Editorial Comment Click here to view the Orginal article by A. C. Cordeiro
doi: 10.1111/joim.12356
The location of adipose tissue is important: epicardial fat in patients with chronic kidney disease In Chinese philosophy, yin and yang are two opposite but complementary and highly interrelated forces that inform many areas including traditional Chinese medicine. Light and dark or water and fire are examples of this duality. Either of the two forces (yin and yang) may be more apparent in a particular context, depending on how they are observed. In modern cardiovascular epidemiology, subcutaneous fat is considered the yang (positive) of the risk of coronary heart disease triggered by obesity. Indeed, fat deposited in peripheral tissues has a lower metabolic activity than central (visceral) fat, the yin (negative) of this duality. Accordingly, the metabolic risk of obesity is more strongly linked to visceral than to subcutaneous fat [1]. In visceral adipocytes, increased fat cell volume secondary to accumulation of lipids releases chemotactic factors including monocyte chemoattractant protein-1 (MCP-1), which triggers local accumulation of monocytes [2]. Infiltrated monocytes transform into macrophages, activated cells that synthesize pro-inflammatory cytokines including interleukin (IL)-1b, tumour necrosis factor (TNF)-a and IL-6. TNF-a inhibits insulin signalling and entry of glucose and free fatty acids into adipocytes and promotes lipolysis. Failure by visceral adipocytes to store triglycerides favours accumulation of fatty acids (such as ceramide or diacylglycerol) in tissues fundamental for whole-body energy metabolism, including liver, pancreas, striated muscle and the myocardium, eventually leading to systemic insulin resistance [3]. The close proximity of inflamed visceral fat to the portal circulation is considered of relevance for the induction of liver steatosis [4]. Metrics of visceral fat, epicardial and paracardial fat To be seen, the yin and yang of central and peripheral fat demand appropriate observation lenses, that is appropriate metrics. Unfortunately, the most applied anthropometric estimate of body fat, body mass index (BMI), is a much remote measure of visceral adiposity and provides an
88
ª 2015 The Association for the Publication of the Journal of Internal Medicine
imperfect estimate of the risk of obesity. Chronic kidney disease (CKD) provides an example of the relevance of body fat metrics for exposing the risk of excessive visceral fat in the development of the disease. BMI is indeed a well-known inverse predictor of mortality in moderate to severe CKD [5] and in kidney failure [6]. This apparent paradox depends on the fact that in these conditions, a low BMI mainly underlies protein–energy wasting and associated comorbidities rather than only a low fat mass. Furthermore, visceral fat mass may be high in individuals with a low BMI and, like in those with a high BMI, may cause a high metabolic risk [7]. The peripheral versus central fat duality in CKD is evident when better measures of visceral adiposity than BMI, such as waist circumference or waist to hip ratio, are adopted. Indeed, these improved metrics predict an almost linear risk of death and renal disease progression in patients with chronic nephropathies [8] and of death and cardiovascular events in haemodialysis patients with kidney failure [9]. Computed tomography (CT) or magnetic resonance imaging allows regional (below and above the diaphragm) and whole-body estimates of subcutaneous and visceral fat. Studies focusing on fat deposits in the thorax using these techniques or echocardiography have revealed that adipose tissue in close proximity to the heart (i.e. epicardial fat) provides prognostic information comparable to that of intra-abdominal visceral fat [10]. Epicardial adipose tissue is encased by the visceral pericardium, surrounds the coronary arteries and is in direct contact with the myocardium; in addition, like mesenteric and omental fat, it is derived from the splanchnopleuric mesoderm. It is interesting that epicardial fat and the pericardial fat that envelop the heart (Fig. 1) have features common to both white and brown adipose tissue. The fact that there is direct contact between epicardial fat and the myocardium may be relevant with regard to myocardial steatosis [11]. Brown fat is abundant in newborns and in hibernating mammals and serves to generate heat in neonates or mammals that do not shiver. White adipocytes include only a single
C. Zoccali & F. Mallamaci
Editorial: The location of adipose tissue is important
Paracardial fat
Epicardial fat Fig. 1 Paracardial fat surrounding the parietal pericardium. Epicardial fat, which is covered by the visceral pericardium, surrounds the coronary arteries and is in direct contact with the myocardium.
