Medical Professional Publications

Chemical Found in Blood Plasma May be Linked to Pulmonary Hypertension in Down Syndrome Patients

Could Serve as a New Therapeutic Target and Biomarker for High Blood Pressure in This Population

A chemical found in blood plasma may serve as a therapeutic target and a biomarker for high blood pressure in Down syndrome patients, suggests new research from Nationwide Children’s Hospital.

Down syndrome patients are at increased risk for developing abnormally high blood pressure known as pulmonary hypertension. “Pulmonary hypertension is increasingly being recognized in Down syndrome patients,” said Clifford L. Cua, MD, clinical cardiologist and cardiac intensivist at Nationwide Children’s and one of the study authors. “It’s important that we begin to identify ways to determine which of these patients are most at risk and identify treatment options we may be able to provide.  Despite the multiple possible causes of high blood pressure in Down syndrome patients, it’s likely that there are common biological pathways that disrupt blood vessel dilation.”

Nitric oxide plays an important part in mechanisms that regulate blood vessel dilation throughout the human body.  Abnormalities in nitric oxide production have been implicated in the development of pulmonary hypertension.

Asymmetric dimethylarginine (ADMA) is a naturally occurring component of human blood plasma that inhibits nitric oxide production. Higher levels of serum ADMA have been found in adult patients with idiopathic pulmonary hypertension as well as pulmonary hypertension due to systemic sclerosis.  

To determine whether plasma levels of ADMA differ between Down syndrome patients with pulmonary hypertension compared to Down syndrome patients without pulmonary hypertension, Dr. Cua and colleagues at Nationwide Children’s Hospital examined blood samples from 18 of these patients.  Venous blood samples were collected on the day of cardiac catheterization in Down syndrome patients suspected of having pulmonary hypertension.  In those patients that did not have an echocardiographic evidence of pulmonary hypertension, blood was drawn at a time when another blood draw was being performed for routine clinical purposes.

The findings showed that plasma levels of ADMA were nearly twofold greater in Down syndrome patients with pulmonary hypertension than in those Down syndrome patients without pulmonary hypertension.

“Larger studies are needed to support this initial finding,” said Leif Nelin, MD, director of the Center for Perinatal Research at The Research Institute and one of the study authors. “Theoretically, increasing arginine levels or inhibiting ADMA in Down syndrome patients with pulmonary hypertension may improve their outcome.”  In addition to suggesting therapeutic targets, this study also suggests that ADMA and/or arginine may be valuable biomarkers in determining presence of pulmonary hypertension in Down syndrome patients.

Cua CL, Rogers LK, Chicoine LG, Augustine M, Jin Y, Nash PL, Nelin LD. Down syndrome patients with pulmonary hypertension have elevated plasma levels of asymmetric dimethylarginine. Eur J Pediatr. 2010 Dec 1. [Epub ahead of print]

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