CURRENT KNOWLEDGE ON THE PREVENTION OF HYPERHOMOCYSTEINEMIA AS A RISK FACTOR FOR CARDIOVASCULAR DISEASES

  • Bojana Miladinovic Katedra za farmaciju, Medicinski fakultet Univerziteta u Nišu
  • Vladana Živković Medicinski fakultet Univerzitet u Nišu
  • Dušanka Kitić Katedra za farmaciju, Medicinski fakultet Univerzitet u Nišu
  • Maja Nikolić Medicinski fakultet Univerzitet u Nišu
DOI: https://doi.org/10.5937/afmnai40-36742
Keywords: homocysteine, prevention, atherosclerosis, chronic noncommunicable diseases

Abstract


Homocysteine ​​is an amino acid that is formed in the metabolism of methionine as the quantitatively most important metabolite. Its chemical structure has been known for 90 years and its biological roles are still being investigated. Under normal conditions, homocysteine ​​is present in plasma at a concentration of 5-9 μmol/l. When the cell capacity for homocysteine ​​is reached, it is transported to the extracellular space, until the intracellular level is normalized. If the cell is unable to reach the required levels of homocysteine, it ​​accumulates in the blood and hyperhomocysteinemia occurs. It has been determined that many factors, such as congenital enzyme deficiency, age, sex, inadequate diet (vitamin B complex deficiency) increase the level of homocysteine ​​in the blood. Impaired kidney function, diabetes, hyperthyroidism, as well as many medications, can have an effect on homocysteinemia. Increased concentration of homocysteine ​​in the blood accelerates the process of atherosclerosis by several different mechanisms and represents an independent risk factor for the occurrence of cardiovascular diseases and adverse cerebral events. The prevalence of hyperhomocysteinemia is estimated at 5% in the general population and 13 - 47% among patients with symptomatic atherosclerotic vascular disease. For these reasons, the level of homocysteine ​​in the blood should be monitored and corrective measures should be implemented, which include sufficient intake of folic acid, vitamins B12 and B6, in doses that depend on fasting homocysteine ​​levels and after the methionine load test.

References


  1. Pencina MJ, Navar AM, Wojdyla D, Sanchez RJ, Khan I, Elassal J. et al. Quantifying Importance of Major Risk Factors for Coronary Heart Disease. Circulation 2019; 139(13):1603-1611. 

  2. Bai MF, Wang X. Risk factors associated with coronary heart disease in women: a systematic review. Herz 2020; 45(Suppl 1):52-57

  3. Nikolić M. Značaj ishrane u sekundarnoj prevenciji i rehabilitaciji koronarne bolesti. Srce i krvni sudovi 2011; 30(4):206-209.

  4. Branković S, Miladinović B, Radenković M, Gočmanac Ignjatović M, Kostić M, Šavikin K, Kitić D. Hypotensive, cardiodepressant, and vasorelaxant activities of black currant (Ribes nigrum ‘Ben Sarek’) juice. Canadian Journal of Physiology and Pharmacology. 94(10): 1102-1105.

  5. Houston M.The role of noninvasive cardiovascular testing, applied clinical nutrition and nutritional supplements in the prevention and treatment of coronary heart disease.Ther Adv Cardiovasc Dis 2018; 12(3):85-108.

  6. Nikolić M. Glikemijski indeks namirnica i glikemijsko opterećenje kao faktori rizika za ishemijsku bolest srca (doktorska disertacija), Niš: Medicinski fakultet, 2004.

  7. Halasz G, Piepoli MF. Focus on atherosclerosis and lipids. Eur J Prev Cardiol 2020; 27(15):1571-1574.

  8. Ruiz-León AM, Lapuente M, Estruch R, Casas R. Clinical Advances in Immunonutrition and Atherosclerosis: A Review. Front Immunol 2019; 10:837.

  9. Kopin L, Lowenstein C. Ann Intern Med 2017; 167(11):ITC81-ITC96.

  10. Carson NA, Cusworth DC, Dent CE, FIield CM, Neill DW, Westall RG. Homocystinuria: A new inborn error of metabolism associated with mental deficiency. Arch Dis Child 1963; 38(201):425-36. 

