High Prevalence of Echocardiographic Abnormalities among HIV-infected Persons in the Era of Highly Active Antiretroviral Therapy.

BACKGROUND in the era of highly active antiretroviral therapy (HAART), human immunodeficiency virus (HIV)-infected persons have higher cardiovascular disease risk. Little is known about asymptomatic abnormalities in cardiac structure and function in this population. METHODS the Study to Understand the Natural History of HIV/AIDS in the Era of Effective Therapy (SUN Study) is a prospective, observational, multi-site cohort of 656 HIV-infected participants who underwent baseline echocardiography during 2004-2006. We examined prevalence of and factors associated with left ventricular systolic dysfunction (LVSD), diastolic dysfunction (DD), pulmonary hypertension (PHTN), left ventricular hypertrophy (LVH), and left atrial enlargement (LAE). RESULTS participant characteristics were as follows: median age, 41 years; 24% women; 29% non-Hispanic black; 73% receiving HAART; and median CD4+ cell count, 462 cells/μL. Among evaluable participants, 18% had LVSD, 26% had DD, 57% had PHTN (right ventricular pressure >30 mm Hg), 6.5% had LVH, and 40% had LAE. In multivariate analyses, significant factors (P < .05) associated with LVSD were history of MI, elevated highly sensitive C-reactive protein (hsCRP) level, and current tobacco smoking; for DD, elevated hsCRP level and hypertension; for PHTN, current use of ritonavir; for LVH, hypertension, diabetes, non-white race, female sex with elevated body mass index, calculated as the weight in kilograms divided by the square of height in meters, of ≥ 25, elevated hsCRP level, and current use of abacavir; for LAE, hypertension and recent marijuana use. CONCLUSIONS in this large contemporary HIV cohort, the prevalence of subclinical functional and structural cardiac abnormalities was greater than expected for age. Abnormalities were mostly associated with expected and often modifiable risks. Lifestyle modification should become a greater priority in the management of chronic HIV disease.

[1]  Michael J Silverberg,et al.  Effect of early versus deferred antiretroviral therapy for HIV on survival. , 2009, The New England journal of medicine.

[2]  H. Hense,et al.  The aging process of the heart: obesity is the main risk factor for left atrial enlargement during aging the MONICA/KORA (monitoring of trends and determinations in cardiovascular disease/cooperative research in the region of Augsburg) study. , 2009, Journal of the American College of Cardiology.

[3]  I. Aban,et al.  Risk behaviours in HIV-positive men who have sex with men participating in an intervention in a primary care setting , 2009, International journal of STD & AIDS.

[4]  J. Meigs,et al.  Association of C-Reactive Protein and HIV Infection With Acute Myocardial Infarction , 2009, Journal of acquired immune deficiency syndromes.

[5]  E. Overton,et al.  Factors associated with renal dysfunction within an urban HIV‐infected cohort in the era of highly active antiretroviral therapy , 2009, HIV medicine.

[6]  P. Lin,et al.  Roles and mechanisms of human immunodeficiency virus protease inhibitor ritonavir and other anti-human immunodeficiency virus drugs in endothelial dysfunction of porcine pulmonary arteries and human pulmonary artery endothelial cells. , 2009, The American journal of pathology.

[7]  K. Wood,et al.  The study to understand the natural history of HIV and AIDS in the era of effective therapy (SUN Study). , 2008, American journal of epidemiology.

[8]  J. Lundgren Use of nucleoside reverse transcriptase inhibitors and risk of myocardial infarction in HIV-infected patients , 2008, AIDS.

[9]  Peter Reiss,et al.  Antiretroviral treatment of adult HIV infection: 2008 recommendations of the International AIDS Society-USA panel. , 2008, JAMA.

[10]  R. Parker,et al.  Endothelial function in human immunodeficiency virus-infected antiretroviral-naive subjects before and after starting potent antiretroviral therapy: The ACTG (AIDS Clinical Trials Group) Study 5152s. , 2008, Journal of the American College of Cardiology.

