Associations of epicardial fat with coronary calcification, insulin resistance, inflammation, and fibroblast growth factor-23 in stage 3-5 chronic kidney disease

BMC Nephrology

Jocelyn S Garland⁵  Cynthia M Pruss³  Wilma M Hopman⁴  Robert L Nolan¹  Alexander R Morton⁶  Rachel M Holden⁶  Jasmine D Kerr² 

[1]Department of Radiology, Queen’s University, Kingston, ON, Canada

[2]Department of Medicine, Queen’s University, Kingston, ON, Canada

[3]Department of Biomedical and Molecular Sciences, Queen’s University, Kingston, ON, Canada

[4]Clinical Research Center, Kingston General Hospital, and Department of Community Health and Epidemiology, Queen’s University, Kingston, Ontario, Canada

[5]Room 2043 Etherington Hall, Queen’s University, Kingston, Ontario, K7L 3N6, Canada

[6]Queen’s University Vascular Calcification Investigators, Queen’s University, Kingston, ON, Canada

关键词: Interleukin-6;    Metabolic syndrome;    Coronary artery calcification;    Chronic kidney disease;    Epicardial fat;   

Others  :  1083012
DOI  :  10.1186/1471-2369-14-26

 received in 2012-07-11, accepted in 2013-01-18,  发布年份 2013

【 摘 要 】

Background

Epicardial fat, quantified in a single multi-slice computed tomography (MSCT) slice, is a reliable estimate of total epicardial fat volume (EFV). We sought to determine risk factors for EFV detected in a single-slice MSCT measurement (ssEFV) in pre-dialysis chronic kidney disease (CKD) patients. Our primary objective was to determine the association between ssEFV and coronary artery calcification (CAC).

Methods

94 pre-dialysis stage 3–5 CKD patients underwent MSCT to measure ssEFV and CAC. ssEFV was quantified at the level of the left main coronary artery. Measures of inflammation, traditional and kidney-related cardiovascular disease risk factors were collected.

Results

Mean age: 63.7 ± 14 years, 56% male, 39% had diabetes, and mean eGFR: 25.1 ± 11.9 mL/min/1.73 m². Mean ssEFV was 5.03 ± 2.4 cm³. By univariate analysis, body mass index (BMI) (r = 0.53; P = <0.0001), abdominal obesity (r = 0.51; P < 0.0001), high density lipoprotein (HDL) cholesterol (r = − 0.39; P = <0.0001), insulin resistance (log homeostasis model assessment of insulin resistance (log HOMA-IR)) (r = 0.38, P = 0.001), log interleukin-6 (IL-6) (r = 0.34; P = 0.001), and log urinary albumin to creatinine ratio (UACR) (r = 0.30, P = 0.004) demonstrated the strongest associations with ssEFV. Log coronary artery calcification (log CAC score) (r = 0.28, P = 0.006), and log fibroblast growth factor-23 (log FGF-23) (r = 0.23, P = 0.03) were also correlated with ssEFV. By linear regression, log CAC score (beta =0.40; 95% confidence interval (CI), 0.01-0.80; P = 0.045), increasing levels of IL-6 (beta = 0.99; 95% CI, 0.38 – 1.61; P = 0.002), abdominal obesity (beta = 1.86; 95% CI, 0.94 - 2.8; P < 0.0001), lower HDL cholesterol (beta = −2.30; 95% CI, – 3.68 to −0.83; P = 0.002) and albuminuria (log UACR, beta = 0.81; 95% CI, 0.2 to 1.4; P = 0.01) were risk factors for increased ssEFV.

Conclusions

In stage 3–5 CKD, coronary calcification and IL-6 and were predictors of ssEFV. Further studies are needed to clarify the mechanism by which epicardial fat may contribute to the pathogenesis of coronary disease, particularly in the CKD population.

【 授权许可】

   
2013 Kerr et al.; licensee BioMed Central Ltd.

【 图 表 】

Figure 1.

