Association Between Serum Uric Acid to HDL-Cholesterol Ratio as a Novel Indicator of Inflammation and Ischemic Changes on Electrocardiogram: The MASHAD Cohort Study
-
Rana Kolahi Ahari
,
Toktam Sahranavard
,
Mohsen Moohebati
,
Hossein Hatamzadeh
,
Maryam Mohammadi-Bajgiran
,
Sahar Ahmadi
,
Alireza Heidari-Bakavoli
,
Sara Saffar Soflaei
,
Majid Ghayour-Mobarhan
Abstract
This study aimed to explore the association between serum uric acid to high-density lipoprotein cholesterol ratio (UHR) and minor and major ischemic electrocardiogram (ECG) changes. The data from the Mashhad Stroke and Heart Atherosclerotic Disorder (MASHAD) cohort study comprised 9035 participants aged 35 to 65 years. A 12-lead resting ECG was recorded at baseline for participants. ECG abnormalities were defined according to the Minnesota coding system and classified into three groups: none, minor, and major ischemic changes. Minor and Major ischemic changes were observed in 6.2% and 14.1% of participants, respectively. Participants in the major ischemic group had higher UHR levels compared to those without ischemic changes on their ECG (odds ratio (OR)=0.023, 95% confidence interval (95% CI)=1.011-1.035, P<0.001). UHR remained correlated with major ischemic ECG changes after adjustment for either age (OR=0.019, 95% CI=1.007-1.031, P=0.001) or various cardiovascular risk factors (OR=0.018, 95% CI=1.006-1.030, P=0.004). UHR was not significantly associated with minor ischemic changes. This research showed, for the first time, that UHR was significantly associated with major ischemic ECG changes. Indeed, the UHR provides additional information for risk stratification of subjects with myocardial ischemia.
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14. Norata GD, Catapano AL. Molecular mechanisms responsible for the antiinflammatory and protective effect of HDL on the endothelium. Vasc Health Risk Manag 2005;1:119-29.
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18. Xuan Y, Zhang W, Wang Y, Wang B, Xia F, Zhang K, et al. Association between uric acid to HDL cholesterol ratio and diabetic complications in men and postmenopausal women. Diabetes Metab Syndr Obes 2023;16:167-77.
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21. Aktas G, Kocak MZ, Bilgin S, Atak BM, Duman TT, Kurtkulagi O. Uric acid to HDL cholesterol ratio is a strong predictor of diabetic control in men with type 2 diabetes mellitus. Aging Male 2020;23:1098-102.
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23. Prineas RJ, Crow RS, Zhang Z-M. The Minnesota code manual of electrocardiographic findings. Springer Science & Business Media 2009.
24. Saffar Soflaei S, Ebrahimi M. A large population-based study on the prevalence of electrocardiographic abnormalities: a result of Mashhad stroke and heart atherosclerotic disorder cohort study. Med J Islam Repub Iran 2023;28:e13086.
25. Kocak MZ, Aktas G, Erkus E, Sincer I, Atak B, Duman T. Serum uric acid to HDL-cholesterol ratio is a strong predictor of metabolic syndrome in type 2 diabetes mellitus. Rev Assoc Med Bras 2019;65:9-15.
26. Kolahi Ahari R, Mansoori A, Sahranavard T, Miri MS, Feizi S, Esmaily H, et al. Serum uric acid to high-density lipoprotein ratio as a novel indicator of inflammation is correlated with the presence and severity of metabolic syndrome: a large-scale study. Endocrinol Diabetes Metab 2023:e446.
27. Zhang Y-N, Wang Q-Q, Chen Y-S, Shen C, Xu C-F. Association between serum uric acid to HDL-cholesterol ratio and nonalcoholic fatty liver disease in lean Chinese adults. Int J Endocrinol 2020;2020.
28. Zhu W, Liang A, Shi P, Yuan S, Zhu Y, Fu J, et al. Higher serum uric acid to HDL-cholesterol ratio is associated with onset of nonalcoholic fatty liver disease in a non-obese Chinese population with normal blood lipid levels. BMC Gastroenterol 2022;22:196.
29. Hui Z, Xia Q, Li H-Z, Cui J-J, Sun Y-Y. Association between serum uric acid to HDL-cholesterol ratio and nonalcoholic fatty liver disease risk among Chinese adults. Biomed Environ Sci 2023;36:1-9.
