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Cardiovascular dysfunction and vitamin D status in childhood acute lymphoblastic leukemia survivors

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Abstract

Background

Vitamin D (25-OHD) has a role in bone health after treatment for cancer. 25-OHD deficiency has been associated with risk factors for cardiovascular disease, but no data focusing on this topic in childhood cancer survivors have been published. We investigated the 25-OHD status in children treated for acute lymphoblastic leukemia (ALL), and evaluated its influence on vascular function.

Methods

25-OHD levels were evaluated in 52 ALL survivors and 40 matched healthy controls. Patients were grouped according to 25-OHD level (< 20 ng/m or ≥ 20 ng/ml). Auxological parameters, biochemical and hemostatic markers of endothelial function (AD, HMW-AD, ET-1, vWFAg, TAT, D-dimers, Fbg, and hs-CRP), ultrasound markers of vascular endothelial function (flow-mediated dilatation, FMD, common carotid intima-media thickness, C-IMT, and antero-posterior diameter of infra-renal abdominal aorta, APAO) were evaluated in the patients.

Results

Cases showed higher prevalence of 25-OHD deficiency than controls (p = 0.002). In univariate analysis via mean comparisons, 25-OHD deficient (< 20 ng/ml) patients showed higher C-IMT values compared to the 25-OHD non-deficient (≥ 20 ng/ml) group (P = 0.023). Significant differences were also found for ET-1 (P = 0.035) and AD-HMW (P = 0.015). In the multiple regression models controlling for some confounders, 25-OHD still was associated with C-IMT (P = 0.0163), ET-1 (P = 0.0077), and AD-HMW (P = 0.0008).

Conclusions

Childhood ALL survivors show higher prevalence of 25-OHD deficiency as compared to controls. The 25-OHD levels appear to be linked to indicators of endothelial and vascular dysfunction. Careful monitoring of 25-OHD balance may help to prevent cardiovascular diseases in childhood ALL survivors, characterized by high cardiovascular risk.

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Funding

No funding was secured for this study.

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Author notes

    Authors and Affiliations

    1. Department of Pediatric Oncology and Hematology, University Hospital of Policlinico, Piazza G. Cesare 11, 70124, Bari, Italy

      Paola Muggeo, Chiara Novielli & Nicola Santoro

    2. Department of Economical, Business and Statistical Sciences, University of Palermo, Palermo, Italy

      Vito Michele Rosario Muggeo

    3. Department of Biomedicine and Human Oncology, Pediatric Section, University “A. Moro”, Bari, Italy

      Paola Giordano, Maria Altomare & Maria Felicia Faienza

    4. Pediatric and Neonatology Unit, Mother and Children Health Care Department, “Madonna delle Grazie” Hospital, ASL Matera, Matera, Italy

      Maurizio Delvecchio

    5. Cardiovascular Diseases Section, Department of Emergency and Organ Transplantation, University “A. Moro”, Bari, Italy

      Marco Matteo Ciccone

    6. Neonatal Intensive Care Unit, Di Venere Hospital, Bari, Italy

      Gabriele D’Amato

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    1. Paola Muggeo
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    9. Maria Felicia Faienza
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    Contributions

    MFF and NS contributed equally to the work. PM has drawn the design of the study, wrote the manuscript until its final version; VMR Muggeo analyzed the data and critically revised the article; PG took part in the conception and the design of the study and revised the article; MD gave contribution to the analysis of data and to the drafting of the manuscript; MA made the acquisition of laboratory data; CN contributed mainly in the acquisition of data and drafting the article; MMC made the acquisition and interpretation of cardiovascular data, he also revised the article; GD contributed to the data interpretation and manuscript revising; MFF participated in the design of the study and interpretation of data, very critically and carefully revised the paper; NS participated in the conception and design of the study and revised the article. All the authors approved the final version.

    Corresponding author

    Correspondence to Paola Muggeo.

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    All procedures performed in the study were in accordance with the ethical standards of the institutional research committee and with the 1964 Helsinki declaration and its later amendments.

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    The authors have no conflicts of interest to disclose. No financial or non-financial benefits have been received or will be received from any party related directly or indirectly to the subject of this article.

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    Muggeo, P., Muggeo, V.M.R., Giordano, P. et al. Cardiovascular dysfunction and vitamin D status in childhood acute lymphoblastic leukemia survivors. World J Pediatr 15, 465–470 (2019). https://doi.org/10.1007/s12519-019-00258-y

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    • DOI: https://doi.org/10.1007/s12519-019-00258-y

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