Cardiac adiposity as a modulator of cardiovascular disease in HIV.
HIV
cardiac adiposity
cardiovascular disease
epicardial adipose tissue
imaging modalities
pharmaceutical interventions
Journal
HIV medicine
ISSN: 1468-1293
Titre abrégé: HIV Med
Pays: England
ID NLM: 100897392
Informations de publication
Date de publication:
11 2021
11 2021
Historique:
revised:
02
08
2021
received:
13
05
2021
accepted:
13
08
2021
pubmed:
14
9
2021
medline:
15
3
2022
entrez:
13
9
2021
Statut:
ppublish
Résumé
With the number of people living with human immunodeficiency virus (HIV) steadily increasing, cardiovascular disease has emerged as a leading cause of non-HIV related mortality. People living with HIV (PLWH) appear to be at increased risk of coronary artery disease and heart failure (HF), while the underlying mechanism appears to be multifactorial. In the general population, ectopic cardiac adiposity has been highlighted as an important modulator of accelerated coronary artery atherosclerosis, arrhythmogenesis and HF with preserved ejection fraction (HFpEF). Cardiac adiposity is also strongly linked with obesity, especially with visceral adipose tissue accumulation. This review aims to summarize the possible role of cardiac fat depositions, assessed by imaging modalities,as potential contributors to the increased cardiac morbidity and mortality seen in PLWH, as well as therapeutic targets in the current ART era. Review of contemporary literature on this topic. Despite antiretroviral therapy (ART), PLWH have evidence of persistent, HIV-related systemic inflammation and body fat alterations. Cardiac adiposity can play an additional role in the pathogenesis of cardiovascular disease in the HIV setting. Imaging modalities such as echocardiography, cardiac multidetector computed tomography and cardiac magnetic resonance have demonstrated increased adipose tissue. Studies show that high cardiac fat depots play an additive role in promoting coronary artery atherosclerosis and HFpEF in PLWH. Systemic inflammation due to HIV infection, metabolic adverse effects of ART, adipose alterations in the ageing HIV population, inflammation and immune activation are likely important mechanisms for adipose dysfunction and disproportionately occurrence of ectopic fat depots in the heart among PLWH. High cardiac adiposity seems to plays an additive role in promoting coronary artery atherosclerosis and HFpEF in PLWH. The underlying mechanisms are multiple and warrant further investigation. Improved understanding of the regulating mechanisms that increase cardiovascular risk in HIV infection may give rise to more tailored therapeutic strategies targeting cardiac fat depots.
Sections du résumé
BACKGROUND
With the number of people living with human immunodeficiency virus (HIV) steadily increasing, cardiovascular disease has emerged as a leading cause of non-HIV related mortality. People living with HIV (PLWH) appear to be at increased risk of coronary artery disease and heart failure (HF), while the underlying mechanism appears to be multifactorial. In the general population, ectopic cardiac adiposity has been highlighted as an important modulator of accelerated coronary artery atherosclerosis, arrhythmogenesis and HF with preserved ejection fraction (HFpEF). Cardiac adiposity is also strongly linked with obesity, especially with visceral adipose tissue accumulation.
AIMS
This review aims to summarize the possible role of cardiac fat depositions, assessed by imaging modalities,as potential contributors to the increased cardiac morbidity and mortality seen in PLWH, as well as therapeutic targets in the current ART era.
MATERIALS & METHODS
Review of contemporary literature on this topic.
DISCUSSION
Despite antiretroviral therapy (ART), PLWH have evidence of persistent, HIV-related systemic inflammation and body fat alterations. Cardiac adiposity can play an additional role in the pathogenesis of cardiovascular disease in the HIV setting. Imaging modalities such as echocardiography, cardiac multidetector computed tomography and cardiac magnetic resonance have demonstrated increased adipose tissue. Studies show that high cardiac fat depots play an additive role in promoting coronary artery atherosclerosis and HFpEF in PLWH. Systemic inflammation due to HIV infection, metabolic adverse effects of ART, adipose alterations in the ageing HIV population, inflammation and immune activation are likely important mechanisms for adipose dysfunction and disproportionately occurrence of ectopic fat depots in the heart among PLWH.
