JACC Vol. 47, No. 6, 2006 Stein 1125March 21, 2006:1124–5 Editorial CommentHAART, metabolic risk factors, and cardiovascular imaging carefully matched triads based on HIV serostatus, antiret-in patients with HIV and control subjects has not been roviral therapy, and cardiovascular risk factors. At baseline,reported previously, so it is unique in that regard. there were no differences in CIMT between the groups of The ﬁnding that CIMT was greater among HIV- HIV-infected patients (7). Three-year follow-up of changesinfected patients with MetS is consistent with the metabolic in CIMT, risk factors, and virological markers are expecteddata provided by the authors. This ﬁnding would have been in early 2006. These studies will help clarify the majormore powerful if it had been corroborated by the aortic contributors to cardiovascular risk in patients with HIVpulse wave velocity data; however, the sample size was infection.relatively small. Also, certain markers of MetS in HIV- Conclusions. In regard to cardiovascular risk in patientsinfected patients did predict increased pulse wave velocity, with HIV, we have incomplete data. Compared with thesuch as blood pressure, 2-h glucose, and fasting insulin, high death rate from AIDS in patients with inadequate viralsuggesting that insulin resistance may be involved in the suppression, cardiovascular event rates are low and controlpathophysiology of vascular dysfunction in patients on of viremia, regardless of the treatment strategy, is moreHAART. It is interesting that markers of inﬂammation and important for long-term survival than any increase inviral load were more associated with CIMT than ﬂow- cardiovascular risk that may be related to metabolic changesmediated vasodilation or pulse wave velocity, but these associated with HAART. Uncontrolled viremia may beassociations are somewhat difﬁcult to interpret in the more of a cardiovascular risk than controlled infection thatabsence of information about the speciﬁc antiretroviral results in hyperlipidemia and insulin resistance. The overallagents used by the subjects, because agents within classes message is that obtaining and maintaining virological con-have different effects on insulin-glucose metabolism and trol is the overriding concern in patients with HIV infec-lipoproteins (1). Although the imaging data in this study do tion. Metabolic and vascular effects secondary to HAART arenot conclusively demonstrate that MetS, as traditionally secondary considerations, but are worthy of rigorous investiga-deﬁned, is useful for identifying increased cardiovascular tion, as suggested by the paper by van Wijk et al. (5).risk in HIV-infected patients, the metabolic abnormalitiesobserved in MetS patients suggest that insulin resistance Reprint requests and correspondence: Dr. James H. Stein,may be involved and that further studies are needed (5). University of Wisconsin Medical School, Cardiology, G7/341Future directions. To better understand cardiovascular CSC, MC 3248, 600 Highland Avenue, Madison, Wisconsin 53792. E-mail: email@example.com in patients on HAART, larger, prospective studies areneeded. The biases inherent in observational and cross- REFERENCESsectional studies are well known, and their results can bemisleading. In designing prospective studies, longitudinal 1. Dubé MP, Stein JH, Aberg JA, et al., for the Adult ACTG Cardio-data regarding changes in structural and functional markers vascular Disease Subcommittee. Guidelines for the evaluation and management of dyslipidemia in HIV-infected adults receiving antiret-of vascular disease, risk factors, antiretroviral therapy, and roviral therapy: recommendations of the HIV Medical Association ofvirological control must be considered, as well as the effect the Infectious Disease Society of America and the Adult AIDS Clinicalof aging itself. Trials Group. Clin Infect Dis 2003;37:613–27. 2. Stein JH. Managing cardiovascular risk in patients with HIV infection. Two well-designed studies sponsored by the AIDS Clin- J Acquir Immune Deﬁc Syndr 2005;38:115–23.ical Trial Group (ACTG) recently have been completed. 3. Fu W, Chai H, Yao Q, Chen C. Effects of HIV protease inhibitorACTG 5152s is a prospective study of 82 HIV-positive, ritonavir on vasomotor function and endothelial nitric oxide synthase expression. J Acquir Immune Deﬁc Syndr 2005;39:152– 8.treatment-naïve patients randomized to receive one of three 4. Zhong DS, Lu XH, Conklin BS, et al. HIV protease inhibitor ritonavirHAART regimens that would be predicted to have very induces cytotoxicity of human endothelial cells. Arterioscler Thrombdifferent effects on lipids and insulin-glucose metabolism. Vasc Biol 2002;22:1560 – 6. 5. van Wijk JPH, de Koning EJP, Castro Cabezas M, et al. Functional andAs expected, ﬂow-mediated dilation was impaired before structural markers of atherosclerosis in human immunodeﬁciency virus-starting treatment, but improved signiﬁcantly and to a infected patients. J Am Coll Cardiol 2006;47:1117–23.similar degree in each arm after as few as four weeks of 6. Stein JH, Cotter BR, Parker RA, et al. Antiretroviral therapy improves endothelial function in individuals with human immunodeﬁciency virusHAART (6). Nitroglycerin-mediated vasodilation did not infection: a prospective, randomized multicenter trial (Adult AIDSchange, indicating that use of HAART rapidly improved Clinical Trials Group Study A5152s) (abstr). Circulation 2005;112:endothelial function and that cardiovascular risk may de- II237. 7. Currier JS, Kendall MA, Zackin R, et al. Carotid artery intima-mediacrease as HIV infection comes under control. ACTG 5078 thickness and HIV infection: traditional risk factors overshadow impactis a prospective cohort study of 134 subjects recruited into of protease inhibitor exposure. AIDS 2005;19:927–33.