Epicardial adipose tissue in people living with HIV: a window towards cardiovascular risk?
Keywords:
adipose tissue, inflammation, HIV, echocardiography, metabolism
Abstract
Introduction: For people living with Human Immunodeficiency Virus (PLHIV), metabolic deregulations have been described, which could be related to a higher cardiovascular risk.
Objective: To assess the epicardial adipose tissue thickness (EATT), and the relationship between this value and clinical and biochemical parameters of cardiovascular risk in adults living with HIV, if compared to a healthy control group.
Methods: Observational, with prospective inclusion. It included PLHIV >18 years and seronegative controls. All of them had their EAT measured in two axes by transthoracic echocardiogram, as well as the carotid intima-media thickness determined by color doppler ultrasound.
Results: 75 patients, 58.7% male, age of 36 years (RIQ 22). 50.7% patients with HIV (CD4+ of 512 cells/mm3; and 80% undetectable). BMI was of 25.2 kg/m2 and waist circumference of 88.5 cm, without between-groups differences. PLHIV had lower HDL, higher C reactive protein, higher D-dimer and higher fasting blood glucose. EATT was higher in PLHIV (4.05 vs 3.49 mm, p=0.021), and this correlated with age, fasting blood glucose and D-dimer. In PLHIV, it correlated with insulinemia, HOMA2- IR index, HDL-c ; and D-dimer. Treatment with Efavirenz was associated with a higher EATT.
Conclusion: PLHIV presented increased systemic inflammation of low grade and higher EATT than the seronegative control group. EATT was associated in PLHIV to insulin resistance.
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References
GBD 2017 HIV collaborators. Global, regional, and national incidence, prevalence, and mortality of HIV, 1980-2017, and forecasts to 2030, for 195 countries and territories: a systematic analysis for the Global Burden of Diseases, Injuries, and Risk Factors Study 2017. Lancet HIV. diciembre de 2019;6(12):e831-59.
2. van Heerden A, Barnabas RV, Norris SA, Micklesfield LK, van Rooyen H, Celum C. High prevalence of HIV and non-communicable disease (NCD) risk factors in rural KwaZulu-Natal, South Africa. J Int AIDS Soc. octubre de 2017;20(2).
3. d’Ettorre G, Ceccarelli G, Pavone P, Vittozzi P, De Girolamo G, Schietroma I, et al. What happens to cardiovascular system behind the undetectable level of HIV viremia? AIDS Res Ther. 27 de abril de 2016;13(1):21.
4. Diaz P, Ferketich A. Smoking and HIV: confronting the epidemic. Lancet HIV. 1 de marzo de 2018;5(3):e109-10.
5. Lipshultz SE, Mas CM, Henkel JM, Franco VI, Fisher SD, Miller TL. HAART to heart: highly active antiretroviral therapy and the risk of cardiovascular disease in HIV-infected or exposed children and adults. Expert Rev Anti Infect Ther. junio de 2012;10(6):661-74.
6. Nagajyothi F, Desruisseaux MS, Weiss LM, Chua S, Albanese C, Machado FS, et al. Chagas disease, adipose tissue and the metabolic syndrome. Mem Inst Oswaldo Cruz. julio de 2009;104(Suppl 1):219-25.
7. Sakkas LI, Bogdanos DP, Katsiari CG. Inflammation and cardiovascular disease. World J Transl Med. 31 de enero de 2019;8(1):1-8.
8. Hsue PY, Hunt PW, Schnell A, Kalapus SC, Hoh R, Ganz P, et al. Role of viral replication, antiretroviral therapy, and immunodeficiency in HIV-associated atherosclerosis. AIDS Lond Engl. 1 de junio de 2009;23(9):1059-67.
9. Iacobellis G, Ribaudo MC, Assael F, Vecci E, Tiberti C, Zappaterreno A, et al. Echocardiographic Epicardial Adipose Tissue Is Related to Anthropometric and Clinical Parameters of Metabolic Syndrome: A New Indicator of Cardiovascular Risk. J Clin Endocrinol Metab. 1 de noviembre de 2003;88(11):5163-8.
10. Iacobellis G, Bianco AC. Epicardial adipose tissue: emerging physiological, pathophysiological and clinical features. Trends Endocrinol Metab TEM. noviembre de 2011;22(11):450-7.
11. Nerlekar N, Brown AJ, Muthalaly RG, Talman A, Hettige T, Cameron JD, et al. Association of Epicardial Adipose Tissue and High-Risk Plaque Characteristics: A Systematic Review and Meta-Analysis. J Am Heart Assoc. 23 de agosto de 2017;6(8):e006379.
