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Pediatr Cardiol. 2012 Dec;33(8):1323-31. doi: 10.1007/s00246-012-0321-9. Epub 2012 Apr 21.

Elevated homocysteine and asymmetric dimethyl arginine levels in pulmonary hypertension associated with congenital heart disease.

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Department of Pediatric Cardiology, Kirikkale University Medical School, Fabrikalar Mahallesi, Sağlık Sokak, 71100, Kirikkale, Turkey.


Pulmonary arterial hypertension (PAH) is a major cause of morbidity and mortality among patients with congenital heart disease (CHD). This study was designed to determine biomarker levels in patients with PAH associated with CHD (PAH-CHD) and CHD patients without PAH and to investigate the relationship of these potential biomarkers with hemodynamic findings. In this prospective single-center study, patients with CHD were analyzed according to the presence or absence of PAH and compared with healthy control subjects. Cardiac catheterization and echocardiographs were performed. Plasma homocysteine, asymmetric dimethyl arginine (ADMA), and nitric oxide (NO) levels were determined by enzyme-linked immunosorbent assay. Homocysteine and ADMA levels were higher in the PAH-CHD group (n = 30) than among CHD patients with left-to-right shunting but no PAH (n = 20; P < 0.001) and healthy control subjects (n = 20; P < 0.001). There was no difference in NO levels. Cyanotic PAH-CHD patients had significantly higher homocysteine than acyanotic patients in the same group. No correlation was shown between echocardiographic/hemodynamic parameters and homocysteine, ADMA, and NO levels. Homocysteine and ADMA levels are increased in patients with PAH-CHD. These parameters have the potential to be used as biomarkers in the diagnosis and follow-up evaluation of patients with PAH-CHD. However, large, multicentered prospective studies are required to facilitate routine use of these biologic markers in the clinical setting.

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