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Canadian Journal of Cardiology

Noninvasive Cardiovascular Imaging: Emergence of a Powerful Tool for Early Identification of Cardiovascular Risk in People Living With HIV

Published:December 17, 2018DOI:https://doi.org/10.1016/j.cjca.2018.11.036

      Abstract

      Antiretroviral therapy (ART) has been pivotal in prolonging the lifespan of people living with HIV (PLWH). However, this also simultaneously increases their risk of cardiovascular disease (CVD) either related to ART, aging, hypertension, immunosenescence, inflammation, immune activation, or other comorbidities. Although the use of risk markers has greatly enhanced the field of cardiovascular (CV) medicine and improved the prognosis and early diagnosis in the general population, this strategy has not been clearly elucidated in PLWH. Developing accurate risk algorithms for PLWH requires an innate understanding of mechanistic factors influencing their risks. Early identification of CV risk will significantly enhance the prospects of PLWH living longer and relatively healthily. Herein, we discuss the use of multimodality noninvasive CV imaging as robust markers for ameliorating CV risk. The ability to prognosticate CV risk and hence prevent CV events in PLWH would represent an important advance in CV medicine, allowing precise detection and early institution of preventative strategies. Using novel CV imaging modalities and strategies would have a positive impact on precision medicine in this patient cohort.

      Résumé

      La thérapie antirétrovirale (TAR) joue un rôle central dans la prolongation de l’espérance de vie des personnes vivant avec le VIH. Toutefois, ce traitement a également pour effet d’accroître le risque de maladie cardiovasculaire (CV) dans cette population, que ce soit en lien avec la TAR ou avec le vieillissement, l’hypertension, l’immunosénescence, l’inflammation, l’activation du système immunitaire ou d’autres affections concomitantes. Si le recours aux marqueurs de risques a permis un rehaussement important du domaine de la médecine CV et une amélioration du pronostic et du diagnostic précoce dans la population générale, cette stratégie n’a pas encore fait ses preuves chez les personnes vivant avec le VIH. Pour élaborer des algorithmes de risque exacts pour les personnes vivant avec le VIH, il faut avoir une connaissance approfondie des facteurs mécanistiques influençant les risques auxquels cette population est exposée. La reconnaissance précoce des risques CV augmentera de façon marquée la probabilité pour les personnes vivant avec le VIH de vivre plus longtemps et, relativement, en meilleure santé. Dans le présent article, nous abordons l’utilisation de l’imagerie CV multimodale non invasive comme marqueur robuste pour réduire le risque CV. La capacité de pronostiquer le risque CV et, par conséquent, de prévenir les événements CV chez les personnes vivant avec le VIH constituerait une avancée importante en médecine CV, en permettant une détection précise et l’instauration précoce de stratégies à visée préventive. L’utilisation des nouvelles modalités et stratégies d’imagerie CV pourrait avoir des répercussions positives sur la médecine de précision dans cette cohorte de patients.
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      References

        • Deeks S.G.
        • Lewin S.R.
        • Havlir D.V.
        The end of AIDS: HIV infection as a chronic disease.
        Lancet. 2013; 382: 1525-1533
        • Freiberg M.S.
        • Chang C.C.
        • Kuller L.H.
        • et al.
        HIV infection and the risk of acute myocardial infarction.
        JAMA Intern Med. 2013; 173: 614-622
        • Freiberg M.S.
        • Chang C.H.
        • Skanderson M.
        • et al.
        Association between HIV infection and the risk of heart failure with reduced ejection fraction and preserved ejection fraction in the antiretroviral therapy era: results from the Veterans Aging Cohort study.
        JAMA Cardiol. 2017; 2: 536-546
        • Triant V.A.
        • Perez J.
        • Regan S.
        • et al.
        Cardiovascular risk prediction functions underestimate risk in HIV infection.
        Circulation. 2018; 137: 2203-2214
        • Friis-Moller N.
        • Thiebaut R.
        • Reiss P.
        • et al.
        Predicting the risk of cardiovascular disease in HIV-infected patients: the data collection on adverse effects of anti-HIV drugs study.