12. Iacobellis G, Sharma AM, Pellicelli AM, Grisorio B, Barbarini G, Barbaro G. Epicardial adipose tissue is related to carotid intima-media thickness and visceral adiposity in HIV-infected patients with highly active antiretroviral therapy-associated metabolic syndrome. Curr HIV Res. marzo de 2007;5(2):275-9.
13. D’Agostino RB, Vasan RS, Pencina MJ, Wolf PA, Cobain M, Massaro JM, et al. General cardiovascular risk profile for use in primary care: the Framingham Heart Study. Circulation. 12 de febrero de 2008;117(6):743-53.
14. Ueda P, Woodward M, Lu Y, Hajifathalian K, Al-Wotayan R, Aguilar-Salinas CA, et al. Laboratory-based and office-based risk scores and charts to predict 10-year risk of cardiovascular disease in 182 countries: a pooled analysis of prospective cohorts and health surveys. Lancet Diabetes Endocrinol. 1 de marzo de 2017;5(3):196-213.
15. Grundy SM, Cleeman JI, Daniels SR, Donato KA, Eckel RH, Franklin BA, et al. Diagnosis and Management of the Metabolic Syndrome. Circulation. 25 de octubre de 2005;112(17):2735-52.
16. Ramírez-López LX, Aguilera AM, Rubio CM, Aguilar-Mateus ÁM. Síndrome metabólico: una revisión de criterios internacionales. Rev Colomb Cardiol. 25 de febrero de 2022;28(1):5885.
17. Rubio MA, Moreno C, Cabrerizo L. Guías para el tratamiento de las dislipemias en el adulto: Adult Treatment Panel III (ATP-III). Endocrinol Nutr. 1 de mayo de 2004;51(5):254-65.
18. Dobiásová M, Frohlich J. The plasma parameter log (TG/HDL-C) as an atherogenic index: correlation with lipoprotein particle size and esterification rate in apoB-lipoprotein-depleted plasma (FER(HDL)). Clin Biochem. octubre de 2001;34(7):583-8.
19. Kim SH, Cho YK, Kim YJ, Jung CH, Lee WJ, Park JY, et al. Association of the atherogenic index of plasma with cardiovascular risk beyond the traditional risk factors: a nationwide population-based cohort study. Cardiovasc Diabetol. 22 de mayo de 2022;21(1):81.
20. Turner RC, Holman RR, Matthews D, Hockaday TD, Peto J. Insulin deficiency and insulin resistance interaction in diabetes: estimation of their relative contribution by feedback analysis from basal plasma insulin and glucose concentrations. Metabolism. noviembre de 1979;28(11):1086-96.
21. Matthews DR, Hosker JP, Rudenski AS, Naylor BA, Treacher DF, Turner RC. Homeostasis model assessment: insulin resistance and beta-cell function from fasting plasma glucose and insulin concentrations in man. Diabetologia. julio de 1985;28(7):412-9.
22. Levy JC, Matthews DR, Hermans MP. Correct homeostasis model assessment (HOMA) evaluation uses the computer program. Diabetes Care. diciembre de 1998;21(12):2191-2.
23. Buccini GS, Wolfthal DL. Valores de corte para índices de insulinorresistencia, insulinosensibilidad e insulinosecreción derivados de la fórmula HOMA y del programa HOMA2: Interpretación de los datos. Rev Argent Endocrinol Metab. marzo de 2008;45(1):03-21.
24. Geloneze B, Vasques ACJ, Stabe CFC, Pareja JC, Rosado LEFP de L, Queiroz EC de, et al. HOMA1-IR and HOMA2-IR indexes in identifying insulin resistance and metabolic syndrome: Brazilian Metabolic Syndrome Study (BRAMS). Arq Bras Endocrinol Metabol. marzo de 2009;53(2):281-7.
25. Mustelier JV, Rego JOC, González AG, Sarmiento JCG, Riverón BV. Echocardiographic parameters of epicardial fat deposition and its relation to coronary artery disease. Arq Bras Cardiol. agosto de 2011;97(2):122-9.
26. Akyol B, Boyraz M, Aysoy C. Relationship of Epicardial Adipose Tissue Thickness with Early Indicators of Atherosclerosis and Cardiac Functional Changes in Obese Adolescents with Metabolic Syndrome. J Clin Res Pediatr Endocrinol. septiembre de 2013;5(3):156-63.
27. Bloch M, John M, Smith D, Rasmussen TA, Wright E. Managing HIV-associated inflammation and ageing in the era of modern ART. HIV Med. octubre de 2020;21 Suppl 3:2-16.
