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Introduction: Ectopic fat deposition may contribute to chronic inflammation in people with HIV (PWH). To inform future mechanistic studies of metabolic risk in this population, we sought to determine which fat measures relate more strongly to inflammation and whether the fat-inflammation relationship is modified by sex or HIV status.
Methods: We conducted a cross-sectional study of 105 PWH and 20 age- and sex-matched HIV-negative controls. Interleukin-6 (IL-6) and high-sensitivity C reactive protein (hs-CRP) levels were measured from plasma. Pericardial fat (PCF) and thoracic periaortic adipose tissue (TAT) volumes and peri-right coronary artery (RCA), left atrium (LA) roof and liver densities were measured from cardiac CT scans. Unadjusted and multivariate adjusted linear regression models were used to determine the relationship between ectopic fat measures and inflammation biomarkers.
Results: Forty subjects had BMI <25, 33 had BMI 25-30, and 52 had BMI >30. Systolic blood pressure and insulin resistance increased with BMI. Subjects with higher BMI had higher CD4+ count. In models adjusted for demographics, HIV status and metabolic risk factors, BMI was positively associated with IL-6 and hs-CRP. Ectopic PCF and TAT volumes were positively associated with IL-6 and hs-CRP; however, these relationships were somewhat attenuated in adjusted models. LA roof (but not peri-RCA) fat radiodensity was inversely associated with hs-CRP in fully adjusted models and the association with IL-6 was borderline statistically significant. IL-6 was more strongly associated with BMI and LA roof density in women than in men (p for interaction=0.05).
Conclusions: Among PWH on antiretroviral therapy, higher BMI and excessive visceral fat burden were associated with circulating markers of systemic inflammation, and this relationship appears to be stronger in women compared to men.
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1. Hogg RS, Heath KV, Yip B, Craib KJ, O'Shaughnessy MV, Schechter MT, Montaner JS. Improved survival among HIV-infected individuals following initiation of antiretroviral therapy. JAMA. 1998;279(6):450-4. PubMed PMID: 9466638.
2. Addy CL, Gavrila A, Tsiodras S, Brodovicz K, Karchmer AW, Mantzoros CS. Hypoadiponectinemia is associated with insulin resistance, hypertriglyceridemia, and fat redistribution in human immunodeficiency virus-infected patients treated with highly active antiretroviral therapy. J Clin Endocrinol Metab. 2003;88(2):627-36. PubMed PMID: 12574192. doi: 10.1210/jc.2002-020795
3. Caron M, Auclair M, Lagathu C, Lombes A, Walker UA, Kornprobst M, Capeau J. The HIV-1 nucleoside reverse transcriptase inhibitors stavudine and zidovudine alter adipocyte functions in vitro. AIDS. 2004;18(16):2127-36. PubMed PMID: 15577645.
4. Carr A, Samaras K, Burton S, Law M, Freund J, Chisholm DJ, Cooper DA. A syndrome of peripheral lipodystrophy, hyperlipidaemia and insulin resistance in patients receiving HIV protease inhibitors. AIDS. 1998;12(7):F51-8. PubMed PMID: 9619798.
5. Dube MP, Parker RA, Tebas P, Grinspoon SK, Zackin RA, Robbins GK, Roubenoff R, Shafer RW, Wininger DA, Meyer WA, 3rd, Snyder SW, Mulligan K. Glucose metabolism, lipid, and body fat changes in antiretroviral-naive subjects randomized to nelfinavir or efavirenz plus dual nucleosides. AIDS. 2005;19(16):1807-18. PubMed PMID: 16227788.
6. Karmon SL, Moore RD, Dobs AS, Keruly J, Barnett S, Cofrancesco J, Jr. Body shape and composition in HIV-infected women: an urban cohort. HIV Med. 2005;6(4):245-52. PubMed PMID: 16011529. doi: 10.1111/j.1468-1293.2005.00284.x
7. Saint-Marc T, Partisani M, Poizot-Martin I, Bruno F, Rouviere O, Lang JM, Gastaut JA, Touraine JL. A syndrome of peripheral fat wasting (lipodystrophy) in patients receiving long-term nucleoside analogue therapy. AIDS. 1999;13(13):1659-67. PubMed PMID: 10509567.
