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: .) Clinical Trial Registration URL: http://clinicaltrials.gov. Unique identifier: NCT01519141

Endothelial activation and cardiometabolic profiles of treated and never-treated HIV infected Africans

“…PWV indicate pulse wave velocity; IMT, intima media thickness; TC, total cholesterol; HDL-C, high density lipoprotein cholesterol; LDL-C, low density lipoprotein cholesterol; TG, triglyceride; CRP, C reactive protein; IL-6, interleukin 6; ICAM, intracellular adhesion molecule; VCAM vascular cell adhesion molecule. agreement with that of Currier et al, who did not detect subclinical atherosclerosis in the HIV infected population [43], but in contrast to several studies that indicate a higher IMT in HIV infected individuals [12,44,45]. According to Hsue et al, this may be explained by the fact that we measured the IMT in the common carotid artery, while the differences seen by them and Lorenz et al, were mainly in the carotid bifurcation region [45] where there is low endothelial shear stress.…”

“…agreement with that of Currier et al, who did not detect subclinical atherosclerosis in the HIV infected population [43], but in contrast to several studies that indicate a higher IMT in HIV infected individuals [12,44,45]. According to Hsue et al, this may be explained by the fact that we measured the IMT in the common carotid artery, while the differences seen by them and Lorenz et al, were mainly in the carotid bifurcation region [45] where there is low endothelial shear stress. Low endothelial shear stress may enhance the effect of chronic inflammation which may lead to the increased expression of vascular adhesion molecules and proinflammatory cytokines [46], which may explain the endothelial activation seen in this study.…”

Can early therapy reduce inflammation?

“…Soluble markers of monocyte and macrophage activation have been linked to both HIV disease progression and serious non-AIDS events [5,12**,17,18,19,38**,39,40,41*]. More recently, higher CD16 expression was found to be an independent predictor of atherosclerosis progression [42], highlighting the need to assess monocyte phenotypes as potential targets of therapeutic interventions.…”

“…However, many studies have shown persistently increased T cell activation and inflammation in chronically treated patients [5,13,18,22-25,31,35,36*,37**,38**,39,41*,44-46]. The potential causes include residual HIV replication, gut mucosal injury and subsequent microbial translocation, tissue fibrosis, co-infections such as cytomegalovirus and hepatitis C virus, and homeostatic drive [47,48].…”

The hidden risk: Incorporating inflammation and HIV serostatus into coronary artery disease screening

“…7 Furthermore, coronary atherosclerotic lesions in HIV-infected patients are often unstable and more prone to rupture, resulting in a 1.5-twofold higher incidence of acute coronary syndrome and myocardial infarction. [8][9][10][11] Expectedly, these pathologic changes leave HIV-infected patients at risk for vascular injury, accelerated atherosclerosis, 12 and ultimately disproportionate cardiovascular mortality. 13 Finally, despite widespread use of ART, we are just now appreciating the burden of inflammation and resulting cardiovascular damage which threatens patient survival.…”