【 参考文献 】

• [1]Ford ES, Li C, Sattar N: Metabolic syndrome and incident diabetes: current state of the evidence. Diabetes Care 2008, 31:1898-1904.
• [2]Galassi A, Reynolds K, He J: Metabolic syndrome and risk of cardiovascular disease: a meta-analysis. Am J Med 2006, 119:812-819.
• [3]Chen J, Muntner P, Hamm L, Jones DW, Batumen V, Fonseca V, Whelton PK, He J: The metabolic syndrome and chronic kidney disease in U.S. adults. Ann Intern Med 2004, 140:167-174.
• [4]Ninomiya T, Kiyohara Y, Kubo M, Yonemoto K, Tanizaki Y, Doi Y, Hirakata H, Iida M: Metabolic syndrome and CKD in a general Japanese population: the Hisayama Study. Am J Kidney Dis 2006, 2006(48):383-391.
• [5]Kadowaki T, Yamauchi T, Kubota N, Hara K, Ueki K, Tobe K: Adiponectin and adiponectin receptors in insulin resistance, diabetes, and the metabolic syndrome. J Clin Invest 2006, 116:1784-1792.
• [6]Kern PA, Ranganathan S, Li C, Wood L, Ranganathan G: Adipose tissue tumor necrosis factor and interleukin-6 expression in human obesity and insulin resistance. Am J Physiol Endocrinol Metab 2001, 280:E745-E751.
• [7]Suganami T, Nishida I, Ogawa Y: A paracrine loop between adipocytes and macrophages aggravates inflammatory changes. Role of free fatty acids and tumor necrosis factor-α. Arterioscler Thromb Vasc Biol 2005, 25:2062-2068.
• [8]Aljada A, Ghanim H, Assian E, Dandona P: Tumor necrosis factor-alpha inhibits insulin-induced increase in endothelial nitric oxide synthase and reduces insulin receptor content and phosphorylation in human aortic endothelial cells. Metabolism 2002, 51:487-491.
• [9]Iacobellis G, Corradi D, Sharma AM: Epicardial adipose tissue: anatomic, biomolecular and clinical relationships with the heart. Nat Clin Pract Cardiovasc Med 2005, 2:536-543.
• [10]Mazurek T, Zhang L, Zalewski A, Mannion JD, Diehl JT, Arafat H, Sarov-Blat L, O’Brien S, Keiper EA, Johnson AG, Martin J, Goldstein BJ, Shi Y: Human epicardial adipose tissue is a source of inflammatory mediators. Circulation 2003, 108:2460-2466.
• [11]Yerramasu A, Dey D, Venuraju S, Anand DV, Atwal S, Corder R, Berman DS, Lahiri A: Increased volume of epicardial fat is an independent risk factor for accelerated progression of sub-clinical coronary atherosclerosis. Atherosclerosis 2012, 220:223-230.
• [12]Aydin H, Toprak A, Deyneli O, Yazici D, Tarcin O, Sancak S, Yavuz D, Alkalin S: Epicardial fat tissue thickness correlates with endothelial dysfunction and other cardiovascular risk factors in patients with metabolic syndrome. Metabol Syndr Relat Dis 2010, 8:229-234.
• [13]Tonbul HZ, Kultigin T, 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, 33:770-775.
• [14]Turkmen K, Kayikcioglu H, Ozbek O, Solak Y, Kayrak M, Samur C, Anil M, Tonbul HZ: The relationship between epicardial adipose tissue and malnutrition, inflammation, atherosclerosis / calcification syndrome in ESRD patients. Clin J Am Soc Nephrol 2011, 6(8):1920-1925.
• [15]Kramer H, Toto R, Peshock R, Cooper R, Victor R: Association between chronic kidney disease and coronary artery calcification: the Dallas heart study. J Am Soc Nephrol 2005, 16(2):507-513.
• [16]Tomiyama C, Higa A, Dalboni MA, Cendoroglo M, Draibe SA, Cuppari L, Carvalho AB, Neto EM, Canziani ME: The impact of traditional and non-traditional risk factors on coronary calcification in pre-dialysis patients. Nephrol Dial Transplant 2006, 21(9):2464-2471.
• [17]Oyama N, Goto D, Ito YM, Ishimori N, Mimura R, Furumoto T, Kato F, Tsutsui H, Tamaki N, Terae S, Shirato H: Single-slice epicardial fat area measurement: do we need to measure the total epicardial fat volume? Jpn J Radiol 2011, 29:104-109.
• [18]Holden RM, Morton AR, Garland JS, Pavlov A, Day AG, Booth SL: Vitamins K and D status in stages 3–5 chronic kidney disease. Clin J Am Soc Nephrol 2010, 5(4):590-597.
• [19]National Kidney Foundation: K/DOQI clinical practice guidelines for chronic kidney disease: evaluation, classification, and stratification. Am J Kidney Dis 2011, 39:S1-S266.
• [20]Hemmelgarn BR, McAlister FA, Grover S, Myers MG, McKay DW, Bolli P, Abbott C, Schiffrin EL, Honos G, Burgess E, Mann K, Wilson T, Penner B, Tremblay G, Milot A, Chockalingam A, Touyz RM, Tobe SW: Canadian hypertension education program. The 2006 Canadian hypertension education program recommendations for the management of hypertension: part I—blood pressure measurement, diagnosis and assessment of risk. Can J Cardiol 2006, 22:573-581.
• [21]Canadian Diabetes Association Clinical Practice Guidelines Expert Committee: Canadian diabetes association 2003 clinical practice guidelines for the prevention and management of diabetes in Canada. Can J Diabetes 2003, 27(suppl 2):S7-S9.
