Nearly half of teens who were perinatally infected with HIV have an increased risk of atherosclerotic cardiovascular disease, researchers found.
When they were assessed with the Pathobiological Determinants of Atherosclerosis in Youth (PDAY) scores, 48% of the infected teens were found to have an elevated risk for having a lesion in the coronary arteries, and about a quarter (24%) were at risk for a lesion in the abdominal aorta, according to Kunjal Patel, DSc, MPH, of the Harvard School of Public Health in Boston, and colleagues.
Those with more severe HIV and longer durations of boosted protease inhibitor use were more likely to have scores indicative of increased cardiovascular risk, the researchers reported online in Circulation: Journal of the American Heart Association.
"PDAY scores may be useful in identifying high-risk youth who may benefit from early lifestyle or clinical interventions," they wrote.
"Our findings suggest lifestyle modifications (e.g., diet and exercise) and switching to new antiretroviral regimens less likely to cause metabolic abnormalities should be considered," they wrote.
Both HIV infection itself and the antiretroviral therapies used to treat it have been associated with increases in various cardiovascular risk factors in prior studies, including those conducted in pediatric populations.
"To identify and motivate high-risk children who may benefit from early interventions, it is clinically useful to obtain a measure of aggregate cardiovascular disease risk by utilizing a scoring system that sums the risks associated with each individual risk factor," the authors wrote.
In the current study, they explored the issue using the separate PDAY scores for the coronary arteries (CA) and for the abdominal aorta (AA), which estimate the risk of having an advanced atherosclerotic lesion in those areas. The scores are derived from the presence or absence of dyslipidemia, cigarette smoking, hypertension, obesity, and hyperglycemia. A score of 1 or higher indicates an elevated risk of having a lesion.
The analysis included 165 teens ages 15 to 19 (median age 16.7) who were perinatally infected with HIV and were participating in the Pediatric HIV/AIDS Cohort Study (PHACS). About two-thirds (68%) were black, 24% were Hispanic, and 7% were white.
Nearly all of the teens (97%) had some lifetime exposure to highly active antiretroviral therapy (HAART), and 87% were still using HAART at the time of the study.
High CA and AA scores came mostly from dyslipidemia, with some risk from high body mass index. Only 1% of the teens had hypertension, 1% were hyperglycemic, and none were considered heavy smokers.
Certain factors predicted both high CA and AA scores, including more severe HIV -- as indicated by a history of an AIDS-defining condition (CDC category C disease) -- and longer use of a boosted protease inhibitor.
"Low levels of HDL cholesterol, often associated with inflammation and endothelial activation, are reported in HIV-infected adults with AIDS or untreated HIV infection," the authors noted regarding the first predictor. "Also, independent of traditional cardiovascular disease risk factors, HIV disease severity is correlated with higher levels of T-cell activation that is further associated with the presence of subclinical carotid artery lesions."
As for the latter predictor, "protease inhibitors promote hyperlipidemia by upregulating fatty acid and cholesterol biosynthesis and secretion, and by increasing lipoprotein production in the liver," they wrote. "Protease inhibitors can also suppress leptin expression and glucose transporter type 4 activity in adipocytes, thereby promoting lipodystrophy, insulin resistance, and diabetes."
For the AA score -- but not the CA score -- virologic suppression also predicted the presence of an elevated risk.
"These effects may reflect toxicities associated with exposure to antiretroviral medications, as children currently on effective therapy are likely to have suppressed viral loads," the authors wrote. "Our observation is also consistent with studies among HIV-infected adults that show the risk for vascular disease with ongoing inflammation is still increased in the presence of viral suppression."
Some limitations of the study included the inability to validate the PDAY scoring system against noninvasive assessments of atherosclerotic disease or cardiovascular events, and the small sample size.
However, the authors wrote, the study "represents an understudied population of perinatally HIV-infected youth aging into young adulthood."
PHACS was supported by the Eunice Kennedy Shriver National Institute of Child Health and Human Development with co-funding from the National Institute on Drug Abuse, the National Institute of Allergy and Infectious Diseases, the Office of AIDS Research, the National Institute of Mental Health, the National Institute of Neurological Disorders and Stroke, the National Institute on Deafness and Other Communication Disorders, the National Heart, Lung and Blood Institute, the National Institute of Dental and Craniofacial Research, and the National Institute on Alcohol Abuse and Alcoholism, through cooperative agreements with the Harvard School of Public Health and the Tulane University School of Medicine.
- Reviewed by Zalman S. Agus, MD Emeritus Professor, Perelman School of Medicine at the University of Pennsylvania and Dorothy Caputo, MA, BSN, RN, Nurse Planner
Circulation: Journal of the American Heart AssociationSource Reference: Patel K, et al "Aggregate risk of cardiovascular disease among adolescents perinatally infected with the human immunodeficiency virus" Circulation 2013; DOI: 10.1161/CIRCULATIONAHA.113.001978.