Background: Data supporting a link between body-fat distribution changes and cardiovascular disease risk in HIV-infected patients are scarce and contradictory. We evaluated endothelial dysfunction, an early event in the development of atherosclerosis, and pro-atherosclerotic plasma biomarkers in HIV-infected patients with lipodystrophy.
Methods: HIV-infected patients with and without lipodystrophy were prospectively enrolled. Endothelial function was measured through flow-mediated dilatation (FMD) of the brachial artery. Plasma levels of several biomarkers of inflammation, endothelial activation and coagulation associated with adipose tissue and endothelial dysfunction were determined.
Results: The study included 110 patients, 55 of them with lipodystrophy. FMD was significantly lower in patients with lipodystrophy than in those without lipodystrophy (median [IQR] 3.1% [0.4-8.9] versus 6.3% [3.3-10.7]; P=0.004). Patients with isolated lipoatrophy exhibited the lowest FMD (2.6% [0-6.6]; P(Kruskal-Wallis)=0.02). Lipodystrophy was associated with significantly higher plasma levels of interleukin 6 (IL-6) and plasminogen activator inhibitor 1 (PAI-1) and lower levels of adiponectin; severe lipodystrophy was associated with higher concentrations of vascular cell adhesion molecule 1 (sVCAM-1). There was an inverse correlation between FMD and IL-6 (Spearman's rho =-0.26; P=0.007). In a multivariate regression model with the lowest quartile of FMD as the dependent variable and lipodystrophy, traditional cardiovascular risk factors, 10-year Framingham risk score, pro-atherosclerotic biomarkers and HIV-related variables as predictors, the only independent predictor of endothelial dysfunction was lipodystrophy (odds ratio 5.22, 95% confidence interval 1.76-15.46; P=0.003).
Conclusions: Lipodystrophy is associated with endothelial dysfunction, independently of the presence of traditional cardiovascular risk factors. This finding and the accompanying profile of pro-atherosclerotic biomarkers support an increased cardiovascular risk in HIV-infected patients with lipodystrophy.