 |
Publisher: Peytchinski Publishing Ltd.
ISSN: 1312-773X (Online)
Issue: 2021, vol. 27, issue1
Subject Area: Medicine
-
DOI: 10.5272/jimab.2021271.3634
Published online: 25 March 2021
Original article
J of IMAB. 2021 Jan-Mar;27(1):3634-3642
ASYMPTOMATIC HYPERURICEMIA AS A POTENTIAL METABOLIC RISK FACTOR FOR CORONARY ARTERY CALCIFICATION IN PATIENTS WITH ATRIAL FIBRILLATION OR HEART FAILURE
Milena Pasheva1
, Yoto Yotov2, Miglena Nikolova1, Daniela Gerova3, Atanas Angelov2, Bistra Galunska1 
,
1) Department of Biochemistry, Molecular medicine and Nutrigenomics, Faculty of Pharmacy, Medical University, Varna, Bulgaria.
2) First Department of Internal Diseases, Faculty of Medicine, Medical University, Varna, Bulgaria.
3) Department of General Medicine and Clinical Laboratory, Faculty of Medicine, Medical University, Varna, Bulgaria.
ABSTRACT:
Purpose: To assess the role of asymptomatic hyperuricemia for the presence and severity of coronary arterial calcium (CAC) in adults with different cardiovascular (CV) pathology and its association with conventional CV risk factors.
Material/Methods: Adults (n=81) of both genders were divided into controls: with moderate- to high risk without known CVD; AF-group: CVD-patients with paroxysmal or persistent atrial fibrillation in sinus rhythm, HF–group: heart failure subjects with preserved ejection fraction. A structured interview was performed at admittance for evaluation of the classical CVD risk factors. CAC score (CACS) was determined by multislice computed tomography. Routine laboratory parameters, including uric acid (UA), were extracted from medical documentation.
Descriptive statistics, Mann-Whitney U-test, one-way ANOVA, chi-square test, Spearman's correlation, and multiple linear regression analysis were applied. The predictive power of serum UA was evaluated using receiver operating characteristic (ROC) analysis. Statistical significance was considered at p<0.05.
Results: Serum UA was significantly higher in subjects with CACS=1-99AU (p=0.030), and with CACS≥100AU (p=0.067) vs. patients without CACS. Within the UA tertiles, highest CACS was found in the tertile with highest serum UA. UA revealed positive relation with CACS (r=0.35, p=0.002), age (r=0.25, p=0.027), body mass index (0.27, p=0.017), waist circumference (r=0.44, p<0.0001), triglycerides (r=0.29, p=0.001), and creatinine (r=0.54, p<0.0001). Multiple linear regression analysis revealed significant association between UA as dependent variable and waist circumference (β=0.63, p=0.061), serum triglycerides (β=0.37, p=0.028), creatinine levels (β=0.45, p<0.0001).
Conclusions: Asymptomatic hyperuricaemia could be an important metabolic factor negatively affecting the chronic cardio-vascular pathology besides the conventional risk factors.
Keywords: uric acid, cardiovascular diseases, coronary arterial calcification,
- Download FULL TEXT /PDF 810 KB/
Please cite this article as: Pasheva M, Yotov Y, Nikolova M, Gerova D, Angelov A, Galunska B. Asymptomatic hyperuricemia as a potential metabolic risk factor for coronary artery calcification in patients with atrial fibrillation or heart failure. J of IMAB. 2021 Jan-Mar;27(1):3634-3642. DOI: 10.5272/jimab.2021271.3634
Correspondence to: Bistra Galunska, Department of Biochemistry, Molecular medicine and Nutrigenomics, Medical University, Varna; 55 Marin Drinov, 9002 Varna, Bulgaria; E-mail: bistra.galunska@gmail.com
REFERENCES:
1. Kiss L, Bagyura Z, Csobay-Novák C, Lux A, Polgár L, Jermendy A, et al. Serum uric acid is independently associated with coronary calcification in an asymptomatic population. J Cardiovasc Transl Res. 2019 Jun;12(3):204-10. [PubMed ]
2. Braga F, Pasqualetti S, Ferraro S, Panteghini M. Hyperuricemia as risk factor for coronary heart disease incidence and mortality in the general population: a systematic review and meta-analysis. Clin Chem Lab Med. 2016 Jan;54(1):7-15. [PubMed]