28. Hearps AC, Maisa A, Cheng WJ, Angelovich TA, Lichtfuss GF, Palmer CS, et al. HIV infection induces age-related changes to monocytes and innate immune activation in young men that persist despite combination antiretroviral therapy. AIDS Lond Engl. 24 de abril de 2012;26(7):843-53.
29. Kamat A, Misra V, Cassol E, Ancuta P, Yan Z, Li C, et al. A Plasma Biomarker Signature of Immune Activation in HIV Patients on Antiretroviral Therapy. PLoS ONE. 17 de febrero de 2012;7(2):e30881.
30. Neuhaus J, Jacobs DR, Baker JV, Calmy A, Duprez D, La Rosa A, et al. Markers of inflammation, coagulation, and renal function are elevated in adults with HIV infection. J Infect Dis. 15 de junio de 2010;201(12):1788-95.
31. Falasca F, Di Carlo D, De Vito C, Bon I, d’Ettorre G, Fantauzzi A, et al. Evaluation of HIV-DNA and inflammatory markers in HIV-infected individuals with different viral load patterns. BMC Infect Dis. 22 de agosto de 2017;17(1):581.
32. Moutachakkir M, Lamrani Hanchi A, Baraou A, Boukhira A, Chellak S. Immunoanalytical characteristics of C-reactive protein and high sensitivity C-reactive protein. Ann Biol Clin (Paris). 1 de abril de 2017;75(2):225-9.
33. Mcdade TW, Tallman PS, Madimenos FC, Liebert MA, Cepon TJ, Sugiyama LS, et al. Analysis of variability of high sensitivity C-reactive protein in lowland ecuador reveals no evidence of chronic low-grade inflammation. Am J Hum Biol. 2012;24(5):675-81.
34. Herder C, Schneitler S, Rathmann W, Haastert B, Schneitler H, Winkler H, et al. Low-Grade Inflammation, Obesity, and Insulin Resistance in Adolescents. J Clin Endocrinol Metab. 1 de diciembre de 2007;92(12):4569-74.
35. Feeney ER, Mallon PWG. Insulin resistance in treated HIV infection. Best Pract Res Clin Endocrinol Metab. junio de 2011;25(3):443-58.
36. Freiberg MS, Bebu I, Tracy R, So-Armah K, Okulicz J, Ganesan A, et al. D-Dimer Levels before HIV Seroconversion Remain Elevated Even after Viral Suppression and Are Associated with an Increased Risk of Non-AIDS Events. PloS One. 2016;11(4):e0152588.
37. Iacobellis G. Local and systemic effects of the multifaceted epicardial adipose tissue depot. Nat Rev Endocrinol. junio de 2015;11(6):363-71.
38. Sinxadi PZ, McIlleron HM, Dave JA, Smith PJ, Levitt NS, Haas DW, et al. Plasma Efavirenz Concentrations Are Associated With Lipid and Glucose Concentrations. Medicine (Baltimore). 15 de enero de 2016;95(2):e2385.
2. van Heerden A, Barnabas RV, Norris SA, Micklesfield LK, van Rooyen H, Celum C. High prevalence of HIV and non-communicable disease (NCD) risk factors in rural KwaZulu-Natal, South Africa. J Int AIDS Soc. octubre de 2017;20(2).
3. d’Ettorre G, Ceccarelli G, Pavone P, Vittozzi P, De Girolamo G, Schietroma I, et al. What happens to cardiovascular system behind the undetectable level of HIV viremia? AIDS Res Ther. 27 de abril de 2016;13(1):21.
4. Diaz P, Ferketich A. Smoking and HIV: confronting the epidemic. Lancet HIV. 1 de marzo de 2018;5(3):e109-10.
5. Lipshultz SE, Mas CM, Henkel JM, Franco VI, Fisher SD, Miller TL. HAART to heart: highly active antiretroviral therapy and the risk of cardiovascular disease in HIV-infected or exposed children and adults. Expert Rev Anti Infect Ther. junio de 2012;10(6):661-74.
6. Nagajyothi F, Desruisseaux MS, Weiss LM, Chua S, Albanese C, Machado FS, et al. Chagas disease, adipose tissue and the metabolic syndrome. Mem Inst Oswaldo Cruz. julio de 2009;104(Suppl 1):219-25.
7. Sakkas LI, Bogdanos DP, Katsiari CG. Inflammation and cardiovascular disease. World J Transl Med. 31 de enero de 2019;8(1):1-8.
8. Hsue PY, Hunt PW, Schnell A, Kalapus SC, Hoh R, Ganz P, et al. Role of viral replication, antiretroviral therapy, and immunodeficiency in HIV-associated atherosclerosis. AIDS Lond Engl. 1 de junio de 2009;23(9):1059-67.