lipid droplet, whereas brown adipocytes contain numerous smaller droplets and are far richer in mitochondria and capillaries than white fat. Thus, epicardial fat has even subtler elements of yin and yang because brown fat burns energy whilst white fat stores energy. Like visceral abdominal fat, perivascular fat (a fat depot associated with epicardial fat) has a reduced potential to make up adiponectin, a vasculoprotective adipokine, in obese individuals. This effect is fully reversible after weight loss. Epicardial fat in CKD Epicardial fat attracts increasing attention in current cardiovascular literature. A PubMed search on 4 January 2015 using the terms ‘Epicardial fat’ and ‘Risk’ yielded 177 references, of which as many as 48 were published in 2014. Although only three cohort studies have investigated the predictive power of this depot, it has already been shown that epicardial fat predicts the progression of coronary disease in intermediate-risk patients [12]. Given the exceedingly high risk of coronary heart disease events in patients with CKD [13] and the complex relationship between metrics of body adiposity and cardiovascular disease risk in these patients [5], studies focusing on epicardial fat in CKD appear to be highly relevant. So far, five studies have been conducted in patients with this disease: four studies in patients with kidney failure [14–17] and one in predialysis stage G3–5 patients [18]. However, all these studies were cross-sectional and relatively small (ranging from
16 to 93 patients). Furthermore, the outcome measure was the coronary calcium score with simultaneous epicardial fat measurement (or a weaker surrogate). The cohort study by Antonio Carlos Cordeiro et al. [19] in a large cohort (n = 277) of predialysis stage G3–5 patients with CKD published in the current issue of the Journal of Internal Medicine comes as fresh air in the field. In this study, the relationships between both epicardial (as assessed by CT) and abdominal visceral adipose tissue and cardiovascular disease risk were investigated cross-sectionally and prospectively and compared. In an analysis categorizing patients with CKD on the basis of epicardial fat quintiles, this variable was associated not only with a high coronary calcium score but also with an increased prevalence of left ventricular hypertrophy and myocardial ischaemia. More importantly, epicardial fat was associated with an increased risk of cardiovascular events independently of visceral (abdominal) fat and other potential confounders. In aetiological terms, this association supports the notion that, due to its proximity to the heart and to its direct contact with the myocardium, epicardial fat may be more relevant for the pathogenesis of cardiac events than distant visceral abdominal tissue. This finding in patients with CKD is in contrast to the lack of an independent association between epicardial fat and the incidence of cardiovascular events in the general population of the Framingham Heart Study [10]. This discrepancy may imply that the risk associated with epicardial fat is more relevant in patients with CKD than in the general population. The study by Cordeiro et al. is based on only 57 cardiovascular events. Therefore, larger studies in the same population are needed to confirm such an intriguing hypothesis. Furthermore, even though independently associated with cardiovascular events, epicardial fat in patients with CKD failed to add discriminant power for these events to a prediction model formed by other risk factors and visceral fat. The findings of the study by Cordeiro et al. clearly indicate that epicardial fat mass per se is unlikely to add any meaningful, independent prognostic power beyond visceral (abdominal) fat and classical and CKD-related risk factors. However, the aetiological hypothesis generated by the findings of this study implicating epicardial fat in cardiovascular disease risk in CKD is interesting. A case–control study comparing the gene expression of cytokines in adipose tissue in predialysis patients with CKD ª 2015 The Association for the Publication of the Journal of Internal Medicine Journal of Internal Medicine, 2015, 278; 88–91
89
C. Zoccali & F. Mallamaci
