HIV Infection Increases the Risk of Atherosclerosis as Much as Traditional Risk Factors

By Liz Highleyman

As people with HIV live longer thanks to effective antiretroviral therapy, cardiovascular disease has become a growing concern. Several studies have shown that HIV positive people are more likely to have various surrogate markers of cardiovascular disease, as well as higher rates of clinical events, but it is not yet clear whether this is due to HIV infection itself, antiretroviral therapy, or some combination of known and unknown factors.

As reported at the 16th Conference on Retroviruses and Opportunistic Infections (CROI 2009) this week in Montreal, Carl Grunfeld and colleagues compared rates of pre-clinical atherosclerosis in HIV positive patients and HIV negative control subjects.

Atherosclerosis, or "hardening of the arteries," can lead to heart attacks and strokes. It is increasingly clear that atherosclerosis involves not only the blockage of arteries by plaque, but also a complex inflammatory process that damages the blood vessel lining.

Pre-clinical atherosclerosis is often assessed by looking at carotid intima-media thickness (IMT), a measure of the health of the carotid arteries that supply the brain. IMT can be measured either in the common carotid artery or in the bulb region where it branches off into the internal carotid artery. Because the bulb is an area of blood turbulence that is more susceptible to arterial damage, changes are easier to detect in the bulb; this method, however, is more difficult than assessing IMT in the internal carotid.

Prior studies have produced conflicting data about the link between HIV infection and atherosclerosis. Five studies that found no association measured IMT in the common carotid only, while two studies that did see a link assessed IMT in both the common carotid and in the internal carotid bulb.

In the present cross-sectional study, the researchers compared carotid IMT, measured in both the common carotid and the internal carotid bulb, in 433 HIV positive patients in the Fat Redistribution and Metabolism in HIV Infection (FRAM) study and 5749 healthy HIV negative control subjects in the Coronary Artery Risk Development In Young Adults (CARDIA) study and the Multi-Ethnic Study of Atherosclerosis (MESA).

At baseline, FRAM participants were younger than those in the general population studies (median 49 vs 60 years) and were more likely to be men (70% vs 47%). In addition, the HIV positive participants were more likely to be current or former smokers and had higher total cholesterol and triglyceride levels, but they had a lower rate of diabetes. More than 90% were taking HAART.

Results

HIV positive patients had greater carotid IMT than HIV negative control subjects, but this was only statistically significant for the internal bulb region:

Internal carotid bulb: 1.17mm vs 1.06 mm (difference of 0.11; P < 0.0001);

Common carotid: 0.88mm vs 0.86mm (difference of 0.02; P = 0.017, non-significant).

Focusing on internal carotid bulb IMT, differences between HIV positive and HIV negative participants were larger after adjusting for confounding factors:

Adjusted for age, sex, and race/ethnicity: difference of 0.19 (P < 0.0001);
Adjusted for demographics and traditional cardiovascular risk factors: difference of 0.15 (P = 0.0001).

For common carotid IMT, the same pattern was seen, but the magnitude was much less:

Adjusted for age, sex, and race/ethnicity: difference of 0.04 (P = 0.0004);
Adjusted for demographics and traditional cardiovascular risk factors: difference of 0.03 (P = 0.005).

In a multivariate analysis, the effect of HIV infection on internal carotid bulb IMT (expressed as difference in mm) was similar to that of major traditional cardiovascular risk factors:

HIV infection: 0.15 mm;
Male sex: 0.13 mm;
Current smoking: 0.17 mm;
Diabetes: 0.12 mm;
Older age (per 10 years): 0.16 mm.

The effect of HIV infection was greater than that of elevated blood pressure or blood lipid levels.

The effect of HIV infection on IMT was larger in women than in men, especially when measured in the internal carotid bulb.

Based on these findings, the investigators concluded, "After adjusting for demographics and traditional cardiovascular disease risk factors, HIV infection is accompanied by more extensive atherosclerosis as measured by carotid IMT."

Speaking at a press conference, Grunfeld said that the strong effect of HIV infection itself on cardiovascular disease would likely far outweigh the "small signal" associated with use of specific antiretroviral drugs.

2/13/09

Reference
C Grunfeld, J Delaney, C Wanke, and other. HIV infection is an independent risk factor for atherosclerosis similar in magnitude to traditional cardiovascular disease risk factors. 16th Conference on Retroviruses and Opportunistic Infections (CROI 2009). Montreal, Canada. February 8-11, 2009. Abstract 146.