The Role of Adipose Tissue Depots in the Pathogenesis of Coronary Artery Disease: Beyond Body Mass Index
Abstract
In recent years, researchers have focused on the role of various adipose tissue depots in the development of coronary artery disease (CAD), extending beyond traditional obesity assessments based on body mass index (BMI). Visceral adipose tissue, epicardial fat, fatty liver disease (currently termed metabolic dysfunction-associated steatotic liver disease), and perivascular adipose tissue actively participate in CAD pathogenesis through mechanisms of systemic inflammation, oxidative stress, endothelial dysfunction, and atherosclerosis.
Visceral fat, characterized by high metabolic activity, secretes proinflammatory cytokines that promote insulin resistance and atherosclerosis. Epicardial fat surrounding the coronary arteries exerts local effects by releasing adipokines that may accelerate the progression of atherosclerotic plaques. Fatty liver disease is associated with dyslipidemia and enhanced systemic inflammation, increasing cardiovascular risk. Perivascular adipose tissue regulates vascular tone and inflammation, and its dysfunction contributes to arterial stiffness and hypertension.
The relevance of studying these adipose depots lies in the need to identify new biomarkers and targets for personalized prevention and treatment of CAD. Traditional obesity assessment methods such as BMI, fail to reflect adipose tissue distribution and metabolic activity, underscoring the importance of more detailed investigation into the role of various fat depots in cardiovascular pathology.
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List of references
World Health Organization. (2021). Cardiovascular diseases (CVDs) fact sheet. Geneva: WHO. https://www.who.int/news-room/fact-sheets/detail/cardiovascular-diseases-(cvds).
GBD 2019 Diseases and Injuries Collaborators. (2020). Global burden of 369 diseases and injuries in 204 countries and territories, 1990–2019: A systematic analysis for the Global Burden of Disease Study 2019. The Lancet, 396(10258), 1204–1222. https://doi.org/10.1016/S0140-6736(20)30925-9.
Ministry of Health of the Republic of Uzbekistan. (2022). Statistical collection "Health of the population."Tashkent.
World Health Organization. (2018). Prevention and control of noncommunicable diseases in Uzbekistan. WHO.
Barquera S., Pedroza-Tob´ıas A., Medina C., et al. (2015). Global overview of the epidemiology of atherosclerotic cardiovascular disease. Archives of Medical Research, 46(5), 328–338. https://doi.org/10.1016/j.arcmed.2015.06.006.
Ford E. S., Ajani U. A., Croft J. B., et al. (2007). Explaining the decrease in U.S. deaths from coronary disease, 1980–2000. The New England Journal of Medicine, 356(23), 2388–2398. https://doi.org/10.1056/NEJMsa053935.
Artinian N. T., Fletcher G. F., Mozaffarian D., et al. (2010). Interventions to promote physical activity and dietary lifestyle changes for cardiovascular risk factor reduction in adults: A scientific statement from the American Heart Association. Circulation, 122(4), 406–441. https://doi.org/10.1161/CIR.0b013e3181e8 edf1.
World Health Organization. (2021). Obesity and overweight: Fact sheet. WHO. https://www.who.int/news- room/fact-sheets/detail/obesity-and-overweight
Azizov V. A., Kurbanov R. D. (2020). Obesity and metabolic disorders in Uzbekistan: Epidemiological trends. Journal of Public Health, 42(3), 456–462.
Global BMI Mortality Collaboration. (2016). Body-mass index and all-cause mortality: Individual- participant-data meta-analysis of 239 prospective studies in four continents. The Lancet, 388(10046), 776–786. https://doi.org/10.1016/S0140-6736(16)30175-1.
Lloyd-Jones D. M., Larson M. G., Leip E. P., et al. (2002). Lifetime risk for developing congestive heart failure: The Framingham Heart Study. Circulation, 106(24), 3068–3072. https://doi.org/10.1161/01.CIR. 0000039105.49749.6F.
