International Journal of Cardiology 199 (2015) 8–9
Contents lists available at ScienceDirect
International Journal of Cardiology journal homepage: www.elsevier.com/locate/ijcard
Letter to the Editor
Epicardial adipose tissue thickness and acute coronary syndrome: A matter of how much or how? Gianfranco Aprigliano a,⁎, Lea Scuteri a, Ida Iafelice a, Laura Li Volsi a, Besart Cuko a, Altin Palloshi a, Matteo Pisani b, Sara Bonizzato a, Michele Bianchi a, Nuccia Morici c a b c
Division of Cardiology, Istituto Clinico Città Studi, Milan, Italy Division of Cardiology, Policlinico di Monza, Milan, Italy Cardio-Thoracic-Vascular Department, SS UTIC/SC Cardiologia 1-Emodinamica, Azienda Ospedaliera Ospedale Niguarda Ca' Granda, Milan, Italy
a r t i c l e
i n f o
Article history: Received 9 May 2015 Received in revised form 22 June 2015 Accepted 27 June 2015 Available online 4 July 2015 Keywords: Epicardial fat tissue Cardiovascular risk Atherogenic cytokines
Visceral adiposity is a metabolically active organ. It may exert the biochemical properties of an endocrine tissue, releasing mRNAs of atherogenic inflammatory cytokines and promoting a pro-atherogenic and prothrombogenic condition leading to an increased cardiovascular risk [1]. Epicardial adipose tissue (EAT) is the visceral fat deposited around subepicardial coronary vessels. Since it is easily detectable throughout non-invasive modalities as echocardiography, it has been increasingly gaining interest in cardiovascular research [2,3]. Several studies have tried to assess the relationship between EAT and the extension of coronary artery disease (CAD), both in patients with stable and unstable ischemic heart disease. Up to now, results have been conflicting and then more evidences have been advocated [4–7]. The purpose of our study was therefore to evaluate the correlation between EAT thickness and the extension of CAD in a consecutive sample of Caucasian patients admitted to hospital for an acute coronary syndrome (ACS). EAT was assessed by operators blinded to the coronary angiography. Two standard echocardiographic views and parasternal long-axis and short-axis views were used for the analysis, according to standard measurement points [4]; the average value was considered for the analysis purpose. The extension of coronary artery disease was assessed by two different methods, the Gensini score [8] and the SYNergy between percutaneous coronary intervention with the TAXUS drug⁎ Corresponding author at: Division of Cardiology, Istituto Clinico Città studi, via Jommelli 17, Milan, Italy. E-mail address: [email protected] (G. Aprigliano).
http://dx.doi.org/10.1016/j.ijcard.2015.06.168 0167-5273/© 2015 Elsevier Ireland Ltd. All rights reserved.
eluting stent and the cardiac surgery (SYNTAX) score [9]. Statistical analyses were performed using STATA, release 13. Comparisons of continuous variables were performed using the unpaired Student t test. Analyses of discrete variables were performed using ᵪ2 tests. EAT was checked for normality distribution. Correlation of EAT with CAD extension were examined by Pearson correlation analyses. The score mean values across quartiles of EAT were compared using the ANOVA test with the Bonferroni correction. The predictive value of EAT on the highest quartile of the Gensini and Syntax score was determined for both EAT measurements separately considered using the receiver operating characteristic curve (ROC). For each curve, a test for the equality of the area under the curves (AUC) was provided, using an algorithm suggested by DeLong and Clarke-Pearson. Finally, a multivariable regression analysis was performed to determine the factors related to significant coronary artery stenosis. Statistical significance was set at p b 0.05. One-hundred and six patients were included. The mean age was 65.3 years [standard deviation (SD) 1.4]. Seventy-six patients were male (71.7%), 38 (35.8%) were current smokers, 46 (43.4%) had dyslipidemia, 21 (19.8%) had diabetes and 70 (66%) had systemic
Fig. 1. Average of Gesini ad SYNTAX score according to quartiles of EAT.
