Serum Uric Acid as a Marker of Coronary Calcification in Patients with Asymptomatic Coronary Artery Disease with Preserved Left Ventricular Pump Function
Objective. To evaluate the interrelation between serum uric acid and artery calcification in asymptomatic coronary artery disease subjects. Design and Methods. 126 subjects with previously documented asymptomatic coronary artery disease were enrolled in the study. Results. Mean value of serum uric acid level was 23.84？mmol/L (95% confidence interval (CI)？ = ？15.75–31.25？mmol/L). In multivariate Cox regression analysis, the results showed that serum uric acid levels (odds ratio , 95% CI？=？1.20–1.82; ), osteopontin ( , 95% CI？=？1.12–1.25; ), osteoprotegerin ( , 95% CI？？=？？1.20–1.89; ), type 2 diabetes mellitus ( , 95% CI？？=？？1.20–1.72; ), and total cholesterol ( , 95% CI？=？1.10–1.22; ) were factors that independently associated with coronary artery calcification. The Cox models suggested that high quartile of serum uric acid level is very significant in predicting Agatston score index. In conclusion, we suggested that high quartile of serum uric acid level (cutoff point equaled 35.9？mmol/L) was a very significant predictor of coronary calcification examined by Agatston score index in subjects with asymptomatic coronary artery disease. 1. Background Hyperuricemia is frequently present in patients with symptomatic heart failure, acute coronary syndromes, arterial hypertension, and atrial fibrillation and in patients with type 2 diabetes mellitus [1–3]. Current evidence suggests that serum uric acid could be a marker of oxidative damage [4]. Serum uric acid is also considered a useful biomarker for mortality and an indicator of a poor prognosis in high-risk patients with several cardiovascular diseases [5–7]. Recently clinical studies have shown that serum uric acid inversely correlates with left ventricular ejection fraction, serum creatinine, and blood urea nitrogen in patients with heart failure [1]. There is a significant association between serum uric acid and circulating levels of proinflammatory cytokines among subjects with chronic heart failure [8]. Serum uric acid is often discussed as a risk factor for acute kidney injury, which adversely affects renal blood flow autoregulation, glomerular filtration rate, and promotes inflammation and angiogenesis [9]. However, the principal mechanism that contributes to biological effects of serum uric acid in patients with asymptomatic coronary artery disease without reducing left ventricular pump function is still to be understood. It has been postulated that serum uric acid plays a pivotal role in the pathogenesis of cardiovascular diseases affecting xanthine oxidase pathway that contributes to the production
References
[1]
Y. Tian, Y. Chen, B. Deng et al., “Serum uric acid as an index of impaired renal function in congestive heart failure,” Journal of Geriatric Cardiology, vol. 9, no. 2, pp. 137–142, 2012.
[2]
Q. Y. Zhao, S. B. Yu, H. Huang et al., “Serum uric acid levels correlate with atrial fibrillation in patients with chronic systolic heart failure,” Chinese Medical Journal (English Edition), vol. 125, no. 10, pp. 1708–1712, 2012.
[3]
M. G. Kaya, H. Uyarel, M. Akpek et al., “Prognostic value of uric acid in patients with ST-elevated myocardial infarction undergoing primary coronary intervention,” The American Journal of Cardiology, vol. 109, no. 4, pp. 486–491, 2012.
[4]
L. Tamariz, S. Agarwal, E. Z. Soliman et al., “Association of serum uric acid with incident atrial fibrillation (from the atherosclerosis risk in communities [ARIC] study,” The American Journal of Cardiology, vol. 108, no. 9, pp. 1272–1276, 2011.
[5]
P. Jeemon and D. Prabhakaran, “Does uric acid qualify as an independent risk factor for cardiovascular mortality?” Clinical Science, vol. 124, no. 4, pp. 255–257, 2013.
[6]
I. Gotsman, A. Keren, C. Lotan, and D. R. Zwas, “Changes in uric acid levels and allopurinol use in chronic heart failure: association with improved survival,” Journal of Cardiac Failure, vol. 18, no. 9, pp. 694–701, 2012.
[7]
T. Kawai, M. Ohishi, Y. Takeya et al., “Serum uric acid is an independent risk factor for cardiovascular disease and mortality in hypertensive patients,” Hypertension Research, vol. 35, no. 11, pp. 1087–1092, 2012.
[8]
A. Gluba, A. Bielecka, D. P. Mikhailidis et al., “An update on biomarkers of heart failure in hypertensive patients,” Journal of Hypertension, vol. 30, no. 9, pp. 1681–1689, 2012.