and in age- and sex-matched individuals demonstrated a threefold increase in interleukin 6 gene expression in patients with CKD [20], supporting the idea that the risk of inflammation driven by adipose tissue may be of greater relevance in patients with CKD than in the general population. If a similar upregulation of IL-6 and other proinflammatory cytokines exists in the epicardial fat of patients with CKD, this depot may be regarded as a potential therapeutic target. Dietary interventions, exercise programmes and bariatric surgery all reduce visceral and epicardial fat mass along with metabolic risk in obese individuals [21]. Experimental treatments that inhibit inflammation in epicardial fat, or epicardial fat removal, are intriguing possibilities to further investigate the role of this adipose tissue in patients with CKD. In a pilot study, it has already been shown that physical exercise reduces epicardial fat in kidney failure patients on dialysis [22]. Obesity has now become the leading risk factor implicated in the current epidemic of CKD [23]. The focus on obesity and fat depots in patients with CKD is not an academic curiosity but a public health priority. Conflict of interest statement No conflicts of interest to declare. C. Zoccali1 & F. Mallamaci1,2
From the 1Clinical Epidemiology and Pathophysiology of Renal Diseases and Hypertension; and 2Nephrology, Dialysis and Renal Transplantation Unit, United Hospitals of Reggio Calabria and Clinical Epidemiology and Pathophysiology of Renal Diseases and Hypertension, Reggio Calabria Unit of the National Research Council of Italy, Institute of Clinical Physiology of Pisa CNR-IFC, Reggio Calabria, Italy
References 1 Fox CS, Massaro JM, Hoffmann U et al. Abdominal visceral and subcutaneous adipose tissue compartments: association with metabolic risk factors in the Framingham Heart Study. Circulation 2007; 116: 39–48. 2 Gustafson B, Hammarstedt A, Andersson CX, Smith U. Inflamed adipose tissue: a culprit underlying the metabolic syndrome and atherosclerosis. Arterioscler Thromb Vasc Biol 2007; 27: 2276–83. 3 Guilherme A, Virbasius JV, Puri V, Czech MP. Adipocyte dysfunctions linking obesity to insulin resistance and type 2 diabetes. Nat Rev Mol Cell Biol 2008; 9: 367–77. 4 Rytka JM, Wueest S, Schoenle EJ, Konrad D. The portal theory supported by venous drainage-selective fat transplantation. Diabetes 2011; 60: 56–63.
90
ª 2015 The Association for the Publication of the Journal of Internal Medicine Journal of Internal Medicine, 2015, 278; 88–91
Editorial: The location of adipose tissue is important
5 Kovesdy CP, Kalantar-Zadeh K. Why is protein-energy wasting associated with mortality in chronic kidney disease? Semin Nephrol 2009; 29: 3–14. 6 Kalantar-Zadeh K, Abbott KC, Salahudeen AK, Kilpatrick RD, Horwich TB. Survival advantages of obesity in dialysis patients. Am J Clin Nutr 2005; 81: 543–54. 7 Litwin SE. Normal weight obesity: is bigger really badder? Circ Cardiovasc Imaging 2012; 5: 286–8. 8 Elsayed EF, Sarnak MJ, Tighiouart H et al. Waist-to-hip ratio, body mass index, and subsequent kidney disease and death. Am J Kidney Dis 2008; 52: 29–38. 9 Postorino M, Marino C, Tripepi G, Zoccali C. Abdominal obesity modifies the risk of hypertriglyceridemia for all-cause and cardiovascular mortality in hemodialysis patients. Kidney Int 2011; 79: 765–72. 10 Britton KA, Massaro JM, Murabito JM, Kreger BE, Hoffmann U, Fox CS. Body fat distribution, incident cardiovascular disease, cancer, and all-cause mortality. J Am Coll Cardiol 2013; 62: 921–5. 11 Harmancey R, Wilson CR, Taegtmeyer H. Adaptation and maladaptation of the heart in obesity. Hypertension 2008; 52: 181–7. 12 Nakanishi R, Rajani R, Cheng VY et al. Increase in epicardial fat volume is associated with greater coronary artery calcification progression in subjects at intermediate risk by coronary calcium score: a serial study using non-contrast cardiac CT. Atherosclerosis 2011; 218: 363–8. 13 Tonelli M, Muntner P, Lloyd A et al. Risk of coronary events in people with chronic kidney disease compared with those with diabetes: a population-level cohort study. Lancet 2012; 380: 807–14. 14 Turkmen K, Kayikcioglu H, Ozbek O et al. The relationship between epicardial adipose tissue and malnutrition, inflammation, atherosclerosis/calcification syndrome in ESRD patients. Clin J Am Soc Nephrol 2011; 6: 1920–5. 15 Tonbul HZ, Turkmen K, Kayikcioglu H, Ozbek O, Kayrak M, Biyik Z. Epicardial adipose tissue and coronary artery calcification in diabetic and nondiabetic end-stage renal disease patients. Ren Fail 2011; 33: 770–5. 