CONCLUSIONS
High cardiac adiposity seems to plays an additive role in promoting coronary artery atherosclerosis and HFpEF in PLWH. The underlying mechanisms are multiple and warrant further investigation. Improved understanding of the regulating mechanisms that increase cardiovascular risk in HIV infection may give rise to more tailored therapeutic strategies targeting cardiac fat depots.
Types de publication
Journal Article
Review
Langues
eng
Sous-ensembles de citation
IM
Pagination
879-891Informations de copyright
© 2021 British HIV Association.
Références
Feinstein MJ, Hsue PY, Benjamin LA, et al. Characteristics, prevention, and management of cardiovascular disease in people living with HIV: a scientific statement from the American heart association. Circulation 2019;140:e98-e124.
Shah ASV, Stelzle D, Lee KK, et al. Global burden of atherosclerotic cardiovascular disease in people living with the human immunodeficiency virus: a systematic review and meta-analysis. Circulation 2018;138:1100-1112.
Hsue PY. Mechanisms of cardiovascular disease in the setting of HIV infection. Can J Cardiol 2019;35:238-248.
Bonou M, Kapelios CJ, Athanasiadi E, Mavrogeni SI, Psichogiou M, Barbetseas J. Imaging modalities for cardiovascular phenotyping in asymptomatic people living with HIV. Vasc Med 2021;26(3):326-337.
Savvoulidis P, Butler J, Kalogeropoulos A. Cardiomyopathy and heart failure in patients with HIV infection. Can J Cardiol 2019;35:299-309.
Belkin MN, Uriel N. Heart health in the age of highly active antiretroviral therapy: a review of HIV cardiomyopathy. Curr Opin Cardiol 2018;33:317-324.
Patel VB, Shah S, Verma S, Oudit GY. Epicardial adipose tissue as a metabolic transducer: role in heart failure and coronary artery disease. Heart Fail Rev 2017;22:889-902.
Bonou M, Mavrogeni S, Kapelios CJ, et al. Cardiac adiposity and arrhythmias: the role of imaging. Diagnostics (Basel) 2021;11(2):362.
Longo M, Zatterale F, Naderi J, et al. Adipose tissue dysfunction as determinant of obesity-associated metabolic complications. Int J Mol Sci 2019;20:2358.
Villasante Fricke AC, Iacobellis G. Epicardial adipose tissue: clinical biomarker of cardio-metabolic risk. Int J Mol Sci 2019;20:5989.
Antonopoulos AS, Sanna F, Sabharwal N, et al. Detecting human coronary inflammation by imaging perivascular fat. Sci Transl Med 2017;9:eaal2658.
Ian J, Neeland IJ, Yokoo T, Leinhard OD, Lavie CJ. Twenty-first century advances in multimodality imaging of obesity for care of the cardiovascular patient. JACC Cardiovasc Imaging 2020;S1936-878X(20)30267-9.
Antoniades C, Kotanidis CP, Berman DS. State-of-the-art review article. Atherosclerosis affecting fat: What can we learn by imaging perivascular adipose tissue? J Cardiovasc. Comput Tomogr. 2019;13:288-296.
Ng ACT, Strudwick M, van der Geest RJ, et al. Impact of epicardial adipose tissue, left ventricular myocardial fat content, and interstitial fibrosis on myocardial contractile function. Circ Cardiovasc Imaging 2018;11:e007372.
Scannell CM, Correia T, Villa ADM, et al. Feasibility of free-breathing quantitative myocardial perfusion using multi-echo Dixon magnetic resonance imaging. Sci Rep 2020;10(1):12684.
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;90:499-504.
Shah RV, Anderson A, Ding J, et al. Pericardial, but not hepatic, fat by CT is associated with CV outcomes and structure: the Multi-Ethnic Study of Atherosclerosis. JACC Cardiovasc Imaging 2017;10:1016-1027.
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. JACC 2013;61:1388-1395.
Oikonomou EK, Marwan M, Desai MY, et al. Non-invasive detection of coronary inflammation using computed tomography and prediction of residual cardiovascular risk (the CRISP CT study): a post-hoc analysis of prospective outcome data. Lancet 2018;392:929-939.
Klüner LV, Oikonomou EK, Antoniades C. Assessing cardiovascular risk by using the fat attenuation index in coronary CT angiography. Radiol Cardiothorac Imaging. 2021;3(1):e200563.
Koethe JR, Lagathu C, Lake JE, et al. HIV and antiretroviral therapy-related fat alterations. Nat Rev Dis Primers. 2020;6:48.
