Certain urine biomarkers related to inflammation and oxidant stress correlate with established predictors of cardiovascular disease and may help assess risk for heart problems among HIV-positive people on antiretroviral therapy according to a small pilot study presented on Wednesday at the XVII International AIDS Conference in Mexico City.
Cardiovascular disease (CVD) among HIV-positive patients is a growing concern as people with HIV are living longer. Several studies have found an association between heart attacks and antiretroviral therapy, and the large SMART treatment interruption trial showed that ongoing HIV replication itself appears to increase the risk of serious heart, liver, and kidney disease.
Inflammation, oxidant stress and endothelial (blood vessel) dysfunction contribute to atherosclerosis—hardening of the arteries, which can lead to heart attacks and strokes—and HIV infection or its treatment may influence these factors,
Various demographic and behavioural risk factors, as well as biological markers such as elevated blood fat levels, predict an increased likelihood of CVD. However, these factors may underestimate the risk of CVD in HIV-positive individuals, and it would be useful to have easily measured laboratory markers that signal the earliest stages of atherosclerosis.
Michael Bolger from Vanderbilt University in the US and colleagues conducted a cross-sectional pilot study to look at relationships between levels of four biomarkers called eicosanoids and traditional CVD risk factors.
The analysis included 33 HIV-positive participants from a larger prospective cohort study. About one-quarter were women, 55% were non-white, and the median age was 45 years. The median CD4 cell count was 515 cells/mm3 and the median HIV viral load was 50 copies/mL. All participants had been HIV-infected for at least one year and on a stable antiretroviral regimen containing two or more nucleoside/nucleotide reverse transcriptase inhibitors (NRTIs) for at least six months; 45% were taking a protease inhibitor.
Study participants did not have pre-existing CVD or diabetes, were not current smokers, and were not using aspirin (which can alter levels of the markers under study), though about half occasionally used non-steroidal anti-inflammatory drugs (NSAIDs). Just over one-quarter (27%) had lipoatrophy (fat loss). Overall, the group was at moderate risk for CVD.
The investigators measured levels of urine metabolites of four eicosanoids: F2-isoprostane (PGF2α), thromboxane (TxB2), prostacyclin (PGI-M), and prostaglandin-E (PGE-M). These eicosanoids are signalling molecules that play a role in a variety of metabolic processes involved in inflammation, oxidant stress and endothelial damage, for example, by promoting blood clotting and blood vessel constriction.
The researchers hypothesised that the metabolic disturbances associated with HIV infection or antiretroviral therapy include increased eicosanoid production. They looked at correlations between eicosanoid levels and traditional cardiovascular risk factors including sex, age and body mass index (BMI), as well as protease inhibitor use and presence of lipoatrophy. They then assessed how well the eicosanoids correlated with levels of non-HDL (“bad”) cholesterol and high sensitivity C-reactive protein (hsCRP), two markers with established links to CVD.
They found that study participants overall had higher levels of PGF2α and PGE-M compared with a reference population, and among study participants, PGE-M levels were about twice as high among men than women.
Within the study group as a whole, there was a significant correlation between PGF2α and hsCRP levels. Among women—but not men—PGI-M and TxB2 were also significantly correlated with hsCRP levels. TxB2 and PGI-M were weakly correlated with increased non-HDL cholesterol levels in men, but with decreased non-HDL levels in women.
There were no clear correlations between eicosanoid levels and lipoatrophy or protease inhibitor use, and no associations with age, race, CD4 cell count, viral load, BMI or NSAID use.
“These markers of inflammation, oxidant stress and endothelial dysfunction correlated with non-HDL and hsCRP,” the researchers concluded. “Sex-specific associations between eiconsanoids and traditional CVD risk factors were seen.”
They suggested that further studies of urinary eicosanoids as potential noninvasive, easily measured CVD markers in this population is warranted, and that inclusion of individuals with pre-existing CVD and diabetes might provide further useful information.