16 Erdur MF, Tonbul HZ, Ozbiner H et al. The relationship between atherogenic index of plasma and epicardial adipose tissue in hemodialysis and peritoneal dialysis patients. Ren Fail 2013; 35: 1193–8. 17 Gaubeta S, Klinghammer L, Jahn D, Schuhback A, Achenbach S, Marwan M. Epicardial fat and coronary artery calcification in patients on long-term hemodialysis. J Comput Assist Tomogr 2014; 38: 768–72. 18 Kerr JD, Holden RM, Morton AR et al. Associations of epicardial fat with coronary calcification, insulin resistance, inflammation, and fibroblast growth factor-23 in stage 3–5 chronic kidney disease. BMC Nephrol 2013; 14: 26. 19 Cordeiro AC, Cassullo Amparo S, Oliveira MAC et al. Epicardial fat accumulation, cardiometabolic profile and cardiovascular events in patients with chronic kidney disease stage 3– 5. J Intern Med 2015; doi:10.1111/joim.12344. 20 Witasp A, Carrero JJ, Heimburger O et al. Increased expression of pro-inflammatory genes in abdominal subcutaneous fat in advanced chronic kidney disease patients. J Intern Med 2011; 269: 410–9. 21 Iacobellis G, Singh N, Wharton S, Sharma AM. Substantial changes in epicardial fat thickness after weight loss in
C. Zoccali & F. Mallamaci
severely obese subjects. Obesity (Silver Spring) 2008; 16: 1693–7. 22 Wilund KR, Tomayko EJ, Wu PT et al. Intradialytic exercise training reduces oxidative stress and epicardial fat: a pilot study. Nephrol Dial Transplant 2010; 25: 2695–701. 23 Bolignano D, Zoccali C. Effects of weight loss on renal function in obese CKD patients: a systematic review. Nephrol Dial Transplant 2013; 28(Suppl 4): iv82–98.
Editorial: The location of adipose tissue is important
Correspondence: Carmine Zoccali, Epidemiologia Clinica e Fisiopatologia delle Malattie Renali e dell’Ipertensione Arteriosa, CNRIFC, c/o Ospedali Riuniti (VI piano), Reggio Calabria, Italy. (e-mail: [email protected]).
ª 2015 The Association for the Publication of the Journal of Internal Medicine Journal of Internal Medicine, 2015, 278; 88–91
91
doi: 10.1111/joim.12356
The location of adipose tissue is important: epicardial fat in patients with chronic kidney disease In Chinese philosophy, yin and yang are two opposite but complementary and highly interrelated forces that inform many areas including traditional Chinese medicine. Light and dark or water and fire are examples of this duality. Either of the two forces (yin and yang) may be more apparent in a particular context, depending on how they are observed. In modern cardiovascular epidemiology, subcutaneous fat is considered the yang (positive) of the risk of coronary heart disease triggered by obesity. Indeed, fat deposited in peripheral tissues has a lower metabolic activity than central (visceral) fat, the yin (negative) of this duality. Accordingly, the metabolic risk of obesity is more strongly linked to visceral than to subcutaneous fat [1]. In visceral adipocytes, increased fat cell volume secondary to accumulation of lipids releases chemotactic factors including monocyte chemoattractant protein-1 (MCP-1), which triggers local accumulation of monocytes [2]. Infiltrated monocytes transform into macrophages, activated cells that synthesize pro-inflammatory cytokines including interleukin (IL)-1b, tumour necrosis factor (TNF)-a and IL-6. TNF-a inhibits insulin signalling and entry of glucose and free fatty acids into adipocytes and promotes lipolysis. Failure by visceral adipocytes to store triglycerides favours accumulation of fatty acids (such as ceramide or diacylglycerol) in tissues fundamental for whole-body energy metabolism, including liver, pancreas, striated muscle and the myocardium, eventually leading to systemic insulin resistance [3]. The close proximity of inflamed visceral fat to the portal circulation is considered of relevance for the induction of liver steatosis [4]. Metrics of visceral fat, epicardial and paracardial fat To be seen, the yin and yang of central and peripheral fat demand appropriate observation lenses, that is appropriate metrics. Unfortunately, the most applied anthropometric estimate of body fat, body mass index (BMI), is a much remote measure of visceral adiposity and provides an
88
ª 2015 The Association for the Publication of the Journal of Internal Medicine