  11. McCully KS. Vascular pathology of homocysteinemia: implications for the pathogenesis of arteriosclerosis. Am J Pathol 1969; 56(1):111-28.

  12. McCully KS. Homocysteine theory of arteriosclerosis: Development and current status. Athreroscl rev 1983;11: 157–246.

  13. McDonald MC, Dempsey GI, Nassar BA. Relation of a Common Mutation in Methylenetetrahydrofolate Reductaze to Plasma Homocysteine and Early Onset Coronary Artery Disease. Clin Biochem 1998; 31: 95 – 100.

  14. Ducker GS, Rabinowitz JD. One-Carbon Metabolism in Health and Disease.Cell Metab 2017; 25(1):27-42.

  15. Mirković D, Majkić N, Ignjatović S. Homocistein: Hemija, metabolizam i uloga u patofiziološkim procesima. Jugoslov Med Biohem 2003; 22: 127– 140.

  16. Kim J, Kim H, Roh H, Kwon Y. Causes of hyperhomocysteinemia and its pathological significance. Arch Pharm Res 2018; 41(4):372-383.

  17. Zaric BL, Obradovic M, Bajic V, Haidara MA, Jovanovic M, Isenovic ER. Homocysteine and Hyperhomocysteinaemia. Curr Med Chem 2019; 26(16):2948-2961.

  18. Chrysant SG, Chrysant GS. The current status of homocysteine as a risk factor for cardiovascular disease: a mini review. Expert Rev Cardiovasc Ther 2018; 16(8):559-565.

  19. Morris AA, Kožich V, Santra S, Andria G, Ben-Omran TI, Chakrapani AB, et al. Guidelines for the diagnosis and management of cystathionine beta-synthase deficiency. J Inherit Metab Dis 2017; 40(1):49-74.

  20. Bublil EM, Majtan T. Classical homocystinuria: From cystathionine beta-synthase deficiency to novel enzyme therapies. Biochimie 2020; 173:48-56.

  21. Srećković M. Ispitivanje homocisteina kao markera ateroskleroze kod pacijenata sa metaboličkim sindromom, Doktorska disertacija, Medicinski fakultet, Univerzitet u Beogradu, 2018.

  22. Guo W, Zhang H, Yang A, Ma P, Sun L, Deng M, et al. Homocysteine accelerates atherosclerosis by inhibiting scavenger receptor class B member1 via DNMT3b/SP1 pathway. J Mol Cell Cardiol 2020; 38:34-48. 

  23. Zhao J, Chen H, Liu N, Chen J, Gu Y, Chen J, et al. Role of Hyperhomocysteinemia and Hyperuricemia in Pathogenesis of Atherosclerosis. J Stroke Cerebrovasc Dis 2017; 26(12):2695-2699.

  24. Xu R, Huang F, Wang Y, Liu Q, Lv Y, Zhang Q. Gender- and age-related differences in homocysteine concentration: a cross-sectional study of the general population of China. Sci Rep 2020; 10(1):17401.

  25. Cohen E, Margalit I, Shochat T, Goldberg E, Krause I. Gender differences in homocysteine concentrations, a population-based cross-sectional study. Nutr Metab Cardiovasc Dis 2019; 29(1):9-14. 

  26. Osadnik T, Pawlas N, Lejawa M, Lisik M, Osadnik K, Fronczek M, et al. Genetic and environmental factors associated with homocysteine concentrations in a population of healthy young adults. Analysis of the MAGNETIC study. Nutr Metab Cardiovasc Dis 2020; 30(6):939-947. 

  27. Duthie SJ, Duthie GG, Russell WR, Kyle JAM, Macdiarmid JI, Rungapamestry V, et al. Effect of increasing fruit and vegetable intake by dietary intervention on nutritional biomarkers and attitudes to dietary change: a randomised trial. Eur J Nutr 2018; 57(5):1855-1872. 

  28. de Oliveira JJ, E Silva AS, Ribeiro AGSV, Barbosa CGR, de Oliveira Silva JA, Pontes AG, et.al. The effect of physical activity on total homocysteine concentrations and cardiovascular risk in older Brazilian adults with type 2 diabetes. J Diabetes Metab Disord 2021; 20(1):407-416.