• [22]Grundy SM, Cleeman JI, Daniels SR, Donato KA, Eckel RH, Franklin BA, Gordon DJ, Krauss RM, Savage PJ, Smith SC Jr, Spertus JA, Costa F: Diagnosis and management of the metabolic syndrome: an American heart association/national heart, lung, and blood institute scientific statement. Circulation 2005, 112:2735-2752.
• [23]Levey AS, Bosch JP, Lewis JB, Greene T, Rogers N, Roth D: A more accurate method to estimate glomerular filtration rate from serum creatinine: a new prediction equation. Modification of diet in renal disease study group. Ann Intern Med 1999, 130:461-470.
• [24]Levey AS, Coresh J, Greene T, Stevens LA, Zhang Y, Hendrikson S, Kusek JW, Van Lente F: Chronic kidney disease epidemiology collaboration. Using standardized serum creatinine values in the modification of diet in renal disease study equation for estimating glomerular filtration rate. Ann Intern Med 2006, 145:247-254.
• [25]Ascaso JF, Pardo S, Real JT, Lorente RI, Priego A, Carmena R: Diagnosing insulin resistance by simple quantitative methods in subjects with normal glucose metabolism. Diabetes Care 2003, 26:3320-3325.
• [26]Wexler L, Brundage B, Crouse J, Detrano R, Fuster V, Maddahi J, Rumberger J, Stanford W, White R, Taubert K: Coronary artery calcification: pathophysiology, epidemiology, imaging methods, and clinical implications. A statement for health professionals from the American heart association writing group. Circulation 1996, 94:1175-1192.
• [27]Agatston AS, Janowitz WR, Hildner F: Quantification of coronary artery calcium using ultra fast computed tomography. J Am Coll Cardiol 1990, 15:827-832.
• [28]Weiner DE, Tighiouart H, Amin MG, Stark PC, MacLeod B, Griffith JL, et al.: Chronic kidney disease as a risk factor for cardiovascular disease and all-cause mortality: a pooled analysis of community-based studies. J Am Soc Nephrol 2004, 15:1307-1315.
• [29]Ding J, Hsu FC, Harris TB, Liu Y, Kritchevsky SB, Szklo M, Ouyang P, Espeland MA, Lohman KK, Criqui MH, Allison M, Bluemke DA, Carr JJ: The association of pericardial fat with incident coronary heart disease: the multi-ethnic study of atherosclerosis (MESA). Am J Clin Nutr 2009, 90:499-504.
• [30]Karastergiou K, Evans I, Ogston N, Mibeisi N, Nair D, Kaski J, Jahangiri M, Mohamed-Ali V: Epicardial adipokines in obesity and coronary artery disease induce atherogenic changes in monocytes and endothelial cells. Arterioscler Thromb Vasc Biol 2010, 30:1340-1346.
• [31]Levin A, Djurdjev O, Beaulieu M, Er L: Variability and risk factors for kidney disease progression and death following attainment of stage 4 CKD in a referred cohort. Am J Kidney Dis 2008, 52:661-671.
• [32]Futrakul N, Sridama V, Futrakul P: Microalbuminuria- a biomarker of renal microvascular disease. Ren Fail 2009, 31:140-143.
• [33]Tamba S, Nakatsuji H, Kishida K, Noguchi M, Ogawa T, Okauchi Y, Nishizawa H, Imagawa A, Nakamura T, Matsuzawa Y, Funahashi T, Shimomura I: Relationship between visceral fat accumulation and urinary albumin-creatinine ratio in middle-aged Japanese men. Atherosclerosis 2010, 211:601-605.
• [34]Shibasaki I, Nishikimi T, Mochizuki Y, Yamada Y, Yoshitatsu M, Inoue Y, Kuwata T, Ogawa H, Tsuchiya G, Ishimitsu T, Fukuda H: Greater expression of inflammatory cytokines, adrenomedullin, and natriuretic peptide receptor-C in epicardial adipose tissue in coronary artery disease. Regul Pept 2010, 165:210-217.
• [35]Shankar A, Sun L, Klein BE, Lee KE, Muntner P, Nieto FJ, Tsai MY, Cruickshanks KJ, Schubert CR, Brazy PC, Coresh J, Klein R: Markers of inflammation predict the long-term risk of developing chronic kidney disease: a population-based cohort study. Kidney Int 2011, 80(11):1231-1238.
• [36]Garland JS, Holden RM, Groome PA, Lam M, Nolan RL, Morton AR, Pickett W: Prevalence and associations of coronary artery calcification in patients with stages 3 to 5 CKD without cardiovascular disease. Am J Kidney Dis 2008, 2008(52):849-858.
• [37]Jüppner H, Wolf M, Salusky IB: FGF-23: more than a regulator of renal phosphate handling? J Bone Miner Res 2010, 25:2091-2097.
• [38]Ix JH, Shlipak MG, Wassel CL, Whooley MA: Fibroblast growth factor-23 and early decrements in kidney function: the heart and soul study. Nephrol Dial Transplant 2010, 25:993-997.
• [39]Balci M, Kirpantur A, Gulbay M, Gurbuz OA: Plasma fibroblast growth factor-23 levels are independently associated with carotid artery atherosclerosis in maintenance hemodialysis patients. Hemodial Int 2010, 14:425-432.
• [40]Mirza MAI, Alsio J, Hammarstedt A, Erben RG, Michaelsson K, Tivesten A, Marsell R, Orwoll E, Karlsson MK, Ljunggren O, Mellstrom D, Lind L, Ohlsson C, Larsson TE: Circulating fibroblast growth factor-23 is associated with fat mass and dyslipidemia in two independent cohorts of elderly individuals. Arterioscler Thromb Vasc Biol 2010, 31:219-227.