Research Article
BibTex RIS Cite

Distribution of asymmetric dimethylarginine in elderly population and its relationship with traditional cardiovascular risk factors

Year 2021, Volume: 2 Issue: 3, 102 - 107, 29.09.2021

Abstract

Objectives: The endogenous nitric oxide synthesis inhib-itor asymmetric dimethylarginine (ADMA) has emerged as a new cardiovascular risk factor, especially in recent years. We conducted this study to evaluate the ADMA plasma concentration distributions and the relationship of ADMA with other cardiovascular risk factors, pulse wave velocity (NDH) and augmentation index (Alx) in elderly individuals.
Methods: This study was carried out as a part of the pro-ject called “health screening for the elderly” in Ankara Mamak district. All the elderly people in the region were invited for health screening with the calls made by the municipality and the headmen. Those who were severely debilitated, such as those with previously known ad-vanced stage organ failure, and whose laboratory tests could not perform were excluded from the study. While 966 people were evaluated in the total, 234 participants were excluded in the analysis. Participants' anamnesis were taken and detailed physical examinations were per-formed. Serum ADMA measurements were made by a single person using the Elisa method. SphygmoCor® Pulse Wave Velocity System device was used for NDH and Alx measurement. NDH measurements were evaluat-ed by a computer program on the same instrument, and results were obtained in m/s ± standard deviation.
Results: The median age of the 966 participants was 70.3±6.4, and %49.6 of the participants were women. We found the mean ADMA level 0.85±0.38 µmol/L. In the correlation analysis evaluation, there was no correlation between ADMA and age, blood pressure, body mass in-dex, LDL cholesterol, HDL cholesterol, triglyceride, creatine, GFR and CRP levels. While there was a signifi-cant positive correlation between ALT levels (rho:0.106, p:0.001) and total cholesterol levels (rho:0.064, p:0.047) with ADMA, there was a negative correlation between fasting blood glucose (rho:-0.072, p:0.026) and ADMA, but all of these relationships were very weak. NDH and Alx were not significantly associated with ADMA con-centrations. In multiple regression analysis, only 1/3 of ADMA levels can be explained when an appropriate model is created with LDL, HDL, triglyceride, total cho-lesterol, ALT, and creatine.
Conclusion: The ADMA mean of the participants in our population was 0.85±0.38 µmol/l. The relationship be-tween ADMA levels and known cardiovascular risk fac-tors is low. Cohort studies are needed to reveal the rela-tionship between ADMA levels and cardiovascular dis-eases.

