Abstract Body

Background: Coronary artery calcification (CAC) scoring significantly improves cardiovascular risk stratification; however, CAC is a late finding of atherosclerotic vascular disease. Increased vascular stiffness (i.e. decreased distensibility) may be an early marker of vascular disease in HIV-infected patients on antiretroviral therapy (ART) prior to the development of vascular calcification. The relationship of chronic systemic immune dysregulation to these early vascular changes in HIV is poorly understood. Methodology: High-resolution carotid ultrasound was used to examine common carotid artery intima-media thickness (CCA-IMT) and distensibility among 147 HIV-infected patients on ART. CAC scoring was performed with computed tomography. T-tests and Spearman correlations were used to examine the relationships between carotid distensibility and biomarkers of inflammation and immune activation among those with and without detectable CAC. Results: Median (interquartile range) age was 46 (40-53) years; 78% were male and 68% African American. Median CD4 count was 613(425, 853) cells/μl and 10-year Framingham risk score was 3(1-7)%. Ninety-three subjects (63%) had zero CAC, but 29 (31%) of those with zero CAC had carotid atherosclerosis by ultrasound (CCA-IMT>1mm or discreet carotid plaque). Median carotid distensibility was higher among those without CAC [26(19-33) vs. 23(19-26) 10-6*Newtons-1*m2, p=0.045, CAC=0 vs. CAC>0, respectively); however, 13 subjects (9% of total population) without any CAC or carotid atherosclerosis had carotid distensibility below the 25th percentile. Distensibility was negatively correlated with CD4+ CD38+HLA-DR+, CD14dimCD16+ (patrolling) monocytes, and IL-6 concentrations among those with CAC=0, but not among those with CAC>0 (see Table). Among subjects with CAC=0, distensibility was significantly or marginally significantly correlated with CCA-IMT (r 0.339, p <0.001) and two measures of endothelial function (r 0.192, p=0.066 for flow-mediated brachial artery dilation; and r 0.374, p<0.001 for hyperemic velocity-time integral). Conclusions: Among HIV-infected patients on ART who do not have coronary artery calcification, impaired carotid distensibility may be a sign of early vascular disease that is associated with immune activation and inflammation.