Inflammation signals heart disease risk in people with HIV

Markers of inflammation usually related to chronic viral infection and implicated in the long-term development of heart disease are likely to be higher in people with HIV than healthy adults of the same age, despite antiretroviral treatment, according to findings published in the journal Clinical Infectious Diseases.

These elevations are associated with more pronounced thickening of a key artery, a sign that strongly predicts subsequent cardiovascular disease.

People with HIV appear to be at higher risk of cardiovascular disease, but the reasons why this is so are the subject of debate. Some evidence points to raised cholesterol levels as a result of antiretroviral treatment as a cause, especially with protease inhibitors, but other research has suggested that HIV itself is causing long-term chronic inflammation which contributes to the development of heart problems, stroke and vascular disease.

In the study, researchers at institutions in Cleveland and Rochester (USA) led by Dr Grace McComsey conducted a cross-sectional study to examine the relationship between markers of inflammation, endothelial activation and carotid artery intima media thickness (a measurement of the narrowing of the arteries).

Elevated levels of a number of inflammatory markers have been associated with cardiovascular disease, as has activation of the cells lining blood vessels (the endothelium) (implying dysfunctional changes). Intima media thickness has been correlated to elevations in inflammatory and activation markers in some, but not all, studies of cardiovascular disease risk, suggesting that regular measurement of these markers might prove useful in studying and predicting the risk of cardiovascular disease.

The Cleveland study was designed to test whether a relationship exists between inflammatory markers and physical signs of heart disease in people with HIV.

Researchers selected 73 HIV-positive patients who had been taking antiretroviral treatment for at least six months, and compared them with an age-matched control group of 21 HIV-negative patients. The study excluded anyone with a known cardiovascular condition, diabetes or any inflammatory condition.

Although participants in the two groups were well-matched by age, race, total cholesterol and body mass index, HIV-positive participants were more likely to be male, to smoke and to have a higher waist-to-hip ratio (often indicative of lipodystrophy). They were also more likely to be taking lipid-lowering medications, but there was no difference in the use of anti-hypertensive drugs or low-dose aspirin.

HIV-positive participants had well-controlled viral load (81% below 50 copies/ml), and none had viral load above 1600 copies/ml.

Despite antiretroviral treatment, measurements showed that HIV-positive participants had significantly higher levels of all inflammation markers apart from soluble tumour necrosis factor receptor 1 and 2, and higher levels of the activation marker sVCAM-1. They also had greater intima media thickness in two separate measures.

Multivariate analysis within the HIV-positive group showed that after controlling for a wide range of variables related to cardiovascular risk, the only inflammatory markers positively correlated with internal intima media thickness were sVCAM-1, myeloperoxidase and TNF-alpha.

The study also found that age was the factor most strongly associated with increased intima media thickness, indicating the extent to which traditional cardiovascular risk factors remain important in people with HIV. The authors admit that their study was not able to fully control for all traditional risk factors, but point out that smoking, which was more frequent in the HIV-positive group, did not affect biomarker levels and was not associated with intima media thickness.

The researchers say that larger studies which follow people with HIV over long periods are needed in order to assess the relationship between inflammatory markers and cardiovascular disease, and to determine the extent to which that relationship is affected by earlier antiretroviral treatment or use of specific classes of drugs.