Direct and conditional effects of epicardial adipose tissue volume on coronary plaque progression in rheumatoid arthritis Epicardial fat and coronary atherosclerosis progression
Main Article Content
Abstract
Objective. Epicardial adipose tissue volume (EATv) associated with coronary atherosclerosis burden, noncalcified plaque and vulnerable plaque characteristics in patients with rheumatoid arthritis. We here evaluate the influence of EATv on plaque progression and factors that modify this relationship.
Methods. We assessed 100 patients without cardiovascular disease and a screening computed tomography angiography for EATv and coronary atherosclerosis who underwent surveillance evaluation for atherosclerosis progression 6.9±0.3 years later. The main outcome was new plaque formation. Robust multivariable logistic regression evaluated the effect of high versus low EATv (based on median) on likelihood of new plaque formation and the moderating effects of prespecified predictors.
Results. High EATv (>107 cm3) predicted new plaque formation, odds ratio (OR) 2.77 (95% confidence interval [95% CI] 1.43-5.37), however, significance was lost in the multivariable model. High EATv associated with new higher-risk noncalcified and mixed plaque after adjusting for cardiovascular risk score, obesity, segment location, time-averaged C-reactive protein, duration of biologic and statin use and cumulative prednisone dose, adjusted OR 2.57, 95% CI 1.02-6.48. High EATv predicted new plaque in patients with disease duration <10 versus >10 years (adjusted OR 5.75, 95% CI 1.77-18.67), with 1 risk factors versus >1 (adjusted OR 3.40, 95% CI 1.46-7.90), those without baseline calcification (adjusted OR 2.65, 95% CI 1.11-6.31) and those with statin treatment for <1 versus >1 year (adjusted OR 3.33, 95% CI 1.13-9.77).
Conclusion. Baseline EATv predicted new higher-risk noncalcified and mixed coronary plaque in rheumatoid arthritis. Notably, EATv conditionally promoted new plaque in patients with earlier disease, low risk factor burden, with no or early atherosclerosis and limited statin exposure. A larger prospective evaluation of EATv as a biomarker of coronary atherosclerosis in rheumatoid arthritis may therefore be warranted.
Keywords:
Rheumatoid arthritis, coronary atherosclerosis, epicardial adipose tissue, computed tomography
Article Details
How to Cite
KARPOUZAS, George A et al.
Direct and conditional effects of epicardial adipose tissue volume on coronary plaque progression in rheumatoid arthritis.
Medical Research Archives, [S.l.], v. 13, n. 2, feb. 2025.
ISSN 2375-1924.
Available at: <https://esmed.org/MRA/mra/article/view/6246>. Date accessed: 16 mar. 2025.
doi: https://doi.org/10.18103/mra.v13i2.6246.
Section
Research Articles
The Medical Research Archives grants authors the right to publish and reproduce the unrevised contribution in whole or in part at any time and in any form for any scholarly non-commercial purpose with the condition that all publications of the contribution include a full citation to the journal as published by the Medical Research Archives.
References
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4. Sacks HS, Fain JN. Human epicardial adipose tissue: a review. Am Heart J. 2007;153(6):907-917.
5. Packer M. Epicardial adipose tissue may mediate deleterious effects of obesity and inflammation on the myocardium. J Am Coll Cardiol. 2018;71(20): 2360-2372.
6. Iacobellis G. Epicardial adipose tissue in contemporary cardiology. Nat Rev Cardiol. 2022; 19(9):593-606.
7. Kitagawa T, Yamamoto H, Sentani K, et al. The relationship between inflammation and neoangiogenesis of epicardial adipose tissue and coronary atherosclerosis based on computed tomography analysis. Atherosclerosis. 2015;243(1):293-299.
8. Wang TD, Lee WJ, Shih FY, et al. Association of epicardial adipose tissue with coronary atherosclerosis is region-specific and independent of conventional risk factors and intra-abdominal adiposity. Atherosclerosis. 2010;213(1):279-287.
