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Markers of Bone Mineral Metabolism and Cardiac Structure and Function in Perinatally HIV-Infected and HIV-Exposed but Uninfected Children and Adolescents

Margossian, Renee MDa; Williams, Paige L. PhDb; Yu, Wendy MPHb; Jacobson, Denise L. PhDb; Geffner, Mitchell E. MDc; DiMeglio, Linda A. MD, MPHd; Van Dyke, Russell B. MDe; Spector, Stephen A. MDf,g; Schuster, Gertrud U. PhDh,i; Stephensen, Charles B. PhDi; Miller, Tracie L. MDj; Lipshultz, Steven E. MDk for the Pediatric HIV/AIDS Cohort Study (PHACS)

JAIDS Journal of Acquired Immune Deficiency Syndromes: June 1, 2019 - Volume 81 - Issue 2 - p 238–246
doi: 10.1097/QAI.0000000000002007
Clinical Science

Background: Disordered bone mineral metabolism and low vitamin D concentrations are associated with cardiovascular abnormalities; few studies have evaluated this relationship in HIV-infected youth.

Setting: The Adolescent Master Protocol is a Pediatric HIV/AIDS Cohort Study network study conducted across 14 US sites.

Methods: Among perinatally HIV-infected (PHIV) and perinatally HIV-exposed but uninfected (PHEU) youth enrolled in the Adolescent Master Protocol, we evaluated associations of vitamin D [measured as 25-hydroxy-vitamin D (25-OHD)], parathyroid hormone (PTH), calcium, phosphate, and fibroblast growth factor-23 (FGF-23) concentrations with echocardiographic measures of left ventricular (LV) structure, function, and concentrations of NT-proBNP, a biomarker of cardiac damage.

Results: Among 485 participants (305 PHIV and 180 PHEU) with echocardiograms and bone mineralization measures, low 25-OHD (<20 ng/mL) was common among all participants (48% PHIV and 44% PHEU), but elevated PTH (>65 pg/mL) was identified more often among PHIV participants than PHEU participants (9% vs 3%, P = 0.02). After adjusting for HIV status and demographic covariates, both low 25-OHD and elevated PTH were associated with lower mean LV mass z-scores, whereas elevated PTH was associated with higher mean fractional shortening z-scores. Participants with low 25-OHD also had slightly higher mean LV end-systolic wall stress z-scores, but differences were more pronounced in PHEU participants than in PHIV participants. FGF-23 was inversely related to end-diastolic septal thickness, both overall and among PHIV participants.

Conclusions: In this cohort of PHIV and PHEU youth, we observed associations of 25-OHD, PTH, and FGF-23 with both structural and functional cardiac parameters, supporting links between bone mineral metabolism and cardiac status.

aDepartment of Cardiology, Boston Children's Hospital, Boston MA;

bCenter for Biostatistics in AIDS Research, Harvard T.H. Chan School of Public Health, Boston, MA;

cThe Saban Research Institute, Children's Hospital Los Angeles, Keck School of Medicine of USC, Los Angeles, CA;

dDivision of Pediatric Endocrinology, Department of Pediatrics, Diabetology and Wells Center for Pediatric Research, Indiana University School of Medicine, Indianapolis, IN;

eDepartment of Pediatrics, Tulane University School of Medicine, New Orleans, LA;

fUniversity of California, La Jolla, CA;

gDepartment of Pediatrics and Rady Children's Hospital, San Diego, CA;

hNutrition Department, University of California, Davis, CA;

iUSDA Western Human Nutrition Research Center, University of California, Davis, CA;

jDivision of Pediatric Clinical Research, Department of Pediatrics, Miller School of Medicine at the University of Miami, Miami, FL

kDepartment of Pediatrics, School of Medicine, Wayne State University, Detroit, MI.

Correspondence to: Renee Margossian, MD, Department of Cardiology, Boston Children's Hospital, 300 Longwood Avenue, Boston, MA 02115 (e-mail:

The Pediatric HIV/AIDS Cohort Study (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 T.H. Chan School of Public Health (HD052102) (Principal Investigator: George Seage; Project Director: Julie Alperen) and the Tulane University School of Medicine (HD052104) (Principal Investigator: Russell Van Dyke; Co-Principal Investigator: Ellen Chadwick; Project Director: Patrick Davis). This work was supported by the National Institutes of Health.

The authors have no conflicts of interest to disclose.

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The conclusions and opinions expressed in this article are those of the authors and do not necessarily reflect those of the National Institutes of Health or U.S. Department of Health and Human Services.

Received September 14, 2018

Accepted February 04, 2019

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