[11]  G. Mensah,et al.  Screening and assessment of coronary heart disease in HIV-infected patients. , 2008, Circulation.

[12]  O. Kirk,et al.  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 , 2008, The Lancet.

[13]  C. Sabin,et al.  Antiretroviral drugs and the risk of myocardial infarction - Reply , 2007 .

[14]  O. Kirk,et al.  Class of antiretroviral drugs and the risk of myocardial infarction. , 2007, The New England journal of medicine.

[15]  J Darbyshire,et al.  CD4+ count-guided interruption of antiretroviral treatment. , 2006, The New England journal of medicine.

[16]  James B Seward,et al.  Left atrial size: physiologic determinants and clinical applications. , 2006, Journal of the American College of Cardiology.

[17]  William Stewart,et al.  Recommendations for chamber quantification. , 2006, European journal of echocardiography : the journal of the Working Group on Echocardiography of the European Society of Cardiology.

[18]  B. Lau,et al.  C-reactive protein is a marker for human immunodeficiency virus disease progression. , 2006, Archives of internal medicine.

[19]  Richard B Devereux,et al.  Recommendations for chamber quantification: a report from the American Society of Echocardiography's Guidelines and Standards Committee and the Chamber Quantification Writing Group, developed in conjunction with the European Association of Echocardiography, a branch of the European Society of Cardio , 2005, Journal of the American Society of Echocardiography : official publication of the American Society of Echocardiography.

[20]  S. Colan,et al.  Mild dilated cardiomyopathy and increased left ventricular mass predict mortality: the prospective P2C2 HIV Multicenter Study. , 2005, American heart journal.

[21]  G. Behrens Cardiovascular risk and body-fat abnormalities in HIV-infected adults. , 2005, The New England journal of medicine.

[22]  D. Kitzman,et al.  Contribution of left ventricular diastolic dysfunction to heart failure regardless of ejection fraction. , 2005, The American journal of cardiology.

[23]  S. Hammer,et al.  C-Reactive protein levels over time and cardiovascular risk in HIV-infected individuals suppressed on an indinavir-based regimen: AIDS Clinical Trials Group 5056s , 2004, AIDS.

[24]  J. Gardin,et al.  American Society of Echocardiography recommendations for use of echocardiography in clinical trials. , 2004, Journal of the American Society of Echocardiography : official publication of the American Society of Echocardiography.

[25]  R. Speich,et al.  Pulmonary arterial hypertension related to HIV infection: improved hemodynamics and survival associated with antiretroviral therapy. , 2004, Clinical infectious diseases : an official publication of the Infectious Diseases Society of America.

[26]  Vilmundur Gudnason,et al.  C-reactive protein and other circulating markers of inflammation in the prediction of coronary heart disease. , 2004, The New England journal of medicine.

[27]  K. Bailey,et al.  Association of newer diastolic function parameters with age in healthy subjects: a population-based study. , 2003, Journal of the American Society of Echocardiography : official publication of the American Society of Echocardiography.

[28]  S. Oka,et al.  Dilated cardiomyopathy in an adult human immunodeficiency virus type 1-positive patient treated with a zidovudine-containing antiretroviral regimen. , 2003, Clinical infectious diseases : an official publication of the Infectious Diseases Society of America.

[29]  Anne L. Taylor,et al.  Coronary heart disease in HIV-infected individuals. , 2003, Journal of acquired immune deficiency syndromes.

[30]  P. Tebas,et al.  Emerging bone problems in patients infected with human immunodeficiency virus. , 2003, Clinical infectious diseases : an official publication of the Infectious Diseases Society of America.

[31]  Douglas W Mahoney,et al.  Burden of systolic and diastolic ventricular dysfunction in the community: appreciating the scope of the heart failure epidemic. , 2003, JAMA.

[32]  James B Seward,et al.  Left atrial volume as a morphophysiologic expression of left ventricular diastolic dysfunction and relation to cardiovascular risk burden. , 2002, The American journal of cardiology.