Hu F. B., Manson J. E., Stampfer M. J., et al. (2001). Diet, lifestyle, and the risk of type 2 diabetes mellitus in women. The New England Journal of Medicine, 345(11), 790–797. https://doi.org/10.1056/NEJMoa0 10492.
Yusuf S., Hawken S., Ounpuu S., et al. (2005). Obesity and the risk of myocardial infarction in 27,000 participants from 52 countries: A case-control study. The Lancet, 366(9497), 1640–1649. https://doi.org/10.1016/S0140-6736(05)67663-5.
Ding J., Hsu F.-C., Harris T. B., et al. (2009). The association of pericardial fat with incident coronary heart disease: The Multi-Ethnic Study of Atherosclerosis (MESA). The American Journal of Clinical Nutrition, 90(3), 499–504. https://doi.org/10.3945/ajcn.2008.27358.
Larsson B., Sva¨rdsudd K., Welin L., et al. (1984). Abdominal adipose tissue distribution, obesity, and risk of cardiovascular disease and death: 13-year follow-up of participants in the study of men born in 1913. British Medical Journal, 288(6428), 1401–1404. https://doi.org/10.1136/bmj.288.6428.1401.
Messier V., Karelis A. D., Prud’homme D., et al. (2010). Identifying metabolically healthy but obese individuals in sedentary postmenopausal women. Obesity, 18(5), 911–917. https://doi.org/10.1038/oby.20 09.364.
Britton K. A., Fox C. S. (2011). Ectopic fat depots and cardiovascular disease. Circulation, 124(9), 837–841. https://doi.org/10.1161/CIRCULATIONAHA.111.077602.
Gruzdeva O., Borodkina D., Uchasova E., et al. (2018). Localization of fat depots and cardiovascular risk. Lipids in Health and Disease, 17(1), 218. https://doi.org/10.1186/s12944-018-0868-4.
Fujioka S., Matsuzawa Y., Tokunaga K., et al. (1987). Contribution of intra-abdominal fat accumulation to the impairment of glucose and lipid metabolism in human obesity. Metabolism, 36(1), 54–59. https://doi.org/10.1016/0026-0495(87)90063-1.
[20] Sjo¨stro¨m L., Kvist H., Cederblad A., et al. (1986). Determination of total adipose tissue and body fat in women by computed tomography, 40K, and tritium. *American Journal of Physiology-Endocrinology and Metabolism, 250*(6), E736–E745. https://doi.org/10.1152/ajpendo.1986.250.6.E736.
Lima M. M., Pareja J. C., Alegre S. M., et al. (2013). Visceral fat resection in humans: Effect on insulin sensitivity, beta-cell function, adipokines, and inflammatory markers. Obesity, 21(1), 182–189. https://doi.org/10.1002/oby.20022.
Han E., Lee Y. H., Lee B. W., et al. (2017). Anatomic fat depots and cardiovascular risk: A focus on the leg fat using nationwide surveys (KNHANES 2008–2011). Cardiovascular Diabetology, 16(1), 54. https://doi.org/10.1186/s12933-017-0538-2.
Anderson P. J., Chan J. C., Chan Y. L., et al. (1997). Visceral fat and cardiovascular risk factors in Chinese NIDDM patients. Diabetes Care, 20(12), 1854–1858. https://doi.org/10.2337/diacare.20.12.1854.
Despre´s J. P. (2012). Body fat distribution and risk of cardiovascular disease: An update. Circulation, 126(10), 1301–1313. https://doi.org/10.1161/CIRCULATIONAHA.111.067264.
Sironi A. M., Petz R., De Marchi D., et al. (2012). Impact of increased visceral and cardiac fat on cardiometabolic risk and disease. Diabetic Medicine, 29(5), 622–627. https://doi.org/10.1111/j.1464-549 1.2011.03436.x.