30. Aktas G, Khalid A, Kurtkulagi O, Duman TT, Bilgin S, Kahveci G, et al. Poorly controlled hypertension is associated with elevated serum uric acid to HDL-cholesterol ratio: a cross-sectional cohort study. Postgrad Med 2022;134:297-302.
31. Wang H, Ba Y, Gao X, Zhuo J, Li Y, Sun J, et al. Association between serum uric acid to high-density lipoprotein-cholesterol ratio and arterial stiffness in a Japanese population. Medicine 2023;102:e34182.
32. Ndrepepa G. Uric acid and cardiovascular disease. Clin Chim Acta 2018;484:150-63.
33. Tian T-T, Li H, Chen S-J, Wang Q, Tian Q-W, Zhang B-B, et al. Serum uric acid as an independent risk factor for the presence and severity of early-onset coronary artery disease: a case-control study. Dis Markers 2018;2018.
34. Wannamethee SG. Serum uric acid and risk of coronary heart disease. Curr Pharm Des 2005;11:4125-32.
35. Duran M, Kalay N, Akpek M, Orscelik O, Elcik D, Ocak A, et al. High levels of serum uric acid predict severity of coronary artery disease in patients with acute coronary syndrome. Angiology 2012;63:448-52.
36. Chen C-C, Hsu Y-J, Lee T-M. Impact of elevated uric acid on ventricular remodeling in infarcted rats with experimental hyperuricemia. Am J Physiol Heart Circ Physiol 2011;301:H1107-17.
37. Li F, Zhao D, Li Q, Lin X, Sun H, Fan Q. Uric acid to high-density lipoprotein cholesterol ratio is a novel marker to predict functionally significant coronary artery stenosis. J Interv Cardiol 2022;2022.
38. Li P, Zhang L, Zhang M, Zhou C, Lin N. Uric acid enhances PKC-dependent eNOS phosphorylation and mediates cellular ER stress: a mechanism for uric acid-induced endothelial dysfunction. Int J Mol Med 2016;37:989-97.
39. Barter P. The role of HDL-cholesterol in preventing atherosclerotic disease. Eur Heart J Suppl 2005;7:F4-8.
40. Xepapadaki E, Zvintzou E, Kalogeropoulou C, Filou S, Kypreos KE. The antioxidant function of HDL in atherosclerosis. Angiology 2020;71:112-21.
41. Feig JE, Hewing B, Smith JD, Hazen SL, Fisher EA. High-density lipoprotein and atherosclerosis regression: evidence from preclinical and clinical studies. Circ Res 2014;114:205-13.
42. Castelli WP, Garrison RJ, Wilson PW, Abbott RD, Kalousdian S, Kannel WB. Incidence of coronary heart disease and lipoprotein cholesterol levels: the Framingham Study. JAMA 1986;256:2835-8.
43. Assmann G, Cullen P, Schulte H. The Münster Heart Study (PROCAM): results of follow-up at 8 years. Eur Heart J 1998;19 Suppl A:A2-11.
2. Mensah GA, Wei GS, Sorlie PD, Fine LJ, Rosenberg Y, Kaufmann PG, et al. Decline in cardiovascular mortality: possible causes and implications. Circ Res 2017;120:366-80.
3. Sawai T, Imano H, Muraki I, Hayama-Terada M, Shimizu Y, Cui R, et al. Changes in ischaemic ECG abnormalities and subsequent risk of cardiovascular disease. Heart Asia 2017;9:36.
4. Moshkovits Y, Goldman A, Chetrit A, Dankner R. Sex specific serum uric acid levels are associated with ischemic changes on ECG and with 20-year all-cause mortality among older adults. PLoS One 2023;18:e0283839.
5. Ström Möller C, Zethelius B, Sundström J, Lind L. Persistent ischaemic ECG abnormalities on repeated ECG examination have important prognostic value for cardiovascular disease beyond established risk factors: a population-based study in middle-aged men with up to 32 years of follow-up. Heart 2007;93:1104-10.
6. Kushiyama A, Nakatsu Y, Matsunaga Y, Yamamotoya T, Mori K, Ueda K, et al. Role of uric acid metabolism-related inflammation in the pathogenesis of metabolic syndrome components such as atherosclerosis and nonalcoholic steatohepatitis. Mediators Inflamm 2016;2016:8603164.
7. Pasalic D, Marinkovic N, Feher-Turkovic L. Uric acid as one of the important factors in multifactorial disorders--facts and controversies. Biochem Med 2012;22:63-75.
8. Sautin YY, Johnson RJ. Uric acid: the oxidant-antioxidant paradox. Nucleosides Nucleotides Nucleic Acids 2008;27:608-19.
