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Endothelial Dysfunction More Common in HIV-Positive Than Negative Adolescents
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18th Conference on Retroviruses and Opportunistic Infections, February 27-March 2, 2011, Boston
Mark Mascolini
Endothelial dysfunction, an early sign of cardiovascular disease, proved more frequent in HIV-positive US adolescents than in HIV-negative youngsters at risk for HIV infection [1]. Both groups had higher than normal levels of an inflammation marker, high-sensitivity C-reactive protein (hsCRP).
Cardiovascular markers have received wide research attention in adults with HIV infection, but their import in HIV-positive children and adolescents remains poorly understood. At the same time, the long-term impact of HIV and antiretroviral therapy on cardiovascular health of people infected at an early age raises growing concern. Adolescent Trials Network (ATN) study 083 aims to determine how 18-month changes in cardiovascular markers can be used to diagnose and monitor heart disease in HIV-positive adolescents.
This analysis focused on 178 US REACH Project youngsters with and at risk for HIV who had blood samples collected 18 months apart. The analysis excluded pregnant adolescents with samples collected fewer than 6 months after delivery, youngsters who became infected during the study period, adolescents who missed visits or had missing data on antiretroviral use, those with cyanotic congenital heart disease, and those taking lipid-lowering agents. The ATN team measured soluble vascular adhesion molecule 1 (sVCAM-1) in these frozen plasma samples as a marker of endothelial function.
The study group included 97 adolescents with HIV and 81 without HIV--123 girls and 55 boys. Most REACH cohort girls were black (73%), as were most boys (66%).
Age averaged 16.7 in girls and 16.9 in boys, and girls weighed significantly more than boys (average 28.6 versus 23.0 kg/m2, P < 0.0001). Among youngsters with HIV, CD4 counts were higher in girls than boys (average 752 versus 565, P = 0.0003), and viral loads were lower in girls (average 11,869 versus 54,597 copies, P = 0.01). A lower proportion of girls than boys smoked (29% versus 47%, P = 0.02), but about three quarters of girls and boys drank alcohol, and about half smoked marijuana.
Of the 97 adolescents with HIV, 67 (69%) were taking combination antiretroviral therapy, but only 11% of treated youngsters had a viral load below 400 copies/mL.
Log-transformed "good" high-density lipoprotein (HDL) cholesterol in the second sample was significantly lower in adolescents with HIV (3.79 versus 3.86, P = 0.03). Log-transformed apolipoprotein A1, a major component of HDL cholesterol, was also significantly lower in the HIV group in the second sample (4.82 versus 4.87, P = 0.04). The square root of sVCAM-1 was significantly higher in HIV-positive youngsters (38.4 versus 33.4, P = 0.001).
Other lipid values measured and hsCRP did not differ significantly between the HIV-positive and HIV-negative groups. But the researchers observed that hsCRP was higher than normal in both groups at the first measure (above 2) and the 18-month measure (above 3). Those high levels, the investigators suggested, may reflect risk factors shared by both groups, such as high rates of smoking and overweight.
Statistical models that considered HIV status, age, gender, smoking, and race found the following significant determinants of 18-month marker and lipid values:
Log triglyceride concentrations at 18 months: Smoking (P = 0.03) and initial triglycerides (P < 0.0001)
Very low-density lipoprotein cholesterol at 18 months: Smoking (P = 0.024) and initial very low-density lipoprotein cholesterol (P < 0.0001)
Apolipoprotein A1 at 18 months: body mass index (P = 0.0065) and initial apolipoprotein A1 (P < 0.0001)
hsCRP at 18 months: body mass index (P < 0.0001) and initial hsCRP (P = 0.002)
The ATN researchers noted that although the HIV-negative group had higher "good" HDL cholesterol, average values for both groups were within American Heart Association guidelines, "possibly reflecting the young age of our population and perhaps the short duration of HIV infection." The ATN team stressed that two established adult cardiovascular risk factors--high weight and smoking--contributed to cardiovascular risk in these young people. For every marker evaluated, the initial value measured strongly predicted the value after 18 months.
Levels of sVCAM-1, the endothelial dysfunction marker, were higher in HIV-positive adolescents than in HIV-negative but at-risk youngsters. "In this population of HIV-infected adolescents who are in early stage [HIV] disease," the researchers stress, "sVCAM is a marker of endothelial dysfunction that appears prior to more traditional biomarkers of cardiovascular risk such as hsCRP or lipid profiles."
Reference
1. Syed S, Balluz R, Kabagambe E, et al. ATN 083: longitudinal changes in cardiovascular risk markers among HIV+ and at risk adolescents. 18th Conference on Retroviruses and Opportunistic Infections. February 27-March 2, 2011. Boston. Abstract 701. Poster online at http://www.retroconference.org/2011/PDFs/701.pdf.
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