St-Pierre J., Lemieux I., Vohl M. C., et al. (2007). Contribution of abdominal obesity and hypertriglyceridemia to impaired fasting glucose and coronary artery disease. The American Journal of Cardiology, 99(3), 369–373. https://doi.org/10.1016/j.amjcard.2006.08.042.
Tarui S., Tokunaga K., Fujioka S., Matsuzawa Y. (1991). Visceral fat obesity: Anthropological and pathophysiological aspects. International Journal of Obesity, 15(1), 1–8.
Neeland I. J., Turer A. T., Ayers C. R., et al. (2012). Dysfunctional adiposity and the risk of prediabetes and type 2 diabetes in obese adults. JAMA, 308(11), 1150–1159. https://doi.org/10.1001/2012.jama.11132.
Canoy D., Boekholdt S. M., Wareham N., et al. (2007). Body fat distribution and risk of coronary heart disease in men and women in the European Prospective Investigation into Cancer and Nutrition in Norfolk cohort: A population-based prospective study. Circulation, 116(25), 2933–2943. https://doi.org/10.1161/CIRCULATIONAHA.106.673756.
Balkau B., Deanfield J. E., Despre´s J. P., et al. (2007). International Day for the Evaluation of Abdominal Obesity (IDEA): A study of waist circumference, cardiovascular disease, and diabetes mellitus in 168,000 primary care patients in 63 countries. Circulation, 116(17), 1942–1951. https://doi.org/10.1161/ CIRCULATIONAHA.106.676379.
Ford E. S., Maynard L. M., Li C. (2014). Trends in mean waist circumference and abdominal obesity among US adults, 1999–2012. JAMA, 312(11), 1151–1153. https://doi.org/10.1001/jama.2014.8362.
Iacobellis G., Bianco A. C., et al. (2017). Epicardial adipose tissue and cardiovascular risk. Nature Reviews Cardiology, 14(10), 593–609. https://doi.org/10.1038/nrcardio.2017.88.
Ding J., Hsu F.-C., Harris T. B., et al. (2019). Association between epicardial adipose tissue and incident coronary artery calcification. JAMA Cardiology, 4(5), 462–470. https://doi.org/10.1001/jamacardio.2019.0324.
Sacks H. S., Fain J. N., Bahouth S. W., et al. (2021). Endocrine and paracrine role of epicardial adipose tissue in cardiovascular disease. Endocrine Reviews, 42(3), 343–365. https://doi.org/10.1210/endrev/bnaa03235.
A.R. Kim, R.B. Alieva, A.B. Shek, S.S. Akhmedova, L.E. Kan. Epicardial fat thickness in the risk stratification of patients with coronary artery disease with cardiometabolic disorders. 2024, 1,2, 6. In Russian: А.Р. Ким, Р.Б. Алиева, А.Б. Шек, Ш.С. Ахмедова, Л.Э. Кан. Толщина эпикардиального жира в риск-стратификации больных ишемической болезнью сердца с кардиометаболическими нарушениями. 2024, 1,2, 6.
Mazurek T., Zhang L., Zalewski A., et al. (2020). Epicardial adipose tissue and plaque vulnerability in acute coronary syndrome. Journal of the American College of Cardiology, 75(15), 1788-1799. https://doi.org/10.1016/j.jacc.2020.02.042.
Iacobellis G., Gra-Menendez S. (2022). Effects of dulaglutide on epicardial fat thickness in type 2 diabetes: The EAT-HF randomized controlled trial. Cardiovascular Diabetology, 21(1), 56. https://doi.org/10.1186/s12933-022-01485-w.
Britton K. A., Pedley A., Massaro J. M., et al. (2013). Prevalence, distribution, and risk factor correlates of high pericardial and intrathoracic fat depots in the Framingham Heart Study. Circulation: Cardiovascular Imaging, 6(1), 88-96. https://doi.org/10.1161/CIRCIMAGING.112.000064.
