Is lipoatrophy associated with vascular dysfunction?

Lipoatrophy is associated with a variety of adverse cardiovascular risk factors such as dyslipidemia and insulin resistance, but as yet there has been no good evidence that cardiovascular event rates are higher or vascular dysfunction is greater among those with lipoatrophy or lipohypertrophy. The group from Indiana University presented data on a large cross-sectional study of vascular endothelial function measured by brachial artery reactivity by ultrasound that included detailed body composition analysis by DEXA and CT methods in 96 subjects in clinical HIV care.

Half were ART-naive, and among the treated subjects 53% were on PI. Interestingly, vascular endothelial function tended to be worse among those subjects on ART with the lowest levels of limb fat compared to those with higher levels – suggesting a mechanism that somehow lipoatrophy (perhaps mediated by metabolic dysfunction) could lead to more cardiovascular disease. There was no relationship between visceral fat and endothelial function, and PI use also did not appear to be related to worse endothelial function by brachial artery reactivity testing.

Although PI use has generally been considered to be associated with endothelial dysfunction, early studies included many subjects on indinavir, which to date is the only PI conclusively shown to directly induce endothelial dysfunction. Another presentation at this meeting in ART-naive subjects reported that with initiation of ART, endothelial dysfunction improved even if subjects received the PI lopinavir-ritonavir. So, it is possible with currently-used PIs, that endothelial dysfunction is not a directly drug-induced problem. Regardless, endothelial dysfunction does occur and presumably will contribute to increased cardiovascular events. The mechanism by which lower limb fat is associated with endothelial dysfunction clearly deserves further study, and perhaps we should be particularly vigilant about managing cardiovascular risk in our patients with lipoatrophy.

Dube et al. Relationship of body composition, antiretroviral use and HIV disease factors to endothelial dysfunction in HIV-infected subjects.