        Eur J Cardiovasc Prev Rehabil. 2010; 17: 491-501
        • Friis-Moller N.
        • Ryom L.
        • Smith C.
        • et al.
        An updated prediction model of the global risk of cardiovascular disease in HIV-positive persons: the data-collection on Adverse Effects of Anti-HIV Drugs (D:A:D) study.
        Eur J Prev Cardiol. 2016; 23: 214-223
        • Raggi P.
        • De Francesco D.
        • Manicardi M.
        • et al.
        Prediction of hard cardiovascular events in HIV patients.
        J Antimicrob Chemother. 2016; 71: 3515-3518
        • Young S.D.
        A “big data” approach to HIV epidemiology and prevention.
        Prev Med. 2015; 70: 17-18
        • Suinesiaputra A.
        • Medrano-Gracia P.
        • Cowan B.R.
        • Young A.A.
        Big heart data: advancing health informatics through data sharing in cardiovascular imaging.
        IEEE J Biomed Health Inform. 2015; 19: 1283-1290
        • Budoff M.J.
        • Raggi P.
        • Beller G.A.
        • et al.
        Noninvasive cardiovascular risk assessment of the asymptomatic diabetic patient: the Imaging Council of the American College of Cardiology.
        JACC Cardiovasc Imaging. 2016; 9: 176-192
        • Deeks S.G.
        • Tracy R.
        • Douek D.C.
        Systemic effects of inflammation on health during chronic HIV infection.
        Immunity. 2013; 39: 633-645
        • Stein J.H.
        • Korcarz C.E.
        • Hurst R.T.
        • et al.
        Use of carotid ultrasound to identify subclinical vascular disease and evaluate cardiovascular disease risk: a consensus statement from the American Society of Echocardiography Carotid Intima-Media Thickness Task Force. Endorsed by the Society for Vascular Medicine.
        J Am Soc Echocardiogr. 2008; 21 (quiz 189-190): 93-111
        • Hsue P.Y.
        • Scherzer R.
        • Hunt P.W.
        • et al.
        Carotid intima-media thickness progression in HIV-infected adults occurs preferentially at the carotid bifurcation and is predicted by inflammation.
        J Am Heart Assoc. 2012; 1
        • Hsue P.Y.
        • Lo J.C.
        • Franklin A.
        • et al.
        Progression of atherosclerosis as assessed by carotid intima-media thickness in patients with HIV infection.
        Circulation. 2004; 109: 1603-1608
        • Phan B.A.P.
        • Weigel B.
        • Ma Y.
        • et al.
        Utility of 2013 American College of Cardiology/American Heart Association Cholesterol Guidelines in HIV-Infected Adults With Carotid Atherosclerosis.
        Circ Cardiovasc Imaging. 2017; 10: e005995
        • Hanna D.B.
        • Post W.S.
        • Deal J.A.
        • et al.
        HIV infection is associated with progression of subclinical carotid atherosclerosis.
        Clin Infect Dis. 2015; 61: 640-650
        • Currier J.S.
        • Kendall M.A.
        • Henry W.K.
        • et al.
        Progression of carotid artery intima-media thickening in HIV-infected and uninfected adults.
        AIDS. 2007; 21: 1137-1145
        • Janjua S.A.
        • Staziaki P.V.
        • Szilveszter B.
        • et al.
        Presence, characteristics, and prognostic associations of carotid plaque among people living with HIV.
        Circ Cardiovasc Imaging. 2017; 10: e005777
        • Lucas G.M.
        • Atta M.G.
        • Fine D.M.
        • et al.
        HIV, cocaine use, and hepatitis C virus: a triad of nontraditional risk factors for subclinical cardiovascular disease.
        Arterioscler Thromb Vasc Biol. 2016; 36: 2100-2107
        • Rose K.A.
        • Vera J.H.
        • Drivas P.
        • et al.
        Atherosclerosis is evident in treated HIV-infected subjects with low cardiovascular risk by carotid cardiovascular magnetic resonance.
        J AIDS. 2016; 71: 514-521
        • Durand M.
        • Sheehy O.
        • Baril J.G.
        • Lelorier J.
        • Tremblay C.L.
