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Evaluation of asymmethric dimethylarginine levels in Down syndrome patients with congenital heart disease

Year 2019, , 235 - 238, 01.09.2019
https://doi.org/10.21601/ortadogutipdergisi.467383

Abstract

Aim: Pulmonary hypertension is a major cause of morbidity and mortality among Down syndrome patients with congenital heart disease. Asymmethric dimethyl arginine (ADMA) is an endogenous inhibitor of nitric oxide synthesis. Increased plasma levels of ADMA may be related with pulmonary hypertension. The aim of this study was to evaluate the relationship between ADMA and pulmonary hypertension in Down syndrome patients with congenital heart disease.
Material and Method: The study group consisted of 21 children with Down syndrome with congenital heart disease. Plasma ADMA concentrations were analyzed according to the presence or absence of pulmonary hypertension.
Results: The mean age of the 21 patients was 29.7±23.5 months (range: 3-88 months). Six patients with congenital heart disease had accompanied with pulmonary hypertension. Fifteen patients had no pulmonary hypertension. The levels of ADMA showed no statistically significant difference between the groups (p >0.05).
Conclusion: No correlation was shown between ADMA levels and pulmonary hypertension in children with Down syndrome with congenital heart disease. However, multicenter prospective studies with enlarged sample sized are needed to provide more realistic results about the connection between ADMA and pulmonary hypertension in Down syndrome children.

References

  • Leiper J, Vallance P. Biological significance of endogenous methylarginines that inhibit nitric oxide synthases. Cardiovascular Research 1999; 43: 542-8.
  • Winkler MS, Nierhaus A, Rösler G, ve ark. Symmetrical (SDMA) and asymmetrical dimethylarginine (ADMA) in sepsis: high plasma levels as combined risk markers for sepsis survival. Critical Care 2018; 22: 216.
  • Kielstein JT, Impraim B, Simmel S, ve ark. Cardiovascular effects of systemic nitric oxide synthase inhibition with asymmetrical dimethylarginine in humans. Circulation 2004; 109: 172-7.
  • Böger RH, Maas R, Schulze F, Schwedhelm E. Asymmetric dimethylarginine (ADMA) as a prospective marker of cardiovascular disease and mortality—an update on patient populations with a wide range of cardiovascular risk. Pharmacological Research 2009; 60: 481-7.
  • Siegerink B, Maas R, Vossen CY, ve ark. Asymmetric and symmetric dimethylarginine and risk of secondary cardiovascular disease events and mortality in patients with stable coronary heart disease: the KAROLA follow-up study. Clinical Research in Cardiology 2013; 102: 193-202.
  • Abbag FI. Congenital heart diseases and other major anomalies in patients with Down syndrome. Saudi Medical J. 2006; 27: 219-22.
  • Alharbi KM, Al-Mazroea AH, Abdallah AM, Almohammadi Y, Carlus SJ, Basit S. Targeted Next-Generation Sequencing of 406 Genes Identified Genetic Defects Underlying Congenital Heart Disease in Down Syndrome Patients. Pediatric Cardiology 2018: 1-5.
  • Martin T, Smith A, Breatnach CR, ve ark. Infants born with down syndrome: burden of disease in the early neonatal period. J Pediatr 2018; 193: 21-6.
  • Kielstein JT, Donnerstag F, Gasper S, ve ark. ADMA increases arterial stiffness and decreases cerebral blood flow in humans. Stroke 2006; 37: 2024-9.
  • Dimitroulas T, Giannakoulas G, Sfetsios T, ve ark. Asymmetrical dimethylarginine in systemic sclerosis-related pulmonary arterial hypertension. Rheumatology 2008; 47: 1682-5.
  • Pullamsetti S, Kiss L, Ghofrani HA, ve ark. Increased levels and reduced catabolism of asymmetric and symmetric dimethylarginines in pulmonary hypertension. The FASEB J 2005; 19: 1175-7.
  • Cua CL, Rogers LK, Chicoine LG, ve ark. Down syndrome patients with pulmonary hypertension have elevated plasma levels of asymmetric dimethylarginine. EurJ Pediatr 2011; 170: 859-63.
  • Warwick G, Thomas P, Yates D. Biomarkers in pulmonary hypertension. European Respiratory J 2008; 32: 503-12.
  • Sanli C, Oguz D, Olgunturk R, ve ark. Elevated homocysteine and asymmetric dimethyl arginine levels in pulmonary hypertension associated with congenital heart disease. Pediatric Cardiol 2012; 33: 1323-31.
  • Lücke T, Kanzelmeyer N, Kemper MJ, Tsikas D, Das AM. Developmental changes in the L-arginine/nitric oxide pathway from infancy to adulthood: plasma asymmetric dimethylarginine levels decrease with age. Clin Chemical Lab Med 2007; 45: 1525-30.
  • Tsikas D. A critical review and discussion of analytical methods in the L-arginine/nitric oxide area of basic and clinical research. Analytical Biochem 2008; 379: 139.
  • Kielstein JT, Bode-Böger SM, Hesse G, ve ark. Asymmetrical dimethylarginine in idiopathic pulmonary arterial hypertension. Arteriosclerosis, Thrombosis, Vascular Biol 2005; 25: 1414-8.