9. Iacobellis G, Ribaudo MC, Assael F, Vecci E, Tiberti C, Zappaterreno A, et al. Echocardiographic Epicardial Adipose Tissue Is Related to Anthropometric and Clinical Parameters of Metabolic Syndrome: A New Indicator of Cardiovascular Risk. J Clin Endocrinol Metab. 1 de noviembre de 2003;88(11):5163-8.
10. Iacobellis G, Bianco AC. Epicardial adipose tissue: emerging physiological, pathophysiological and clinical features. Trends Endocrinol Metab TEM. noviembre de 2011;22(11):450-7.
11. Nerlekar N, Brown AJ, Muthalaly RG, Talman A, Hettige T, Cameron JD, et al. Association of Epicardial Adipose Tissue and High-Risk Plaque Characteristics: A Systematic Review and Meta-Analysis. J Am Heart Assoc. 23 de agosto de 2017;6(8):e006379.
12. Iacobellis G, Sharma AM, Pellicelli AM, Grisorio B, Barbarini G, Barbaro G. Epicardial adipose tissue is related to carotid intima-media thickness and visceral adiposity in HIV-infected patients with highly active antiretroviral therapy-associated metabolic syndrome. Curr HIV Res. marzo de 2007;5(2):275-9.
13. D’Agostino RB, Vasan RS, Pencina MJ, Wolf PA, Cobain M, Massaro JM, et al. General cardiovascular risk profile for use in primary care: the Framingham Heart Study. Circulation. 12 de febrero de 2008;117(6):743-53.
14. Ueda P, Woodward M, Lu Y, Hajifathalian K, Al-Wotayan R, Aguilar-Salinas CA, et al. Laboratory-based and office-based risk scores and charts to predict 10-year risk of cardiovascular disease in 182 countries: a pooled analysis of prospective cohorts and health surveys. Lancet Diabetes Endocrinol. 1 de marzo de 2017;5(3):196-213.
15. Grundy SM, Cleeman JI, Daniels SR, Donato KA, Eckel RH, Franklin BA, et al. Diagnosis and Management of the Metabolic Syndrome. Circulation. 25 de octubre de 2005;112(17):2735-52.
16. Ramírez-López LX, Aguilera AM, Rubio CM, Aguilar-Mateus ÁM. Síndrome metabólico: una revisión de criterios internacionales. Rev Colomb Cardiol. 25 de febrero de 2022;28(1):5885.
17. Rubio MA, Moreno C, Cabrerizo L. Guías para el tratamiento de las dislipemias en el adulto: Adult Treatment Panel III (ATP-III). Endocrinol Nutr. 1 de mayo de 2004;51(5):254-65.
18. Dobiásová M, Frohlich J. The plasma parameter log (TG/HDL-C) as an atherogenic index: correlation with lipoprotein particle size and esterification rate in apoB-lipoprotein-depleted plasma (FER(HDL)). Clin Biochem. octubre de 2001;34(7):583-8.
19. Kim SH, Cho YK, Kim YJ, Jung CH, Lee WJ, Park JY, et al. Association of the atherogenic index of plasma with cardiovascular risk beyond the traditional risk factors: a nationwide population-based cohort study. Cardiovasc Diabetol. 22 de mayo de 2022;21(1):81.
20. Turner RC, Holman RR, Matthews D, Hockaday TD, Peto J. Insulin deficiency and insulin resistance interaction in diabetes: estimation of their relative contribution by feedback analysis from basal plasma insulin and glucose concentrations. Metabolism. noviembre de 1979;28(11):1086-96.
21. Matthews DR, Hosker JP, Rudenski AS, Naylor BA, Treacher DF, Turner RC. Homeostasis model assessment: insulin resistance and beta-cell function from fasting plasma glucose and insulin concentrations in man. Diabetologia. julio de 1985;28(7):412-9.
22. Levy JC, Matthews DR, Hermans MP. Correct homeostasis model assessment (HOMA) evaluation uses the computer program. Diabetes Care. diciembre de 1998;21(12):2191-2.
23. Buccini GS, Wolfthal DL. Valores de corte para índices de insulinorresistencia, insulinosensibilidad e insulinosecreción derivados de la fórmula HOMA y del programa HOMA2: Interpretación de los datos. Rev Argent Endocrinol Metab. marzo de 2008;45(1):03-21.