        Association between HIV infection, antiretroviral therapy, and risk of acute myocardial infarction: a cohort and nested case-control study using Quebec's public health insurance database.
        J AIDS. 2011; 57: 245-253
        • Triant V.A.
        • Lee H.
        • Hadigan C.
        • Grinspoon S.K.
        Increased acute myocardial infarction rates and cardiovascular risk factors among patients with human immunodeficiency virus disease.
        J Clin Endocrinol Metab. 2007; 92: 2506-2512
        • Obel N.
        • Thomsen H.F.
        • Kronborg G.
        • et al.
        Ischemic heart disease in HIV-infected and HIV-uninfected individuals: a population-based cohort study.
        Clin Infect Dis. 2007; 44: 1625-1631
        • Lang S.
        • Mary-Krause M.
        • Cotte L.
        • et al.
        Increased risk of myocardial infarction in HIV-infected patients in France, relative to the general population.
        AIDS. 2010; 24: 1228-1230
        • Silverberg M.J.
        • Leyden W.A.
        • Xu L.
        • et al.
        Immunodeficiency and risk of myocardial infarction among HIV-positive individuals with access to care.
        J AIDS. 2014; 65: 160-166
        • Hecht H.S.
        Coronary artery calcium scanning: past, present, and future.
        JACC Cardiovasc Imaging. 2015; 8: 579-596
        • 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 Cardiovasc Comput Tomogr. 2015; 9: 553-558
        • Choi E.K.
        • Choi S.I.
        • Rivera J.J.
        • et al.
        Coronary computed tomography angiography as a screening tool for the detection of occult coronary artery disease in asymptomatic individuals.
        J Am Coll Cardiol. 2008; 52: 357-365
        • D'Ascenzo F.
        • Cerrato E.
        • Calcagno A.
        • et al.
        High prevalence at computed coronary tomography of non-calcified plaques in asymptomatic HIV patients treated with HAART: a meta-analysis.
        Atherosclerosis. 2015; 240: 197-204
        • Kristoffersen U.S.
        • Lebech A.M.
        • 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; 8e72066
        • Virmani R.
        • Kolodgie F.D.
        • Burke A.P.
        • Farb A.
        • Schwartz S.M.
        Lessons from sudden coronary death: a comprehensive morphological classification scheme for atherosclerotic lesions.
        Arterioscler Thromb Vasc Biol. 2000; 20: 1262-1275
        • Kolodgie F.D.
        • Virmani R.
        • Burke A.P.
        • et al.
        Pathologic assessment of the vulnerable human coronary plaque.
        Heart. 2004; 90: 1385-1391
        • Leber A.W.
        • Knez A.
        • Becker A.
        • et al.
        Accuracy of multidetector spiral computed tomography in identifying and differentiating the composition of coronary atherosclerotic plaques: a comparative study with intracoronary ultrasound.
        J Am Coll Cardiol. 2004; 43: 1241-1247
        • Motoyama S.
        • Sarai M.
        • Harigaya H.
        • et al.
        Computed tomographic angiography characteristics of atherosclerotic plaques subsequently resulting in acute coronary syndrome.
        J Am Coll Cardiol. 2009; 54: 49-57
        • Zanni M.V.
        • Abbara S.
        • Lo J.
        • et al.
        Increased coronary atherosclerotic plaque vulnerability by coronary computed tomography angiography in HIV-infected men.
        AIDS. 2013; 27: 1263-1272
        • Burdo T.H.
        • Lo J.
        • Abbara S.
        • et al.
        Soluble CD163, a novel marker of activated macrophages, is elevated and associated with noncalcified coronary plaque in HIV-infected patients.
        J Infect Dis. 2011; 204: 1227-1236
      1. Post W, Haberlen S, Zhang L, et al. HIV infection is associated with progression of high risk coronary plaques in the MACS (Abstract no.77). Conference on Retroviruses and Opportunistic Infections (CROI) 2018. Boston, Massachusetts; 2018.

        • Fitch K.V.
        • Lo J.
        • Abbara S.
        • et al.
        Increased coronary artery calcium score and noncalcified plaque among HIV-infected men: relationship to metabolic syndrome and cardiac risk parameters.
