A relation of serum Homocysteine and Uric acid in Bosnian Diabetic patients with Acute Miocardial Infarction

  • Marijana Marković Boras Department of Laboratory Medicine, University Clinical Hospital Mostar
  • Adlija Čaušević 2Department of Biochemistry and Clinical Analysis,Faculty of Pharmacy, University of Sarajevo, Sarajevo, Bosnia and Herzegovina
  • Marina Ćurlin Faculty of Health Studies, University of Mostar, Mostar, Bosnia and Herzegovina
Keywords: Diabetes Mellitus type 2; Homocysteine; Myocardial infarction; Uric acid



Coronary artery disease as a consequence of atherosclerosis is the most common cause of morbidity and mortality in type 2 Diabetes Mellitus (DM) patients. Homocysteine (HCY), as one of the risk factors, and uric acid (UA) as the most common antioxidant in serum have their roles in the processes of inflammation and atherogenesis, which underlie the pathogenesis of acute myocardial infarction (AMI). The effect of HCY in cardiovascular disease is thought to manifest primarily through oxidative damage, impling potential correlation between the HCY level and antioxidant status. Since the data related to diagnostic significance of both HCY and UA in diabetic patients with AMI are conflicting, and so far not reported in Bosnian patients, the aim of this research was to examine the association of HCY and UA levels with glomerular filtration rate (eGFR) and explore the pathophysiological significance of these data in Bosnian diabetic patients with AMI.


This prospective research included 52 DM type 2 patients diagnosed with AMI. Blood samples were taken on admission, and used for biochemical analysis. Results of the biochemical analyses were statistically analyzed.


Elevated HCY and UA levels were observed in diabetic patients. Females have higher HCY compared to males. Positive correlation was revealed between HCY and UA and was confirmed with different HCY levels in subgroups with different UA level. Negative correlation was observed between UA and HbA1c, as well as between both HCY and UA with eGFR.


These results contribute to clarification of the biochemical mechanisms characteristic in AMI patients with DM. According to these results, we believe that joint measurement of HCY and UA could enable a better assessment of the prognosis for this group of patients.  This kind of assessment, as well as regression analysis can identify high-risk patients at an earlier stage, when appropriate interventions can influence a better outcome in such patients.


