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NewsletterLiterature Reviews Coronary artery calcification, atherogenic lipid changes, and increased erythrocyte volume in black injection drug users infected with human immunodeficiency virus-1 treated with protease inhibitors Meng Q, et al. Am Heart J 2002; 144:642-8
Reviewer: KW Tim Park, MD
Background: Protease inhibitors (PIs) are the mainstay of highly active antiviral therapy (HAART) for patients with acquired immunodeficiency syndrome (AIDS). Examples of PIs include amprenavir, indinavir, lopinavir, nelfinavir, ritonavir, and saquinavir. With the advent of HAART, mortality and morbidity rates related to AIDS have decreased in patients infected with the human immunodeficiency virus 1 (HIV-1); however, mortality from "non-AIDS-related" causes such as coronary artery disease (CAD) have actually increased (1). Many patients receiving a PI develop hyperlipidemia, hyperglycemia, central obesity, and endothelial dysfunction, all of which are risk factors for atherosclerotic vascular disease. This study examined the effects of PIs on the markers of atherosclerosis in African American adult patients with HIV. Methods: Between 2000 and 2001, African Americans between the ages of 25 and 45, with no previously reported clinical heart problems or risk factors for heart problems such as diabetes mellitus and cigarette smoking and with no history of using anabolic steroids, immunomodulators, and lipid-lowering medications were enrolled. Of a total of 187 subjects enrolled, 98 (M:F = 69:29) were infected with HIV and were receiving stable doses of antiretroviral medications. Of the 98, 55 had been taking stable doses of a PI for > 6 months, whereas the remaining 43 had a stable antiviral regimen that did not include a PI. These 2 groups were compared for the lipid profiles, C-reactive protein levels, blood cell morphologic changes, and coronary artery calcification scores (CACS). CACS were obtained by electron beam computed tomography scanning and scores in 4 anatomic sites (left main, left anterior descending, left circumflex, and right coronary arteries) were summed. CACS are considered to be a sensitive and established marker of subclinical CAD (2). Results: The 2 study groups did not differ significantly in age (39.3 ± 4.5 vs. 37.8 ± 5.1 (mean ± SD)), gender distribution, or comorbidity profiles. Other than for the use of a PI, therapeutic regimen for HIV was not significantly different between the groups; every study participant was taking a nucleoside reverse transcriptase inhibitor such as combivir, lamivudine, zidovudine, and stavudine. Patients receiving PIs had been taking them for 29.6 ± 12.2 months. Patients on PIs had significantly higher total serum cholesterol (TC) and LDL-C levels than those not on PIs. The proportions of abnormal TC (> 5.2 mmol/L) and LDL-C (> 3.12 mmol/L) levels were significantly higher in the PI group than in the non-PI group (26.1 % vs. 2.8 % for TC and 32.6 % vs. 2.9 % for LDL-C, P < 0.01 each). TC and LDL-C levels were indicated by means of linear regression analyses to be associated with log-transformed duration of the PI therapy. The PI group had a marginally higher mean corpuscular volume of red cells than the non-PI group (92.2 ± 9.3 vs. 86.8 ± 7.2 mm3, P < 0.05). C-reactive protein levels were not significantly different between the PI and non-PI groups. CACS were significantly higher in the PI group than in the non-PI group (11.0 ± 28.6 vs. 1.7 ± 5.8, P < 0.05). Conclusion and Comments: This study examined patients without concurrent traditional risk factors for CAD. Yet the study found that patients on PIs had elevated levels of TC and LDL-C as well as elevated erythrocyte volumes, a marker possibly related to acute coronary events (3). The abnormal lipid profile may in part be explained by PI-related reductions in lipolytic enzymes and associated changes in lipid metabolism (4). The PI group of patients also had evidence of subclinical CAD, as shown by increased CACS. However, C-reactive protein levels were not elevated in the PI group, suggesting that the basis of the accelerated CAD might not be inflammatory in nature. The findings of this study appear to suggest that the use of a PI for HIV may be another independent risk factor for CAD - at least, in the cohort examined in the study. However, large retrospective studies have produced conflicting results on whether the PI therapy does represent an increased risk for CAD. In the most recent such study, Klein et al. reported on their experience with the Kaiser group of northern California (5). In their review of more than 4000 male patients with HIV between the ages of 35 and 64, age-adjusted hospitalization rates from CAD or myocardial infarction (MI) were not significantly different before vs. after PIs (6.2 vs. 6.7 events per 1,000 person-years, NS) or before vs. after HAART (5.7 vs. 6.8, NS). When these HIV patients were compared to demographically matched controls, the CAD hospitalization rates were significantly higher in the HIV group (6.5 vs. 3.8, P=0.003). Thus, it is not clear whether the increased incidence of early CAD in HIV patients is due to the use of PIs or due to another HIV-related mechanism. Whatever the mechanism, HIV patients with PI perhaps should be looked at as having an independent risk factor for CAD and may represent a new group of relatively young patients presenting for coronary intervention or surgery. References:
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