imperfect estimate of the risk of obesity. Chronic kidney disease (CKD) provides an example of the relevance of body fat metrics for exposing the risk of excessive visceral fat in the development of the disease. BMI is indeed a well-known inverse predictor of mortality in moderate to severe CKD [5] and in kidney failure [6]. This apparent paradox depends on the fact that in these conditions, a low BMI mainly underlies protein–energy wasting and associated comorbidities rather than only a low fat mass. Furthermore, visceral fat mass may be high in individuals with a low BMI and, like in those with a high BMI, may cause a high metabolic risk [7]. The peripheral versus central fat duality in CKD is evident when better measures of visceral adiposity than BMI, such as waist circumference or waist to hip ratio, are adopted. Indeed, these improved metrics predict an almost linear risk of death and renal disease progression in patients with chronic nephropathies [8] and of death and cardiovascular events in haemodialysis patients with kidney failure [9]. Computed tomography (CT) or magnetic resonance imaging allows regional (below and above the diaphragm) and whole-body estimates of subcutaneous and visceral fat. Studies focusing on fat deposits in the thorax using these techniques or echocardiography have revealed that adipose tissue in close proximity to the heart (i.e. epicardial fat) provides prognostic information comparable to that of intra-abdominal visceral fat [10]. Epicardial adipose tissue is encased by the visceral pericardium, surrounds the coronary arteries and is in direct contact with the myocardium; in addition, like mesenteric and omental fat, it is derived from the splanchnopleuric mesoderm. It is interesting that epicardial fat and the pericardial fat that envelop the heart (Fig. 1) have features common to both white and brown adipose tissue. The fact that there is direct contact between epicardial fat and the myocardium may be relevant with regard to myocardial steatosis [11]. Brown fat is abundant in newborns and in hibernating mammals and serves to generate heat in neonates or mammals that do not shiver. White adipocytes include only a single
C. Zoccali & F. Mallamaci
Editorial: The location of adipose tissue is important
Paracardial fat
Epicardial fat Fig. 1 Paracardial fat surrounding the parietal pericardium. Epicardial fat, which is covered by the visceral pericardium, surrounds the coronary arteries and is in direct contact with the myocardium.
lipid droplet, whereas brown adipocytes contain numerous smaller droplets and are far richer in mitochondria and capillaries than white fat. Thus, epicardial fat has even subtler elements of yin and yang because brown fat burns energy whilst white fat stores energy. Like visceral abdominal fat, perivascular fat (a fat depot associated with epicardial fat) has a reduced potential to make up adiponectin, a vasculoprotective adipokine, in obese individuals. This effect is fully reversible after weight loss. Epicardial fat in CKD Epicardial fat attracts increasing attention in current cardiovascular literature. A PubMed search on 4 January 2015 using the terms ‘Epicardial fat’ and ‘Risk’ yielded 177 references, of which as many as 48 were published in 2014. Although only three cohort studies have investigated the predictive power of this depot, it has already been shown that epicardial fat predicts the progression of coronary disease in intermediate-risk patients [12]. Given the exceedingly high risk of coronary heart disease events in patients with CKD [13] and the complex relationship between metrics of body adiposity and cardiovascular disease risk in these patients [5], studies focusing on epicardial fat in CKD appear to be highly relevant. So far, five studies have been conducted in patients with this disease: four studies in patients with kidney failure [14–17] and one in predialysis stage G3–5 patients [18]. However, all these studies were cross-sectional and relatively small (ranging from
16 to 93 patients). Furthermore, the outcome measure was the coronary calcium score with simultaneous epicardial fat measurement (or a weaker surrogate). The cohort study by Antonio Carlos Cordeiro et al. [19] in a large cohort (n = 277) of predialysis stage G3–5 patients with CKD published in the current issue of the Journal of Internal Medicine comes as fresh air in the field. In this study, the relationships between both epicardial (as assessed by CT) and abdominal visceral adipose tissue and cardiovascular disease risk were investigated cross-sectionally and prospectively and compared. In an analysis categorizing patients with CKD on the basis of epicardial fat