9. Hassan M, Said K, Rizk H, et al. Segmental peri-coronary epicardial adipose tissue volume and coronary plaque characteristics. Eur Heart J Cardiovasc Imaging. 2016;17(10):1169-1177.
10. McKenney-Drake ML, Rodenbeck SD, Bruning RS, et al. Epicardial adipose tissue removal potentiates outward remodeling and arrests coronary atherogenesis. Ann Thorac Surg. 2017; 103(5):1622-1630.
11. Hwang IC, Park HE, Choi SY. Epicardial adipose tissue contributes to the development of non-calcified coronary plaque: a 5-year computed tomography follow-up study. J Atheroscler Thromb. 2017;24(3):262-274.
12. Gorter PM, de Vos AM, van der Graaf Y, et al. Relation of epicardial and pericoronary fat to coronary atherosclerosis and coronary artery calcium in patients undergoing coronary angiography. Am J Cardiol. 2008;102(4):380-385.
13. Mahabadi AA, Massaro JM, Rosito GA, et al. Association of pericardial fat, intrathoracic fat, and visceral abdominal fat with cardiovascular disease burden: the Framingham Heart Study. Eur Heart J. 2009;30(7):850-856.
14. Ding J, Hsu FC, Harris TB, et al. The association of pericardial fat with incident coronary heart disease: the Multi-Ethnic Study of Atherosclerosis (MESA). Am J Clin Nutr. 2009;90(3):499-504.
15. Zhou J, Chen Y, Zhang Y, et al. Epicardial fat volume improves the prediction of obstructive coronary artery disease above traditional risk factors and coronary calcium score. Circ Cardiovasc Imaging. 2019;12(1):e008002.
16. Cheng VY, Dey D, Tamarappoo B, et al. Pericardial fat burden on ECG-gated noncontrast CT in asymptomatic patients who subsequently experience adverse cardiovascular events. JACC Cardiovasc Imaging. 2010;3(4):352-360.
17. Forouzandeh F, Chang SM, Muhyieddeen K, et al. Does quantifying epicardial and intrathoracic fat with noncontrast computed tomography improve risk stratification beyond calcium scoring alone? Circ Cardiovasc Imaging. 2013;6(1):58-66.
18. Kunita E, Yamamoto H, Kitagawa T, et al. Prognostic value of coronary artery calcium and epicardial adipose tissue assessed by non-contrast cardiac computed tomography. Atherosclerosis. 2014;233(2):447-453.
19. Karpouzas GA, Rezaeian P, Ormseth SR, Hollan I, Budoff MJ. Epicardial adipose tissue volume as a marker of subclinical coronary atherosclerosis in rheumatoid arthritis. Arthritis Rheumatol. 2021; 73(8):1412-1420.
20. Mahabadi AA, Lehmann N, Kälsch H, et al. Association of epicardial adipose tissue with progression of coronary artery calcification is more pronounced in the early phase of atherosclerosis: results from the Heinz Nixdorf recall study. JACC Cardiovasc Imaging. 2014;7(9):909-916.
21. Motoyama S, Ito H, Sarai M, et al. Plaque characterization by coronary computed tomography angiography and the likelihood of acute coronary events in mid-term follow-up. J Am Coll Cardiol. 2015;66(4):337-346.
22. Gu H, Gao Y, Wang H, et al. Sex differences in coronary atherosclerosis progression and major adverse cardiac events in patients with suspected coronary artery disease. J Cardiovasc Comput Tomogr. 2017;11(5):367-372.
23. Inoue K, Motoyama S, Sarai M, et al. Serial coronary CT angiography-verified changes in plaque characteristics as an end point: evaluation of effect of statin intervention. JACC Cardiovasc Imaging. 2010;3(7):691-698.
24. Karpouzas GA, Ormseth SR, Hernandez E, Budoff MJ. Biologics may prevent cardiovascular events in rheumatoid arthritis by Inhibiting coronary plaque formation and stabilizing high-risk lesions. Arthritis Rheumatol. 2020;72:1467-1475.