9. Braga TT, Foresto-Neto O, Camara NOS. The role of uric acid in inflammasome-mediated kidney injury. Curr Opin Nephrol Hypertens 2020;29:423-31.
10. Yang Y, Zhang J, Jia L, Su J, Ma M, Lin X. The interaction between uric acid and high-density lipoprotein cholesterol on the prognosis of patients with acute myocardial infarction. Front Cardiovasc Med 2023;10:1226108.
11. Mitsuhashi H, Yatsuya H, Matsushita K, Zhang H, Otsuka R, Muramatsu T, et al. Uric acid and left ventricular hypertrophy in Japanese men. Circ J 2009;73:667-72.
12. Chen Y, Xia Y, Han X, Yang Y, Yin X, Qiu J, et al. Association between serum uric acid and atrial fibrillation: a cross-sectional community-based study in China. BMJ Open 2017;7:e019037.
13. Zhou L, Li C, Gao L, Wang A. High-density lipoprotein synthesis and metabolism. Mol Med Rep 2015;12:4015-21.
14. Norata GD, Catapano AL. Molecular mechanisms responsible for the antiinflammatory and protective effect of HDL on the endothelium. Vasc Health Risk Manag 2005;1:119-29.
15. Park B, Jung D-H, Lee Y-J. Predictive value of serum uric acid to HDL cholesterol ratio for incident ischemic heart disease in non-diabetic Koreans. Biomedicines 2022;10:1422.
16. Dikker O, Aktaş A, Şahin M, Doğan M, Dağ H. The association of serum uric acid levels and various uric acid-related ratios with insulin resistance and obesity: a preliminary study in adolescents. Children 2023;10:1493.
17. Liu R, Peng Y, Wu H, Diao X, Ye H, Huang X, et al. Uric acid to high-density lipoprotein cholesterol ratio predicts cardiovascular mortality in patients on peritoneal dialysis. Nutr Metab Cardiovasc Dis 2021;31:561-9.
18. Xuan Y, Zhang W, Wang Y, Wang B, Xia F, Zhang K, et al. Association between uric acid to HDL cholesterol ratio and diabetic complications in men and postmenopausal women. Diabetes Metab Syndr Obes 2023;16:167-77.
19. Yang Y, Zhang J, Jia L, Su J, Ma M, Lin X. Uric acid to high-density lipoprotein cholesterol ratio predicts adverse cardiovascular events in patients with coronary chronic total occlusion. Nutr Metab Cardiovasc Dis 2023.
20. Xie Y, Huang K, Zhang X, Wu Z, Wu Y, Chu J, et al. Association of serum uric acid-to-high-density lipoprotein cholesterol ratio with nonalcoholic fatty liver disease in American adults: a population-based analysis. Front Med 2023;10:1164096.
21. Aktas G, Kocak MZ, Bilgin S, Atak BM, Duman TT, Kurtkulagi O. Uric acid to HDL cholesterol ratio is a strong predictor of diabetic control in men with type 2 diabetes mellitus. Aging Male 2020;23:1098-102.
22. Ghayour-Mobarhan M, Moohebati M, Esmaily H, Ebrahimi M, Parizadeh SM, Heidari-Bakavoli AR, et al. Mashhad stroke and heart atherosclerotic disorder (MASHAD) study: design, baseline characteristics and 10-year cardiovascular risk estimation. Int J Public Health 2015;60:561-72.
23. Prineas RJ, Crow RS, Zhang Z-M. The Minnesota code manual of electrocardiographic findings. Springer Science & Business Media 2009.
24. Saffar Soflaei S, Ebrahimi M. A large population-based study on the prevalence of electrocardiographic abnormalities: a result of Mashhad stroke and heart atherosclerotic disorder cohort study. Med J Islam Repub Iran 2023;28:e13086.
25. Kocak MZ, Aktas G, Erkus E, Sincer I, Atak B, Duman T. Serum uric acid to HDL-cholesterol ratio is a strong predictor of metabolic syndrome in type 2 diabetes mellitus. Rev Assoc Med Bras 2019;65:9-15.
26. Kolahi Ahari R, Mansoori A, Sahranavard T, Miri MS, Feizi S, Esmaily H, et al. Serum uric acid to high-density lipoprotein ratio as a novel indicator of inflammation is correlated with the presence and severity of metabolic syndrome: a large-scale study. Endocrinol Diabetes Metab 2023:e446.
