September 2, 2010
Lipodystrophy, PIs, Don’t Negatively Affect Cardiovascular Health Measure
None of several factors sometimes associated with poorer cardiovascular health—trunk fat accumulation, limb fat loss, or modern protease inhibitor (PIs) use—diminished blood vessel function in people living with HIV, according to a study published in the August issue of AIDS Research and Human Retroviruses. These data suggest that body composition changes (lipodystrophy) and PI use might have less of an effect on cardiovascular health than found in some previous studies.
Nearly 15 years ago, researchers began noting two anomalies in people living with HIV using combination antiretroviral (ARV) therapy, notably those involving protease inhibitors: changes in body composition and changes in markers of cardiovascular health. Since those early discoveries, numerous studies have concluded that protease inhibitors and lipodystrophy likely play a role in the onset of cardiovascular disease in many people living with HIV.
Questions remain, however, about the degree that these factors affect cardiovascular health, especially with the use of modern-day protease inhibitors believed to be better tolerated than their first-generation predecessors. To help answer this question, Michael Dubé, MD, and his colleagues from the Indiana University School of Medicine in Indianapolis set out to determine the impact of lipodystrophy and modern PI-use on one measure of cardiovascular health called endothelial function.
The endothelium are made up of cells lining the walls of blood vessels, which help the blood vessel expand or contract as needed to alter blood flow throughout the body. As people get older, or suffer from symptoms of cardiovascular disease, the ability of the endothelium to dilate blood vessels can diminish. One way to measure endothelial function is to conduct ultrasound readings on the brachial artery in the upper arm—before and after pressure is applied to the artery—in a process called flow-mediated dilation (FMD).
Dubé and his colleagues conducted FMD testing on 96 people living with HIV, who were recruited through their HV clinic. The average age of the participants was 40, a little over half were male, and 51 percent were taking ARV drugs—of whom 57 percent were on a PI. In addition to measuring FMD, Dubé and his colleagues conducted detailed tests of the accumulation of gut fat, loss of fat in the leg, viral load, CD4 count and proteins associated with cardiovascular inflammation.
Dubé’s team found no association between any of these factors and a reduction in FMD. There was a trend toward lower FMD in people on ARVs, who had more severe lipodystrophy, but this did not reach statistical significance, meaning that the association could have occurred by chance.
The authors acknowledge that an association between lipodystrophy might have become apparent if they had a larger number of study participants or had measured changes in fat and FMD over time. This is an area, they say, that would benefit from further exploration.
Their finding that PIs had no impact on FMD is consistent with other more recent studies looking at modern PIs, such as Reyataz (atazanavir) and Kaletra (lopinavir plus ritonavir), which were the predominant PIs used by those in this study. Only older studies, generally with Crixivan (indinavir) or full-dose Norvir (ritonavir), found reductions in endothelial function. Contrary to previous studies, Dubé and his colleagues found no association between modern PIs and markers of cardiovascular inflammation, such as high sensitivity C-reactive protein (hsCRP) or Interleukin-6 (IL-6). The authors state that inflammatory markers may simply not be perfect predictors of the physical function of blood vessels.
“We did not find that measures of fat distribution…or circulating markers of inflammation and endothelial activation were associated with physiologically measured endothelial function in HIV-infected patients,” the authors concluded. “Additional study is needed to understand the underlying mechanisms for HIV-related endothelial dysfunction.”
Search: Endothelial dysfunction, Flow-mediated dilation, brachial artery, cardiovascular, protease inhibitors, Kaletra, lopinavir, norvir, Reyataz, atazanavir, inflammation, lipodystrophy, lipoatrophy, Michael Dube
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