References

  • 1. Harrison DG. Endothelial dysfunction in atheroscle-rosis. Basic Research in Cardiology 1994;89 Suppl 1:87-102.
  • 2. Sibal L, Agarwal SC, Home PD, Boger RH. The role of asymmetric dimethylarginine (ADMA) in endothe-lial dysfunction and cardiovascular disease. Current Cardiology Reviews 2010;6(2):8290.
  • 3. MacAllister RJ, Parry H, Kimoto M, et al. Regulation of nitric oxide synthesis by dimethylarginine dimethy-laminohydrolase. British Journal of Pharmacology 1996;119(8):1533-40.
  • 4. Cooke JP. Asymmetrical dimethylarginine: The Uber marker? Circulation 2004;109(15):1813-8.
  • 5. Schnabel R, Blankenberg S, Lubos E, Lackner KJ, Rupprecht HJ, Espinola K. ADMA and the risk of cardiovascular events and death in patients with coro-nary artery disease: Results from the AtheroGene Study. Circ Res 2005;97:53-9.
  • 6. Iribarren C, Husson G, Sydow K, Wang B-Y, Sidney S, Cooke JP. Asymmetric dimethyl-arginine and coro-nary artery calcification in young adults entering midd-le age: The CARDIA Study. European Journal of Car-diovascular Prevention and Rehabilitation 2007;14(2):222-9.
  • 7. Ngo DT, Sverdlov AL, McNeil JJ, Horowitz JD. Correlates of arterial stiffness in an ageing population: role of asymmetric dimethylarginine. Pharmacol Res 2009;60(6):503-7.
  • 8. Schlesinger S, Sonntag SR, Lieb W, Maas R. Asym-metric and symmetric dimethylarginine as risk markers for total mortality and cardiovascular outcomes: A systematic review and meta-analysis of prospective studies. PloS One 2016;11(11), e0165811.
  • 9. Schulze F, Maas R, Freese R, Schwedhelm E, Silber-horn E, Böger RH. Determination of a reference value for N(G), N(G)- dimethyl-L-arginine in 500 subjects. European Journal of Clinical Investigation 2005;35(10):622-6.
  • 10. Sydow K, Fortmann SP, Fair JM, et al. Distribution of asymmetric dimethylarginine among 980 healthy, older adults of different ethnicities. Clinical Chemistry 2010; 56(1):111-20.
  • 11. Anderssohn M, Schwedhelm E, Lüneburg N, Vasan RS, Böger RH. Asymmetric dimethylarginine as a medi-ator of vascular dysfunction and a marker of cardiovas-cular disease and mortality: An intriguing interaction with diabetes mellitus. Diabetes & Vascular Disease Research 2010;7(2):105-18.
  • 12. Schwedhelm E. Quantification of ADMA: Analyti-cal approaches. Vascular Medicine (London, England), 2005;10 Suppl 1:S89-95.
  • 13. Chirinos JA, David R, Bralley A, et al. Endogenous nitric oxide synthase inhibitors, arterial hemodyna-mics, and subclinical vascular disease: The PREVEN-CION Study. Hypertension 2008;52(6):1051-9.
  • 14. Päivä H, Kähönen M, Lehtimäki T, et al. Asymmet-ric dimethylarginine (ADMA) has a role in regulating systemic vascular tone in young healthy subjects: The cardiovascular risk in young Finns study. American Journal of Hypertension 2008;21(8):873-8.
  • 15. Yilmaz MI, Saglam M, Caglar K, et al. The determi-nants of endothelial dysfunction in CKD: Oxidative stress and asymmetric dimethylarginine. Am J Kidney Dis 2006;47(1):42-50.
  • 16. Liu X, Xu X, Shang R, Che Y. Asymmetric di-methylarginine (ADMA) as an important risk factor for the increased cardiovascular diseases and heart failure in chronic kidney disease. Nitric Oxide: Biology and Chemistry 2018;78:113-20.
  • 17. Lluch P, Segarra G, Medina P. Asymmetric dimethy-larginine as a mediator of vascular dysfunction in cirr-hosis. World Journal of Gastroenterology 2015;21(32):9466-75.
  • 18. Adams MR, Kinlay S, Blake GJ, Orford JL, Ganz P, Selwyn AP. Atherogenic lipids and endothelial dys-function: Mechanisms in the genesis of ischemic synd-romes. Annual Review of Medicine 2000;51:149-67.
  • 19. Maas R, Schwedhelm E, Kahl L, et al. Simultaneous assessment of endothelial function, nitric oxide synt-hase activity, nitric oxide-mediated signaling, and oxidative stress in individuals with and without hy-percholesterolemia. Clinical Chemistry 2008;54(2):292-300.

Yaşlı popülasyonda asimetrik dimetilarjinin dağılımı ve geleneksel kardiyovasküler risk faktörleri ile arasındaki ilişki

Year 2021, Volume: 2 Issue: 3, 102 - 107, 29.09.2021

Abstract

Amaç: Endojen nitrik oksit sentez inhibitörü asimetrik dimetilarjinin (ADMA) özellikle son yıllarda yeni bir kardiyovasküler risk faktörü olarak ortaya çıkmaktadır. Biz bu çalışmayı AD-MA plazma konsantrasyon dağılımlarını, AD-MA’nın diğer kardiyovasküler risk faktörleriyle, nabız dalga hızı (NDH) ve augmentasyon indek-siyle (Alx) ilişkisini değerlendirmek için yaptık.
Yöntem: Bu çalışma, Ankara Mamak ilçesinde “yaşlılarda sağlık taraması” ismiyle yürütülen projenin bir parçası olarak gerçekleştirildi. Beledi-ye ve muhtarların yaptığı çağrılarla bölgedeki tüm yaşlılar sağlık taraması için davet edildiler. Daha önceden bilinen ileri evre organ yetmezliği olanlar gibi ileri derecede düşkün olanlar ve laboratuvar tetkiklerini yaptıramayanlar çalışmaya alınmadı-lar. Toplamda 966 kişi değerlendirmeye alınırken, 234 katılımcı kriterleri karşılamaması nedeni ile analize alınmadı. Katılımcılar öyküleri alındı ve ayrıntılı fizik muayeneleri yapıldı. Serum ADMA ölçümleri ELISA yöntemi kullanılarak tek bir kişi tarafından yapıldı. NDH ve Alx ölçümünde SphygmoCor® Pulse Wave Velocity System cihazı kullanıldı. NDH ölçümleri aynı cihazdaki bir bilgisayar programı tarafından değerlendirildi ve sonuçlar m/sn ± standart sapma şeklinde elde edildi.
Bulgular: Çalışmaya alınan 966 katılımcının ortanca yaşı 70.3±6.4 olup, katılımcıların %49.6'sı kadındı. Tüm popülasyonun ADMA ortalamasını 0.85±0.38 µmol/L olarak bulduk. Yapılan kore-lasyon analizi değerlendirmesinde, ADMA ile yaş, kan basıncı, vücut kitle indeksi, LDL kolesterol, HDL kolesterol, trigliserit, kreatin, GFR, CRP düzeyleri arasında korelasyon yoktu. ALT düzey-leri (rho:0.106, p:0.001) ve total kolesterol düzey-leri (rho:0.064, p:0.047) ile ADMA düzeyleri arasında anlamlı pozitif korelasyon var iken açlık kan şekeri (rho:-0.072, p:0.026) ile ADMA düzey-leri arasında anlamlı negatif korelasyon vardı ancak bu ilişkilerin tümü çok zayıf düzeydeydi. NDH ve Alx’in ADMA konsantrasyonları ile anlamlı ilişkisi yoktu. Çoklu regresyon analizinde LDL, HDL, trigliserit, total kolesterol, ALT, krea-tin ile uygun model oluşturulduğunda ADMA düzeylerinin ancak 1/3’lük kısmı açıklanabilmek-tedir.
Sonuç: Popülasyonumuzdaki katılımcıların AD-MA ortalaması 0.85±0.38 µmol/l’dir. ADMA düzeylerinin bilinen kardiyovasküler risk faktör-leriyle ilişkisi düşük düzeydedir. ADMA düzeyle-rinin kardiyovasküler hastalıklar ile ilişkisini ortaya koyacak kohort çalışmalara ihtiyaç bulun-maktadır.