Konjenital kalp hastalığı bulunan Down sendromlu olguların asimetrik dimetilarjinin düzeylerinin değerlendirilmesi

Year 2019, , 235 - 238, 01.09.2019
https://doi.org/10.21601/ortadogutipdergisi.467383

Abstract

Amaç: Konjenital kalp hastalığı bulunan Down sendromlu hastalarda pulmoner hipertansiyon önemli bir morbidite ve mortalite nedenidir. Asimetrik dimetil arjinin (ADMA) nitrik oksit sentezinin endojen inhibitörüdür. Artmış plazma ADMA seviyeleri pulmoner hipertansiyonla ilişkili olabilir. Bu çalışmanın amacı konjenital kalp hastalığı bulunan Down sendromlu hastalarda pulmoner hipertansiyon ve ADMA arasındaki ilişkinin değerlendirilmesidir.
Gereç ve Yöntem: Çalışma grubunu konjenital kalp hastalığı bulunan 21 Down sendromlu çocuk oluşturmaktadır. Plazma ADMA konsantrasyonları pulmoner hipertansiyon olup olmamasına göre analiz edildi.
Bulgular: 21 hastanın ortalama yaşı 29,7±23,5 ay (3-88 ay) idi. Konjenital kalp hastalıklı altı hastaya pulmoner hipertansiyon eşlik etmekte idi. On beş hastada pulmoner hipertansiyon yoktu. ADMA seviyeleri açısından gruplar arasında istatistiksel olarak fark saptanmadı (p >0,05).
Sonuçlar: Konjenital kalp hastalığı bulunan Down sendromlu çocuklarda pulmoner hipertansiyon ile ADMA seviyeleri arasında ilişki görülmedi. Bununla birlikte, Down sendromlu çocuklarda ADMA ve pulmoner hipertansiyon arasındaki ilişkinin saptanmasında daha gerçekçi sonuçlar elde etmek için geniş örneklem içeren prospektif, çok merkezli çalışmalara ihtiyaç vardır.