Corradi D., Maestri R., Callegari S., et al. (2004). The ventricular epicardial fat is related to the myocardial mass in normal, ischemic and hypertrophic hearts. Cardiovascular Pathology, 13(6), 313-316. https://doi.org/10.1016/j.carpath.2004.08.005.
Wang C. P., Hsu H. L., Hung W. C., et al. (2009). Increased epicardial adipose tissue (EAT) volume in type 2 diabetes mellitus and association with metabolic syndrome and severity of coronary atherosclerosis. Clinical Endocrinology, 70(6), 876-882. https://doi.org/10.1111/j.1365-2265.2008.03411.x.
Visseren F. L. J., Mach F., Smulders Y. M., et al. (2021). 2021 ESC Guidelines on cardiovascular disease prevention in clinical practice. European Heart Journal, 42(34), 3227-3337. https://doi.org/10.1093/ eurheartj/ehab484.
Rosito G. A., Massaro J. M., Hoffmann U., et al. (2022). Genetic determinants of epicardial adipose tissue volume and coronary artery disease risk. Circulation: Genomic and Precision Medicine, 15(3), e003487. https://doi.org/10.1161/CIRCGEN.121.003487.
Stahl E. P., Dhindsa D. S., Lee S. K., et al. (2019). Non-alcoholic fatty liver disease and the heart. Journal of the American College of Cardiology, 73(8), 948-963. https://doi.org/10.1016/j.jacc.2018.11.050.
Yusupalieva D. B., Alieva R. B., Nizamov U. I., et al. (2025). Comparative analysis of cardiometabolic parameters in patients with coronary heart disease with and without non-alcoholic fatty liver disease. Exploratory Cardiology, 3, 101260. [DOI if available]
Gastaldelli A., Kozakova M., Højlund K., et al. (2009). Fatty liver is associated with insulin resistance, risk of coronary heart disease, and early atherosclerosis in a large European population. Hepatology, 49(5), 1537-1544. https://doi.org/10.1002/hep.22845.
Rinella M. E., Lazarus J. V., Ratziu V., et al. (2023). A multisociety Delphi consensus statement on new fatty liver disease nomenclature. Journal of Hepatology, 79(6), 1542-1556. https://doi.org/10.1016/j.jhep. 2023.06.003.
Loomba R., Seguritan V., Li W., et al. (2021). Association between fatty liver and circulating levels of inflammatory markers in adults without major comorbidities. JAMA Network Open, 4(5), e2110063. https://doi.org/10.1001/jamanetworkopen.2021.10063.
Yki-Ja¨rvinen H., Luukkonen P. K., Hodson L., Moore J. B. (2021). Dietary carbohydrates and fats in nonalcoholic fatty liver disease. Nature Reviews Gastroenterology Hepatology, 18(11), 770-786. https://doi.org/10.1038/s41575-021-00472-y.
De Backer G., Jankowski P., Kotseva K., et al. (2022). EUROASPIRE V: Lifestyle and risk factor management in people at high cardiovascular risk from 16 European countries. European Journal of Preventive Cardiology, 29(7), 1097-1110. https://doi.org/10.1093/eurjpc/zwab154.
Petta, S., Valenti, L., Marchesini, G., et al. (2023). Increased expression of fibrinogen and PAI-1 in non-alcoholic fatty liver disease: A link with liver fibrosis and vascular damage. Liver International, 43(2), 345-357. https://doi.org/10.1111/liv.15482.
Targher G., Corey K. E., Byrne C. D., Roden M. (2021). Risk of cardiovascular disease in patients with nonalcoholic fatty liver disease. New England Journal of Medicine, 385(16), 1547-1558. https://doi.org/10.1056/NEJMra203093552.
Mantovani A., Petracca G., Beatrice G., et al. (2022). Non-alcoholic fatty liver disease and risk of fatal and non-fatal cardiovascular events: An updated systematic review and meta-analysis. The Lancet Gastroenterology Hepatology, 7(10), 851–861. https://doi.org/10.1016/S2468-1253(22)00244-9.
