Can the risk of cardiovascular disease in HIV-infected patients be estimated from conventional risk prediction tools?

Received 16 July 2007; accepted 16 July 2007; electronically published 12 September 2007. Reprints or correspondence: Dr. Nina Friis-Møller, Copenhagen HIV Programme, DAD Coordinating Centre, Section 044, Hvidovre University Hospital, Copenhagen 2650, Denmark (nfm@cphiv.dk). Clinical Infectious Diseases 2007; 45:1082–4 2007 by the Infectious Diseases Society of America. All rights reserved. 1058-4838/2007/4508-0024$15.00 DOI: 10.1086/521936 Although the striking benefits of combination antiretroviral therapy continue to prevail, a number of complications to treatment have been observed, including the increased risk of metabolic complications and the risk of cardiovascular disease associated with some antiretroviral drugs. The preponderance of studies assessing clinical outcomes have identified a risk associated with protease inhibitor (PI) treatment [1–4]. In general, the incidence of cardiovascular disease is not high in most HIV-infected populations studied, which consist mainly of younger individuals (although, for all age groups, the incidence has been found to be higher among HIVinfected individuals than among matched HIV-uninfected control groups) [5–7]. For the individual, the absolute risk of cardiovascular disease results from the composite risk factor profile, comprising age, sex, diabetes status, family history of cardiovascular disease, and modifiable risks. With the aging of the HIV-infected population, brought about by improved survival among HIV-infected patients, it is likely that rates of cardiovascular disease in this population will increase in the future unless interventions to reduce risk factors are actively pursued. At present, cardiovascular disease is one of the most frequent causes of death in the HIVinfected population. Asymptomatic patients who are thought to be at high risk of cardiovascular disease need to be identified so that they can be offered advice about medical interventions and lifestyle changes. Current guidelines recommend that the risk of cardiovascular disease be estimated from a conventional risk-prediction model, such as the Framingham score, which combines different risk factors into a numeric estimate of absolute risk. However, few studies have explored whether such models accurately predict the risk in HIV-infected patients. Such models may not accurately predict the risk in this population, because (1) these patients are generally younger than populations for whom risk-prediction tools were developed, (2) there may be an independent effect of the underlying HIV infection, (3) an independent effect of PI treatment has been observed, and (4) the effect of some of the conventional risk factors may differ from what has been observed in the background population, as outlined below. In the Data Collection on Adverse Effects of Anti-HIV Drugs cohort collaboration, which includes HIV-infected persons from Europe, Australia, and the United States, an earlier prediction model from the Framingham Study [8] was found to slightly under-predict the risk of myocardial infarction, whereas the underestimation was even greater for a European prediction model [9]. The report by Kaplan et al. [10] in this issue of Clinical Infectious Diseases has applied a more recent Framingham risk prediction tool [11] to 2 large US cohorts of HIV-infected patients, the Women’s Interagency HIV Study (consisting of female patients) and the Multicenter AIDS Cohort Study (consisting of male patients), with HIV-uninfected comparison groups. Of note, the applied Framingham score does not incorporate diabetes, and in this study, the presence of diabetes was instead considered to be a “coronary heart disease [CHD] equivalent,” conferring a 10-year risk of CHD of 25% [12]. Overall, in the study by Kaplan et al. [10], 17% of HIV-infected men and 12%