Lipocalin 2: could it be a new biomarker in pediatric pulmonary hypertension associated with congenital heart disease?

¹ Department of Echocardiography, Capital Medical University, Beijing Children’s Hospital, National Center for Children’s Health, 100045 Beijing, China

² Division of Cardiology, Capital Medical University, Beijing Anzhen Hospital, 100045 Beijing, China

³ Section of Cardiology, Baylor College of Medicine, Houston, TX 77030, USA

⁴ Department of Medicine, Indiana University School of Medicine, Indianapolis, IN 46617, USA

⁵ Department of Cardiac Surgery, Capital Medical University, Beijing Children’s Hospital, National Center for Children’s Health, 100045 Beijing, China

^*Correspondence: maning_echo@163.com (Ning Ma)
Academic Editor: Brian Tomlinson

Rev. Cardiovasc. Med. 2021, 22(2), 531–536; https://doi.org/10.31083/j.rcm2202061

Submitted: 7 April 2021 | Revised: 28 May 2021 | Accepted: 10 June 2021 | Published: 30 June 2021

(This article belongs to the Special Issue State-of-the-Art Cardiovascular Medicine in Asia 2021)

This is an open access article under the CC BY 4.0 license (https://creativecommons.org/licenses/by/4.0/).

Abstract

The role of lipocalin 2 (LCN2) in pulmonary hypertension (PH) in pediatric patients with congenital heart disease (CHD) remains unclear. We sought to investigate whether LCN2 could be a potential biomarker for PH in pediatric patients who underwent surgery for CHD. From December 2018 to February 2020, patients undergoing surgical repair for congenital defects with and without PH were identified. Healthy children without CHD and PH served as controls. A mean pulmonary artery pressure (mPAP) $>$ 20 mmHg was used as the definition of PH. Blood samples and echocardiograms were obtained in all patients and right heart catheterization was performed in 79 patients. Multivariable logistic regression analysis was used to determine potential predictors for PH. Among 102 patients, the median age was 10 [Interquartile range (IQR) 7.0–13] months, and 37.5% were female. Compared to non-PH patients and controls, PH patients showed elevated levels of LCN2 (P $<$ 0.001). In addition, LCN2 levels positively correlated with the invasive haemodynamic indices of PH. In univariate regression, LCN2 (odds ratio = 2.69 [1.06–5.31], P $<$ 0.001), N-Terminal pro Brain Natriuretic Peptide (NT-proBNP) (OR = 1.91 [1.21–7.56], P = 0.03) and high-sensitive troponin T (hsTnT) (OR = 1.36 [1.01–3.57], P = 0.01) were associated with PH; however, only LCN2 (OR = 1.68 [1.04–4.52], P = 0.03) was significantly associated with PH on multivariate analysis. In conclusion, children with PH had increased LCN2 expression. LCN2 levels positively correlated with invasive indices of PH. These results indicate LCN2 could be a useful biomarker for prediction of PH in pediatric CHD cases.

Keywords

Congenital heart disease

Pulmonary hypertension

Lipocalin 2

Biomarkers

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