One common method is using ultrasound to assess the thickness of artery walls – known as intima-media thickness (IMT) – in the carotid arteries that supply blood to the brain. However, results can vary depending on whether a measurement is taken in the main artery, in one of its two branches (the internal and external carotid) or at the bifurcation or 'fork' where they split.
Priscilla Hsue from the University of California, San Francisco and colleagues compared IMT progression in the common carotid, internal carotid and bifurcation regions in individuals with and without HIV.
Dr Hsue – who gave a comprehensive overview of inflammation, atherosclerosis and cardiovascular disease earlier in the conference – explained that due to blood flow dynamics, the bifurcation may be more susceptible to inflammation and atherosclerosis. As a result, early injury may be detectable in this region before it appears in other parts of the artery. But the bifurcation region is harder to measure, so many researchers have favoured the other sites.
The study included 285 HIV-positive participants, primarily from the observational SCOPE cohort at San Francisco General Hospital. Most (72%) were on antiretroviral therapy and 47% had suppressed viral load on treatment. In addition, 22 participants were from a cohort of elite controllers who maintained undetectable virus without therapy. Finally, 40 HIV-negative people served as controls.
About 85% of participants were men, roughly 70% were white and the median age was about 45 years. HIV-positive participants had been infected for a median 13 years and had been on antiretroviral therapy for nearly four years. The current CD4 cell count was 433 cells/mm3, but the nadir (lowest-ever level) had been 150 cells/mm3.
With regard to traditional cardiovascular risk factors, HIV-positive participants had significantly lower LDL (bad) cholesterol at baseline, but higher levels of triglycerides and high-sensitivity C-reactive protein (CRP), a biomarker of inflammation. HIV-positive people were also somewhat more likely to smoke than their HIV-negative counterparts (68% vs 53%) and had higher prevalence of high blood pressure (28% vs 13%), diabetes (7% vs 3%) and prior heart disease or strokes (8% vs 3%), but none of these differences reached statistical significance.
The researchers measured IMT at twelve segments of the carotid artery and calculated annualised rates of progression. At baseline, IMT was greater amongst HIV-positive people than HIV-negative controls, both overall (0.86 vs 0.71 mm) and in each carotid region.
After a median two years of follow-up, overall IMT progression was significantly more rapid in HIV-positive people compared with HIV-negative controls (0.046 vs 0.012 per year). The difference remained significant after adjusting for traditional risk factors such as smoking.
However, the effect varied depending on measurement site. Amongst participants with HIV, IMT progression was most evident in the bifurcation region followed by the internal carotid and then the common carotid. The difference in progression between HIV-positive and HIV-negative people was largest in the bifurcation region (0.074 vs 0.013 mm/year), followed by the internal carotid (0.046 mm/year vs none), but was not statistically significant in the common carotid (0.074 vs 0.013 mm/year).
Amongst people on suppressive therapy and elite controllers, IMT progression was significantly greater compared with uninfected people in the bifurcation region but not in the common carotid.
CRP levels were more closely linked to IMT progression in the bifurcation region. After adjusting for traditional risk factors and HIV status, CRP was independently associated with IMT progression in the bifurcation region, whilst traditional risk factors were more predictive in other regions. When the analysis was adjusted to take CRP levels into account, the independent effect of HIV was reduced.
Based on these findings, the researchers concluded that, "HIV-related inflammation contributes to increased risk of atherosclerosis in the setting of HIV."
Asked about the clinical relevance of the findings, Dr Hsue said that although the measured IMT changes were very small, IMT progression has been strongly correlated with increased risk of cardiovascular disease in the HIV-negative general population.