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Cardiac biomarkers in HIV-exposed uninfected children

Wilkinson, James D.a; Williams, Paige L.b; Leister, Erinb; Zeldow, Bretb; Shearer, William T.c; Colan, Steven D.d; Siberry, George K.e; Dooley, Laurie B.f; Scott, Gwendolyn B.a; Rich, Kenneth C.g; Lipshultz, Steven E.a; for the Pediatric HIVAIDS Cohort Study (PHACS)

doi: 10.1097/QAD.0b013e32835cf21c
Clinical Science

Objectives: To evaluate associations of cardiac biomarkers with in-utero antiretroviral drug exposures and cardiac function/structure measured by echocardiograms in HIV-exposed but uninfected (HEU) children.

Design and methods: We analyzed the association of three cardiac biomarkers (cardiac troponin T, cTnT; high sensitivity C-reactive protein, hsCRP; and N-terminal pro-brain natriuretic peptide, NT-proBNP) with prenatal antiretroviral drug exposures, maternal–child characteristics, and echocardiographic parameters.

Results: Among 338 HEU children (mean age 4.3 years), 51% had at least one elevated cardiac biomarker. Maternal tobacco use was associated with elevated NT-proBNP [adjusted odds ratio (aOR) 2.28, P = 0.02]. Maternal alcohol and abacavir use were associated with elevated cTnT levels (aOR 3.56, P = 0.01 and aOR 2.33, P = 0.04, respectively). Among 94 children with paired echocardiogram-biomarker measurements, cTnT measurements were correlated with increased left-ventricular thickness-to-dimension ratio (r = 0.21, P = 0.04); and elevated cTnT was associated with higher mean left-ventricular end-diastolic (LVED) posterior wall thickness (P = 0.04). hsCRP measurements were negatively correlated with septal thickness (r = −0.22, P = 0.03) and elevated hsCRP was associated with lower mean left-ventricular contractility Z-scores (P = 0.04). NT-proBNP measurements were correlated with increased LVED dimension (r = 0.20, P = 0.05) and elevated NT-proBNP was associated with lower mean end-systolic septal thickness (P = 0.03).

Conclusion: Our findings suggest that cardiac biomarkers may help identify HEU children who require further cardiac evaluation including echocardiography. Potential cardiac effects of prenatal abacavir exposure in this population need further investigation.

aDepartment of Pediatrics, University of Miami Miller School of Medicine, Miami, Florida

bCenter for Biostatistics in AIDS Research, Harvard School of Public Health, Boston, Massachusetts

cDepartment of Pediatrics and Pathology & Immunology, Baylor College of Medicine and Texas Children's Hospital, Houston, Texas

dDepartment of Cardiology, Boston Children's Hospital, Boston, Massachusetts

eEunice Kennedy Shriver National Institute of Child Health & Human Development, National Institutes of Health, Bethesda, Maryland

fFrontier Science and Technology Research Foundation, Boston, Massachusetts

gDepartment of Pediatrics, University of Illinois, Chicago, Illinois, USA.

Correspondence to Steven E. Lipshultz, MD, Department of Pediatrics (D820), Miller School of Medicine, University of Miami, P.O. Box 016820, Miami, FL 33101, USA. Tel: +1 305 243 3993; fax: +1 305 243 3990; e-mail:

Received 4 September, 2012

Revised 20 November, 2012

Accepted 22 November, 2012

© 2013 Lippincott Williams & Wilkins, Inc.