[33]  K. Dingemans,et al.  Cardiomyopathy with mitochondrial damage associated with nucleoside reverse-transcriptase inhibitors. , 2002, The New England journal of medicine.

[34]  John M Williamson,et al.  Protease inhibitors and cardiovascular outcomes in patients with HIV-1 , 2002, The Lancet.

[35]  D. Vlahov,et al.  Use of HIV protease inhibitors is associated with left ventricular morphologic changes and diastolic dysfunction. , 2002, Journal of acquired immune deficiency syndromes.

[36]  B. Horne,et al.  Usefulness of high-sensitivity C-reactive protein in predicting long-term risk of death or acute myocardial infarction in patients with unstable or stable angina pectoris or acute myocardial infarction. , 2002, The American journal of cardiology.

[37]  Arthur E. Weyman,et al.  Clinical Correlates and Reference Intervals for Pulmonary Artery Systolic Pressure Among Echocardiographically Normal Subjects , 2001, Circulation.

[38]  R. Lancashire,et al.  Prevalence of left-ventricular systolic dysfunction and heart failure in the Echocardiographic Heart of England Screening study: a population based study , 2001, The Lancet.

[39]  M. Schambelan,et al.  Metabolic effects of indinavir in healthy HIV-seronegative men , 2001, AIDS.

[40]  R. D'Agostino,et al.  Increased PAI-1 and tPA antigen levels are reduced with metformin therapy in HIV-infected patients with fat redistribution and insulin resistance. , 2001, The Journal of clinical endocrinology and metabolism.

[41]  O. Turriziani,et al.  Changes in host cell molecules acquired by circulating HIV-1 in patients treated with highly active antiretroviral therapy and interleukin-2 , 2001, AIDS.

[42]  E. Pujol,et al.  Ventricular mass and diastolic function in patients infected by the human immunodeficiency virus , 2000, Heart.

[43]  R. Raddino,et al.  Impact of highly active antiretroviral therapy in HIV-positive patients with cardiac involvement. , 2000, The Journal of infection.

[44]  James N Gribble,et al.  Interview Mode and Measurement of Sexual Behaviors: Methodological Issues. , 1999, Journal of sex research.

[45]  G. Barbarini,et al.  Incidence of dilated cardiomyopathy and detection of HIV in myocardial cells of HIV-positive patients. Gruppo Italiano per lo Studio Cardiologico dei Pazienti Affetti da AIDS. , 1998, The New England journal of medicine.

[46]  K. Miller,et al.  Visceral abdominal-fat accumulation associated with use of indinavir , 1998, The Lancet.

[47]  R. Speich,et al.  HIV-associated primary pulmonary hypertension. A case control study. Swiss HIV Cohort Study. , 1997, American journal of respiratory and critical care medicine.

[48]  M. Domanski,et al.  Effect of zidovudine and didanosine treatment on heart function in children infected with human immunodeficiency virus. , 1995, The Journal of pediatrics.

[49]  S. Daniels,et al.  Left ventricular mass and body size in normotensive children and adults: assessment of allometric relations and impact of overweight. , 1992, Journal of the American College of Cardiology.

[50]  N. Schiller,et al.  Noninvasive estimation of right atrial pressure from the inspiratory collapse of the inferior vena cava. , 1990, The American journal of cardiology.

[51]  D. Buff Primary pulmonary hypertension. , 1987, Annals of internal medicine.

[52]  Amalio Telenti,et al.  Antiretroviral Treatment of Adult HIV Infection2010 Recommendations of the International AIDS Society–USA Panel , 2010 .

[53]  S. Hammer,et al.  Antiretroviral Treatment of Adult HIV Infection 2008 Recommendations of the International AIDS Society–USA Panel , 2008 .

[54]  G. Simonneau,et al.  Prevalence of HIV-related pulmonary arterial hypertension in the current antiretroviral therapy era. , 2008, American journal of respiratory and critical care medicine.