quintiles, this variable was associated not only with a high coronary calcium score but also with an increased prevalence of left ventricular hypertrophy and myocardial ischaemia. More importantly, epicardial fat was associated with an increased risk of cardiovascular events independently of visceral (abdominal) fat and other potential confounders. In aetiological terms, this association supports the notion that, due to its proximity to the heart and to its direct contact with the myocardium, epicardial fat may be more relevant for the pathogenesis of cardiac events than distant visceral abdominal tissue. This finding in patients with CKD is in contrast to the lack of an independent association between epicardial fat and the incidence of cardiovascular events in the general population of the Framingham Heart Study [10]. This discrepancy may imply that the risk associated with epicardial fat is more relevant in patients with CKD than in the general population. The study by Cordeiro et al. is based on only 57 cardiovascular events. Therefore, larger studies in the same population are needed to confirm such an intriguing hypothesis. Furthermore, even though independently associated with cardiovascular events, epicardial fat in patients with CKD failed to add discriminant power for these events to a prediction model formed by other risk factors and visceral fat. The findings of the study by Cordeiro et al. clearly indicate that epicardial fat mass per se is unlikely to add any meaningful, independent prognostic power beyond visceral (abdominal) fat and classical and CKD-related risk factors. However, the aetiological hypothesis generated by the findings of this study implicating epicardial fat in cardiovascular disease risk in CKD is interesting. A case–control study comparing the gene expression of cytokines in adipose tissue in predialysis patients with CKD ª 2015 The Association for the Publication of the Journal of Internal Medicine Journal of Internal Medicine, 2015, 278; 88–91
89
C. Zoccali & F. Mallamaci
and in age- and sex-matched individuals demonstrated a threefold increase in interleukin 6 gene expression in patients with CKD [20], supporting the idea that the risk of inflammation driven by adipose tissue may be of greater relevance in patients with CKD than in the general population. If a similar upregulation of IL-6 and other proinflammatory cytokines exists in the epicardial fat of patients with CKD, this depot may be regarded as a potential therapeutic target. Dietary interventions, exercise programmes and bariatric surgery all reduce visceral and epicardial fat mass along with metabolic risk in obese individuals [21]. Experimental treatments that inhibit inflammation in epicardial fat, or epicardial fat removal, are intriguing possibilities to further investigate the role of this adipose tissue in patients with CKD. In a pilot study, it has already been shown that physical exercise reduces epicardial fat in kidney failure patients on dialysis [22]. Obesity has now become the leading risk factor implicated in the current epidemic of CKD [23]. The focus on obesity and fat depots in patients with CKD is not an academic curiosity but a public health priority. Conflict of interest statement No conflicts of interest to declare. C. Zoccali1 & F. Mallamaci1,2
From the 1Clinical Epidemiology and Pathophysiology of Renal Diseases and Hypertension; and 2Nephrology, Dialysis and Renal Transplantation Unit, United Hospitals of Reggio Calabria and Clinical Epidemiology and Pathophysiology of Renal Diseases and Hypertension, Reggio Calabria Unit of the National Research Council of Italy, Institute of Clinical Physiology of Pisa CNR-IFC, Reggio Calabria, Italy
References 1 Fox CS, Massaro JM, Hoffmann U et al. Abdominal visceral and subcutaneous adipose tissue compartments: association with metabolic risk factors in the Framingham Heart Study. Circulation 2007; 116: 39–48. 2 Gustafson B, Hammarstedt A, Andersson CX, Smith U. Inflamed adipose tissue: a culprit underlying the metabolic syndrome and atherosclerosis. Arterioscler Thromb Vasc Biol 2007; 27: 2276–83. 3 Guilherme A, Virbasius JV, Puri V, Czech MP. Adipocyte dysfunctions linking obesity to insulin resistance and type 2 diabetes. Nat Rev Mol Cell Biol 2008; 9: 367–77. 4 Rytka JM, Wueest S, Schoenle EJ, Konrad D. The portal theory supported by venous drainage-selective fat transplantation. Diabetes 2011; 60: 56–63.
