HIV infection itself appears to increase the thickness of the carotid artery and is therefore a significant independent risk factor for developing cardiovascular disease (CVD)—ultimately increasing the risk of a heart attack or stroke—according to a new study presented Wednesday, February 11, at the 16th Conference on Retroviruses and Opportunistic Infections (CROI) in Montreal.

Ever since researchers first noticed that protease inhibitors could significantly increase a person's cholesterol and triglycerides, they have attempted to quantify the additional risk that people with HIV may have in developing CVD. Subsequent research over the years has suggested that some protease inhibitors and the nucleoside reverse transcriptase inhibitor abacavir (found in Ziagen, Epzicom and Trizivir) may increase a person's CVD risk somewhat. Research also appeared to show that people with HIV were more likely than their HIV-negative peers to have heart attacks. Thus far, however, no study has adequately quantified the additional risk that the virus itself may confer.

To explore this, Carl Grunfeld, MD, from the University of California in San Francisco, and his colleagues compared the carotid artery thickness of 433 HIV-positive patients to 5,749 HIV-negative patients. The thickness of the carotid artery in the neck—called carotid intima-media thickness—can be measured using ultrasound; when found to be thicker than normal, it tends to predict the likelihood of cardiovascular events such as heart attacks.

Specifically, Grunfeld and his colleagues looked at the thickness of the artery in two spots. Previous research, focusing a segment of the artery known as the common carotid, had failed to consistently show thickening in people with HIV. Grunfeld and his team reasoned that increased thickness of the internal carotid, which is higher up and closer to the brain, would be a better indicator of inflammation that may be caused by HIV infection, due to the turbulent nature of the blood flow there.

Sure enough, Grunfeld's team found a significant increase in thickness in the internal carotid artery in people with HIV. In fact, HIV infection alone was associated with the same amount, if not more, of thickening in the internal carotid artery that is associated with other factors such as age, smoking and diabetes. The impact was even more pronounced in HIV-positive women.

Grunfeld showed that the increases in thickness of the internal carotid artery were not as significant in the common carotid, where most previous studies had looked. He said this could explain why some previous studies had failed to find associations between HIV and artery thickening.

Grunfeld conceded in his talk that although the study's sample size was large, he could not yet directly link increases in artery thickness to clinical events such as heart attacks. He did, however, indicate that studies in the general population consistently demonstrate that people with thicker carotid arteries have a much higher risk of CVD.

When asked what the underlying mechanism may be, he indicated it is likely a complex combination of each person's immune system response to HIV along with the negative influence of some HIV treatments.