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      Cardiovascular Risk Factors Accelerate Kidney Function Decline in Post−Myocardial Infarction Patients: The Alpha Omega Cohort Study

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          Abstract

          Introduction

          Impaired kidney function is a robust risk factor for cardiovascular mortality. Age-related annual kidney function decline of 1.0 ml/min per 1.73 m 2 after age 40 years is doubled in post−myocardial infarction (MI) patients.

          Methods

          We investigated the impact of the number of cardiovascular risk factors (including unhealthy lifestyle) on annual kidney function decline, in 2426 post-MI patients (60−80 years) of the prospective Alpha Omega Cohort study. Glomerular filtration rate was estimated by serum cystatin C (eGFR cysC) and combined creatinine−cystatin C (eGFR cr-cysC), using the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equations from 2012. Data were analyzed by multivariable linear and logistic regression.

          Results

          At baseline, mean (SD) eGFR cysC and eGFR cr-cysC were 81.5 (19.6) and 78.5 (18.7) ml/min per 1.73 m 2, respectively. Of all patients, 79% were men, 19% had diabetes, 56% had high blood pressure (≥140/90 mm Hg), 16% were current smokers, 56% had high serum low-density lipoprotein (LDL of ≥2.5 mmol/l), and 23% were obese (body mass index of ≥30.0 kg/m 2). After multivariable adjustment, the additional annual eGFR cysC decline (95% confidence interval) was as follows: in patients with versus without diabetes, −0.90 (−1.23 to −0.57) ml/min per 1.73 m 2; in patients with high versus normal blood pressure, −0.50 (−0.76 to −0.24) ml/min per 1.73 m 2; in obese versus nonobese patients, −0.31 (−0.61 to 0.01) ml/min per 1.73 m 2; and in current smokers versus nonsmokers, −0.19 (−0.54 to 0.16) ml/min per 1.73 m 2. High LDL was not associated with accelerated eGFR cysC decline. Similar results were obtained with eGFR cr-cysC.

          Conclusion

          In older, stable post-MI patients without cardiovascular risk factors, the annual kidney function decline was −0.90 (−1.16 to −0.65) ml/min per 1.73 m 2. In contrast, in post-MI patients with ≥3 cardiovascular risk factors, the annual kidney function decline was 2.5-fold faster, at −2.37 (−2.85 to −1.89) ml/min per 1.73 m 2.

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          Most cited references32

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          2013 ACC/AHA Guideline on the Treatment of Blood Cholesterol to Reduce Atherosclerotic Cardiovascular Risk in Adults

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            Recent advances in the relationship between obesity, inflammation, and insulin resistance.

            It now appears that, in most obese patients, obesity is associated with a low-grade inflammation of white adipose tissue (WAT) resulting from chronic activation of the innate immune system and which can subsequently lead to insulin resistance, impaired glucose tolerance and even diabetes. WAT is the physiological site of energy storage as lipids. In addition, it has been more recently recognized as an active participant in numerous physiological and pathophysiological processes. In obesity, WAT is characterized by an increased production and secretion of a wide range of inflammatory molecules including TNF-alpha and interleukin-6 (IL-6), which may have local effects on WAT physiology but also systemic effects on other organs. Recent data indicate that obese WAT is infiltrated by macrophages, which may be a major source of locally-produced pro-inflammatory cytokines. Interestingly, weight loss is associated with a reduction in the macrophage infiltration of WAT and an improvement of the inflammatory profile of gene expression. Several factors derived not only from adipocytes but also from infiltrated macrophages probably contribute to the pathogenesis of insulin resistance. Most of them are overproduced during obesity, including leptin, TNF-alpha, IL-6 and resistin. Conversely, expression and plasma levels of adiponectin, an insulin-sensitising effector, are down-regulated during obesity. Leptin could modulate TNF-alpha production and macrophage activation. TNF-alpha is overproduced in adipose tissue of several rodent models of obesity and has an important role in the pathogenesis of insulin resistance in these species. However, its actual involvement in glucose metabolism disorders in humans remains controversial. IL-6 production by human adipose tissue increases during obesity. It may induce hepatic CRP synthesis and may promote the onset of cardiovascular complications. Both TNF-alpha and IL-6 can alter insulin sensitivity by triggering different key steps in the insulin signalling pathway. In rodents, resistin can induce insulin resistance, while its implication in the control of insulin sensitivity is still a matter of debate in humans. Adiponectin is highly expressed in WAT, and circulating adiponectin levels are decreased in subjects with obesity-related insulin resistance, type 2 diabetes and coronary heart disease. Adiponectin inhibits liver neoglucogenesis and promotes fatty acid oxidation in skeletal muscle. In addition, adiponectin counteracts the pro-inflammatory effects of TNF-alpha on the arterial wall and probably protects against the development of arteriosclerosis. In obesity, the pro-inflammatory effects of cytokines through intracellular signalling pathways involve the NF-kappaB and JNK systems. Genetic or pharmacological manipulations of these effectors of the inflammatory response have been shown to modulate insulin sensitivity in different animal models. In humans, it has been suggested that the improved glucose tolerance observed in the presence of thiazolidinediones or statins is likely related to their anti-inflammatory properties. Thus, it can be considered that obesity corresponds to a sub-clinical inflammatory condition that promotes the production of pro-inflammatory factors involved in the pathogenesis of insulin resistance.
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              KDIGO 2012 clinical practice guideline for the evaluation and management of chronic kidney disease

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                Author and article information

                Contributors
                Journal
                Kidney Int Rep
                Kidney Int Rep
                Kidney International Reports
                Elsevier
                2468-0249
                16 March 2018
                July 2018
                16 March 2018
                : 3
                : 4
                : 879-888
                Affiliations
                [1 ]Department of Nephrology, Leiden University Medical Center, Leiden, The Netherlands
                [2 ]Department of Clinical Epidemiology, Leiden University Medical Center, Leiden, The Netherlands
                [3 ]Division of Human Nutrition, Wageningen University, Wageningen, The Netherlands
                [4 ]Department of Psychiatry, Leiden University Medical Center, Leiden, The Netherlands
                [5 ]Department of Epidemiology, University Medical Center Groningen, Groningen, The Netherlands
                [6 ]Department of Nephrology, Jeroen Bosch Hospital, Den Bosch, The Netherlands
                Author notes
                [] Correspondence: Kevin Esmeijer, Department of Nephrology, Leiden University Medical Center (Building 1, C7-Q), Albinusdreef 2, 2333 ZA Leiden, The Netherlands. k.esmeijer@ 123456lumc.nl
                Article
                S2468-0249(18)30060-3
                10.1016/j.ekir.2018.03.005
                6035162
                29989031
                dd8d9931-3ec9-4639-8c5a-421f3dfcea8d
                © 2018 International Society of Nephrology. Published by Elsevier Inc.

                This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).

                History
                : 7 December 2017
                : 16 February 2018
                : 12 March 2018
                Categories
                Clinical Research

                cardiovascular risk factors,kidney function decline,lifestyle

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