8. Gallego-Escuredo JM, Villarroya J, Domingo P, Targarona EM, Alegre M, Domingo JC, Villarroya F, Giralt M. Differentially altered molecular signature of visceral adipose tissue in HIV-1-associated lipodystrophy. J Acquir Immune Defic Syndr. 2013;64(2):142-8. PubMed PMID: 23714743. doi: 10.1097/QAI.0b013e31829bdb67
9. Grunfeld C, Pang M, Doerrler W, Shigenaga JK, Jensen P, Feingold KR. Lipids, lipoproteins, triglyceride clearance, and cytokines in human immunodeficiency virus infection and the acquired immunodeficiency syndrome. J Clin Endocrinol Metab. 1992;74(5):1045-52. PubMed PMID: 1373735. doi: 10.1210/jcem.74.5.1373735
10. Thompson-Paul AM, Wei SC, Mattson CL, Robertson M, Hernandez-Romieu AC, Bell TK, Skarbinski J. Obesity Among HIV-Infected Adults Receiving Medical Care in the United States: Data From the Cross-Sectional Medical Monitoring Project and National Health and Nutrition Examination Survey. Medicine (Baltimore). 2015;94(27):e1081. PubMed PMID: 26166086. Pubmed Central PMCID: PMC4504569. doi: 10.1097/MD.0000000000001081
11. Koethe JR, Jenkins CA, Lau B, Shepherd BE, Justice AC, Tate JP, Buchacz K, Napravnik S, Mayor AM, Horberg MA, Blashill AJ, Willig A, Wester CW, Silverberg MJ, Gill J, Thorne JE, Klein M, Eron JJ, Kitahata MM, Sterling TR, Moore RD, North American ACCoR, Design. Rising Obesity Prevalence and Weight Gain Among Adults Starting Antiretroviral Therapy in the United States and Canada. AIDS research and human retroviruses. 2016;32(1):50-8. PubMed PMID: 26352511. Pubmed Central PMCID: PMC4692122. doi: 10.1089/aid.2015.0147
12. Godfrey C, Bremer A, Alba D, Apovian C, Koethe JR, Koliwad S, Lewis D, Lo J, McComsey GA, Eckard A, Srinivasa S, Trevillyan J, Palmer C, Grinspoon S. Obesity and Fat Metabolism in HIV-infected Individuals: Immunopathogenic Mechanisms and Clinical Implications. The Journal of infectious diseases. 2019. PubMed PMID: 30893434. doi: 10.1093/infdis/jiz118
13. Poirier P, Giles TD, Bray GA, Hong Y, Stern JS, Pi-Sunyer FX, Eckel RH, American Heart A, Obesity Committee of the Council on Nutrition PA, Metabolism. Obesity and cardiovascular disease: pathophysiology, evaluation, and effect of weight loss: an update of the 1997 American Heart Association Scientific Statement on Obesity and Heart Disease from the Obesity Committee of the Council on Nutrition, Physical Activity, and Metabolism. Circulation. 2006;113(6):898-918. PubMed PMID: 16380542. doi: 10.1161/CIRCULATIONAHA.106.171016
14. Eckel RH, York DA, Rossner S, Hubbard V, Caterson I, St Jeor ST, Hayman LL, Mullis RM, Blair SN, American Heart A. Prevention Conference VII: Obesity, a worldwide epidemic related to heart disease and stroke: executive summary. Circulation. 2004;110(18):2968-75. PubMed PMID: 15520336. doi: 10.1161/01.CIR.0000140086.88453.9A
15. Longenecker CT, Jiang Y, Yun CH, Debanne S, Funderburg NT, Lederman MM, Storer N, Labbato DE, Bezerra HG, McComsey GA. Perivascular fat, inflammation, and cardiovascular risk in HIV-infected patients on antiretroviral therapy. Int J Cardiol. 2013;168(4):4039-45. PubMed PMID: 23886531. Pubmed Central PMCID: PMC3805774. doi: 10.1016/j.ijcard.2013.06.059
16. Longenecker CT, Margevicius S, Liu Y, Schluchter MD, Yun CH, Bezerra HG, McComsey GA. Effect of Pericardial Fat Volume and Density on Markers of Insulin Resistance and Inflammation in Patients With Human Immunodeficiency Virus Infection. The American journal of cardiology. 2017;120(8):1427-33. PubMed PMID: 28822563. Pubmed Central PMCID: PMC5614847. doi: 10.1016/j.amjcard.2017.07.019
17. Webel AR, Moore SM, Longenecker CT, Currie J, Horvat Davey C, Perazzo J, Sattar A, Josephson RA. Randomized Controlled Trial of the SystemCHANGE Intervention on Behaviors Related to Cardiovascular Risk in HIV+ Adults. Journal of acquired immune deficiency syndromes. 2018;78(1):23-33. PubMed PMID: 29373392. Pubmed Central PMCID: PMC5889354. doi: 10.1097/QAI.0000000000001635
18. 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. 1985;28(7):412-9. PubMed PMID: 3899825.
