Carotid Intima-Media Thickness Progression in HIV-Infected Adults Occurs Preferentially at the Carotid Bifurcation and Is Predicted by Inflammation

Abstract

Background: Shear stress gradients and inflammation have been causally associated with atherosclerosis development in carotid bifurcation regions. The mechanism underlying higher levels of carotid intima-media thickness observed among HIV-infected individuals remains unknown.

Methods and results: We measured carotid intima-media thickness progression and development of plaque in the common carotid, bifurcation region, and internal carotid artery in 300 HIV-infected persons and 47 controls. The median duration of follow-up was 2.4 years. When all segments were included, the rate of intima-media thickness progression was greater in HIV-infected subjects compared with controls after adjustment for traditional risk factors (0.055 vs. 0.024 mm/year, P=0.016). Rate of progression was also greater in the bifurcation region (0.067 vs. 0.025 mm/year, P=0.042) whereas differences were smaller in the common and internal regions. HIV-infected individuals had a greater incidence of plaque compared with controls in the internal (23% vs. 6.4%, P=0.0037) and bifurcation regions (34% vs. 17%, P=0.014). Among HIV-infected individuals, the rate of progression in the bifurcation region was more rapid compared with the common carotid, internal, or mean intima-media thickness; in contrast, progression rates among controls were similar at all sites. Baseline hsCRP was elevated in HIV-infected persons and was a predictor of progression in the bifurcation region.

Conclusions: Atherosclerosis progresses preferentially in the carotid bifurcation region in HIV-infected individuals. hsCRP, a marker of inflammation, is elevated in HIV and is associated with progression in the bifurcation region. These data are consistent with a model in which the interplay between hemodynamic shear stresses and HIV-associated inflammation contribute to accelerated atherosclerosis. (J Am Heart Assoc. 2012;1:jah3-e000422 doi: 10.1161/JAHA.111.000422.)

Clinical trial registration: URL: http://clinicaltrials.gov. Unique identifier: NCT01519141.

Keywords: AIDS; atherosclerosis; carotid arteries; inflammation.

Figure 1.

IMT Levels and Progression by Region and HIV status. (A) Unadjusted IMT levels at baseline: The IMT levels at baseline for all HIV-infected individuals were significantly higher as compared with uninfected controls at the internal, common, bifurcation region, and mean IMT (P<0.001 for all). (B) Mean IMT progression (adjusted): After adjustment for demographics, traditional factors, and hsCRP, IMT progression in the carotid bifurcation region and calculated mean IMT were higher among HIV-infected individuals as compared with controls, while there was no statistically significant difference in IMT progression in the internal and common carotid progression.

Figure 2.

Unadjusted association of hsCRP with IMT levels and IMT progression in the bifurcation region: In the bifurcation region, higher hsCRP levels were associated with higher levels of IMT at baseline (A) and IMT progression over time (B) in both HIV-infected and HIV-uninfected participants. Higher solid line denotes predicted IMT (with dotted 95%CI confidence bounds) calculated from unadjusted generalized additive model (GAM). P-values are from spline and linear portion of the fit. A) HIV (red): Spline: p=0.090; linear: p=0.0008; Control (blue): Spline: p=0.0081; linear: p<.0001. B) HIV (red): Spline: p=0.29; linear: p=0.017 Control (blue): Spline: p=0.016; linear: p=0.21.