Current Atherosclerosis Reports

, Volume 12, Issue 2, pp 119–124 | Cite as

The Spectrum of Atherosclerotic Coronary Artery Disease in HIV Patients



The incidence of HIV is on the rise. With the advent of antiretroviral therapy, the average life expectancy of HIV patients has increased by several decades, but the increasing life expectancy has shifted the spectrum of HIV-associated morbidity and mortality away from opportunistic infections and toward chronic medical conditions. In fact, coronary artery disease has become the leading cause of mortality in patients with HIV. The pathophysiology of atherosclerosis in patients with HIV is very complex, including direct endothelial damage from viremia, a heightened overall state of inflammation from immune activation, higher prevalence and contribution from traditional atherosclerotic risk factors, and direct effects from antiretroviral therapy itself. This review focuses on the patterns, predictors, and pathophysiology of atherosclerotic disease in patients with HIV. In addition, the risks and benefits of evidence-based highly active antiretroviral therapy are critically evaluated.


HIV Atherosclerosis Coronary artery disease Highly Active Anti Retroviral Theraphy (HAART) 



No potential conflicts of interest relevant to this article were reported.


Papers of particular interest, published recently, have been highlighted as: •• Of major importance

  1. 1.
    Grinspoon SK, Grunfeld C, Kotler DP, et al.: State of the science conference: initiative to decrease cardiovascular risk and increase quality of care for patients living with HIV/AIDS: executive summary. Circulation 2008, 118:198–210.CrossRefPubMedGoogle Scholar
  2. 2.
    Grinspoon S, Carr A: Cardiovascular risk and body fat abnormalities in HIV-infected adults. N Engl J Med 2005, 352:48–62.CrossRefPubMedGoogle Scholar
  3. 3.
    Ho JE, Hsue PY: Cardiovascular manifestations of HIV infection. Heart 2009, 95:1193–1202.CrossRefPubMedGoogle Scholar
  4. 4.
    Palella FJ Jr, Delaney KM, Moorman AC, et al., for HIV Outpatient Study Investigators: Declining morbidity and mortality among patients with advanced human immunodeficiency virus infection. N Engl J Med 1998, 338:853–860.CrossRefPubMedGoogle Scholar
  5. 5.
    Currier JS, Lundgren JD, Carr A, et al.: Epidemiological evidence for cardiovascular disease in HIV-infected patients and relationship to highly active antiretroviral therapy. Circulation 2008, 118:e29–35.CrossRefPubMedGoogle Scholar
  6. 6.
    Hsue PY, Squires K, Bolger AF, et al.: Screening and assessment of coronary heart disease in HIV-infected patients. Circulation 2008, 118:e41–47.CrossRefPubMedGoogle Scholar
  7. 7.
    Currier JS, Taylor A, Boyd F, et al.: Coronary heart disease in HIV-infected individuals. J Acquir Immune Defic Syndr 2004, 33:506–512.Google Scholar
  8. 8.
    Triant VA, Lee H, Hadigan C, Grinspoon SK: Increased acute myocardial infarction rates and cardiovascular risk factors among patients with human immunodeficiency virus disease. J Clin Endocrinol Metab 2007, 92:2506–2512.CrossRefPubMedGoogle Scholar
  9. 9.
    Klein D, Hurley L, Quesenberry CB, et al.: Do protease inhibitors increase the risk for coronary heart disease in patients with HIV-1 infection? JAIDS 2002, 30:471–477.PubMedGoogle Scholar
  10. 10.
    Tabib A, Leroux C, Mornex JF, et al.: Accelerated coronary atherosclerosis and arteriosclerosis in young human-immunodeficiency-virus-positive patients. Coron Artery Dis 2000, 11:41–46.CrossRefPubMedGoogle Scholar
  11. 11.
    Micheletti RG, Fishbein GA, Fishbein MC, et al.: Coronary atherosclerotic lesions in human immunodeficiency virus-infected patients: a histopathologic study. Cardiovasc Pathol 2008, 17:117–1123.CrossRefPubMedGoogle Scholar
  12. 12.
    Mehta NJ, Khan IA: HIV-associated coronary artery disease. Angiology 2003, 54:269–275.CrossRefPubMedGoogle Scholar
  13. 13.
    Stein JH, Hadigan CM, Brown TT, et al., for Working Group 6: Prevention strategies for cardiovascular disease in HIV-infected patients. Circulation 2008, 118:e54–e60.CrossRefPubMedGoogle Scholar
  14. 14.