27. Zhang Y-N, Wang Q-Q, Chen Y-S, Shen C, Xu C-F. Association between serum uric acid to HDL-cholesterol ratio and nonalcoholic fatty liver disease in lean Chinese adults. Int J Endocrinol 2020;2020.
28. Zhu W, Liang A, Shi P, Yuan S, Zhu Y, Fu J, et al. Higher serum uric acid to HDL-cholesterol ratio is associated with onset of nonalcoholic fatty liver disease in a non-obese Chinese population with normal blood lipid levels. BMC Gastroenterol 2022;22:196.
29. Hui Z, Xia Q, Li H-Z, Cui J-J, Sun Y-Y. Association between serum uric acid to HDL-cholesterol ratio and nonalcoholic fatty liver disease risk among Chinese adults. Biomed Environ Sci 2023;36:1-9.
30. Aktas G, Khalid A, Kurtkulagi O, Duman TT, Bilgin S, Kahveci G, et al. Poorly controlled hypertension is associated with elevated serum uric acid to HDL-cholesterol ratio: a cross-sectional cohort study. Postgrad Med 2022;134:297-302.
31. Wang H, Ba Y, Gao X, Zhuo J, Li Y, Sun J, et al. Association between serum uric acid to high-density lipoprotein-cholesterol ratio and arterial stiffness in a Japanese population. Medicine 2023;102:e34182.
32. Ndrepepa G. Uric acid and cardiovascular disease. Clin Chim Acta 2018;484:150-63.
33. Tian T-T, Li H, Chen S-J, Wang Q, Tian Q-W, Zhang B-B, et al. Serum uric acid as an independent risk factor for the presence and severity of early-onset coronary artery disease: a case-control study. Dis Markers 2018;2018.
34. Wannamethee SG. Serum uric acid and risk of coronary heart disease. Curr Pharm Des 2005;11:4125-32.
35. Duran M, Kalay N, Akpek M, Orscelik O, Elcik D, Ocak A, et al. High levels of serum uric acid predict severity of coronary artery disease in patients with acute coronary syndrome. Angiology 2012;63:448-52.
36. Chen C-C, Hsu Y-J, Lee T-M. Impact of elevated uric acid on ventricular remodeling in infarcted rats with experimental hyperuricemia. Am J Physiol Heart Circ Physiol 2011;301:H1107-17.
37. Li F, Zhao D, Li Q, Lin X, Sun H, Fan Q. Uric acid to high-density lipoprotein cholesterol ratio is a novel marker to predict functionally significant coronary artery stenosis. J Interv Cardiol 2022;2022.
38. Li P, Zhang L, Zhang M, Zhou C, Lin N. Uric acid enhances PKC-dependent eNOS phosphorylation and mediates cellular ER stress: a mechanism for uric acid-induced endothelial dysfunction. Int J Mol Med 2016;37:989-97.
39. Barter P. The role of HDL-cholesterol in preventing atherosclerotic disease. Eur Heart J Suppl 2005;7:F4-8.
40. Xepapadaki E, Zvintzou E, Kalogeropoulou C, Filou S, Kypreos KE. The antioxidant function of HDL in atherosclerosis. Angiology 2020;71:112-21.
41. Feig JE, Hewing B, Smith JD, Hazen SL, Fisher EA. High-density lipoprotein and atherosclerosis regression: evidence from preclinical and clinical studies. Circ Res 2014;114:205-13.
42. Castelli WP, Garrison RJ, Wilson PW, Abbott RD, Kalousdian S, Kannel WB. Incidence of coronary heart disease and lipoprotein cholesterol levels: the Framingham Study. JAMA 1986;256:2835-8.
43. Assmann G, Cullen P, Schulte H. The Münster Heart Study (PROCAM): results of follow-up at 8 years. Eur Heart J 1998;19 Suppl A:A2-11.
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| Issue | Vol 64 No 1 (2026) | |
| Section | Original Articles | |
| Keywords | ||
| Uric acid to HDL-cholesterol ratio Electrocardiogram Ischemic ECG abnormalities | ||
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How to Cite
1.
Kolahi Ahari R, Sahranavard T, Moohebati M, Hatamzadeh H, Mohammadi-Bajgiran M, Ahmadi S, Heidari-Bakavoli A, Saffar Soflaei S, Ghayour-Mobarhan M. Association Between Serum Uric Acid to HDL-Cholesterol Ratio as a Novel Indicator of Inflammation and Ischemic Changes on Electrocardiogram: The MASHAD Cohort Study. Acta Med Iran. 2026;64(1).
