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      The role of plasma triglyceride/high-density lipoprotein cholesterol ratio to predict cardiovascular outcomes in chronic kidney disease

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          Abstract

          Background

          Cardiovascular disease (CVD) risk is substantially increased in subjects with chronic kidney disease (CKD). The Triglycerides (TG) to High-Density Lipoprotein Cholesterol (HDL-C) ratio is an indirect measure of insulin resistance and an independent predictor of cardiovascular risk. No study to date has been performed to evaluate whether the TG/HDL-C ratio predicts CVD risk in patients with CKD.

          Methods

          A total of 197 patients (age 53 ± 12 years) with CKD Stages 1 to 5, were enrolled in this longitudinal, observational, retrospective study. TG/HDL-C ratio, HOMA-IR indexes, serum asymmetric dimethyl arginine (ADMA), high sensitivity C-reactive protein (CRP), parathyroid hormone (PTH), calcium, phosphorous, estimated glomerular filtration rate (eGFR), and albumin levels were measured. Flow mediated vasodilatation (FMD) of the brachial artery was assessed by using high-resolution ultrasonography.

          Results

          A total of 11 cardiovascular (CV) deaths and 43 nonfatal CV events were registered in a mean follow-up period of 30 (range 9 to 35) months. Subjects with TG/HDL-C ratios above the median values (>3.29) had significantly higher plasma ADMA, PTH, and phosphorous levels (p = 0.04, p = 0.02, p = 0.01 respectively) and lower eGFR and FMD values (p = 0.03, p < 0.001 respectively). The TG/HDL-C ratio was an independent determinant of FMD (β = −0.25 p = 0.02) along with TG, HDL-C, hsCRP, serum albumin, phosphate levels, systolic blood pressure, PTH, eGFR and the presence of diabetes mellitus. The TG/HDL-C ratio was also a significant independent determinant of cardiovascular outcomes [HR: 1.36 (1.11-1.67) (p = 0.003)] along with plasma ADMA levels [HR: 1.31 (1.13-1.52) (p < 0.001)] and a history of diabetes mellitus [HR: 4.82 (2.80-8.37) (p < 0.001)].

          Conclusion

          This study demonstrates that the elevated TG/HDL-C ratio predicts poor CVD outcome in subjects with CKD. Being a simple, inexpensive, and reproducible marker of CVD risk, the TG/HDL-C ratio may emerge as a novel and reliable indicator among the many well-established markers of CVD risk in CKD.

          Systematic review registration

          Clinical trial registration number and date: NCT02113462 / 10-04-2014.

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          Most cited references29

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          Non-invasive detection of endothelial dysfunction in children and adults at risk of atherosclerosis.

          Endothelial dysfunction is an early event in experimental studies of atherogenesis, preceding formation of plaques. We have devised a non-invasive method for testing endothelial function, to find out whether abnormalities are present in symptom-free children and young adults at high risk of atherosclerosis. With high-resolution ultrasound, we measured the diameter of the superficial femoral and brachial arteries at rest, during reactive hyperaemia (with increased flow causing endothelium-dependent dilatation), and after sublingual glyceryl trinitrate (GTN; causing endothelium-independent dilatation) in 100 subjects--50 controls without vascular risk factors (aged 8-57 years), 20 cigarette smokers (aged 17-62 years), 10 children with familial hypercholesterolaemia (FH; aged 8-16 years), and 20 patients with established coronary artery disease (CAD). Adequate scans were obtained in all but 6 cases. Flow-mediated dilatation was observed in arteries from all control subjects. Dilatation was inversely related to baseline vessel diameter (r = -0.81, p < 0.0001); in arteries of 6.0 mm or less, mean dilatation was 10 (SE 2)%. In smokers, FH children, and adults with CAD, flow-mediated dilatation was much reduced or absent (p < 0.001 for comparison with each relevant control group). Dilatation in response to GTN was present in all groups. Endothelial dysfunction is present in children and adults with risk factors for atherosclerosis, such as smoking and hypercholesterolaemia, before anatomical evidence of plaque formation in the arteries studied. This may be an important early event in atherogenesis.
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            Emerging biomarkers for evaluating cardiovascular risk in the chronic kidney disease patient: how do new pieces fit into the uremic puzzle?