G. Aprigliano et al. / International Journal of Cardiology 199 (2015) 8–9
9
Fig. 2. Correlation among EAT and Gensini and SYNTAX score.
hypertension. In 67 cases the admission diagnosis was an ST-elevation ACS (63.2%). The mean waist circumference was 104.8 cm (SD 7.9 cm; 95% confidence interval—CI—89.1–120.1); mean EAT was 6.7 mm (SD 0.2; 95% CI 6.4–7.1). There was non-significant difference in baseline characteristics between patients in the highest quartile of EAT (≥ 7.85 mm), compared to the others. The mean Gensini score was 66.4 (SD 3.8; 95% CI 58.9–73.9), whereas the mean Syntax score was 19.1 (SD 1.07; 95% CI 17.0–21.2). Even if both the scores were on average higher in the fourth quartile of EAT (Fig. 1), the ANOVA test did not find relevant differences among groups and the Pearson analyses did not show any significant correlation among EAT, Gensini score and Syntax score (p = 0.23 and 0.20, respectively) (Fig. 2), whereas Gensini and Syntax score showed an optimal correlation between them (r = 0.86, p b 0.01). At the ROC curve analysis the predictive value of EAT on the highest quartile of Gensini and Syntax score was low and comparable among measurements computed in long-axis and short-axis views [for the Gensini score AUC: 0.539 (95% CI 0.411–0.668) and 0.557 (95% CI 0.429–0.684), respectively (p = 0.694); for the Syntax score AUC 0.596 (95% CI 0.415–0.777) and 0.585 (95% CI 0.417–0.753), respectively (p = 0.874)]. Interestingly, at multivariable analysis, only gender and waist circumference were independently related to the Gensini and Syntax scores. Overall considered, our results showed no correlation between EAT thickness, as measured by echocardiography, and the extension of coronary artery disease in ACS patients. However, the documented relationship between waist circumference and CAD extension suggests that visceral adiposity is an important marker of cardiovascular risk. Interestingly, mean EAT found in our paper (6.7 mm) matches very well with the values reported in other studies [6,10] (5.6 and 5.5 mm respectively) that analyzed EAT in ACS patients. On the contrary, in the report of Chaowalit [5], that analyzed a cohort of stable CAD patients, EAT mean value was significantly lower (2.2 mm). These results support the hypothesis of an important role of EAT in promoting ACS independently from the extension of the atherosclerotic burden. EAT could be a surrogate of visceral adiposity, but may be different and more accurate modalities of assessment should be used.
Furthermore, as for other endocrine tissues, it is possible that not only the quantity of EAT, but mostly its quality and activity, expressed as capacity of pro-inflammatory mediator release, may affect the coronary plaque burden and its outcome. In conclusion, our findings generate the hypothesis that EAT could be considered a marker of plaque instability.
Conflicts of interest None.
References [1] T. Funahashi, T. Nakamura, I. Shimomura, et al., Role of adipocytokines on the pathogenesis of atherosclerosis in visceral obesity, Intern. Med. 38 (1999) 202–206. [2] G. Iacobellis, F. Assael, M.C. Ribaudo, et al., Epicardial fat from echocardiography: a new method for visceral adipose tissue prediction, Obes. Res. 11 (2003) 304–310. [3] G. Iacobellis, Local and systemic effects of the multifaceted epicardial adipose tissue depot, Nat. Rev. Endocrinol. (2015 Apr 7)http://dx.doi.org/10.1038/nrendo.2015.58 (Epub ahead of print, Review). [4] J.W. Jeong, M.H. Jeong, K.H. Yun, S.K. Oh, et al., Echocardiographic epicardial fat thickness and coronary artery disease, Circ. J. 71 (2007) 536–539. [5] N. Chaowalit, V.K. Somers, P.A. Pellikka, C.S. Rihal, F. Lopez-Jimenez, Subepicardial adipose tissue and the presence and severity of coronary artery disease, Atherosclerosis 186 (2006) 354–359. [6] Tao Wang, Qiang Liu, Cuixia Liu, et al., Correlation of echocardiographic epicardial fat thickness with severity of coronary artery disease in patients with acute myocardial infarction, Echocardiography 31 (2014) 1177–1181. [7] Y. Tanami, M. Jinzaki, S. Kishi, et al., Lack of association between epicardial fat volume and extent of coronary artery calcification, severity of coronary artery disease, or presence of myocardial perfusion abnormalities in a diverse, symptomatic patient population: results from the CORE320 multicenter study, Circ. Cardiovasc. Imaging 8 (2015) e002676. [8] G.G. Gensini, A more meaningful scoring system for determining the severity of coronary heart disease (letter), Am. J. Cardiol. 51 (1983) 606. [9] G. Sianos, M.A. Morel, A.P. Kappetein, et al., The SYNTAX score: an angiographic tool grading the complexity of coronary artery disease, EuroIntervention 1 (2005) 219–227. [10] B. Altun, Y. Colkesen, E. Gazi, et al., Could epicardial adipose tissue thickness by echocardiography be correlated with acute coronary syndrome risk scores, Echocardiography 30 (2013) 1130–1134.