Schafer JJ, Sassa KN, O'Connor JR, Shimada A, Keith SW, DeSimone JA. Changes in body mass index and atherosclerotic disease risk score after switching from tenofovir disoproxil fumarate to tenofovir alafenamide. Open Forum Infect Dis. 2019;6:ofz414.
Sax PE, Erlandson KM, Lake JE, et al. Weight gain following initiation of antiretroviral therapy: risk factors in randomized comparative clinical trials. Clin Infect Dis 2020;71:1379.
Glidden DV, Mulligan K, McMahan V, et al. Metabolic effects of preexposure prophylaxis with coformulatedtenofovirdisoproxil fumarate and emtricitabine. Clin Infect Dis 2018;67:411-419.
Fiorenza CG, Chou SH, Mantzoros CS. Lipodystrophy: pathophysiology and advances in treatment. Nat Rev Endocrinol. 2011;7:137-150.
Natsag J, Erlandson KM, Sellmeyer DE, et al. HIV infection is associated with increased fatty infiltration of the thigh muscle with aging independent of fat distribution. PLoS One 2017;12:e0169184.
Guaraldi G, Lonardo A, Maia L, Palella FJ Jr. Metabolic concerns in aging HIV-infected persons: from serum lipid phenotype to fatty liver. AIDS 2017;31(Suppl 2):S147-S156.
Guaraldi G, Scaglioni R, Zona S, et al. Epicardial adipose tissue is an independent marker of cardiovascular risk in HIV-infected patients. AIDS 2011;25:1199-1205.
Zona S, Raggi P, Bagni P, et al. Parallel increase of subclinical atherosclerosis and epicardial adipose tissue in patients with HIV. Am Heart J 2012;163:1024-1030.
Longenecker CT, Jiang Y, Yun C-H, et al. Perivascular fat, inflammation, and cardiovascular risk in HIV-infected patients on antiretroviral therapy. Int J Cardiol 2013;168:4039-4045.
Knudsen AD, Krebs-Demmer L, Bjørge NID, et al. Pericardial adipose tissue volume is independently associated with human immunodeficiency virus status and prior use of stavudine, didanosine, or indinavir. J Infect Dis 2020;222:54-61.
Diaz-Zamudio M, Dey D, LaBounty T, et al. Increased pericardial fat accumulation is associated with increased intramyocardial lipid content and duration of highly active antiretroviral therapy exposure in patients infected with human immunodeficiency virus: a 3T cardiovascular magnetic resonance feasibility study. J Cardiovasc Magn Reson 2015;17:91.
Srinivasa S, Lu MT, Fitch KV, et al. Epicardial adipose tissue volume and cardiovascular risk indices among asymptomatic women with and without HIV. Antivir Ther 2018;23:1-9.
Luetkens JA, Doerner J, Schwarze-Zander C, et al. Cardiac magnetic resonance reveals signs of subclinical myocardial inflammation in asymptomatic HIV-infected patients. Circ Cardiovasc Imaging 2016;9:e004091.
Song G, Qiao W, Sun L, Yu X. A meta-analysis of different types of cardiac adipose tissue in HIV patients. BioMed Res Int 2020;2020:8234618.
Longenecker CT, Margevicius S, Liu Y, et al. Effect of pericardial fat volume and density on markers of insulin resistance and inflammation in patients with human immunodeficiency virus infection. Am J Cardiol 2017;120:1427-1433.
Chen M, Hung CL, Yun CH, Webel AR, Longenecker CT. Sex differences in the association of fat and inflammation among people with treated HIV infection. Pathog Immun. 2019;4:163-179.
Brener M, Ketlogetswe K, Budoff M, et al. Epicardial fat is associated with duration of antiretroviral therapy and coronary atherosclerosis. AIDS 2014;28:1635-1644.
Iacobellis G, Pellicelli AM, Sharma AM, Grisorio B, Barbarini G, Barbaro G. Relation of subepicardial adipose tissue to carotid intima-media thickness in patients with human immunodeficiency virus. Am J Cardiol 2007;99:1470-1472.
Marsico F, Lo Vecchio A, Paolillo S, et al. Left ventricular function, epicardial adipose tissue, and carotid intima-media thickness in children and adolescents with vertical HIV infection. J Acquir Immune Defic Syndr 2019;82:462-467.