            Premature cardiovascular disease (CVD), including stroke, peripheral vascular disease, sudden death, coronary artery disease, and congestive heart failure, is a notorious problem in patients with chronic kidney disease (CKD). Because the presence of CVD is independently associated with kidney function decline, it appears that the relationship between CKD and CVD is reciprocal or bidirectional, and that it is this association that leads to the vicious circle contributing to premature death. As randomized, placebo-controlled trials have so far been disappointing and unable to show a survival benefit of various treatment strategies, such a lipid-lowering, increased dialysis dose and normalization of hemoglobin, the risk factor profile seems to be different in CKD compared with the general population. Indeed, seemingly paradoxical associations between traditional risk factors and cardiovascular outcome in patients with advanced CKD have complicated our efforts to identify the real cardiovascular culprits. This review focuses on the many new pieces that need to be fit into the complicated puzzle of uremic vascular disease, including persistent inflammation, endothelial dysfunction, oxidative stress, and vascular ossification. Each of these is not only highly prevalent in CKD but also more strongly linked to CVD in these patients than in the general population. However, a causal relationship between these new markers and CVD in CKD patients remains to be established. Finally, two novel disciplines, proteomics and epigenetics, will be discussed, because these tools may be helpful in the understanding of the discussed vascular risk factors.
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              Chronic kidney disease: a public health priority and harbinger of premature cardiovascular disease.

              The epidemics of cardiovascular disease, obesity, diabetes, HIV and cancer have all received much attention from the public, media and policymakers. By contrast, chronic kidney disease (CKD) has remained largely a 'silent' epidemic. This is unfortunate because early diagnosis of renal disease based on proteinuria and/or reduced estimated glomerular filtration rate could enable early intervention to reduce the high risks of cardiovascular events, end-stage renal disease (ESRD) and death that are associated with CKD. Given the global increase in the incidence of the leading causes of CKD--hypertension, obesity and diabetes mellitus--better disease management and prevention planning are needed, as effective strategies are available to slow the progression of CKD and reduce cardiovascular risk. CKD may be regarded as a clinical model of accelerated vascular disease and premature ageing, and the risk-factor profile changes during the progression from mild/moderate CKD to ESRD. Although many randomized controlled trials in patients with mild to moderate CKD have shown beneficial effects of interventions aimed at preventing the progression of CKD, most trials have been unable to demonstrate a beneficial effect of interventions aimed at improving outcome in ESRD. Thus, novel treatment strategies are needed in this high-risk patient group. © 2010 The Association for the Publication of the Journal of Internal Medicine.
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                Author and article information

                Contributors
                alpersonmez@yahoo.com
                mahmutiyilmaz@yahoo.com
                mdsaglam@yahoo.com
                hilmiumut@hotmail.com
                mahmut_gok@yahoo.com.tr
                drhakkicetinkaya@yahoo.com
                drmuratkaraman@gmail.com
                cemhaymana@hotmail.com
                teyileten@gmail.com
                heceperen@yahoo.com
                agvural@gata.edu.tr
                manfredi.rizzo@unipa.it
                Peter.Toth@cghmc.com
                Journal
                Lipids Health Dis
                Lipids Health Dis
                Lipids in Health and Disease
                BioMed Central (London )
                1476-511X
                16 April 2015
                16 April 2015
                2015
                : 14
                : 29
                Affiliations
                [ ]Department of Endocrinology and Metabolism, Gulhane School of Medicine, 06018 Etlik, Ankara Turkey
                [ ]Department of Nephrology, Gulhane School of Medicine, 06018 Etlik, Ankara Turkey
                [ ]Department of Radiology, Gulhane School of Medicine, 06018 Etlik, Ankara Turkey
                [ ]Biomedical Department of Internal Medicine and Medical Specialties, University of Palermo, Palermo, Italy
                [ ]University of Illinois School of Medicine, Peoria, Il USA
                Article
                31
                10.1186/s12944-015-0031-4
                4407467
                25885289
                d8451222-403a-4f23-aea3-ea0d62312bdf
                © Sonmez et al.; licensee BioMed Central . 2015

                This is an Open Access article distributed under the terms of the Creative Commons Attribution License ( http://creativecommons.org/licenses/by/4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly credited. The Creative Commons Public Domain Dedication waiver ( http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.

                History
                : 4 November 2014
                : 1 April 2015
                Categories
                Research
                Custom metadata
                © The Author(s) 2015

                Biochemistry
                asymmetric dimethyl arginine,chronic kidney disease,flow mediated dilatation,triglyceride to hdl-cholesterol ratio

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