Cardiac risk factors in HIV-infected patients are significantly improved with diabetes drug

Researchers at the Massachusetts General Hospital (MGH) and the Framingham Heart Study have shown for the first time that specific markers of increased cardiovascular risk, tPA and PAI-1, which may affect the formation of atherogenic clot, are significantly increased in HIV-infected patients with evidence of fat redistribution. tPA and PAI-1 levels were compared to the expected levels in age and weight-matched subjects of the Framingham Offspring Study.

Importantly, metformin, a drug commonly used to treat diabetes, was shown to significantly reduce these markers, while improving blood pressure and fat redistribution. A significant percentage of patients with HIV disease are experiencing severe changes in fat redistribution with initiation of highly active antiretroviral therapy, and such fat redistribution is associated with significant abnormalities in insulin, glucose, lipids and other hormone levels, according to Steven Grinspoon, MD, of the MGH Neuroendocrine Unit and senior author on the study.

According to James Meigs, MD, a co-author and member of the General Medical unit and Framingham Heart Study, �These markers predict increased risk of myocardial infarction and other cardiovascular events in the Framingham Study and other large epidemiologic studies, and may also predict increased risk among HIV-infected patients, who have other predisposing factors including high insulin and lipid levels.� �The mechanisms of the lipodystrophy syndrome are not known, but significant loss of peripheral fat and increased visceral fat are seen�, according to Colleen Hadigan, MD, of the Neuroendocrine Unit and first author of the study. The study, published in the Journal of Clinical Endocrinology and Metabolism, reports follow-up data from an initial article published in JAMA last year by the same MGH team. tPA and PAI levels decreased approximately 15% in the active treatment group as compared to the placebo group, even using a low dose of metformin over a limited study duration of 12 weeks. Preliminary data presented the week of February 5th at the 8th Conference on Retroviruses and Opportunistic Infections suggest that HIV-infected patients may suffer from increasing rates of myocardial and other coronary event rates, making the finding of the MGH team important as the first demonstration of a potential therapy to modulate increased CVD risk factors.

The other authors of the study include Jessica Rabe, B.A of the Neuroendocrine Unit, Ralph D�Agostino, Ph.D. and Peter Wilson, M.D. of the Framingham Study, as well as Isabella Lipinska, Ph.D and Greg Tofler, M.D. of Cardiac Division of the Beth Israel-Deaconess Medical Center.