    Savès M, Chêne G, Ducimetière P, et al., for the French WHO MONICA Project and the APROCO (ANRS EP11) Study Group: Risk factors for coronary heart disease in patients treated for human immunodeficiency virus infection compared with the general population. Clin Infect Dis 2003, 37:292–298.CrossRefPubMedGoogle Scholar
  15. 15.
    Gritz ER, Vidrine DJ, Lazev AB, et al.: Smoking behavior in a low-income multiethnic HIV/AIDS population. Nicotine Tob Res 2004, 6:71–77.CrossRefPubMedGoogle Scholar
  16. 16.
    Kaplan RC, Kingsley LA, Sharrett AR, et al.: Ten-year predicted coronary heart disease risk in HIV-infected men and women. Clin Infect Dis 2007, 45:1074–1081.CrossRefPubMedGoogle Scholar
  17. 17.
    Tien PC, Schneider MF, Cole SR, et al.: Antiretroviral therapy exposure and incidence of diabetes mellitus in the Women’s Interagency HIV Study. AIDS 2007, 21:1739–1745.CrossRefPubMedGoogle Scholar
  18. 18.
    Hadigan C: Diabetes, insulin resistance, and HIV. Curr Infect Dis Rep 2006, 8:69–75.CrossRefPubMedGoogle Scholar
  19. 19.
    Visnegarwala F, Chen L, Raghavan S, Tedaldi E: Prevalence of diabetes mellitus and dyslipidemia among antiretroviral naive patients co-infected with hepatitis C virus (HCV) and HIV-1 compared to patients without co-infection. J Infect 2005, 50:331–337.CrossRefPubMedGoogle Scholar
  20. 20.
    Hansson GK: Inflammation, atherosclerosis, and coronary artery disease. N Engl J Med 2005, 352:1685–1695.CrossRefPubMedGoogle Scholar
  21. 21.
    Dubé MP, Lipshultz SE, Fichtenbaum CJ, et al.: Working Group 3: Effects of HIV infection and antiretroviral therapy on the heart and vasculature. Circulation 2008, 118:e36–e40.CrossRefPubMedGoogle Scholar
  22. 22.
    Solages A, Vita JA, Thornton DJ, et al.: Endothelial function in HIV-infected persons. Clin Infect Dis 2006, 42:1325–1332.CrossRefPubMedGoogle Scholar
  23. 23.
    Seigneur M, Constans J, Blann A, et al.: Soluble adhesion molecules and endothelial cell damage in HIV infected patients. Thromb Haemost 1997, 77:646–649.PubMedGoogle Scholar
  24. 24.
    Melendez MM, McNurlan MA, Mynarcik DC, et al.: Endothelial adhesion molecules are associated with inflammation in subjects with HIV disease. Clin Infect Dis 2008, 46:775–780.CrossRefPubMedGoogle Scholar
  25. 25.
    Ehrenreich H, Rieckmann P, Sinowatz F, et al.: Potent stimulation of monocytic endothelin-1 production by HIV-1 glycoprotein 120. J Immunol 1993, 150:4601–4609.PubMedGoogle Scholar
  26. 26.
    Baker JV, Peng G, Rapkin J, et al.: CD4+ count and risk of non-AIDS diseases following initial treatment for HIV infection. AIDS 2008, 22:841–848.CrossRefPubMedGoogle Scholar
  27. 27.
    Kaplan RC, Kingsley LA, Gange SJ, et al.: Low CD4+ T-cell count as a major atherosclerosis risk factor in HIV-infected women and men. AIDS 2008, 22:1615–1624.CrossRefPubMedGoogle Scholar
  28. 28.
    Blum A, Hadas V, Burke M, et al.: Viral load of the human immunodeficiency virus could be an independent risk factor for endothelial dysfunction. Clin Cardiol 2005, 28:149–153.CrossRefPubMedGoogle Scholar
  29. 29.
    Hsue PY, Lo JC, Franklin A, et al.: Progression of atherosclerosis as assessed by carotid intima-media thickness in patients with HIV infection. Circulation 2004, 109:1603–1608.CrossRefPubMedGoogle Scholar
  30. 30.
    Carr A, Samaras K, Burton S, et al.: A syndrome of peripheral lipodystrophy, hyperlipidemia and insulin resistance in patients receiving HIV protease inhibitors. AIDS 1998, 12:F51–F58.CrossRefPubMedGoogle Scholar
  31. 31.
    Carr A, Samaras K, Thorisdottir A, et al.: Diagnosis, prediction, and natural course of HIV-1 protease-inhibitor-associated lipodystrophy, hyperlipidaemia, and diabetes mellitus: a cohort study. Lancet 1999, 353:2093–2099.CrossRefPubMedGoogle Scholar
  32. 32.
    Mulligan K, Grunfeld C, Tai VW, et al.: Hyperlipidemia and insulin resistance are induced by protease inhibitors independent of changes in body composition in patients with HIV infection. J Acquir Immune Defic Syndr 2000, 23:35–43.PubMedGoogle Scholar
  33. 33.
    Passalaris JD, Sepkowitz KA, Glesby MJ: Coronary artery disease and human immunodeficiency virus infection. Clin Infect Dis 2000, 31:787–797.CrossRefPubMedGoogle Scholar
  34. 34.