References

  • 1. Harrison DG. Endothelial dysfunction in atheroscle-rosis. Basic Research in Cardiology 1994;89 Suppl 1:87-102.
  • 2. Sibal L, Agarwal SC, Home PD, Boger RH. The role of asymmetric dimethylarginine (ADMA) in endothe-lial dysfunction and cardiovascular disease. Current Cardiology Reviews 2010;6(2):8290.
  • 3. MacAllister RJ, Parry H, Kimoto M, et al. Regulation of nitric oxide synthesis by dimethylarginine dimethy-laminohydrolase. British Journal of Pharmacology 1996;119(8):1533-40.
  • 4. Cooke JP. Asymmetrical dimethylarginine: The Uber marker? Circulation 2004;109(15):1813-8.
  • 5. Schnabel R, Blankenberg S, Lubos E, Lackner KJ, Rupprecht HJ, Espinola K. ADMA and the risk of cardiovascular events and death in patients with coro-nary artery disease: Results from the AtheroGene Study. Circ Res 2005;97:53-9.
  • 6. Iribarren C, Husson G, Sydow K, Wang B-Y, Sidney S, Cooke JP. Asymmetric dimethyl-arginine and coro-nary artery calcification in young adults entering midd-le age: The CARDIA Study. European Journal of Car-diovascular Prevention and Rehabilitation 2007;14(2):222-9.
  • 7. Ngo DT, Sverdlov AL, McNeil JJ, Horowitz JD. Correlates of arterial stiffness in an ageing population: role of asymmetric dimethylarginine. Pharmacol Res 2009;60(6):503-7.
  • 8. Schlesinger S, Sonntag SR, Lieb W, Maas R. Asym-metric and symmetric dimethylarginine as risk markers for total mortality and cardiovascular outcomes: A systematic review and meta-analysis of prospective studies. PloS One 2016;11(11), e0165811.
  • 9. Schulze F, Maas R, Freese R, Schwedhelm E, Silber-horn E, Böger RH. Determination of a reference value for N(G), N(G)- dimethyl-L-arginine in 500 subjects. European Journal of Clinical Investigation 2005;35(10):622-6.
  • 10. Sydow K, Fortmann SP, Fair JM, et al. Distribution of asymmetric dimethylarginine among 980 healthy, older adults of different ethnicities. Clinical Chemistry 2010; 56(1):111-20.
  • 11. Anderssohn M, Schwedhelm E, Lüneburg N, Vasan RS, Böger RH. Asymmetric dimethylarginine as a medi-ator of vascular dysfunction and a marker of cardiovas-cular disease and mortality: An intriguing interaction with diabetes mellitus. Diabetes & Vascular Disease Research 2010;7(2):105-18.
  • 12. Schwedhelm E. Quantification of ADMA: Analyti-cal approaches. Vascular Medicine (London, England), 2005;10 Suppl 1:S89-95.
  • 13. Chirinos JA, David R, Bralley A, et al. Endogenous nitric oxide synthase inhibitors, arterial hemodyna-mics, and subclinical vascular disease: The PREVEN-CION Study. Hypertension 2008;52(6):1051-9.
  • 14. Päivä H, Kähönen M, Lehtimäki T, et al. Asymmet-ric dimethylarginine (ADMA) has a role in regulating systemic vascular tone in young healthy subjects: The cardiovascular risk in young Finns study. American Journal of Hypertension 2008;21(8):873-8.
  • 15. Yilmaz MI, Saglam M, Caglar K, et al. The determi-nants of endothelial dysfunction in CKD: Oxidative stress and asymmetric dimethylarginine. Am J Kidney Dis 2006;47(1):42-50.
  • 16. Liu X, Xu X, Shang R, Che Y. Asymmetric di-methylarginine (ADMA) as an important risk factor for the increased cardiovascular diseases and heart failure in chronic kidney disease. Nitric Oxide: Biology and Chemistry 2018;78:113-20.
  • 17. Lluch P, Segarra G, Medina P. Asymmetric dimethy-larginine as a mediator of vascular dysfunction in cirr-hosis. World Journal of Gastroenterology 2015;21(32):9466-75.
  • 18. Adams MR, Kinlay S, Blake GJ, Orford JL, Ganz P, Selwyn AP. Atherogenic lipids and endothelial dys-function: Mechanisms in the genesis of ischemic synd-romes. Annual Review of Medicine 2000;51:149-67.
  • 19. Maas R, Schwedhelm E, Kahl L, et al. Simultaneous assessment of endothelial function, nitric oxide synt-hase activity, nitric oxide-mediated signaling, and oxidative stress in individuals with and without hy-percholesterolemia. Clinical Chemistry 2008;54(2):292-300.
There are 19 citations in total.

