagnosis of several diseases, especially those involving the cardiovascular system. Sepsis is a complex condition that can lead to multiorgan failure, shock and death. The number of people developing sepsis is still increasing (approximately 750,000 cases of sepsis occur annually in the USA). Both ANP and pro-ANP have attracted interest as new markers for sepsis. Reports indicate that ANP or BNP levels are elevated in septic patients. However, many mechanisms are still unexplained. This situation is complicated by the fact that contradictory results have been published. There are several reasons for this controversy including differences in the techniques used to assay natriuretic peptides. Nevertheless, natriuretic peptides might eventually prove useful for the diagnosis and/or the treatment of septic patients.

Does gender influence the patency of infrainguinal bypass grafts

Infrainguinal revascularization is an effective method of treatment for femoropopliteal/tibial occlusive diseases. However, these bypass grafts are prone to stenosis. In this retrospective study, the authors investigate the association of gender with patency of infrainguinal bypass grafts. The outcomes for consecutive 375 male and 200 female patients who underwent infrainguinal bypass surgery for arterial occlusive disease are compared, and associations with characteristics of the patients, surgical procedure, and graft stenosis are determined. It is found that several demographic, biochemical, and etiological factors could influence the patency of bypass procedures in different genders. However, infrainguinal arterial reconstruction procedures performed in women have a worse outcome when compared with that in men.

Liraglutide improves carotid intima-media thickness in patients with type 2 diabetes and non-alcoholic fatty liver disease: an 8-month prospective pilot study

Objective: To explore the effects of the glucagon-like peptide-1 receptor analogue liraglutide on subclinical atherosclerosis in diabetic subjects with non-alcoholic fatty liver disease (NAFLD). Research design and methods: In this 8-month prospective study, 29 subjects with type 2 diabetes (T2DM) and NAFLD (16 men and 13 women, mean age: 61 ± 10 years) were matched for age and gender with 29 subjects with T2DM without NAFLD (16 men and 13 women, mean age: 61 ± 8 years). Liraglutide 0.6 mg/day for 2 weeks, followed by 1.2 mg/day, was given in addition to metformin. Main outcome measures: Anthropometric variables, glucometabolic parameters and carotid intima-media thickness (IMT) using B-mode real-time ultrasound were assessed at baseline and 4 and 8 months. Results: Glycated hemoglobin reduced significantly in both groups. No significant changes were found in body weight, waist circumference and lipids. Carotid IMT decreased significantly in the T2DM patients with NAFLD (from 0.96 ± 0.27 to 0.82 ± 0.17 to 0.85 ± 0.12 mm, p = 0.0325), but not in the T2DM patients without NAFLD (from 0.91 ± 0.23 to 0.88 ± 0.17 to 0.85 ± 0.15 mm, p = 0.4473). Conclusion: Eight months of liraglutide use in patients with T2DM and NAFLD significantly reduced carotid IMT, a surrogate marker of atherosclerosis, independently of glucometabolic changes.

Percutaneous Coronary Interventions Affect Concentrations of Interleukin 6 and Its Soluble Receptors in Coronary Sinus Blood in Patients With Stable Angina

Coronary stenting may create local inflammatory reaction. Interleukin 6 effects depend on the presence of soluble receptors (sIL-6R and sgp130) that facilitate or impede interleukin 6 signal transduction. Concentrations of interleukin 6 and its soluble receptors were assessed in aorta and coronary sinus after stenting in optimally treated stable angina patients scheduled for elective stenting. Baseline levels of interleukin 6 and its soluble receptors in patients did not differ from healthy controls. Initial levels of sIL-6R in aorta were significantly higher than in coronary sinus but this difference disappeared after intervention. Stenting caused interleukin 6 concentration increase to a similar extent both in coronary sinus and in aorta. Moreover, there was significantly higher sgp130 concentration in coronary sinus than in aorta. Coronary intervention increases concentration of interleukin 6 in patients with stable angina. It affects the cardiac level of interleukin 6 soluble receptors what may influence the local inflammatory reaction.

Physical Exercise and DNA Injury

Regular, low-intensity physical activity is currently advocated for lowering the risk of developing many acute and especially chronic diseases. However, several lines of evidence attest that strenuous exercise may enhance inflammation and trigger the generation of free radical-mediated damage, thus overwhelming the undisputable benefits of regular, medium-intensity physical activity. Since reactive oxygen species are actively generated during high-intensity exercise, and these reactive compounds are known to impact DNA stability, we review here the current evidence about strenuous exercise and DNA injury. Despite the outcome of the various studies cannot be pooled due to considerable variation in design, sample population, outcome, and analytical techniques used to assess DNA damage, it seems reasonable to conclude that medium- to high-volume exercise triggers a certain amount of DNA injury, which appears to be transitory and directly proportional to exercise intensity. This damage, reasonably attributable to direct effect of free radicals on nucleic acids, is efficiently repaired in vivo within 24-72h. Therefore, physical exercise should not bear long-term consequences for athletes health provided that an appropriate time of recovery between volumes of high-intensity exercise is set. Regular exertion, with a step-by-step increase of exercise load, also seems to be the most safe approach for eluding DNA instability.

Ventricular Assist Device – How to Obtain Optimal Benefits?

Agata Bielecka-Dabrowa1, Maciej Banach1, Jacek Rysz2 and Gerry O’Driscoll3 1Department of Hypertension, Chair of Nephrology and Hypertension, Medical University of Lodz 2Department of Nephrology, Hypertension and Family Medicine, Chair of Nephrology and Hypertension, Medical University of Lodz 3Department of Heart Failure and Cardiac Transplant Service, Royal Perth Hospital, 1,2Poland 3Western Australia