    Friis-Møller N, Reiss P, Sabin CA, et al., for the DAD study group: Class of antiretroviral drugs and the risk of myocardial infarction. N Engl J Med 2007, 356:1723–1735.CrossRefPubMedGoogle Scholar
  35. 35.
    D:A:D Study Group: Use of nucleoside reverse transcriptase inhibitors and risk of myocardial infarction in HIV-infected patients enrolled in the D:A:D study: a multi-cohort collaboration. Lancet 2008, 371:1417–1425.CrossRefGoogle Scholar
  36. 36.
    Triant VA, Lee H, Hadigan C, Grinspoon SK: Increased acute myocardial infarction rates and cardiovascular risk factors among patients with human immunodeficiency virus disease. J Clin Endocrinol Metab 2007, 92: 2506–2512.CrossRefPubMedGoogle Scholar
  37. 37.
    Stein JH: Cardiovascular risks of antiretroviral therapy. N Engl J Med 2007, 356:1773–1775.CrossRefPubMedGoogle Scholar
  38. 38.
    D:A:D Study Group: Lipid profiles in HIV-infected patients receiving combination antiretroviral therapy: are different antiretroviral drugs associated with different lipid profiles? J Infect Dis 2004, 189:1056–1074.CrossRefGoogle Scholar
  39. 39.
    Bastard JP, Caron M, Vidal H, et al.: Association between altered expression of adipogenic factor SREBP1 in lipoatrophic adipose tissue from HIV-1-infected patients and abnormal adipocyte differentiation and insulin resistance. Lancet 2002, 359:1026–1031.CrossRefPubMedGoogle Scholar
  40. 40.
    Caron M, Auclair M, Vigouroux C, et al.: The HIV protease inhibitor indinavir impairs sterol regulatory element-binding protein-1 intranuclear localization, inhibits preadipocyte differentiation, and induces insulin resistance. Diabetes 2001, 50:1378–1388.CrossRefPubMedGoogle Scholar
  41. 41.
    Shankar SS, Dubé MP, Gorski JC, et al.: Indinavir impairs endothelial function in healthy HIV-negative men. Am Heart J 2005, 150:933.e1–933.e37.CrossRefGoogle Scholar
  42. 42.
    Fu W, Chai H, Yao Q, et al.: Effects of HIV protease inhibitor ritonavir on vasomotor function and endothelial nitric oxide synthase expression. J Acquir Immune Defic Syndr 2005, 39:152–158.PubMedGoogle Scholar
  43. 43.
    Baliga RS, Liu C, Hoyt DG, et al.: Vascular endothelial toxicity induced by HIV protease inhibitor: evidence of oxidant-related dysfunction and apoptosis. Cardiovasc Toxicol 2004, 4:199–206.CrossRefPubMedGoogle Scholar
  44. 44.
    •• Wang X, Chai H, Yao Q, Chen C: Molecular mechanisms of HIV protease inhibitor-induced endothelial dysfunction. J Acquir Immune Defic Syndr 2007, 44:493–499. This article outlines the role of ART in endothelial dysfunction.CrossRefPubMedGoogle Scholar
  45. 45.
    Dressman J, Kincer J, Matveev SV, et al.: HIV protease inhibitors promote atherosclerotic lesion formation independent of dyslipidemia by increasing CD36-dependent cholesteryl ester accumulation in macrophages. J Clin Invest 2003, 111:389–397.PubMedGoogle Scholar
  46. 46.
    Sutliff RL, Dikalov S, Weiss D, et al.: Nucleoside reverse transcriptase inhibitors impair endothelium-dependent relaxation by increasing superoxide. Am J Physiol Heart Circ Physiol 2002, 283:H2363–H2370.PubMedGoogle Scholar
  47. 47.
    Sadr WM, Lundgren JD, Neaton JD, et al., for Strategies for Management of Antiretroviral Therapy (SMART) Study Group: El−, CD4+ count-guided interruption of antiretroviral treatment. N Engl J Med 2006, 355:2283–2296.CrossRefPubMedGoogle Scholar
  48. 48.
    Dubé MP, Stein JH, Aberg JA, et al., for Adult AIDS Clinical Trials Group Cardiovascular Subcommittee; HIV Medical Association of the Infectious Disease Society of America: Guidelines for the evaluation and management of dyslipidemia in human immunodeficiency virus (HIV)-infected adults receiving antiretroviral therapy: recommendations of the HIV Medical Association of the Infectious Disease Society of America and the Adult AIDS Clinical Trials Group. Clin Infect Dis 2003, 37:613–627.CrossRefPubMedGoogle Scholar

Copyright information

© Springer Science+Business Media, LLC 2010

Authors and Affiliations

  • Abdul Hakeem
    • 1
  • Sabha Bhatti
    • 1
  • Mehmet Cilingiroglu
    • 1
  1. 1.Division of Cardiovascular Diseases, Department of Medicine, College of MedicineUniversity of CincinnatiCincinnatiUSA

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