HIV infection independently increases the severity of atherosclerosis as much as traditional cardiovascular risk factors such as smoking and diabetes, researchers reported on Wednesday at the Sixteenth Conference on Retroviruses and Opportunistic Infections in Montreal.
Numerous studies have shown that people with HIV are more likely to develop heart disease, but the underlying mechanisms are not completely understood. Atherosclerosis, or 'hardening of the arteries' due to inflammation and plaque build-up, can lead to heart attacks and strokes. There has been controversy about whether HIV itself increases the risk, or whether it is attributable to traditional risk factors such as the effect of antiretroviral therapy on blood lipid levels.
Carl Grunfeld and his colleagues with the Fat Redistribution and Metabolism in HIV Infection (FRAM) study sought to determine whether having HIV is an independent risk factor for atherosclerosis after controlling for other relevant factors. FRAM is an ongoing study of metabolic complications of HIV disease conducted at multiple US medical centres.
One commonly used surrogate marker for asymptomatic or pre-clinical atherosclerosis is intima-media thickness (IMT), a way to assess narrowing of the arteries using ultrasound.
Carotid IMT can be measured in two ways: in the common carotid artery or in the so-called 'bulb' region where it branches off into the internal carotid artery supplying the brain. The bulb is an area of blood turbulence, making it more susceptible to atherosclerotic damage. It is more difficult to measure IMT in the internal carotid bulb than in the common carotid, but results may be more accurate.
In this cross-sectional study, investigators compared carotid IMT – measured in both the common carotid and the internal carotid bulb – in 433 HIV-positive FRAM participants and 5749 healthy HIV-negative individuals in the Coronary Artery Risk Development In Young Adults (CARDIA) study and the Multi-Ethnic Study of Atherosclerosis (MESA).
FRAM participants were on average younger than those in the general population studies (49 vs 60 years) and were more likely to be men (70% vs 47%). With regard to traditional cardiovascular risk factors, FRAM participants were about twice as likely to be current smokers (36% vs 15%) and had higher mean total cholesterol and triglyceride levels, but were less likely to have diabetes (9% vs 14%).
The investigators found that HIV-positive patients had significantly greater carotid IMT than HIV-negative individuals when measured in the internal carotid bulb (1.17mm vs 1.06), although the difference did not reach statistical significance when looking at the common carotid (0.88mm vs 0.86mm).
After adjusting for age, sex, and race/ethnicity, the difference in IMT was considerably larger in the internal carotid bulb than in the common carotid (0.19mm vs 0.043mm, respectively).
After adjusting further for traditional cardiovascular risk factors, including smoking, diabetes, high blood pressure and blood lipid levels, the effect of HIV infection on carotid IMT was somewhat weaker, but still apparent. Again, the effect was more obvious in the internal carotid bulb than in the common carotid (difference of 0.15mm vs 0.033, respectively).
Furthermore, the effect of HIV on atherosclerosis appeared to be somewhat stronger amongst women than men, especially when measuring IMT in the internal carotid bulb.
The researchers estimated that, even after adjusting for other risk factors, HIV infection independently increased the extent of atherosclerosis by about the same amount as the strongest traditional risk factors such smoking, diabetes and male sex.
Dr Grunfeld explained that the difference in IMT measured in the common carotid versus the internal carotid bulb might help explain conflicting results from previous studies, some of which showed that HIV and its treatment increased the risk of atherosclerosis and some of which did not see this effect. Although more difficult, carotid IMT measurement in the internal bulb is more likely to reveal an effect, and he recommended using both methods if possible.
Discussing the findings, Dr Grunfeld noted that cardiovascular risk in people with HIV is probably a multi-factorial phenomenon involving both host and viral factors. But the effect of HIV is "very large" – much greater than the small effect associated with use of specific antiretroviral drugs – and on the question of whether HIV itself is associated with atherosclerosis, he said: "I believe we've cleared that up."
Grunfeld C et al. HIV infection is an independent risk factor for atherosclerosis similar in magnitude to traditional cardiovascular disease risk factors. Sixteenth Conference on Retroviruses and Opportunistic Infections, Montreal, abstract 146, 2009.