A study published in a special edition of JAMA for the International AIDS Conference has revealed that the higher risk of cardiovascular disease in HIV-infected patients seems to be linked to higher inflammation in the arteries.

Researchers from Massachusetts General Hospital (MGH) discovered that levels of inflammation in HIV-positive people’s aortas, without cardiovascular disease and no elevated traditional risk factors, were similar to those of patients with established cardiovascular disease.

Leading investigator, Steven Grinspoon, MD, director of the MGH Program in Nutritional Metabolism and a member of the Neuroendocrine Unit, said:

“Several recent studies, including ones that we’ve done, have found that HIV-infected patients have about twice the risk of heart attack and stroke as non-infected individuals do. These new data suggest a plausible mechanism through which increased arterial inflammation related to activation of the immune system may increase the risk of cardiovascular events in these patients.”

The researchers believe that inflammation may also be one of the risk factors for cardiovascular events in HIV-positive people, aside from the typical risk factors, including accumulation of abdominal fat, smoking, high blood pressure and elevated cholesterol levels.

Earlier evidence indicates that the link was based on measurements of inflammatory markers, such as C-reactive protein in the bloodstream. However, the new study is the first research to provide direct evidence of increased inflammation in the arterial walls of patients with HIV.

The researchers evaluated the results of PET and CT scans of 81 participants, which were categorized into various groups. One group consisted of 27 HIV-infected individuals without known cardiovascular disease who all received antiretroviral therapy, another group had 27 non-infected controls without atherosclerosis matched to the HIV group for age, gender and traditional cardiovascular risk factors, and the third group consisted of 27 non-infected controls with atherosclerosis matched to the HIV group by gender.

All PET scans used FDG, a radiopharmaceutical that accumulates in locations of inflammatory activity. The researchers selected prospective imaging data for both control groups from a patient database that contained data of people who had been scanned for clinical diagnosis of non-HIV related conditions.

Results from the FDG PET scans demonstrated higher elevated levels of inflammation in HIV-positive participants aortas compared with those seen in control participants without atherosclerosis. They observed that the levels were similar to those in control participants with cardiovascular disease.

The researchers noted that no influence of traditional risk factors contributed to arterial inflammation levels in the HIV group, and neither did the type of antiviral treatment the patients had received and that patients’, whose viral levels were at undetectable levels also showed increased inflammation. When measuring the circulating inflammatory markers, the team discovered that levels of soluble CD163, a marker of monocyte activation, were higher in those in the HIV group, whereas the markers of generalized inflammation were no different. Grinspoon explains:

“Activated monocytes – part of the innate immune system – may be attracted to plaque lesions in the arteries, where they become activated macrophages that release substances contributing, over time, to plaque rupture and heart attack. Activated macrophages also can release chemical signals that attract more monocytes, setting up a vicious cycle. We previously showed that increased CD163 levels were associated with non-calcified plaque, which is more susceptible to rupture.

Our new findings that levels of CD163, but not other inflammatory markers, are related to inflammation signified by the uptake of FDG – even among patients without detectible virus – suggest that soluble CD163 could be a useful marker of risk-associated inflammation in HIV patients.”

Grinspoon, who is a professor of Medicine at Harvard Medical School points out that the findings do not imply that modification of traditional risk factors are not significant in HIV-positive patients, yet he stresses that new therapies should also be taken into account and target nontraditional risk factors like arterial inflammation. He continues saying that even though FDG-PET scanning would be unsuitable for mass screening of patients; researchers should nevertheless investigate into measurements of inflammatory markers like CD163 levels.

The team is currently researching the possibility of whether statin treatment could reduce arterial inflammation in HIV-infected patients, as most patients only have modestly elevated levels of cholesterol.

Grinspoon concludes:

“Our data also suggest that targeting monocyte activation may be a unique strategy to reduce arterial inflammation in these patients, have implications about the pathogenesis of cardiovascular disease in other inflammatory conditions, and emphasize a new way to look at risk in such patients.”

Written by Grace Rattue