90
ª 2015 The Association for the Publication of the Journal of Internal Medicine Journal of Internal Medicine, 2015, 278; 88–91
Editorial: The location of adipose tissue is important
5 Kovesdy CP, Kalantar-Zadeh K. Why is protein-energy wasting associated with mortality in chronic kidney disease? Semin Nephrol 2009; 29: 3–14. 6 Kalantar-Zadeh K, Abbott KC, Salahudeen AK, Kilpatrick RD, Horwich TB. Survival advantages of obesity in dialysis patients. Am J Clin Nutr 2005; 81: 543–54. 7 Litwin SE. Normal weight obesity: is bigger really badder? Circ Cardiovasc Imaging 2012; 5: 286–8. 8 Elsayed EF, Sarnak MJ, Tighiouart H et al. Waist-to-hip ratio, body mass index, and subsequent kidney disease and death. Am J Kidney Dis 2008; 52: 29–38. 9 Postorino M, Marino C, Tripepi G, Zoccali C. Abdominal obesity modifies the risk of hypertriglyceridemia for all-cause and cardiovascular mortality in hemodialysis patients. Kidney Int 2011; 79: 765–72. 10 Britton KA, Massaro JM, Murabito JM, Kreger BE, Hoffmann U, Fox CS. Body fat distribution, incident cardiovascular disease, cancer, and all-cause mortality. J Am Coll Cardiol 2013; 62: 921–5. 11 Harmancey R, Wilson CR, Taegtmeyer H. Adaptation and maladaptation of the heart in obesity. Hypertension 2008; 52: 181–7. 12 Nakanishi R, Rajani R, Cheng VY et al. Increase in epicardial fat volume is associated with greater coronary artery calcification progression in subjects at intermediate risk by coronary calcium score: a serial study using non-contrast cardiac CT. Atherosclerosis 2011; 218: 363–8. 13 Tonelli M, Muntner P, Lloyd A et al. Risk of coronary events in people with chronic kidney disease compared with those with diabetes: a population-level cohort study. Lancet 2012; 380: 807–14. 14 Turkmen K, Kayikcioglu H, Ozbek O et al. The relationship between epicardial adipose tissue and malnutrition, inflammation, atherosclerosis/calcification syndrome in ESRD patients. Clin J Am Soc Nephrol 2011; 6: 1920–5. 15 Tonbul HZ, Turkmen K, Kayikcioglu H, Ozbek O, Kayrak M, Biyik Z. Epicardial adipose tissue and coronary artery calcification in diabetic and nondiabetic end-stage renal disease patients. Ren Fail 2011; 33: 770–5. 16 Erdur MF, Tonbul HZ, Ozbiner H et al. The relationship between atherogenic index of plasma and epicardial adipose tissue in hemodialysis and peritoneal dialysis patients. Ren Fail 2013; 35: 1193–8. 17 Gaubeta S, Klinghammer L, Jahn D, Schuhback A, Achenbach S, Marwan M. Epicardial fat and coronary artery calcification in patients on long-term hemodialysis. J Comput Assist Tomogr 2014; 38: 768–72. 18 Kerr JD, Holden RM, Morton AR et al. Associations of epicardial fat with coronary calcification, insulin resistance, inflammation, and fibroblast growth factor-23 in stage 3–5 chronic kidney disease. BMC Nephrol 2013; 14: 26. 19 Cordeiro AC, Cassullo Amparo S, Oliveira MAC et al. Epicardial fat accumulation, cardiometabolic profile and cardiovascular events in patients with chronic kidney disease stage 3– 5. J Intern Med 2015; doi:10.1111/joim.12344. 20 Witasp A, Carrero JJ, Heimburger O et al. Increased expression of pro-inflammatory genes in abdominal subcutaneous fat in advanced chronic kidney disease patients. J Intern Med 2011; 269: 410–9. 21 Iacobellis G, Singh N, Wharton S, Sharma AM. Substantial changes in epicardial fat thickness after weight loss in
C. Zoccali & F. Mallamaci
severely obese subjects. Obesity (Silver Spring) 2008; 16: 1693–7. 22 Wilund KR, Tomayko EJ, Wu PT et al. Intradialytic exercise training reduces oxidative stress and epicardial fat: a pilot study. Nephrol Dial Transplant 2010; 25: 2695–701. 23 Bolignano D, Zoccali C. Effects of weight loss on renal function in obese CKD patients: a systematic review. Nephrol Dial Transplant 2013; 28(Suppl 4): iv82–98.
Editorial: The location of adipose tissue is important
Correspondence: Carmine Zoccali, Epidemiologia Clinica e Fisiopatologia delle Malattie Renali e dell’Ipertensione Arteriosa, CNRIFC, c/o Ospedali Riuniti (VI piano), Reggio Calabria, Italy. (e-mail: [email protected]).
ª 2015 The Association for the Publication of the Journal of Internal Medicine Journal of Internal Medicine, 2015, 278; 88–91
91