19. Yun CH, Lin TY, Wu YJ, Liu CC, Kuo JY, Yeh HI, Yang FS, Chen SC, Hou CJ, Bezerra HG, Hung CL, Cury RC. Pericardial and thoracic peri-aortic adipose tissues contribute to systemic inflammation and calcified coronary atherosclerosis independent of body fat composition, anthropometric measures and traditional cardiovascular risks. European journal of radiology. 2012;81(4):749-56. PubMed PMID: 21334840. doi: 10.1016/j.ejrad.2011.01.035
20. Konishi M, Sugiyama S, Sato Y, Oshima S, Sugamura K, Nozaki T, Ohba K, Matsubara J, Sumida H, Nagayoshi Y, Sakamoto K, Utsunomiya D, Awai K, Jinnouchi H, Matsuzawa Y, Yamashita Y, Asada Y, Kimura K, Umemura S, Ogawa H. Pericardial fat inflammation correlates with coronary artery disease. Atherosclerosis. 2010;213(2):649-55. PubMed PMID: 21040916. dio: 10.1016/j.atherosclerosis.2010.10.007
21. Esterson YB, Grimaldi GM. Radiologic Imaging in Nonalcoholic Fatty Liver Disease and Nonalcoholic Steatohepatitis. Clin Liver Dis. 2018;22(1):93-108. PubMed PMID: 29128063. doi: 10.1016/j.cld.2017.08.005
22. Buggey J, Longenecker CT. Heart fat in HIV: marker or mediator of risk? Current opinion in HIV and AIDS. 2017;12(6):572-8. PubMed PMID: 28796027. Pubmed Central PMCID: PMC5638646. doi: 10.1097/COH.0000000000000414
23. Bays HE. Adiposopathy is "sick fat" a cardiovascular disease? Journal of the American College of Cardiology. 2011;57(25):2461-73. PubMed PMID: 21679848. doi: 10.1016/j.jacc.2011.02.038
24. 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(3):499-504. PubMed PMID: 19571212. Pubmed Central PMCID: PMC2728641. doi: 10.3945/ajcn.2008.27358
25. Mahabadi AA, Reinsch N, Lehmann N, Altenbernd J, Kalsch H, Seibel RM, Erbel R, Mohlenkamp S. Association of pericoronary fat volume with atherosclerotic plaque burden in the underlying coronary artery: a segment analysis. Atherosclerosis. 2010;211(1):195-9. PubMed PMID: 20223460. doi: 10.1016/j.atherosclerosis.2010.02.013
26. Iacobellis G, Bianco AC. Epicardial adipose tissue: emerging physiological, pathophysiological and clinical features. Trends in endocrinology and metabolism: TEM. 2011;22(11):450-7. PubMed PMID: 21852149. doi: 10.1016/j.tem.2011.07.003
27. Lake JE, Moser C, Johnston L, Magyar C, Nelson SD, Erlandson KM, Brown TT, McComsey GA. CT Fat Density Accurately Reflects Histologic Fat Quality in Adults with HIV On and Off Antiretroviral Therapy. The Journal of clinical endocrinology and metabolism. 2019. PubMed PMID: 31329901. doi: 10.1210/jc.2018-02785
28. Antonopoulos AS, Sanna F, Sabharwal N, Thomas S, Oikonomou EK, Herdman L, Margaritis M, Shirodaria C, Kampoli A-M, Akoumianakis I, Petrou M, Sayeed R, Krasopoulos G, Psarros C, Ciccone P, Brophy CM, Digby J, Kelion A, Uberoi R, Anthony S, Alexopoulos N, Tousoulis D, Achenbach S, Neubauer S, Channon KM, Antoniades C. Detecting human coronary inflammation by imaging perivascular fat. Science Translational Medicine. 2017;9.
29. Varghese M, Griffin C, McKernan K, Eter L, Lanzetta N, Agarwal D, Abrishami S, Singer K. Sex Differences in Inflammatory Responses to Adipose Tissue Lipolysis in Diet-Induced Obesity. Endocrinology. 2019;160(2):293-312. PubMed PMID: 30544158. Pubmed Central PMCID: PMC6330175. doi: 10.1210/en.2018-00797
30. Price JC, Wang R, Seaberg EC, Budoff MJ, Kingsley LA, Palella FJ, Witt MD, Post WS, Thio CL. The Association of Inflammatory Markers With Nonalcoholic Fatty Liver Disease Differs by Human Immunodeficiency Virus Serostatus. Open Forum Infect Dis. 2017;4(3):ofx153. PubMed PMID: 28929125. Pubmed Central PMCID: PMC5601080. doi: 10.1093/ofid/ofx153