        J AIDS. 2010; 55: 495-499
        • Foldyna B.
        • Fourman L.T.
        • Lu M.T.
        • et al.
        Sex differences in subclinical coronary atherosclerotic plaque among individuals with HIV on antiretroviral therapy.
        J AIDS. 2018; 78: 421-428
        • Lai H.
        • Moore R.
        • Celentano D.D.
        • et al.
        HIV infection itself may not be associated with subclinical coronary artery disease among African Americans without cardiovascular symptoms.
        J Am Heart Assoc. 2016; 5e002529
        • Lo J.
        • Abbara S.
        • Shturman L.
        • et al.
        Increased prevalence of subclinical coronary atherosclerosis detected by coronary computed tomography angiography in HIV-infected men.
        AIDS. 2010; 24: 243-253
        • Miller P.E.
        • Haberlen S.A.
        • Metkus T.
        • et al.
        HIV and coronary arterial remodeling from the Multicenter AIDS Cohort Study (MACS).
        Atherosclerosis. 2015; 241: 716-722
        • Post W.S.
        • Budoff M.
        • Kingsley L.
        • et al.
        Associations between HIV infection and subclinical coronary atherosclerosis.
        Ann Intern Med. 2014; 160: 458-467
        • Tarr P.E.
        • Ledergerber B.
        • Calmy A.
        • et al.
        Subclinical coronary artery disease in Swiss HIV-positive and HIV-negative persons.
        Eur Heart J. 2018; 39: 2147-2154
        • Rudd J.H.
        • Myers K.S.
        • Bansilal S.
        • et al.
        (18)Fluorodeoxyglucose positron emission tomography imaging of atherosclerotic plaque inflammation is highly reproducible: implications for atherosclerosis therapy trials.
        J Am Coll Cardiol. 2007; 50: 892-896
        • Figueroa A.L.
        • Abdelbaky A.
        • Truong Q.A.
        • et al.
        Measurement of arterial activity on routine FDG PET/CT images improves prediction of risk of future CV events.
        JACC Cardiovasc Imaging. 2013; 6: 1250-1259
        • Law M.G.
        • Friis-Moller N.
        • El-Sadr W.M.
        • et al.
        The use of the Framingham equation to predict myocardial infarctions in HIV-infected patients: comparison with observed events in the D:A:D Study.
        HIV Med. 2006; 7: 218-230
        • Subramanian S.
        • Tawakol A.
        • Burdo T.H.
        • et al.
        Arterial inflammation in patients with HIV.
        JAMA. 2012; 308: 379-386
        • Tawakol A.
        • Lo J.
        • Zanni M.V.
        • et al.
        Increased arterial inflammation relates to high-risk coronary plaque morphology in HIV-infected patients.
        J AIDS. 2014; 66: 164-171
        • Zanni M.V.
        • Toribio M.
        • Robbins G.K.
        • et al.
        Effects of antiretroviral therapy on immune function and arterial inflammation in treatment-naive patients with human immunodeficiency virus infection.
        JAMA Cardiol. 2016; 1: 474-480
        • Ntsekhe M.
        • Mayosi B.M.
        Cardiac manifestations of HIV infection: an African perspective.
        Nat Clin Pract Card. 2009; 6: 120-127
        • Paulus W.J.
        • Tschope C.
        A novel paradigm for heart failure with preserved ejection fraction: comorbidities drive myocardial dysfunction and remodeling through coronary microvascular endothelial inflammation.
        J Am Coll Cardiol. 2013; 62: 263-271
        • Hsue P.Y.
        • Hunt P.W.
        • Ho J.E.
        • et al.
        Impact of HIV infection on diastolic function and left ventricular mass.
        Circ Heart Fail. 2010; 3: 132-139
        • Remick J.
        • Georgiopoulou V.
        • Marti C.
        • et al.
        Heart failure in patients with human immunodeficiency virus infection: epidemiology, pathophysiology, treatment, and future research.
        Circulation. 2014; 129: 1781-1789
        • Butler J.
        • Kalogeropoulos A.P.
        • Anstrom K.J.