1 Mendis S, Thygesen K, Kuulasmaa K, Giampaoli S, Mähönen M, Ngu Blackett K et al. Writing group on behalf of the participating experts of the WHO consultation for revision of WHO defnition of myocardial infarction. World health organization defnition of myocardial infarction: 2008-09 revision. Int J Epidemiol 2011; 40:139-46.
2 Matheus AS, Tannus LR, Cobas RA, Palma CC, Negrato CA, Gomes MB. Impact of diabetes on cardiovascular disease: an update. Int J Hypertens 2013; 653789.
3 Ballotari P, Ranieri SC, Luberto F, Caroli S, Greci M, Giorgi Rossi P et al. Sex differences in cardiovascular mortality in diabetics and nondiabetic subjects: a population-based study (Italy). Int J Endocrinol 2015; 2015:914057.
4 Pooja S, Pradhan R, Lekharu R. A study of serum homocysteine levels in acute myocardial infarction patients. Int J Curr Res 2014; 6:08:8171-3.
5 Alam N, Khan HI, Chowdhury AW, Haque MS, Ali MS, Sabah KM et al. Elevated serum homocysteine level has a positive correlation with serum cardiac troponin I in patients with acute myocardial infarction. Bangladesh Med Res Counc Bull 2012; 38: 9-13.
6 Iqbal MP, Ishaq M, Kazmi KA, Yousuf FA, Mehboobali N, Ali SA et al. Role of vitamin B6, B12 and folic acid on hyperhomocysteinemia in a Pakistani population of patient with acute myocardial infarction. Nutr Metab Cardiovasc Dis 2005;15:100-8.
7 Joshi M, Baipadithaya G,1 Balakrishnan A, Hegde M, Vohra M, Ahamed R et al. Elevated homocysteine levels in type 2 diabetes induce constitutive neutrophil extracellular traps. Sci Rep 2016; 6: 36362.
8 Platt DE, Hariri E, Salameh P, Merhi M, Sabbah N, Helou M et al. Type II diabetes mellitus and hyperhomocysteinemia: a complex interaction. Diabetol Metab Syndr 2017; 9:19.
9 Kumar J, Ingelsson E, Lind L, Fall T. No Evidence of a Causal Relationship between Plasma Homocysteine and Type 2 Diabetes: A Mendelian Randomization Study. Front Cardiovasc Med 2015; 2:11.
10 Čaušević A, Semiz S, Macić-Džanković A, Cico B, Dujić T, Malenica M et al. Relevance of uric acid in progression of type 2 diabetes mellitus. Bosn J Basic Med Sci 2010; 10(1):54-9.
11 Ganguly, Alam. Role of Homocysteine in the development of cardiovascular disease. Nutr J 2015; 14: 6.
12 Cohen E, Levi A, Vecht-Lifshitz SE, Goldberg E, Garty M, Krause IA. ssessment of a possible link between hyperhomocysteinemia and hyperuricemia. J Investig Med 2015; 63(3): 534-8.
13 American Diabetes Association. Classification and Diagnosis of Diabetes. Diabetes Care 2015; 38(1): 8-16.
14 Marković Boras M, Čaušević A, Brizić I, Mikulić I, Vasilj M, Jelić-Knezović N. A relation of serum homocysteine, uric acid and C-reactive protein level in patients with acute myocardial infarction. Med Glas (Zenica) 2018; 15(2):101-8.
15 Yokoi Y, Kondo T, Okumura N, Shimokata K, Osugi S, Maeda K et al. Serum uric acid as a predictor of future hypertension: Stratified analysis based on body mass index and age. Prev Med 2016; 90:201-6.
16 Moshki M, Zareie M, Hashemizadeh H. Sex differences in Acute Myocardial Infarction. Nurs Midwifery Stud 2015; 4(1): e22395.
17 Fagard R. Smoking amplifies cardiovascular risk in patients with hypertension and diabetes. Diabetes care 2009;32(2);429-31.
18 Wu CY, Hu HY, Chou YJ, Huang N, Chou YC, Li CP. High Blood Pressure and All-Cause and Cardiovascular Disease Mortalities in Community-Dwelling Older Adults. Medicine (Baltimore) 2015; 94(47): e2160.
19 Wan E, Yu E, Chin W, Fong D, Choi E, Lam C. Association of Blood Pressure and Risk of Cardiovascular and Chronic Kidney Disease in Hong Kong Hypertensive Patients. Hipertension 2019; 74(2):331-40.
20 Tan J, Zhang X, Wang W, Yin P, Guo X, Zhou M. Smoking, Blood Pressure, and Cardiovascular Disease Mortality in a Large Cohort of Chinese Men with 15 Years Follow-up. Int J Environ Res Public Health 2018;15(5):1026.
