Immune Activation and Coronary Atherosclerosis in HIV-Infected Women: Where Are We Now, and Where Will We Go Next?

Abstract

Understanding the pathophysiology of coronary heart disease (CHD) in the human immunodeficiency virus (HIV)– infected population with access to antiretroviral therapy (ART) has become an important focus of recent research. CHD is, in fact, an emerging complication for individuals infected with HIV and presents a challenge for physicians involved in the care of HIV-infected patients. Cardiovascular disease is currently the third leading cause of death in HIV-infected individuals, after AIDS-related complications and malignancies. CHD is now the leading cardiovascular cause of death and morbidities, far more than heart failure, in HIV-infected patients on ART [1], whereas congestive heart failure related to immunocompromise is the leading cause of death in countries with poor access to ART [2].Many factors have been associated with myocardial infarction in the HIV population, ranging from traditional risk factors (eg, hypertension, tobacco use, dyslipidemia, diabetes, family history of premature CHD, microalbuminuria, and chronic renal failure) [3] to infection with hepatitis C virus [3], genetic factors [4], HIV itself [5], chronic inflammation [6], and immune activation [7]. Little is known about CHD in HIVinfected women. In several studies on acute coronary syndrome in HIV-infected patients, the proportion of women varied from 3% to 19% (mean, 10%) [1]. These figures are similar to those reported for HIV-uninfected women from the general population in a North American registry, where women aged <50 years accounted for <10% of cases of myocardial infarction [8]. The age distributions of HIV-infected and HIV-uninfected populations are, however, very different; those in the HIV-infected population are 10 to 15 years younger. Data from a North American epidemiological study have shown that the relative risk (RR) of myocardial infarction is higher in HIVinfected women than in uninfected female controls, with an RR of 2.98 [9]. Similarly, a French epidemiological study reported that the standardized morbidity ratio (SMR) was 2.7 for HIV-infected women vs uninfected female controls [10]. Of note, both the RR and the SMR were higher in HIV-infected women than in HIV-infected men (RR 1.4, SMR 1.4 [9, 10]). In the Women’s Interagency HIV Study (primary prevention study), 12% of HIV-infected women had a highly predicted 10-year risk of CHD, similar to that in the HIV-uninfected women; the mean age of the women was 40 years [11]. These data indicate that there are unmet needs in HIV-infected women at risk for CHD. How do we identify these women, how do we prevent an acute event, and what mechanisms are involved in their elevated risk of myocardial infarction? Fitch et al, in their article published in this issue of the Journal, focus on subclinical coronary atherosclerosis in HIVinfected women without symptoms or history of cardiovascular disease [12]. Using computed tomographic angiography (CTA), the authors report, for the first time, an increased prevalence of specific noncalcified coronary plaques and increased immune activation (monocyte activation) in asymptomatic HIV-infected women, when compared with female controls. These noncalcified plaques are potentially more prone to rupture than calcified plaques and, therefore, more likely to cause an acute coronary event. Fitch et al also found that age, HIV infection, and immune activation (particularly Received and accepted 1 August 2013; electronically published 16 September 2013. Correspondence: Franck Boccara, Department of Cardiology, Saint Antoine Hospital, Univ-Paris 6, AP-HP, 184 rue du Faubourg St Antoine, 75571 Paris Cedex 12, France (franck.boccara@ sat.aphp.fr). The Journal of Infectious Diseases 2013;208:1729–31 © The Author 2013. Published by Oxford University Press on behalf of the Infectious Diseases Society of America. All rights reserved. For Permissions, please e-mail: journals. permissions@oup.com. DOI: 10.1093/infdis/jit511