Kristoffersen US, Lebech AM, Wiinberg N, et al. Silent ischemic heart disease and pericardial fat volume in HIV-infected patients: a case-control myocardial perfusion scintigraphy study. PLoS One 2013;8:e72066.
Raggi P, Zona S, Scaglioni R, et al. Epicardial adipose tissue and coronary artery calcium predict incident myocardial infarction and death in HIV-infected patients. J CardiovascComputTomogr. 2015;9:553-558.
Iantorno M, Soleimanifard S, Schär M, et al. Regional coronary endothelial dysfunction is related to the degree of local epicardial fat in people with HIV. Atherosclerosis 2018;278:7-14.
Buggey J, Yun L, Hung CL, et al. HIV and pericardial fat are associated with abnormal cardiac structure and function among Ugandans. Heart 2020;106:147-153.
Fourman LT, Lu MT, Lee H, et al. Differential relationships of hepatic and epicardial fat to body composition in HIV. Physiol Rep. 2017;5:e13386.
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;24:2127-2130.
Cannavale G, Francone M, Galea N, et al. Fatty images of the heart: spectrum of normal and pathological findings by computed tomography and cardiac magnetic resonance imaging. Biomed Res Int 2018;2018:5610347.
Neilan TG, Nguyen KL, Zaha VG, et al. Myocardial steatosis among antiretroviral therapy-treated people with human immunodeficiency virus participating in the REPRIEVE Trial. J Infect Dis 2020;222:S63-S69.
Holloway CJ, Ntusi N, Suttie J, et al. Comprehensive cardiac magnetic resonance imaging and spectroscopy reveal a high burden of myocardial disease in HIV patients. Circulation 2013;128:814-822.
Chew KW, Liu CY, Ambale-Venkatesh B, et al. Subclinical myocardial disease by cardiac magnetic resonance imaging and spectroscopy in healthy HIV/Hepatitis C virus-coinfected persons. J Int Med Res 2017;45:1693-1707.
Nelson MD, Szczepaniak LS, LaBounty TM, et al. Cardiac steatosis and left ventricular dysfunction in HIV-infected patients treated with highly active antiretroviral therapy. JACC Cardiovasc Imaging 2014;7:1175-1177.
Thiara DK, Liu CY, Raman F, et al. Abnormal myocardial function is related to myocardial steatosis and diffuse myocardial fibrosis in HIV-infected adults. J Infect Dis 2015;212:1544-1551.
Toribio M, Neilan TG, Awadalla M, et al. Intramyocardial triglycerides among women with vs without HIV: hormonal correlates and functional consequences. J Clin Endocrinol Metab 2019;104:6090-6100.
Lai S, Gerstenblith G, Moore RD, et al. Cocaine use may modify HIV/ART-associated myocardial steatosis and hepatic steatosis. Drug Alcohol Depend 2017;177:84-92.
Saco-Ledo G, Valenzuela PL, Castillo-García A, et al. Physical exercise and epicardial adipose tissue: a systematic review and meta-analysis of randomized controlled trials. Obes Rev 2021;22:e13103.
Launbo N, Zobel EH, von Scholten BJ, Faerch K, Jørgensen PG, Christensen RH. Targeting epicardial adipose tissue with exercise, diet, bariatric surgery or pharmaceutical interventions: A systematic review and meta-analysis. Obes Rev 2021;22:e13136.
Raggi P, Gadiyaram V, Zhang C, Chen Z, Lopaschuk G, Stillman AE. Statins reduce epicardial adipose tissue attenuation independent of lipid lowering: a potential pleiotropic effect. J Am Heart Assoc 2019;8:e013104.
vanEyk HJ, Paiman EHM, Bizino MB, et al. A double-blind, placebo controlled, randomised trial to assess the effect of liraglutide on ectopic fat accumulation in South Asian type 2 diabetes patients. CardiovascDiabetol. 2019;18:1-12.
Lima-Martínez MM, Paoli M, Rodney M, et al. Effect of sitagliptin on epicardial fat thickness in subjects with type 2 diabetes and obesity: a pilot study. Endocrine 2016;51:448-455.
Iacobellis G, Gra-Menendez S. Effects of dapagliflozin on epicardial fat thickness in patients with type 2 diabetes and obesity. Obesity (Silver Spring). 2020;28:1068-1074.