25. Agatston AS, Janowitz WR, Hildner FJ, Zusmer NR, Viamonte M, Detrano R. Quantification of coronary artery calcium using ultrafast computed tomography. J Am Coll Cardiol. 1990;15(4):827-832.
26. Budoff MJ, Dowe D, Jollis JG, et al. Diagnostic performance of 64-multidetector row coronary computed tomographic angiography for evaluation of coronary artery stenosis in individuals without known coronary artery disease: results from the prospective multicenter ACCURACY (Assessment by Coronary Computed Tomographic Angiography of Individuals Undergoing Invasive Coronary Angiography) trial. J Am Coll Cardiol. 2008;52(21):1724-1732.
27. Leipsic J, Abbara S, Achenbach S, et al. SCCT guidelines for the interpretation and reporting of coronary CT angiography: a report of the Society of Cardiovascular Computed Tomography Guidelines Committee. J Cardiovasc Comput Tomogr. 2014; 8(5):342-358.
28. Pohle K, Achenbach S, Macneill B, et al. Characterization of non-calcified coronary atherosclerotic plaque by multi-detector row CT: comparison to IVUS. Atherosclerosis. 2007;190(1):174-180.
29. D’Agostino RB, Vasan RS, Pencina MJ, et al. General cardiovascular risk profile for use in primary care: the Framingham Heart Study. Circulation. 2008;117(6):743-753.
30. Nichol A, Bailey M, Egi M, et al. Dynamic lactate indices as predictors of outcome in critically ill patients. Crit Care. 2011;15(5):R242.
31. Swirski FK, Nahrendorf M. Leukocyte behavior in atherosclerosis, myocardial infarction, and heart failure. Science. 2013;339(6116):161-166.
32. Aikawa E, Nahrendorf M, Figueiredo JL, et al. Osteogenesis associates with inflammation in early-stage atherosclerosis evaluated by molecular imaging in vivo. Circulation. 2007;116(24):2841-2850.
33. Lo J, Abbara S, Rocha-Filho JA, Shturman L, Wei J, Grinspoon SK. Increased epicardial adipose tissue volume in HIV-infected men and relationships to body composition and metabolic parameters. AIDS. 2010;24(13):2127-2130.
34. Okada K, Ohshima S, Isobe S, et al. Epicardial fat volume correlates with severity of coronary artery disease in nonobese patients. J Cardiovasc Med (Hagerstown). 2014;15(5):384-390.
35. Tsushima H, Yamamoto H, Kitagawa T, et al. Association of epicardial and abdominal visceral adipose tissue with coronary atherosclerosis in patients with a coronary artery calcium score of zero. Circ J. 2015;79(5):1084-1091.
36. Bettencourt N, Toschke AM, Leite D, et al. Epicardial adipose tissue is an independent predictor of coronary atherosclerotic burden. Int J Cardiol. 2012;158(1):26-32.
37. Iwayama T, Nitobe J, Watanabe T, et al. Role of epicardial adipose tissue in coronary artery disease in non-obese patients. J Cardiol. 2014;63(5):344-349.
38. Ormseth MJ, Lipson A, Alexopoulos N, et al. Association of epicardial adipose tissue with cardiometabolic risk and metabolic syndrome in patients with rheumatoid arthritis. Arthritis Care Res (Hoboken). 2013;65(9):1410-1415.
39. Tzolos E, Williams MC, McElhinney P, et al. Pericoronary adipose tissue attenuation, low-attenuation plaque burden, and 5-year risk of myocardial infarction. JACC Cardiovasc Imaging. 2022;15(6):1078-1088.
40. Karpouzas GA, Ormseth SR, Hernandez E, Budoff MJ. Impact of cumulative inflammation, cardiac risk factors, and medication exposure on coronary atherosclerosis progression in rheumatoid arthritis. Arthritis Rheumatol. 2020;72(3):400-408.
