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HIV Infection Sharply Increases Risk of Atherosclerosis, but Antiretroviral Therapy Has a Minor Effect

HIV positive participants in the FRAM study had greater average intima-media thickness -- an early indicator of atherosclerosis -- in 2 regions of the carotid artery, even after adjusting for traditional cardiovascular risk factors, investigators reported in the September 10, 2009 issue of AIDS.

Atherosclerosis, or loss of elasticity and build-up of plaque in the arteries, can restrict blood supply to the heart, leading to myocardial infarction, and bits of plaque can lodge in arteries in the brain, causing a stroke.

As people with HIV live longer due to effective combination antiretroviral therapy (ART), cardiovascular disease has become an increasingly important cause of morbidity and mortality, the study authors noted as background. But it remains controversial whether HIV infection contributes to accelerated atherosclerosis independent of traditional cardiovascular risk factors.

Carl Grunfeld from the University of California at San Francisco and colleagues performed a cross-sectional study of more than 400 HIV positive participants without pre-existing cardiovascular disease in the FRAM (Fat Redistribution and Metabolic Change in HIV Infection) study, comparing them to HIV negative participants in the MESA (Multi-Ethnic Study of Atherosclerosis) cohort.

They assessed preclinical atherosclerosis by measuring carotid intima-media thickness (IMT), or thickness of the walls of the arteries in the neck that supply the brain. They looked at IMT at 2 sites in the artery, known as the internal/bulb and common regions.

Results

Mean intima-media thickness of the internal carotid was significantly greater in HIV positive compared with HIV negative participants (1.17 vs 1.06 mm, respectively; difference 0.11 mm; P < 0.0001).
In a multivariate analysis adjusting for demographic characteristics, the mean difference in internal carotid IMT between HIV positive and HIV negative participants was 0.19 mm (P < 0.0001).
After further adjusting for traditional cardiovascular risk factors, the association between HIV and carotid IMT was "modestly attenuated," but still significant (0.15 mm; P = 0.0001).
Looking at the common carotid region, HIV infection was again independently associated with greater intima-media thickness (0.03 mm; P = 0.005).
The association between HIV infection and intima-media thickness was similar to that of smoking (internal carotid 0.17 mm, common carotid 0.02 mm).

"Even after adjustment for traditional cardiovascular disease risk factors, HIV infection was accompanied by more extensive atherosclerosis measured by IMT," the investigators concluded. "The association of HIV infection with IMT was similar to that of traditional cardiovascular disease risk factors, such as smoking."

"The stronger association of HIV infection with IMT in the internal/bulb region compared with the common carotid may explain previous discrepancies in the literature," they added.

The impact of HIV infection on preclinical atherosclerosis overrides any small differences related to antiretroviral therapy or specific drug classes, according to Grunfeld. "The effect [of HIV] is so big that no drug or class of drugs stands out as being an effective contributor," he said.

Medical Service, Department of Veterans Affairs Medical Center, University of California, San Francisco, CA.

9/11/09

Reference
C Grunfeld, JA Delaney, C Wanke, and others. Preclinical atherosclerosis due to HIV infection: carotid intima-medial thickness measurements from the FRAM study. AIDS 23(14): 1841-1849. September 10, 2009. (Abstract).