        • et al.
        Diastolic dysfunction in individuals with human immunodeficiency virus infection: literature review, rationale and design of the Characterizing Heart function on Antiretroviral Therapy (CHART) Study.
        J Card Fail. 2018; 24: 255-265
        • Galie N.
        • Humbert M.
        • Vachiery J.L.
        • et al.
        2015 ESC/ERS Guidelines for the diagnosis and treatment of pulmonary hypertension: the Joint Task Force for the Diagnosis and Treatment of Pulmonary Hypertension of the European Society of Cardiology (ESC) and the European Respiratory Society (ERS): Endorsed by: Association for European Paediatric and Congenital Cardiology (AEPC), International Society for Heart and Lung Transplantation (ISHLT).
        Eur Heart J. 2016; 37: 67-119
        • Wever Pinzon O.
        • Silva Enciso J.
        • Romero J.
        • et al.
        Risk stratification and prognosis of human immunodeficiency virus-infected patients with known or suspected coronary artery disease referred for stress echocardiography.
        Circ Cardiovasc Imaging. 2011; 4: 363-370
        • Wever-Pinzon O.
        • Bangalore S.
        • Romero J.
        • Silva Enciso J.
        • Chaudhry F.A.
        Inotropic contractile reserve can risk-stratify patients with HIV cardiomyopathy: a dobutamine stress echocardiography study.
        JACC Cardiovasc Imaging. 2011; 4: 1231-1238
        • Butt A.A.
        • Chang C.C.
        • Kuller L.
        • et al.
        Risk of heart failure with human immunodeficiency virus in the absence of prior diagnosis of coronary heart disease.
        Arch Intern Med. 2011; 171: 737-743
        • Moon J.C.
        • Messroghli D.R.
        • Kellman P.
        • et al.
        Myocardial T1 mapping and extracellular volume quantification: a Society for Cardiovascular Magnetic Resonance (SCMR) and CMR Working Group of the European Society of Cardiology consensus statement.
        J Cardiovasc Magn Reson. 2013; 15: 92
        • Holloway C.J.
        • 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
        • Anderson D.W.
        • Virmani R.
        • Reilly J.M.
        • et al.
        Prevalent myocarditis at necropsy in the acquired immunodeficiency syndrome.
        J Am Coll Cardiol. 1988; 11: 792-799
        • Puntmann V.O.
        • Peker E.
        • Chandrashekhar Y.
        • Nagel E.
        T1 Mapping in characterizing myocardial disease: a comprehensive review.
        Circ Res. 2016; 119: 277-299
        • Thiara D.K.
        • Liu C.Y.
        • 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
        • Howard L.C.
        • Liu C.Y.
        • Purdy J.B.
        • Walter P.
        • Bluemke D.A.
        • Hadigan C.
        Lipolytic rate associated with intramyocardial lipid in an HIV cohort without increased lipolysis.
        J Clin Endocrinol Metab. 2016; 101: 151-156
        • Luetkens J.A.
        • 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; 9e004091
        • Ntusi N.
        • O'Dwyer E.
        • Dorrell L.
        • et al.
        HIV-1-related cardiovascular disease is associated with chronic inflammation, frequent pericardial effusions, and probable myocardial edema.
        Circ Cardiovasc Imaging. 2016; 9e004430
        • Catzin-Kuhlmann A.
        • Orea-Tejeda A.
        • Castillo-Martinez L.
        • et al.
        Human immunodeficiency virus-infected subjects have no altered myocardial perfusion.
        Int J Cardiol. 2007; 122: 90-92
        • Mariano-Goulart D.
        • Jacquet J.M.
        • Molinari N.
        • et al.
        Should HIV-infected patients be screened for silent myocardial ischaemia using gated myocardial perfusion SPECT?.
        Eur J Nucl Med Mol Imaging. 2013; 40: 271-279
        • Knudsen A.
        • Christensen T.E.
        • Ghotbi A.A.
        • et al.
        Normal myocardial flow reserve in HIV-infected patients on stable antiretroviral therapy: a cross-sectional study using Rubidium-82 PET/CT.
        Medicine (Baltimore). 2015; 94e1886