References

  • Leiper J, Vallance P. Biological significance of endogenous methylarginines that inhibit nitric oxide synthases. Cardiovascular Research 1999; 43: 542-8.
  • Winkler MS, Nierhaus A, Rösler G, ve ark. Symmetrical (SDMA) and asymmetrical dimethylarginine (ADMA) in sepsis: high plasma levels as combined risk markers for sepsis survival. Critical Care 2018; 22: 216.
  • Kielstein JT, Impraim B, Simmel S, ve ark. Cardiovascular effects of systemic nitric oxide synthase inhibition with asymmetrical dimethylarginine in humans. Circulation 2004; 109: 172-7.
  • Böger RH, Maas R, Schulze F, Schwedhelm E. Asymmetric dimethylarginine (ADMA) as a prospective marker of cardiovascular disease and mortality—an update on patient populations with a wide range of cardiovascular risk. Pharmacological Research 2009; 60: 481-7.
  • Siegerink B, Maas R, Vossen CY, ve ark. Asymmetric and symmetric dimethylarginine and risk of secondary cardiovascular disease events and mortality in patients with stable coronary heart disease: the KAROLA follow-up study. Clinical Research in Cardiology 2013; 102: 193-202.
  • Abbag FI. Congenital heart diseases and other major anomalies in patients with Down syndrome. Saudi Medical J. 2006; 27: 219-22.
  • Alharbi KM, Al-Mazroea AH, Abdallah AM, Almohammadi Y, Carlus SJ, Basit S. Targeted Next-Generation Sequencing of 406 Genes Identified Genetic Defects Underlying Congenital Heart Disease in Down Syndrome Patients. Pediatric Cardiology 2018: 1-5.
  • Martin T, Smith A, Breatnach CR, ve ark. Infants born with down syndrome: burden of disease in the early neonatal period. J Pediatr 2018; 193: 21-6.
  • Kielstein JT, Donnerstag F, Gasper S, ve ark. ADMA increases arterial stiffness and decreases cerebral blood flow in humans. Stroke 2006; 37: 2024-9.
  • Dimitroulas T, Giannakoulas G, Sfetsios T, ve ark. Asymmetrical dimethylarginine in systemic sclerosis-related pulmonary arterial hypertension. Rheumatology 2008; 47: 1682-5.
  • Pullamsetti S, Kiss L, Ghofrani HA, ve ark. Increased levels and reduced catabolism of asymmetric and symmetric dimethylarginines in pulmonary hypertension. The FASEB J 2005; 19: 1175-7.
  • Cua CL, Rogers LK, Chicoine LG, ve ark. Down syndrome patients with pulmonary hypertension have elevated plasma levels of asymmetric dimethylarginine. EurJ Pediatr 2011; 170: 859-63.
  • Warwick G, Thomas P, Yates D. Biomarkers in pulmonary hypertension. European Respiratory J 2008; 32: 503-12.
  • Sanli C, Oguz D, Olgunturk R, ve ark. Elevated homocysteine and asymmetric dimethyl arginine levels in pulmonary hypertension associated with congenital heart disease. Pediatric Cardiol 2012; 33: 1323-31.
  • Lücke T, Kanzelmeyer N, Kemper MJ, Tsikas D, Das AM. Developmental changes in the L-arginine/nitric oxide pathway from infancy to adulthood: plasma asymmetric dimethylarginine levels decrease with age. Clin Chemical Lab Med 2007; 45: 1525-30.
  • Tsikas D. A critical review and discussion of analytical methods in the L-arginine/nitric oxide area of basic and clinical research. Analytical Biochem 2008; 379: 139.
  • Kielstein JT, Bode-Böger SM, Hesse G, ve ark. Asymmetrical dimethylarginine in idiopathic pulmonary arterial hypertension. Arteriosclerosis, Thrombosis, Vascular Biol 2005; 25: 1414-8.
There are 17 citations in total.

Details

Primary Language Turkish
Subjects Health Care Administration
Journal Section Original article
Authors

Esma Altınel Açoğlu 0000-0003-0333-6979

Emine Polat 0000-0003-3034-5037

Publication Date September 1, 2019
Published in Issue Year 2019

Cite

Vancouver Altınel Açoğlu E, Polat E. Konjenital kalp hastalığı bulunan Down sendromlu olguların asimetrik dimetilarjinin düzeylerinin değerlendirilmesi. otd. 2019;11(3):235-8.

e-ISSN: 2548-0251

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