Contents lists available at ScienceDirect
International Journal of Cardiology journal homepage: www.elsevier.com/locate/ijcard
Letter to the Editor
Epicardial adipose tissue thickness and acute coronary syndrome: A matter of how much or how? Gianfranco Aprigliano a,⁎, Lea Scuteri a, Ida Iafelice a, Laura Li Volsi a, Besart Cuko a, Altin Palloshi a, Matteo Pisani b, Sara Bonizzato a, Michele Bianchi a, Nuccia Morici c a b c
Division of Cardiology, Istituto Clinico Città Studi, Milan, Italy Division of Cardiology, Policlinico di Monza, Milan, Italy Cardio-Thoracic-Vascular Department, SS UTIC/SC Cardiologia 1-Emodinamica, Azienda Ospedaliera Ospedale Niguarda Ca' Granda, Milan, Italy
a r t i c l e
i n f o
Article history: Received 9 May 2015 Received in revised form 22 June 2015 Accepted 27 June 2015 Available online 4 July 2015 Keywords: Epicardial fat tissue Cardiovascular risk Atherogenic cytokines
Visceral adiposity is a metabolically active organ. It may exert the biochemical properties of an endocrine tissue, releasing mRNAs of atherogenic inflammatory cytokines and promoting a pro-atherogenic and prothrombogenic condition leading to an increased cardiovascular risk [1]. Epicardial adipose tissue (EAT) is the visceral fat deposited around subepicardial coronary vessels. Since it is easily detectable throughout non-invasive modalities as echocardiography, it has been increasingly gaining interest in cardiovascular research [2,3]. Several studies have tried to assess the relationship between EAT and the extension of coronary artery disease (CAD), both in patients with stable and unstable ischemic heart disease. Up to now, results have been conflicting and then more evidences have been advocated [4–7]. The purpose of our study was therefore to evaluate the correlation between EAT thickness and the extension of CAD in a consecutive sample of Caucasian patients admitted to hospital for an acute coronary syndrome (ACS). EAT was assessed by operators blinded to the coronary angiography. Two standard echocardiographic views and parasternal long-axis and short-axis views were used for the analysis, according to standard measurement points [4]; the average value was considered for the analysis purpose. The extension of coronary artery disease was assessed by two different methods, the Gensini score [8] and the SYNergy between percutaneous coronary intervention with the TAXUS drug⁎ Corresponding author at: Division of Cardiology, Istituto Clinico Città studi, via Jommelli 17, Milan, Italy. E-mail address: [email protected] (G. Aprigliano).
http://dx.doi.org/10.1016/j.ijcard.2015.06.168 0167-5273/© 2015 Elsevier Ireland Ltd. All rights reserved.
eluting stent and the cardiac surgery (SYNTAX) score [9]. Statistical analyses were performed using STATA, release 13. Comparisons of continuous variables were performed using the unpaired Student t test. Analyses of discrete variables were performed using ᵪ2 tests. EAT was checked for normality distribution. Correlation of EAT with CAD extension were examined by Pearson correlation analyses. The score mean values across quartiles of EAT were compared using the ANOVA test with the Bonferroni correction. The predictive value of EAT on the highest quartile of the Gensini and Syntax score was determined for both EAT measurements separately considered using the receiver operating characteristic curve (ROC). For each curve, a test for the equality of the area under the curves (AUC) was provided, using an algorithm suggested by DeLong and Clarke-Pearson. Finally, a multivariable regression analysis was performed to determine the factors related to significant coronary artery stenosis. Statistical significance was set at p b 0.05. One-hundred and six patients were included. The mean age was 65.3 years [standard deviation (SD) 1.4]. Seventy-six patients were male (71.7%), 38 (35.8%) were current smokers, 46 (43.4%) had dyslipidemia, 21 (19.8%) had diabetes and 70 (66%) had systemic
Fig. 1. Average of Gesini ad SYNTAX score according to quartiles of EAT.