41. Parisi V, Petraglia L, D’Esposito V, et al. Statin therapy modulates thickness and inflammatory profile of human epicardial adipose tissue. Int J Cardiol. 2019;274:326-330.
42. Lima-Martínez MM, Campo E, Salazar J, et al. Epicardial fat thickness as cardiovascular risk factor and therapeutic target in patients with rheumatoid arthritis treated with biological and nonbiological therapies. Arthritis. 2014;2014:782850.
43. Karpouzas GA, Bui VL, Ronda N, Hollan I, Ormseth SR. Biologics and atherosclerotic cardiovascular risk in rheumatoid arthritis: a review of evidence and mechanistic insights. Expert Rev Clin Immunol. 2021;17(4):355-374.
44. Mahabadi AA, Berg MH, Lehmann N, et al. Association of epicardial fat with cardiovascular risk factors and incident myocardial infarction in the general population: the Heinz Nixdorf Recall Study. J Am Coll Cardiol. 2013;61(13):1388-1395.
45. Rosito GA, Massaro JM, Hoffmann U, et al. Pericardial fat, visceral abdominal fat, cardiovascular disease risk factors, and vascular calcification in a community-based sample: the Framingham Heart Study. Circulation. 2008;117(5):605-613.
46. Ito T, Suzuki Y, Ehara M, et al. Impact of epicardial fat volume on coronary artery disease in symptomatic patients with a zero calcium score. Int J Cardiol. 2013;167(6):2852-2858.
47. Jamialahmadi T, Simental-Mendia LE, Eid AH, et al. Efficacy of statin therapy in reducing epicardial adipose tissue: a systematic review and meta-analysis. Arch Med Sci. 2024;20(3):997-1001.
48. Alexopoulos N, Melek BH, Arepalli CD, et al. Effect of intensive versus moderate lipid-lowering therapy on epicardial adipose tissue in hyperlipidemic post-menopausal women: a substudy of the BELLES trial (Beyond Endorsed Lipid Lowering with EBT Scanning). J Am Coll Cardiol. 2013;61(19):1956-1961.
49. Tong M, Ren K, Chen L, Zhao GJ. Statin ameliorates adipose inflammation via NLRP3 suppression. Int J Cardiol. 2020;301:154.
50. Packer M. Drugs that ameliorate epicardial adipose tissue inflammation may have discordant effects in heart failure with a preserved ejection fraction as compared with a reduced ejection fraction. J Card Fail. 2019;25(12):986-1003.
51. Raggi P, Gadiyaram V, Zhang C, Chen Z, Lopaschuk G, Stillman AE. Statins reduce epicardial adipose tissue attenuation independent of lipid lowering. J Am Heart Assoc. 2019;8(12):e013104.
52. Huang CY, Lin TT, Yang YH, et al. Effect of statin therapy on the prevention of new-onset acute coronary syndrome in patients with rheumatoid arthritis. Int J Cardiol. 2018;253:1-6.
53. Karpouzas GA, Ormseth SR, Hernandez E, Budoff MJ. The impact of statins on coronary atherosclerosis progression and long-term cardiovascular disease risk in rheumatoid arthritis. Rheumatology (Oxford). 2022;61(5):1857-1866.
2. Holmqvist ME, Wedrén S, Jacobsson LTH, et al. Rapid increase in myocardial infarction risk following diagnosis of rheumatoid arthritis amongst patients diagnosed between 1995 and 2006. J Intern Med. 2010;268(6):578-585.
3. Wang JC, Normand SLT, Mauri L, Kuntz RE. Coronary artery spatial distribution of acute myocardial infarction occlusions. Circulation. 2004; 110(3):278-284.
4. Sacks HS, Fain JN. Human epicardial adipose tissue: a review. Am Heart J. 2007;153(6):907-917.
5. Packer M. Epicardial adipose tissue may mediate deleterious effects of obesity and inflammation on the myocardium. J Am Coll Cardiol. 2018;71(20): 2360-2372.
