By Liz Highleyman

Research has shown that certain antiretroviral drugs are associated with metabolic toxicities that predict an increased risk of cardiovascular disease. One such manifestation is increased carotid intima-media thickness (IMT) -- or thickness of the lining of the carotid arteries in the neck -- a sign of atherosclerosis.

As described in the December 2006 Journal of Clinical Endocrinology & Metabolism, Steven Grinspoon, MD, and colleagues from Massachusetts General Hospital in Boston conducted a study to assess carotid IMT in relation to HIV serostatus and use of antiretroviral therapy.

The study included 97 HIV positive women and 86 healthy HIV negative women matched for age and body mass index (BMI). The investigators assessed carotid IMT, presence of metabolic syndrome, and risk factors for increased IMT.

Results

• Carotid IMT was not increased in HIV positive women compared with HIV negative women (median 0.62 mm vs 0.61 mm; P = 0.07).

• Carotid IMT was significantly greater among HIV positive women receiving protease inhibitors (PIs) compared with non-PI-treated women and HIV negative control subjects (median 0.65, 0.61, and 0.61, respectively; P < 0.05).

• The prevalence of metabolic syndrome was significantly higher among the HIV positive women compared with HIV negative subjects (31% vs 4%; P = 0.001).

• Among HIV positive women, metabolic syndrome was more common among those taking PIs compared with non-PI-treated women (45% vs 19%; P = 0.001).

• Metabolic syndrome score correlated with IMT among HIV negative women, but not among those with HIV.

• The risk factors most strongly associated with IMT in multivariate regression modeling were age and waist-to-hip ratio in the control group, and age and waist circumference in the HIV positive group.

Conclusion

"These data demonstrate increased carotid IMT in HIV-infected women receiving PI therapy, which may be due to associated metabolic abnormalities related to PI therapy or more direct effects of this medication class on the vasculature," the authors concluded. "Additional studies of the mechanisms by which PI uses results in subclinical atherosclerosis are needed."

"Antiretroviral drugs save lives, so they are critical for HIV infected men and women alike, but our data do suggest that use of these drugs, particularly protease inhibitors, among women, may be associated with accelerated atherosclerosis," Grinspoon told Reuters Health. "Thus, patients put on these medications should have a careful monitoring for the development of coronary artery disease risk factors."

Program in Nutritional Metabolism (S.J., S.E.D., K.V.F., J.R.K., S.G.), Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts 02114; Massachusetts General Hospital Biostatistical Center (H.L.), Boston Heart Foundation (L.C.H., J.M.C., R.S.L.), Massachusetts General Hospital, Boston, Massachusetts 02114; and Department of Infectious Diseases (S.J.), Skejby Hospital, DK-8200 Aarhus, Denmark

02/02/07

Reference
S Johnsen, S E Dolan, K V Fitch, and others. Carotid Intimal Medial Thickness in Human Immunodeficiency Virus-Infected Women: Effects of Protease Inhibitor Use, Cardiac Risk Factors, and the Metabolic Syndrome. Journal of Clinical Endocrinology & Metabolism 91(12): 4916-4924. December 2006.