Abstract P342: Macrophage Markers are Associated with Atherosclerotic Plaque and Distensibility in the Women’s Interagency HIV Study

Abstract

Background: Atherosclerosis is characterized by infiltration of monocytes into the arterial wall, where they form atherosclerotic plaque. The inflammation pathways leading to cardiovascular disease through atherosclerosis may involve monocyte and macrophage activity in response to viral infection, including HIV and hepatitis C virus (HCV). We examined the association of three plasma markers of monocyte and macrophage activity, galectin-3 binding protein (Gal-3BP), soluble CD163 (sCD163), and soluble CD14 (sCD14), with subclinical atherosclerosis, in a subset of women participating in the Women’s Interagency HIV Study (WIHS). We hypothesized that higher levels are associated with greater disease. Methods: The WIHS is a longitudinal study of HIV-infected and -uninfected women from 6 U.S. sites. We analyzed 4 groups of 66 women each: HIV+/HCV+, HIV+/HCV-, HIV-/HCV+, and HIV-/HCV-, matched by age, race/ethnicity, and smoking status. Carotid artery B-mode ultrasound assessed two measures of subclinical atherosclerosis: distensibility (in 10 -6 *m 2 /N) and presence of atherosclerotic plaque (IMT >1.5 mm). We created an inflammatory macrophage score (sum of the presence of plasma levels above the median for each marker, range 0-3) and assessed its independent cross-sectional association with subclinical CAD, using regression models with generalized estimating equations to take into account the matched design and controlling for known risk factors. We also assessed associations of Gal-3BP, sCD163, and sCD14 plasma levels individually with subclinical atherosclerosis. Results: 264 women were included (median age 46 [IQR 41-50], 62% black, 26% Hispanic, median distensibility 15.22 [IQR 11.05-21.76]). In models accounting for age, race/ethnicity, smoking, BMI, and CRP, higher macrophage scores were significantly associated with both a 1.5-fold greater odds of plaque (per elevated marker, 95% CI 1.06 to 2.09) and lower distensibility (β -1.40 units per marker, 95% CI -2.62 to -0.17). Gal-3BP alone was associated with both outcomes in adjusted analyses (OR plaque 1.51 per SD of Gal-3BP, 95% CI 1.01 to 2.26; β distensibility -1.48 units per SD, 95% CI -2.37 to -0.58). sCD163 was associated with a greater odds of plaque only (OR 1.90 per SD, 95% CI 1.16 to 3.12), while sCD14 was associated with lower distensibility (β -1.09 units per SD, 95% CI -2.14 to -0.03). When we stratified by HIV and HCV status, Gal-3BP levels were higher among HCV+ women than HCV- women (mean 12.4 vs. 8.6 μg/mL, p<0.01), but did not differ by HIV status (mean 10.3 vs. 10.7 μg/mL, p=0.34). HIV+/HCV+ women had the highest levels of sCD163 and sCD14. Conclusions: Our data show that the macrophage inflammatory markers Gal-3BP, sCD163 and sCD14 are associated with subclinical carotid atherosclerosis in the setting of HIV and HCV infection. HCV infection may be more strongly associated with these markers than HIV infection.