6. Iacobellis G. Epicardial adipose tissue in contemporary cardiology. Nat Rev Cardiol. 2022; 19(9):593-606.
7. Kitagawa T, Yamamoto H, Sentani K, et al. The relationship between inflammation and neoangiogenesis of epicardial adipose tissue and coronary atherosclerosis based on computed tomography analysis. Atherosclerosis. 2015;243(1):293-299.
8. Wang TD, Lee WJ, Shih FY, et al. Association of epicardial adipose tissue with coronary atherosclerosis is region-specific and independent of conventional risk factors and intra-abdominal adiposity. Atherosclerosis. 2010;213(1):279-287.
9. Hassan M, Said K, Rizk H, et al. Segmental peri-coronary epicardial adipose tissue volume and coronary plaque characteristics. Eur Heart J Cardiovasc Imaging. 2016;17(10):1169-1177.
10. McKenney-Drake ML, Rodenbeck SD, Bruning RS, et al. Epicardial adipose tissue removal potentiates outward remodeling and arrests coronary atherogenesis. Ann Thorac Surg. 2017; 103(5):1622-1630.
11. Hwang IC, Park HE, Choi SY. Epicardial adipose tissue contributes to the development of non-calcified coronary plaque: a 5-year computed tomography follow-up study. J Atheroscler Thromb. 2017;24(3):262-274.
12. Gorter PM, de Vos AM, van der Graaf Y, et al. Relation of epicardial and pericoronary fat to coronary atherosclerosis and coronary artery calcium in patients undergoing coronary angiography. Am J Cardiol. 2008;102(4):380-385.
13. Mahabadi AA, Massaro JM, Rosito GA, et al. Association of pericardial fat, intrathoracic fat, and visceral abdominal fat with cardiovascular disease burden: the Framingham Heart Study. Eur Heart J. 2009;30(7):850-856.
14. Ding J, Hsu FC, Harris TB, et al. The association of pericardial fat with incident coronary heart disease: the Multi-Ethnic Study of Atherosclerosis (MESA). Am J Clin Nutr. 2009;90(3):499-504.
15. Zhou J, Chen Y, Zhang Y, et al. Epicardial fat volume improves the prediction of obstructive coronary artery disease above traditional risk factors and coronary calcium score. Circ Cardiovasc Imaging. 2019;12(1):e008002.
16. Cheng VY, Dey D, Tamarappoo B, et al. Pericardial fat burden on ECG-gated noncontrast CT in asymptomatic patients who subsequently experience adverse cardiovascular events. JACC Cardiovasc Imaging. 2010;3(4):352-360.
17. Forouzandeh F, Chang SM, Muhyieddeen K, et al. Does quantifying epicardial and intrathoracic fat with noncontrast computed tomography improve risk stratification beyond calcium scoring alone? Circ Cardiovasc Imaging. 2013;6(1):58-66.
18. Kunita E, Yamamoto H, Kitagawa T, et al. Prognostic value of coronary artery calcium and epicardial adipose tissue assessed by non-contrast cardiac computed tomography. Atherosclerosis. 2014;233(2):447-453.
19. Karpouzas GA, Rezaeian P, Ormseth SR, Hollan I, Budoff MJ. Epicardial adipose tissue volume as a marker of subclinical coronary atherosclerosis in rheumatoid arthritis. Arthritis Rheumatol. 2021; 73(8):1412-1420.
20. Mahabadi AA, Lehmann N, Kälsch H, et al. Association of epicardial adipose tissue with progression of coronary artery calcification is more pronounced in the early phase of atherosclerosis: results from the Heinz Nixdorf recall study. JACC Cardiovasc Imaging. 2014;7(9):909-916.
21. Motoyama S, Ito H, Sarai M, et al. Plaque characterization by coronary computed tomography angiography and the likelihood of acute coronary events in mid-term follow-up. J Am Coll Cardiol. 2015;66(4):337-346.