Gandoy-Fieiras N, Gonzalez-Juanatey JR, Eiras S. Myocardium metabolism in physiological and pathophysiological states: implications of epicardial adipose tissue and potential therapeutic targets. Int J Mol Sci 2020;21:2641.
Rider OJ, Francis JM, Tyler D, Byrne J, Clarke K, Neubauer S. Effects of weight loss on myocardial energetics and diastolic function in obesity. Int J CardiovascImag. 2013;29:1043-1050.
Utz W, Engeli S, Haufe S, et al. Moderate dietary weight loss reduces myocardial steatosis in obese and overweight women. Int J Cardiol 2013;167:905-909.
Cope RJ, Fischetti BS, Kavanagh RK, Lepa TM, Sorbera MA. Safety and efficacy of weight-loss pharmacotherapy in persons living with HIV: a review of the literature and potential drug-drug interactions with antiretroviral therapy. Pharmacotherapy 2019;39:1204-1215.
Scherzer R, Heymsfield SB, Lee D, et al. Decreased limb muscle and increased central adiposity are associated with 5-year all-cause mortality in HIV infection. AIDS 2011;25:1405-1414.
Lake JE, Stanley TL, Apovian CM, et al. Practical review of recognition and management of obesity and lipohypertrophy in human immunodeficiency virus infection. Clin Infect Dis 2017;64:1422-1429.
Godfrey C, Bremer A, Alba D, et al. Obesity and fat metabolism in human immunodeficiency virus-infected individuals: immunopathogenic mechanisms and clinical implications. J Infect Dis 2019;220:420-431.
Mulligan K, Khatami H, Schwarz JM, et al. The effects of recombinant human leptin on visceral fat, dyslipidemia, and insulin resistance in patients with human immunodeficiency virus-associated lipoatrophy and hypoleptinemia. J Clin Endocrinol Metab 2009;94:1137-1144.
Kohli R, Shevitz A, Gorbach S, Wanke C. A randomized placebo-controlled trial of metformin for the treatment of HIV lipodystrophy. HIV Med. 2007;8:420-426.
Stanley TL, Falutz J, Mamputu JC, Soulban G, Potvin D, Grinspoon SK. Effects of tesamorelin on inflammatory markers in HIV patients with excess abdominal fat: relationship with visceral adipose reduction. AIDS 2011;25:1281-1288.
Falutz J, Mamputu JC, Potvin D, et al. Effects of tesamorelin (TH9507), a growth hormone-releasing factor analog, in human immunodeficiency virus-infected patients with excess abdominal fat: a pooled analysis of two multicenter, double-blind placebo-controlled phase 3 trials with safety extension data. J Clin Endocrinol Metab 2010;95:4291-4304.
Stanley TL, Falutz J, Marsolais C, et al. Reduction in visceral adiposity is associated with an improved metabolic profile in HIV-infected patients receiving tesamorelin. Clin Infect Dis 2012;54:1642-1651.
Grinspoon SK, Fitch KV, Overton ETurner, et al. Rationale and design of the Randomized Trial to Prevent Vascular Events in HIV (REPRIEVE). Am Heart J 2019; 212: 23-35.
Funderburg NT, Funderburg NT, Jiang Y, et al. Rosuvastatin reduces vascular inflammation and T-cell and monocyte activation in HIV-infected subjects on antiretroviral therapy. J Acquir Immune Defic Syndr 2015;68:396-404.
Best C, Struthers H, Laciny E, Royal M, Reeds DN, Yarasheski KE. Sitagliptin reduces inflammation and chronic immune cell activation in HIV+ adults with impaired glucose tolerance. J Clin Endocrinol Metab 2015;100:2621-2629.
Hsue PY, Ribaudo HJ, Deeks SG, et al. Safety and impact of low-dose methotrexate on endothelial function and inflammation in individuals with treated human immunodeficiency virus: AIDS Clinical Trials Group Study A5314. Clin Infect Dis 2019;68:1877-1886.
Stein JH, Yeh E, Weber JM, et al. Brachial artery echogenicity and grayscale texture changes in HIV-infected individuals receiving low-dose methotrexate. Arterioscler Thromb Vasc Biol 2018;38:2870-2878.
Hsue PY, Li D, Ma Y, et al. IL-1beta inhibition reduces atherosclerotic inflammation in HIV infection. J Am Coll Cardiol 2018;72:2809-2811.