Loomba R., Abraham M., Unalp-Arida A., et al. (2022). Association between fibrosis stage and outcomes of patients with nonalcoholic fatty liver disease: A systematic review and meta-analysis. Gastroenterology, 162(5), 1600–1615. https://doi.org/10.1053/j.gastro.2022.01.022.
Singh A., Le P., Lopez R., et al. (2023). Fibrosis progression in nonalcoholic fatty liver disease: A systematic review and meta-analysis of paired-biopsy or imaging studies. Clinical Gastroenterology and Hepatology, 21(3), 573–585. https://doi.org/10.1016/j.cgh.2022.07.006.
European Association for the Study of the Liver (EASL). (2023). EASL Clinical Practice Guidelines on non-invasive tests for evaluation of liver disease severity and prognosis—2023 update. Journal of Hepatology, 79(5), 1226–1265. https://doi.org/10.1016/j.jhep.2023.06.017.
Marso S. P., Bain S.C., Consoli A., et al. (2016). Semaglutide and cardiovascular outcomes in patients with type 2 diabetes. New England Journal of Medicine, 375(19), 1834–1844. https://doi.org/10.1056/ NEJMoa1607141.
MICROB-PREDICT Consortium. (2023). Gut microbiome-derived metabolites modulate cardiovascular risk in metabolic-associated fatty liver disease. Nature Medicine, 29(8), 2050–2062. https://doi.org/10.1 038/s41591-023-02433-1.
Ratziu V., Sanyal A. J., Loomba R., et al. (2023). Elafibranor for the treatment of non-alcoholic steatohepatitis: Interim results from RESOLVE-IT phase 3 trial. Journal of Hepatology, 79(1), 107–118. https://doi.org/10.1016/j.jhep.2023.03.003.
Ma X., Sun Y., Cheng Y., et al. (2020). Association of perivascular adipose tissue attenuation with acute coronary syndrome and coronary plaque vulnerability: A computed tomography study. Cardiovascular Diabetology, 19(1), 127. https://doi.org/10.1186/s12933-020-01110-8.
Frontini A., Giordano A., Cinti S. (2010). Distribution and development of brown adipocytes in the murine and human adipose organ. Cell Metabolism, 11(4), 253–256. https://doi.org/10.1016/j.cmet.2010.03.004.
Sacks H.S., Fain J.N., Cheema P., et al. (2011). Inflammatory genes in epicardial fat contiguous with coronary atherosclerosis in the metabolic syndrome and type 2 diabetes: Changes associated with pioglitazone. Diabetes Care, 34(3), 730–733. https://doi.org/10.2337/dc10-1753.
Chatterjee T.K., Stoll L.L., Denning, G. M., et al. (2009). Proinflammatory phenotype of perivascular adipocytes: Influence of high-fat feeding. Circulation Research, 104(4), 541–549. https://doi.org/10.1161/ CIRCRESAHA.108.182998.
Katsiki N., Mikhailidis D. (2020). Perivascular adipose tissue in cardiovascular diseases. Anatolian Journal of Cardiology, 23(1), 58. https://doi.org/10.14744/AnatolJCardiol.2019.91380.
Cesaro A., De Michele G., Fimiani F., et al. (2023). Visceral adipose tissue and residual cardiovascular risk: A pathological link and new therapeutic options. Frontiers in Cardiovascular Medicine, 10, 1187735. https://doi.org/10.3389/fcvm.2023.1187735.
Elshorbagy A., Vallejo-Vaz A. J., Barkas F., EAS FH Studies Collaboration. (2023). Overweight, obesity, and cardiovascular disease in heterozygous familial hypercholesterolaemia: The EAS FH Studies Collaboration registry. Atherosclerosis, 374, 107–115. https://doi.org/10.1016/j.atherosclerosis.2023.06.001.
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