22. Gu H, Gao Y, Wang H, et al. Sex differences in coronary atherosclerosis progression and major adverse cardiac events in patients with suspected coronary artery disease. J Cardiovasc Comput Tomogr. 2017;11(5):367-372.
23. Inoue K, Motoyama S, Sarai M, et al. Serial coronary CT angiography-verified changes in plaque characteristics as an end point: evaluation of effect of statin intervention. JACC Cardiovasc Imaging. 2010;3(7):691-698.
24. Karpouzas GA, Ormseth SR, Hernandez E, Budoff MJ. Biologics may prevent cardiovascular events in rheumatoid arthritis by Inhibiting coronary plaque formation and stabilizing high-risk lesions. Arthritis Rheumatol. 2020;72:1467-1475.
25. Agatston AS, Janowitz WR, Hildner FJ, Zusmer NR, Viamonte M, Detrano R. Quantification of coronary artery calcium using ultrafast computed tomography. J Am Coll Cardiol. 1990;15(4):827-832.
26. Budoff MJ, Dowe D, Jollis JG, et al. Diagnostic performance of 64-multidetector row coronary computed tomographic angiography for evaluation of coronary artery stenosis in individuals without known coronary artery disease: results from the prospective multicenter ACCURACY (Assessment by Coronary Computed Tomographic Angiography of Individuals Undergoing Invasive Coronary Angiography) trial. J Am Coll Cardiol. 2008;52(21):1724-1732.
27. Leipsic J, Abbara S, Achenbach S, et al. SCCT guidelines for the interpretation and reporting of coronary CT angiography: a report of the Society of Cardiovascular Computed Tomography Guidelines Committee. J Cardiovasc Comput Tomogr. 2014; 8(5):342-358.
28. Pohle K, Achenbach S, Macneill B, et al. Characterization of non-calcified coronary atherosclerotic plaque by multi-detector row CT: comparison to IVUS. Atherosclerosis. 2007;190(1):174-180.
29. D’Agostino RB, Vasan RS, Pencina MJ, et al. General cardiovascular risk profile for use in primary care: the Framingham Heart Study. Circulation. 2008;117(6):743-753.
30. Nichol A, Bailey M, Egi M, et al. Dynamic lactate indices as predictors of outcome in critically ill patients. Crit Care. 2011;15(5):R242.
31. Swirski FK, Nahrendorf M. Leukocyte behavior in atherosclerosis, myocardial infarction, and heart failure. Science. 2013;339(6116):161-166.
32. Aikawa E, Nahrendorf M, Figueiredo JL, et al. Osteogenesis associates with inflammation in early-stage atherosclerosis evaluated by molecular imaging in vivo. Circulation. 2007;116(24):2841-2850.
33. Lo J, Abbara S, Rocha-Filho JA, Shturman L, Wei J, Grinspoon SK. Increased epicardial adipose tissue volume in HIV-infected men and relationships to body composition and metabolic parameters. AIDS. 2010;24(13):2127-2130.
34. Okada K, Ohshima S, Isobe S, et al. Epicardial fat volume correlates with severity of coronary artery disease in nonobese patients. J Cardiovasc Med (Hagerstown). 2014;15(5):384-390.
35. Tsushima H, Yamamoto H, Kitagawa T, et al. Association of epicardial and abdominal visceral adipose tissue with coronary atherosclerosis in patients with a coronary artery calcium score of zero. Circ J. 2015;79(5):1084-1091.
36. Bettencourt N, Toschke AM, Leite D, et al. Epicardial adipose tissue is an independent predictor of coronary atherosclerotic burden. Int J Cardiol. 2012;158(1):26-32.
37. Iwayama T, Nitobe J, Watanabe T, et al. Role of epicardial adipose tissue in coronary artery disease in non-obese patients. J Cardiol. 2014;63(5):344-349.
