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      The effect of bezafibrate and omega-3 fatty acids on lymphocyte cytokine release and systemic inflammation in patients with isolated hypertriglyceridemia

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          Abstract

          Purpose

          The aim of this study was to compare the effects of fibrates and omega-3 fatty acids on lymphocyte secretory function and systemic inflammation in patients with isolated hypertriglyceridemia.

          Methods

          The study included 107 patients with isolated hypertriglyceridemia who received bezafibrate (200 mg twice daily), omega-3 fatty acids (1 g twice daily) or placebo for 12 weeks. The lipid profile, fasting and 2-h post-glucose load plasma glucose levels, homeostasis model assessment index (HOMA), plasma high-sensitivity C-reactive protein (hsCRP) levels and lymphocyte release of interleukin-2, interferon-γ and tumor necrosis factor-α were assessed at baseline, on the day of randomization, and after 4 and 12 weeks of treatment.

          Results

          Both bezafibrate and omega-3 fatty acids reduced plasma triglyceride levels. Bezafibrate additionally decreased total and low-density lipoprotein-cholesterol levels and the HOMA and insignificantly decreased post-glucose load plasma glucose, as well as increased high-density lipoprotein-cholesterol. Bezafibrate treatment was associated with a reduction in lymphocyte release of interleukin-2, interferon-γ and tumor necrosis factor-α, which was accompanied by a reduction in plasma hsCRP levels. Omega-3 fatty acid did not significantly reduce lymphocyte cytokine release and plasma hsCRP. The anti-inflammatory effects of both drugs did not correlate with their action on plasma lipids, but in the case of the former the effect was related to the improvement in insulin sensitivity.

          Conclusion

          Our results indicate that bezafibrate is superior to omega-3 fatty acid in inhibiting systemic inflammation and lymphocyte secretory function.

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          Most cited references28

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          Cytokines in atherosclerosis: pathogenic and regulatory pathways.

          Atherosclerosis is a chronic disease of the arterial wall where both innate and adaptive immunoinflammatory mechanisms are involved. Inflammation is central at all stages of atherosclerosis. It is implicated in the formation of early fatty streaks, when the endothelium is activated and expresses chemokines and adhesion molecules leading to monocyte/lymphocyte recruitment and infiltration into the subendothelium. It also acts at the onset of adverse clinical vascular events, when activated cells within the plaque secrete matrix proteases that degrade extracellular matrix proteins and weaken the fibrous cap, leading to rupture and thrombus formation. Cells involved in the atherosclerotic process secrete and are activated by soluble factors, known as cytokines. Important recent advances in the comprehension of the mechanisms of atherosclerosis provided evidence that the immunoinflammatory response in atherosclerosis is modulated by regulatory pathways, in which the two anti-inflammatory cytokines interleukin-10 and transforming growth factor-beta play a critical role. The purpose of this review is to bring together the current information concerning the role of cytokines in the development, progression, and complications of atherosclerosis. Specific emphasis is placed on the contribution of pro- and anti-inflammatory cytokines to pathogenic (innate and adaptive) and regulatory immunity in the context of atherosclerosis. Based on our current knowledge of the role of cytokines in atherosclerosis, we propose some novel therapeutic strategies to combat this disease. In addition, we discuss the potential of circulating cytokine levels as biomarkers of coronary artery disease.
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            Hypertriglyceridemia: its etiology, effects and treatment.

            Elevated plasma triglyceride concentration is a common biochemical finding, but the evidence for the benefit of treating this lipid disturbance remains less robust than that for treating elevated low-density lipoprotein-cholesterol. Part of the difficulty in the provision of specific recommendations has been the frequent coexistence of elevated triglycerides with other conditions that affect cardiovascular disease risk, such as depressed high-density lipoprotein-cholesterol, obesity, metabolic syndrome, proinflammatory and prothrombotic biomarkers, and type 2 diabetes. Recent investigations of outcomes of cardiovascular disease when medications are used to reduce triglyceride levels suggest that, although a net benefit probably exists, both relative and absolute risk reductions seem underwhelming when compared with the benefit of reducing low-density lipoprotein-cholesterol levels with treatment. However, the totality of evidence suggests that elevated triglyceride levels likely contribute independently to increased risk of cardiovascular disease, although there is no consensus about appropriate target levels. Furthermore, severe hypertriglyceridemia is associated with an increased risk of acute pancreatitis, irrespective of its effect on risk of cardiovascular disease. We review the causes and classification of elevated triglyceride levels, the clinical manifestations of primary hypertriglyceridemia and the management of patients with elevated triglyceride levels.
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              Comparison of factors associated with 30-day mortality after coronary artery bypass grafting in patients with versus without diabetes mellitus. Israeli Coronary Artery Bypass (ISCAB) Study Consortium.

              The purpose of this study was to identify factors associated with 30-day mortality after coronary artery bypass graft surgery (CABG) among diabetic patients, and to compare them with risk factors among nondiabetics. A subanalysis of a prospective national cohort study was performed which included patients who underwent CABG in 14 medical centers in Israel during 1994. Data including patient demographic and historical information, comorbidity, and cardiac catheterization results were collected by trained nurses. Data were derived from direct patient interviews, charts, catheterization reports, surgical reports, and national vital records. Multivariate logistic regression analysis was used to identify factors associated with a 30-day mortality in diabetic and nondiabetic patient populations. The results showed that crude mortality was 5.0% among diabetic patients (n = 1,034) and 2.5% among nondiabetics (n = 3,350; p < 0.001). The risk profile in diabetics was found to be worse. Multivariate logistic regression analysis identified female gender, 3-vessel disease, and left main disease as independent risk factors for 30-day, past-CABG mortality unique to diabetic patients. Left ventricular dysfunction was found to effect a greater risk among diabetic patients, whereas chronic renal failure was associated with greater risk among nondiabetics. In conclusion, we found differences in patterns of risk factors for post-CABG mortality between diabetics and nondiabetics. These findings may help physicians to identify patients at high risk for CABG mortality.
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                Author and article information

                Contributors
                +48-32-2088512 , +48-32-2088512 , r.krysiak@interia.pl
                Journal
                Eur J Clin Pharmacol
                European Journal of Clinical Pharmacology
                Springer-Verlag (Berlin/Heidelberg )
                0031-6970
                1432-1041
                1 June 2011
                1 June 2011
                November 2011
                : 67
                : 11
                : 1109-1117
                Affiliations
                Department of Internal Medicine and Clinical Pharmacology, Medical University of Silesia, Medyków 18, 40-752 Katowice, Poland
                Article
                1063
                10.1007/s00228-011-1063-y
                3192275
                21630032
                8406c360-8028-44f5-936b-4c04eab65028
                © The Author(s) 2011
                History
                : 2 November 2010
                : 10 May 2011
                Categories
                Pharmacodynamics
                Custom metadata
                © Springer-Verlag 2011

                Pharmacology & Pharmaceutical medicine
                proinflammatory cytokines,bezafibrate,lymphocytes,omega-3 fatty acids,low-grade inflammation,isolated hypertriglyceridemia

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