  29. Froese DS, Fowler B, Baumgartner MR. Vitamin B (12), folate, and the methionine remethylation cycle-biochemistry, pathways, and regulation. J Inherit Metab Dis 2019; 42(4):673-685.

  30. Kaye AD, Jeha GM, Pham AD, Fuller MC, Lerner ZI, Sibley GT, et al. Folic Acid Supplementation in Patients with Elevated Homocysteine Levels. Adv Ther 2020; 37(10):4149-4164.

  31. Katsiki N, Perez-Martinez P, Mikhailidis DP. Homocysteine and Non-Cardiac Vascular Disease. Curr Pharm Des 2017; 23(22):3224-3232. 

  32. Vezzoli A, Dellanoce C, Caimi TM, Vietti D, Montorsi M, Mrakic-Sposta S, et al. Influence of Dietary Supplementation for Hyperhomocysteinemia Treatments. Nutrients 2020; 12(7):1957. 

  33. Nikolić M, Jović S: Ishrana i zdravlje. In: Nikolić M (ed.) Dijetetika, Niš:Medicinski fakultet, WUS 2007; 11-40.

  34. Tian T, Yang KQ, Cui JG, Zhou LL, Zhou XL. Folic Acid Supplementation for Stroke Prevention in Patients with Cardiovascular Disease. Am J Med Sci 2017; 354(4):379-387. 

  35. Brown MJ, Ameer MA, Beier K. Vitamin B6 Deficiency. 2021 Jul 25. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2021 Jan–.PMID: 29261855 

  36. Martí-Carvajal AJ, Solà I, Lathyris D, Dayer M. Homocysteine-lowering interventions for preventing cardiovascular events. Cochrane Database Syst Rev 2017; 8(8):CD006612.

  37. Živković V. Uloga homocisteina u nastanku kardiovaskularnih bolesti. Diplomski rad, Medicinski fakultet Univerziteta u Nišu, 2021.

  38. Langan RC, Goodbred AJ. Vitamin B12 Deficiency: Recognition and Management. Am Fam Physician 2017; 96(6):384-389.

  39. Nikolić M, Miladinović B, Perović M. Voće i povrće kao funkcionalna hrana u primarnoj prevenciji kardiovaskularnih bolesti. Zdrav zaštita 2017; 1:47-53.

  40. Esse R, Barroso M, Tavares de Almeida I, Castro R. The Contribution of Homocysteine Metabolism Disruption to Endothelial Dysfunction: State-of-the-Art. Int J Mol Sci 2019; 20(4):867.

  41. Niu X, Chen J, Wang J, Li J, Zeng D, Wang S, et al. A Cross-sectional Study on the Relationship Between Homocysteine and Lipid Profiles Among Chinese Population from Hunan. Lipids 2021; 56(1):93-100.

  42. Miñana G, Gil-Cayuela C, Fácila L, Bodi V, Valero E, Mollar A, et al. Homocysteine and long-term recurrent infarction following an acute coronary syndrome. Cardiol J 2021; 28(4):598-606. 

  43. Zhu M, Mao M, Lou X. Elevated homocysteine level and prognosis in patients with acute coronary syndrome: a meta-analysis. Biomarkers 2019; 24(4):309-316. 

  44. Li N, Tian L, Ren J, Li Y, Liu Y. Evaluation of homocysteine in the diagnosis and prognosis of coronary slow flow syndrome. Biomark Med 2019; 13(17):1439-1446. 

  45. Vasan RS, Beiser A, D’Agostino RB, Levy D, Selhub J, Jacques PF, et al. Plasma homocysteine and risk for congestive heart failure in adults without prior myocardial infarction. JAMA 2003; 289:1251– 1257.

  46. Kang SS, Rosenson RS. Analytic Approaches for the Treatment of Hyperhomocysteinemia and Its Impact on Vascular Disease. Cardiovasc Drugs Ther 2018; 32(2):233-240.


    47. Al Mutairi F. Hyperhomocysteinemia: Clinical Insights. J Cent Nerv Syst Dis 2020; 12:1179573520962230. 

Published
2025/12/09
Issue
Vol. 40 No. 1 (2023): Acta facultatis medicae Naissensis
Section
Pregledni rad / Review article