3. Kanellis J, Watanabe S, Li JH, Kang DH, Li P, Nakagawa T, et al. Uric acid stimulates monocyte chemoattractant protein-1 production in vascular smooth muscle cells via mitogen-activated protein kinase and cyclooxygenase-2. J Hypertens. 2003 May;41(6):1287–93. [PubMed]
4. Choi Y-J, Yoon Y, Lee K-Y. Uric acid induces endothelial dysfunction by vascular insulin resistance associated with the impairment of nitric oxide synthesis. FASEB J. 2014 Jul;28(7):3197-204. PubMed ]
5. Xia S, Deng SB, Wang Y, Xiao J, Du JL, Zhang Y, et al. Clinical analysis of the risk factors of slow coronary flow. Heart Vessel. 2011 Sep;26(5):480-6. PubMed ]
6. Cheng T, Lin J, Chao H, Chen Y, Chen C, Chan P, et al. Uric acid activates extracellular signal regulated kinases and thereafter endothelin-1 expression in rat cardiac fibroblasts. Int J Cardiol. 2010 Feb 18;139(1):42-9. PubMed ]
7. Ranjith N, Myeni NN, Sartorius B, Mayise C. Association between hyperuricemia and major adverse cardiac events in patients with acute myocardial infarction. Metab Syndr Relat Disord. 2016 Feb;15(1):18-25. PubMed ]
8. Ndrepepa G, Braun S, Haase HU, Schulz S, Ranftl S, Hadamitzky M, et al. Prognostic value of uric acid in patients with acute coronary syndromes. Am J Cardiol. 2012 May ;109(9):1260-5. PubMed ]
9. Rothenbacher D, Kleiner A, Koenig W, Primatesta P, Breitling LP, Brenner H. Relationship between inflammatory cytokines and uric acid levels with adverse cardiovascular outcomes in patients with stable coronary heart disease. PLoS One. 2012; 7(9) :e45907. [PubMed]
10. Kim H, Kim S, Choi AR, Kim S, Choi HY, Kim HJ, et al. Asymptomatic hyperuricemia is independently associated with coronary artery calcification in the absence of overt coronary artery disease: a single-center cross-sectional study. Medicine. 2017 Apr;96(14):1-7. PubMed ]
11. Krishnan E, Pandya BJ, Chung L, Dabbous O. Hyperuricemia and the risk for subclinical coronary atherosclerosis- data from a prospective observational cohort study. Arthritis Res Ther. 2011 Apr;13(2):R66:1-8. PubMed ]
12. Grossman C, Shemesh J, Koren-Morag N, Bornstein G, Ben-Zvi I, Grossman E. Serum uric acid is associated with coronary artery calcification. J Clin Hypertens (Greenwich). 2014 Jun;16(6):424-8. [PubMed]
13. Neogi T, Terkeltaub R, Ellison RC, Hunt S, Zhang Y. Serum urate is not associated with coronary artery calcification: the NHLBI Family Heart Study. J Rheumatol. 2011 Jan;38(1):111-7. [PubMed ]
14. Cheong E, Ryu S, Lee JY, Lee SH, Sung JW, Cho DS, et al. Association between serum uric acid and cardiovascular mortality and all-cause mortality: a cohort study. J Hypertens. 2017 May;35(1):3–9. PubMed]
15. Piepoli, MF, Hoes AW, Agewall S, Albus C, Brotons C, Catapano AL, et al. ESC Scientific Document Group, 2016 European Guidelines on cardiovascular disease prevention in clinical practice: The sixth joint task force of the European society of cardiology and other societies on cardiovascular disease prevention in clinical practice (constituted by representatives of 10 societies and by invited experts). Developed with the special contribution of the European association for cardiovascular prevention&Rehabilitation (EACPR). Eur Heart J .2016;37(29):2315-81. [PubMed]
16. Mach F, Baigent C, Catapano AL, Koskinas KC, Casula M, Badimon L, et al. ESC Scientific Document Group. 2019 ESC/EAS Guidelines for the management of dyslipidaemias: lipid modification to reduce cardiovascular risk: The task force for the management of dyslipidaemias of the European society of cardiology (ESC) and European atherosclerosis society (EAS). Eur Heart J. 2020;41(1):111–88.
17. Aronne L. Classification of Obesity and Assessment of Obesity-Related Health Risks. Obes Res. 2002 Dec;2:105-15. [PubMed]
18. Agatston AS, Janowitz WR, Hildner FJ, Zusmer NR, Jr MV, Detrano R.. Quantification of coronary artery calcium using ultrafast computed tomography. Am J Cardiol. 1990 Mar;15(4):827-32. [PubMed].
19. Letsas KP, Korantzopoulos P, Filippatos GS, Mihas CC, Markou V, Gavrielatos G, et al. Uric acid elevation in atrial fibrillation. Hellenic J Cardiol. 2010 May-Jun;51(3):209–13. [PubMed].
