Insulin resistance may be a strong predictor of cardiovascular disease risk among people with HIV, says a report published in the April 23rd edition of AIDS. According to the study authors, determining the presence of insulin resistance in addition to calculating traditional risk scores may provide a fuller picture of cardiovascular disease risk in this population.
Cardiovascular disease (CVD) is the culmination of manifold genetic and environmental causes. Many of the known factors have been included in the widely used Framingham risk score, which evaluates the traditional risk factors of age, sex, smoking, blood lipid and sugar levels and blood pressure, to calculate the ten-year risk of developing CVD.
HIV and its treatment are thought to increase risk of CVD, though the exact mechanisms remain unknown. Thus, the development of CVD in people with HIV may be different from in HIV-negative people, and the markers used to evaluate CVD risk in the general population may not apply to people with HIV.
Two markers of CVD are blood vessel thickness and endothelial dysfunction. Blood vessels thicken with atherosclerosis, one of the steps towards CVD, and so blood vessel thickness is thought to be an early sign of CVD.
Endothelial dysfunction, often measured as the inability of the brachial artery to dilate, is thought to be an even earlier sign of CVD.
Measures of these to parameters can be used as surrogate markers of the risk of CVD, but several small studies of these two markers in HIV-positive people have shown mixed results.
In the current study, a research team from the US and Ireland hypothesised that blood vessel thickness would be greater and vasodilation impaired in HIV-positive people. To test this, they used a cross-sectional study to compare several surrogate markers of CVD risk, including blood vessel thickness, vasodilation and the traditional risk factors, between a group of 50 people with HIV and a group of 50 matched HIV-negative controls.
The study group had an average age of 42 years, 34% were women and 50% were African-American. All HIV-positive participants were on antiretroviral therapy and 90% had an undetectable viral load. The HIV disease was stable, with an average CD4 cell count of 547 cells/mm3.
HIV-negative controls who showed no signs of kidney or vascular disease were randomly chosen from existing trials at the research centre in the US and were matched to the HIV-positive participants for age, sex, race and body mass index.
In disagreement with their hypothesis that the HIV-positive group would have increased markers of CVD risk, measurements of blood vessel thickness and vasodilation were also similar between HIV-positive and HIV-negative groups. Furthermore, there were no significant differences in other traditional risk CVD factors; the mean calculated Framingham ten-year risk scores were low in both groups (≤ 3%).
Focusing on the HIV-positive group, investigators then analysed a wide range of metabolic and clinical parameters to identify predictors for the two CVD risk markers. In multivariate analysis, only the presence of insulin resistance was a significant predictor of both decreased vasodilation and increased blood vessel thickness (p
Insulin resistance, the investigators conclude, may be an important, unrecognised CVD risk factor in the HIV population and requires further study.
Since the standard Framingham risk score does not adequately account for insulin resistance and hasn’t been validated in the HIV-positive population, the investigators suggest that determining insulin resistance might give a better evaluation of long-term CVD risk for people with HIV. Insulin resistance is a condition in which normal insulin levels no longer control blood glucose levels, leading eventually to diabetes, a recognised risk factor for cardiovascular disease. Prior to the development of diabetes, exercise and weight loss have been shown to reduce insulin resistance.
Second, they suggest that addressing insulin resistance may be another avenue for managing CVD risk in this population.
The finding of no difference between groups with respect to blood vessel thickness and vasodilation was unexpected, given the considerable body of evidence linking HIV infection and an increased risk of cardiovascular disease. Several studies, including the D:A:D cohort of over 23,000 participants, have observed a link between antiretroviral use and heart attack. However, investigators point out that older studies used drugs that are now known to have multiple metabolic complications.
The investigators suggest that the similarity in risk factors between groups in their study “may be due, in part, to the long-term use of modern, metabolically ‘friendly’ antiretroviral regimens.” In their study, 76% of people taking a protease inhibitor-based regimen were taking ritonavir-boosted atazanavir (Reyataz), one of the newest anti-HIV drugs. Given the small study size, they conclude that long-term studies are need to better understand the CVD risk associated with specific drugs, especially with the emergence of new drug classes.
Mondy KE et al. Insulin resistance predicts endothelial dysfunction and cardiovascular risk in HIV-infected persons on long-term highly active antiretroviral therapy. AIDS 22: 849 – 856, 2008.