Details

Primary Language Turkish
Subjects Health Care Administration
Journal Section Articles
Authors

Ersen Karakılıç

Sim Kutlay This is me 0000-0001-6385-2129

Teslime Atlı This is me 0000-0001-7359-4856

Publication Date September 29, 2021
Submission Date September 16, 2021
Published in Issue Year 2021 Volume: 2 Issue: 3

Cite

APA Karakılıç, E., Kutlay, S., & Atlı, T. (2021). Yaşlı popülasyonda asimetrik dimetilarjinin dağılımı ve geleneksel kardiyovasküler risk faktörleri ile arasındaki ilişki. Troia Medical Journal, 2(3), 102-107.
AMA Karakılıç E, Kutlay S, Atlı T. Yaşlı popülasyonda asimetrik dimetilarjinin dağılımı ve geleneksel kardiyovasküler risk faktörleri ile arasındaki ilişki. Troia Med J. September 2021;2(3):102-107.
Chicago Karakılıç, Ersen, Sim Kutlay, and Teslime Atlı. “Yaşlı popülasyonda Asimetrik Dimetilarjinin dağılımı Ve Geleneksel kardiyovasküler Risk faktörleri Ile arasındaki ilişki”. Troia Medical Journal 2, no. 3 (September 2021): 102-7.
EndNote Karakılıç E, Kutlay S, Atlı T (September 1, 2021) Yaşlı popülasyonda asimetrik dimetilarjinin dağılımı ve geleneksel kardiyovasküler risk faktörleri ile arasındaki ilişki. Troia Medical Journal 2 3 102–107.
IEEE E. Karakılıç, S. Kutlay, and T. Atlı, “Yaşlı popülasyonda asimetrik dimetilarjinin dağılımı ve geleneksel kardiyovasküler risk faktörleri ile arasındaki ilişki”, Troia Med J, vol. 2, no. 3, pp. 102–107, 2021.
ISNAD Karakılıç, Ersen et al. “Yaşlı popülasyonda Asimetrik Dimetilarjinin dağılımı Ve Geleneksel kardiyovasküler Risk faktörleri Ile arasındaki ilişki”. Troia Medical Journal 2/3 (September 2021), 102-107.
JAMA Karakılıç E, Kutlay S, Atlı T. Yaşlı popülasyonda asimetrik dimetilarjinin dağılımı ve geleneksel kardiyovasküler risk faktörleri ile arasındaki ilişki. Troia Med J. 2021;2:102–107.
MLA Karakılıç, Ersen et al. “Yaşlı popülasyonda Asimetrik Dimetilarjinin dağılımı Ve Geleneksel kardiyovasküler Risk faktörleri Ile arasındaki ilişki”. Troia Medical Journal, vol. 2, no. 3, 2021, pp. 102-7.
Vancouver Karakılıç E, Kutlay S, Atlı T. Yaşlı popülasyonda asimetrik dimetilarjinin dağılımı ve geleneksel kardiyovasküler risk faktörleri ile arasındaki ilişki. Troia Med J. 2021;2(3):102-7.