38. Ormseth MJ, Lipson A, Alexopoulos N, et al. Association of epicardial adipose tissue with cardiometabolic risk and metabolic syndrome in patients with rheumatoid arthritis. Arthritis Care Res (Hoboken). 2013;65(9):1410-1415.
39. Tzolos E, Williams MC, McElhinney P, et al. Pericoronary adipose tissue attenuation, low-attenuation plaque burden, and 5-year risk of myocardial infarction. JACC Cardiovasc Imaging. 2022;15(6):1078-1088.
40. Karpouzas GA, Ormseth SR, Hernandez E, Budoff MJ. Impact of cumulative inflammation, cardiac risk factors, and medication exposure on coronary atherosclerosis progression in rheumatoid arthritis. Arthritis Rheumatol. 2020;72(3):400-408.
41. Parisi V, Petraglia L, D’Esposito V, et al. Statin therapy modulates thickness and inflammatory profile of human epicardial adipose tissue. Int J Cardiol. 2019;274:326-330.
42. Lima-Martínez MM, Campo E, Salazar J, et al. Epicardial fat thickness as cardiovascular risk factor and therapeutic target in patients with rheumatoid arthritis treated with biological and nonbiological therapies. Arthritis. 2014;2014:782850.
43. Karpouzas GA, Bui VL, Ronda N, Hollan I, Ormseth SR. Biologics and atherosclerotic cardiovascular risk in rheumatoid arthritis: a review of evidence and mechanistic insights. Expert Rev Clin Immunol. 2021;17(4):355-374.
44. Mahabadi AA, Berg MH, Lehmann N, et al. Association of epicardial fat with cardiovascular risk factors and incident myocardial infarction in the general population: the Heinz Nixdorf Recall Study. J Am Coll Cardiol. 2013;61(13):1388-1395.
45. Rosito GA, Massaro JM, Hoffmann U, et al. Pericardial fat, visceral abdominal fat, cardiovascular disease risk factors, and vascular calcification in a community-based sample: the Framingham Heart Study. Circulation. 2008;117(5):605-613.
46. Ito T, Suzuki Y, Ehara M, et al. Impact of epicardial fat volume on coronary artery disease in symptomatic patients with a zero calcium score. Int J Cardiol. 2013;167(6):2852-2858.
47. Jamialahmadi T, Simental-Mendia LE, Eid AH, et al. Efficacy of statin therapy in reducing epicardial adipose tissue: a systematic review and meta-analysis. Arch Med Sci. 2024;20(3):997-1001.
48. Alexopoulos N, Melek BH, Arepalli CD, et al. Effect of intensive versus moderate lipid-lowering therapy on epicardial adipose tissue in hyperlipidemic post-menopausal women: a substudy of the BELLES trial (Beyond Endorsed Lipid Lowering with EBT Scanning). J Am Coll Cardiol. 2013;61(19):1956-1961.
49. Tong M, Ren K, Chen L, Zhao GJ. Statin ameliorates adipose inflammation via NLRP3 suppression. Int J Cardiol. 2020;301:154.
50. Packer M. Drugs that ameliorate epicardial adipose tissue inflammation may have discordant effects in heart failure with a preserved ejection fraction as compared with a reduced ejection fraction. J Card Fail. 2019;25(12):986-1003.
51. Raggi P, Gadiyaram V, Zhang C, Chen Z, Lopaschuk G, Stillman AE. Statins reduce epicardial adipose tissue attenuation independent of lipid lowering. J Am Heart Assoc. 2019;8(12):e013104.
52. Huang CY, Lin TT, Yang YH, et al. Effect of statin therapy on the prevention of new-onset acute coronary syndrome in patients with rheumatoid arthritis. Int J Cardiol. 2018;253:1-6.
53. Karpouzas GA, Ormseth SR, Hernandez E, Budoff MJ. The impact of statins on coronary atherosclerosis progression and long-term cardiovascular disease risk in rheumatoid arthritis. Rheumatology (Oxford). 2022;61(5):1857-1866.