G. Aprigliano et al. / International Journal of Cardiology 199 (2015) 8–9
9
Fig. 2. Correlation among EAT and Gensini and SYNTAX score.
hypertension. In 67 cases the admission diagnosis was an ST-elevation ACS (63.2%). The mean waist circumference was 104.8 cm (SD 7.9 cm; 95% confidence interval—CI—89.1–120.1); mean EAT was 6.7 mm (SD 0.2; 95% CI 6.4–7.1). There was non-significant difference in baseline characteristics between patients in the highest quartile of EAT (≥ 7.85 mm), compared to the others. The mean Gensini score was 66.4 (SD 3.8; 95% CI 58.9–73.9), whereas the mean Syntax score was 19.1 (SD 1.07; 95% CI 17.0–21.2). Even if both the scores were on average higher in the fourth quartile of EAT (Fig. 1), the ANOVA test did not find relevant differences among groups and the Pearson analyses did not show any significant correlation among EAT, Gensini score and Syntax score (p = 0.23 and 0.20, respectively) (Fig. 2), whereas Gensini and Syntax score showed an optimal correlation between them (r = 0.86, p b 0.01). At the ROC curve analysis the predictive value of EAT on the highest quartile of Gensini and Syntax score was low and comparable among measurements computed in long-axis and short-axis views [for the Gensini score AUC: 0.539 (95% CI 0.411–0.668) and 0.557 (95% CI 0.429–0.684), respectively (p = 0.694); for the Syntax score AUC 0.596 (95% CI 0.415–0.777) and 0.585 (95% CI 0.417–0.753), respectively (p = 0.874)]. Interestingly, at multivariable analysis, only gender and waist circumference were independently related to the Gensini and Syntax scores. Overall considered, our results showed no correlation between EAT thickness, as measured by echocardiography, and the extension of coronary artery disease in ACS patients. However, the documented relationship between waist circumference and CAD extension suggests that visceral adiposity is an important marker of cardiovascular risk. Interestingly, mean EAT found in our paper (6.7 mm) matches very well with the values reported in other studies [6,10] (5.6 and 5.5 mm respectively) that analyzed EAT in ACS patients. On the contrary, in the report of Chaowalit [5], that analyzed a cohort of stable CAD patients, EAT mean value was significantly lower (2.2 mm). These results support the hypothesis of an important role of EAT in promoting ACS independently from the extension of the atherosclerotic burden. EAT could be a surrogate of visceral adiposity, but may be different and more accurate modalities of assessment should be used.
Furthermore, as for other endocrine tissues, it is possible that not only the quantity of EAT, but mostly its quality and activity, expressed as capacity of pro-inflammatory mediator release, may affect the coronary plaque burden and its outcome. In conclusion, our findings generate the hypothesis that EAT could be considered a marker of plaque instability.
Conflicts of interest None.
References [1] T. Funahashi, T. Nakamura, I. Shimomura, et al., Role of adipocytokines on the pathogenesis of atherosclerosis in visceral obesity, Intern. Med. 38 (1999) 202–206. [2] G. Iacobellis, F. Assael, M.C. Ribaudo, et al., Epicardial fat from echocardiography: a new method for visceral adipose tissue prediction, Obes. Res. 11 (2003) 304–310. [3] G. Iacobellis, Local and systemic effects of the multifaceted epicardial adipose tissue depot, Nat. Rev. Endocrinol. (2015 Apr 7)http://dx.doi.org/10.1038/nrendo.2015.58 (Epub ahead of print, Review). [4] J.W. Jeong, M.H. Jeong, K.H. Yun, S.K. Oh, et al., Echocardiographic epicardial fat thickness and coronary artery disease, Circ. J. 71 (2007) 536–539. [5] N. Chaowalit, V.K. Somers, P.A. Pellikka, C.S. Rihal, F. Lopez-Jimenez, Subepicardial adipose tissue and the presence and severity of coronary artery disease, Atherosclerosis 186 (2006) 354–359. [6] Tao Wang, Qiang Liu, Cuixia Liu, et al., Correlation of echocardiographic epicardial fat thickness with severity of coronary artery disease in patients with acute myocardial infarction, Echocardiography 31 (2014) 1177–1181. [7] Y. Tanami, M. Jinzaki, S. Kishi, et al., Lack of association between epicardial fat volume and extent of coronary artery calcification, severity of coronary artery disease, or presence of myocardial perfusion abnormalities in a diverse, symptomatic patient population: results from the CORE320 multicenter study, Circ. Cardiovasc. Imaging 8 (2015) e002676. [8] G.G. Gensini, A more meaningful scoring system for determining the severity of coronary heart disease (letter), Am. J. Cardiol. 51 (1983) 606. [9] G. Sianos, M.A. Morel, A.P. Kappetein, et al., The SYNTAX score: an angiographic tool grading the complexity of coronary artery disease, EuroIntervention 1 (2005) 219–227. [10] B. Altun, Y. Colkesen, E. Gazi, et al., Could epicardial adipose tissue thickness by echocardiography be correlated with acute coronary syndrome risk scores, Echocardiography 30 (2013) 1130–1134.
