Biomarkers of Pulmonary Hypertension Are Altered in Children with Down Syndrome and Pulmonary Hypertension

Area of Science:

• Pediatric Cardiology
• Pulmonary Hypertension Research
• Genetics and Disease

Background:

• Down syndrome is an independent risk factor for pulmonary hypertension (PH).
• Biomarker performance in PH may differ in unique genetic populations like those with Down syndrome.
• Accurate PH diagnosis and prognosis are crucial in pediatric populations.

Purpose of the Study:

• To evaluate the diagnostic performance of serum biomarkers for pulmonary hypertension (PH) in children with Down syndrome.
• To identify the most effective biomarkers for distinguishing PH, resolved PH, and no PH in children with Down syndrome.
• To assess if established PH biomarkers require population-specific evaluation.

Main Methods:

• Measured serum levels of endostatin, ST2, galectin-3, NT-proBNP, IL-6, and HDGF in four groups: Down syndrome with PH, Down syndrome with resolved PH, Down syndrome without PH, and non-Down syndrome PH.
• Utilized a classification tree model to differentiate PH status within the Down syndrome cohort.
• Assessed the discriminative ability of each biomarker for PH in children with Down syndrome.

Main Results:

• Endostatin, galectin-3, HDGF, and ST2 were elevated in children with Down syndrome irrespective of PH status.
• NT-proBNP and IL-6 levels did not significantly differ between Down syndrome with PH and non-Down syndrome PH groups.
• A classification tree identified NT-proBNP and galectin-3 as the most effective markers for distinguishing PH, resolved PH, and no PH in children with Down syndrome.

Conclusions:

• Standard proteomic markers for PH can be altered in genetically unique populations, such as individuals with Down syndrome.
• Population-specific nomograms are essential for accurate interpretation of clinical biomarkers in diverse groups.
• Biomarker evaluation in specific populations like Down syndrome is crucial for improving PH diagnosis and prognosis.