21 Cui Y, Bu H, Ma X, Zhao S, Li X, Lu S. The Relation between Serum Uric Acid and HbA1c Is Dependent upon Hyperinsulinemia in Patients with Newly Diagnosed Type 2 Diabetes Mellitus. J Diabetes Res 2016; 2016: 7184123.
22 Boukhris M, Tomasello SD, Marzà F, Bregante S, Pluchinotta FR, Galassi AR. Coronary Heart Disease in Postmenopausal Women with Type II Diabetes Mellitus and the Impact of Estrogen Replacement Therapy: A Narrative Review. Int J Endocrinol 2014; 2014:413920.
23 Mehta LS, Beckie TM, DeVon HA, Grines CL, Krumholz HM, Johnson MN et al. Acute Myocardial Infarction in Women: A Scientific Statement From the American Heart Association. Circulation 2016; 133(9): 916-47.
24 Cacciapuoti F. Hyper-homocysteinemia Inducing Hyperuricemia: What are the Mechanisms? J Rheum Dis 2017; 24: 127-130.
25 Muiesan ML, Agabiti-Rosei C, Paini A, Salvetti M, 2016. Uric Acid and Cardiovascular Disease: An Update. Eur Cardiol 2016; 11(1): 54-59.
26 Jang S, Jeong M, Song J, Park K, Sim D, Kim J. Clinical impact of serum uric acid in patients with acute myocardial infarction. JACC 2014;63(12):239.
27 Lv Q, Meng XF, He FF, Chen S, Su H, Xiong J et al. High serum uric acid and increased risk of type 2 diabetes: a systemic review and meta-analysis of prospective cohort studies. PLoS One 2013; 8(2): e56864.
28 Wijnbergen I, Tijssen J, van 't Veer M, Michels R, Pijls NH. Gender differences in long-term outcome after primary percutaneous intervention for ST-segment elevation myocardial infarction. Catheter Cardiovasc Interv. 2013;82(3):379-84.
29 Nadkar MY, Jain VI. Serum uric acid in acute myocardial infarction. J Assoc Physicians India 2008; 56:759-62.
30 Hong YS, Lee MJ, Kim KH, Lee SH, Lee YH, Kim BG, et al. The C677 mutation in methylene tetrahydrofolate reductase gene: correlation with uric acid and cardiovascular risk factors in elderly Korean men. J Korean Med Sci 2004; 19: 209-13.
31 Kiseljaković E, Valjevac A, Hasić S, Nakas-Ićindić E, Dzubur A, Jadrić R. Association of homocysteine with traditional and non-traditional risk factors in patients with atherosclerotic vascular disease. Med Glas (Zenica) 2011; 8(1):126-33.
32 Fu S, Luo L, Ye P, Xiao W. Multimarker analysis for new biomarkers in relation to central arterial stiffness and hemodynamics in a Chinese community-dwelling population. Angiology 2015; 66(10): 950-6.
33 Stewart DJ, Langlois S, Noone D. Hyperuricemia and Hypertension: Links and Risks. Integr Blood Press Control 2019; 12:43–62.
34 Fu S, Yao Y, Zhao Y, Luan F. Relationships of Hyperhomocysteinemia and Hyperuricemia With Metabolic Syndrome and Renal Function in Chinese Centenarians. Front Endocrinol 2018; 9, 502.
35 Sederholm Lawesson S, Alfredsson J, Szummer K, Fredrikson M, Swahn E. Prevalence and prognostic impact of chronic kidney disease in STEMI from a gender perspective: data from the SWEDEHEART register, a large Swedish prospective cohort. BMJ Open 2015;5:e008188.
36 Noman A, Ang DSC, Ogston S, Lang CC, Struthers AD. Effect of high-dose allopurinol on exercise in patients with chronic stable angina: a randomised, placebo controlled crossover trial. Lancet 2010; 375:2161-7.
37 Loeffler LF, Navas-Acien A, Brady TM, Miller ER, Fadrowski JJ. Uric acid level and elevated blood pressure in US adolescents: National Health and Nutrition Examination Survey, 1999-2006. Hypertension 2012; 59(4): 811–17.
38 Ostrakhovitch EA, Tabibzadeh S. Homocysteine in chronic kidney disease. Adv Clin Chem 2015;72:77–106.
39 Gill A, Kukreja S, Malhotra N, Chhabra N. Correlation of the serum insulin and the serum uric Acid levels with the glycated haemoglobin levels in the patients of type 2 diabetes mellitus. J Clin Diagn Res 2013; 7(7): 1295-7.
40 Toyoki D, Shibata S, Kuribayashi-Okuma E, Xu N, Ishizawa K, Hosoyamada M. Insulin stimulates uric acid reabsorption via regulating urate transporter 1 and ATP-binding cassette subfamily G member 2. Am J Physiol Renal Physiol 2017;313(3):826-34.
Original paper