24. Geloneze B, Vasques ACJ, Stabe CFC, Pareja JC, Rosado LEFP de L, Queiroz EC de, et al. HOMA1-IR and HOMA2-IR indexes in identifying insulin resistance and metabolic syndrome: Brazilian Metabolic Syndrome Study (BRAMS). Arq Bras Endocrinol Metabol. marzo de 2009;53(2):281-7.
25. Mustelier JV, Rego JOC, González AG, Sarmiento JCG, Riverón BV. Echocardiographic parameters of epicardial fat deposition and its relation to coronary artery disease. Arq Bras Cardiol. agosto de 2011;97(2):122-9.
26. Akyol B, Boyraz M, Aysoy C. Relationship of Epicardial Adipose Tissue Thickness with Early Indicators of Atherosclerosis and Cardiac Functional Changes in Obese Adolescents with Metabolic Syndrome. J Clin Res Pediatr Endocrinol. septiembre de 2013;5(3):156-63.
27. Bloch M, John M, Smith D, Rasmussen TA, Wright E. Managing HIV-associated inflammation and ageing in the era of modern ART. HIV Med. octubre de 2020;21 Suppl 3:2-16.
28. Hearps AC, Maisa A, Cheng WJ, Angelovich TA, Lichtfuss GF, Palmer CS, et al. HIV infection induces age-related changes to monocytes and innate immune activation in young men that persist despite combination antiretroviral therapy. AIDS Lond Engl. 24 de abril de 2012;26(7):843-53.
29. Kamat A, Misra V, Cassol E, Ancuta P, Yan Z, Li C, et al. A Plasma Biomarker Signature of Immune Activation in HIV Patients on Antiretroviral Therapy. PLoS ONE. 17 de febrero de 2012;7(2):e30881.
30. Neuhaus J, Jacobs DR, Baker JV, Calmy A, Duprez D, La Rosa A, et al. Markers of inflammation, coagulation, and renal function are elevated in adults with HIV infection. J Infect Dis. 15 de junio de 2010;201(12):1788-95.
31. Falasca F, Di Carlo D, De Vito C, Bon I, d’Ettorre G, Fantauzzi A, et al. Evaluation of HIV-DNA and inflammatory markers in HIV-infected individuals with different viral load patterns. BMC Infect Dis. 22 de agosto de 2017;17(1):581.
32. Moutachakkir M, Lamrani Hanchi A, Baraou A, Boukhira A, Chellak S. Immunoanalytical characteristics of C-reactive protein and high sensitivity C-reactive protein. Ann Biol Clin (Paris). 1 de abril de 2017;75(2):225-9.
33. Mcdade TW, Tallman PS, Madimenos FC, Liebert MA, Cepon TJ, Sugiyama LS, et al. Analysis of variability of high sensitivity C-reactive protein in lowland ecuador reveals no evidence of chronic low-grade inflammation. Am J Hum Biol. 2012;24(5):675-81.
34. Herder C, Schneitler S, Rathmann W, Haastert B, Schneitler H, Winkler H, et al. Low-Grade Inflammation, Obesity, and Insulin Resistance in Adolescents. J Clin Endocrinol Metab. 1 de diciembre de 2007;92(12):4569-74.
35. Feeney ER, Mallon PWG. Insulin resistance in treated HIV infection. Best Pract Res Clin Endocrinol Metab. junio de 2011;25(3):443-58.
36. Freiberg MS, Bebu I, Tracy R, So-Armah K, Okulicz J, Ganesan A, et al. D-Dimer Levels before HIV Seroconversion Remain Elevated Even after Viral Suppression and Are Associated with an Increased Risk of Non-AIDS Events. PloS One. 2016;11(4):e0152588.
37. Iacobellis G. Local and systemic effects of the multifaceted epicardial adipose tissue depot. Nat Rev Endocrinol. junio de 2015;11(6):363-71.
38. Sinxadi PZ, McIlleron HM, Dave JA, Smith PJ, Levitt NS, Haas DW, et al. Plasma Efavirenz Concentrations Are Associated With Lipid and Glucose Concentrations. Medicine (Baltimore). 15 de enero de 2016;95(2):e2385.
Published
2023-04-13
How to Cite
Castro, M. G., Ubriego, L., Butarelli, E., Miño, H., Cogliano, F., Rodeles, L., Savarino, R., & Crespo, A. (2023). Epicardial adipose tissue in people living with HIV: a window towards cardiovascular risk?. Actualizaciones En Sida E Infectología, 31(111), 17-28. https://doi.org/10.52226/revista.v31i111.152
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Original article
Copyright (c) 2023 Maximiliano Gabriel Castro, Lucía Ubriego, Elisa Butarelli, Hugo Miño, Florencia Cogliano, Luz Rodeles, Roberto Savarino, Alejandro Crespo
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