20. Tamariz L, Hernandez F, Bush A, Palacio A, Hare JM. Association between serum uric acid and atrial fibrillation: a systematic review and meta-analysis. Heart Rhythm. 2014 Jul;11(7):1102-8. [PubMed]
21. Muiesan ML, Agabiti-Rosei C, Paini A, Salvetti M. Uric Acid and Cardiovascular Disease: An Update. Eur Cardiol. 2016 Aug;11(1):54-9. [PubMed]
22. Shimano M, Shibata R, Inden Y, Yoshida N, Uchikawa T, Tsuji Y, et al. Reactive oxidative metabolites are associated with atrial conduction disturbance in patients with atrial fibrillation. Heart Rhythm. 2009 Jul;6(7):935-40. [PubMed]
23. Carnes CA , Chung MK, Nakayama T, Nakayama H, Baliga RS, Piao S, et al. Ascorbate attenuates atrial pacing-induced peroxynitrite formation and electrical remodeling and decreases the incidence of postoperative atrial fibrillation. Circ Res. 2001 Sep;89(6):32-8. [PubMed]
24. Gonzalez DR, Treuer A, Sun QA, Stamler J, Hare J. S-nitrosylation of cardiac ion channels. J Cardiovasc Pharmacol. 2009 Sep;54(3):188-95. [PubMed]
25. Tamariz L, Harzand A, Palacio A, Verma S, Jones J, Hare J. Uric acid as a predictor of all-cause mortality in heart failure: a meta-analysis. Congest Heart Fail. 2011 Jan-Feb;17(1):25-30. [PubMed]
26. Reyes AJ. The increase in serum uric acid concentration caused by diuretics might be beneficial in heart failure. Eur J Heart Fail. 2005 Jun;7(4):461-7. [PubMed]
27. Borghi C, Cosentino ER, Rinaldi ER, Cicero AF. Uricaemia and ejection fraction in elderly heart failure outpatients. Eur J Clin Invest. 2014 Jun;44(6):573-8. [PubMed]
28. Liang L, Hou X, Bainey K, Zhang Y, Tymchak W, Qi Zh, et al. The association between hyperuricemia and coronary artery calcification development: A systematic review and meta-analysis. Clinical Cardiology. 2019 Nov;42(11):1079-86. [PubMed]
29. Jun J, Lee YB, Lee SE, Ahn JY, Kim G, Jin SM, et al. Elevated serum uric acid predicts the development of moderate coronary artery calcification independent of conventional cardiovascular risk factors. Atherosclerosis. 2018 May;(272):233-9. [PubMed]
30. Oguz N, Kırça M, Çetin A, Yesilkaya A. Effect of uric acid on inflammatory COX-2 and ROS pathways in vascular smooth muscle cells. J Recept Signal Transduct. 2017 Oct;37(5):500-5. [PubMed]
31. Liu Z, Chen T, Niu H, Ren W, Li X, Cui L, et al. The establishment and characteristics of rat model of atherosclerosis induced by hyperuricemia. Stem Cells Int. 2016;2016:1365257. [PubMed]
32. Otsuka F, Sakakura K, Yahagi K, Joner M, Virmani R. Has our understanding of calcification in human coronary atherosclerosis progressed? Arterioscler Thromb Vasc Biol 2014;34:724–36. [PubMed]
33. Larsen TR, Gerke O, Diederichsen AC, Lambrechtsen J, Steffensen FH, Sand NP, et al. The association between uric acid levels and different clinical manifestations of coronary artery disease. Coron Artery Dis. 2018 May;29(3):194-03. [PubMed]
34. Kuzuya M, Ando F, Iguchi A, Shimokata H. Effect of Aging on Serum Uric Acid Levels: Longitudinal Changes in a Large Japanese Population Group. J Gerontol A Biol Sci Med Sci. 2002 Oct;57(10):660-4. [PubMed].
35. Duan Y, Liang W, Zhu L, Zhang T, Wang L, Nie Z, et al. Association between serum uric acid levels and obesity among university students (China). Nutr Hosp. 2015 Jun;31(6):2407-11. [PubMed].
36. Zhang J, Zhang Y, Wu Q, Chen B. Uric Acid Induces Oxidative Stress via an Activation of the Renin-Angiotensin System in 3T3-L1 Adipocytes. Endocrine. 2015 Feb;48(1):135-42. [PubMed].
37. Sharaf El Din UA, Salem MM, Abdulazim DO. Uric acid in the pathogenesis of metabolic, renal, and cardiovascular diseases: a review. J Adv Res. 2017 Sep;8(5):537-48. [PubMed].
38. Feig DI. Uric acid-a novel mediator and marker of risk in chronic kidney disease? Curr Opin Nephrol Hypertens. 2009 Nov;18(6):526-30. [PubMed].
39. Al-Daghri NM, Al-Attas OS, Wani K, Sabico S, Alokail MS. Serum Uric Acid to Creatinine Ratio and Risk of Metabolic Syndrome in Saudi Type 2 Diabetic Patients. Sci Rep. 2017 Sep 21;7(1):12104. [PubMed].
40. Mankovsky B, Kurashvili R, Sadikot S. Is serum uric acid a risk factor for atherosclerotic cardiovascular disease? A review of the clinical evidence. Part 1. Diabetes & Metabolic Syndrome: Clinical Research & Reviews. 2010 Jul-Sep;4(3):176-84. [PubMed].
Received: 14 December 2020
Published online: 25 March 2021