[9]
A. A. Ejaz, B. Dass, V. Lingegowda et al., “Effect of uric acid lowering therapy on the prevention of acute kidney injury in cardiovascular surgery,” International Urology and Nephrology, 2012.
[10]
A. Harzand, L. Tamariz, and J. M. Hare, “Uric acid, heart failure survival, and the impact of xanthine oxidase inhibition,” Congestive Heart Failure, vol. 18, no. 3, pp. 179–182, 2012.
[11]
P. Puddu, G. M. Puddu, E. Cravero, L. Vizioli, and A. Muscari, “The relationships among hyperuricemia, endothelial dysfunction, and cardiovascular diseases: molecular mechanisms and clinical implications,” Journal of Cardiology, vol. 59, no. 3, pp. 235–242, 2012.
[12]
E. Krishnan, A. Hariri, O. Dabbous, and B. J. Pandya, “Hyperuricemia and the echocardiographic measures of myocardial dysfunction,” Congestive Heart Failure, vol. 18, no. 3, pp. 138–143, 2012.
[13]
M. Kaufman and M. Guglin, “Uric acid in heart failure: a biomarker or therapeutic target?” Heart Failure Reviews, 2012.
[14]
B. Ky, B. French, W. C. Levy et al., “Multiple biomarkers for risk prediction in chronic heart failure,” Circulation: Heart Failure, vol. 5, no. 2, pp. 183–190, 2012.
[15]
C. F. Kuo, L. C. See, K. H. Yu, I. J. Chou, M. J. Chiou, and S. F. Luo, “Significance of serum uric acid levels on the risk of all-cause and cardiovascular mortality,” Rheumatology, vol. 52, no. 1, pp. 127–134, 2013.
[16]
N. B. Schiller, P. M. Shah, M. Crawford et al., “Recommendations for quantitation of the left ventricle by two-dimensional echocardiography. American society of echocardiography committee on standards, subcommittee on quantitation of two-dimensional echocardiograms,” Journal of the American Society of Echocardiography, vol. 2, no. 5, pp. 358–367, 1989.
[17]
D. A. Bluemke, S. Achenbach, M. Budoff et al., “Noninvasive coronary artery imaging: magnetic resonance angiography and multidetector computed tomography angiography: a scientific statement from the American heart association committee on cardiovascular imaging and intervention of the council on cardiovascular radiology and intervention, and the councils on clinical cardiology and cardiovascular disease in the young,” Circulation, vol. 118, no. 5, pp. 586–606, 2008.
[18]
A. S. Agatston, W. R. Janowitz, R. J. Gibbons, J. Maddahi, L. Wexler, and R. White, “Ultrafast computed tomography in coronary screening,” Circulation, vol. 89, no. 4, pp. 1908–1909, 1994.
[19]
M. J. Budoff, S. Achenbach, R. S. Blumenthal et al., “Assessment of coronary artery disease by cardiac computed tomography: a scientific statement from the American heart association committee on cardiovascular imaging and intervention, council on cardiovascular radiology and intervention, and committee on cardiac imaging, council on clinical cardiology,” Circulation, vol. 114, no. 16, pp. 1761–1791, 2006.
[20]
A. S. Agatston, W. R. Janowitz, F. J. Hildner, N. R. Zusmer, M. Viamonte Jr., and R. Detrano, “Quantification of coronary artery calcium using ultrafast computed tomography,” Journal of the American College of Cardiology, vol. 15, no. 4, pp. 827–832, 1990.
[21]
A. S. Levey, L. A. Stevens, C. H. Schmid et al., “A new equation to estimate glomerular filtration rate,” Annals of Internal Medicine, vol. 150, no. 9, pp. 604–612, 2009.
[22]
N. W. Tietz, Ed., Clinical Guide to Laboratory Tests, WB Saunders, Philadelphia, Pa, USA, 3rd edition, 1995.
[23]
M. Resl, M. Clodi, S. Neuhold et al., “Serum uric acid is related to cardiovascular events and correlates with N-terminal pro-B-type natriuretic peptide and albuminuria in patients with diabetes mellitus,” Diabetic Medicine, vol. 29, no. 6, pp. 721–725, 2012.
[24]
A. Amin, F. Vakilian, and M. Maleki, “Serum uric acid levels correlate with filling pressures in systolic heart failure,” Congestive Heart Failure, vol. 17, no. 2, pp. 80–84, 2011.
[25]
M. C. Hsieh, H. M. Su, S. Y. Wang et al., “Significant correlation between left ventricular systolic and diastolic dysfunction and decreased glomerular filtration rate,” Renal Failure, vol. 33, no. 10, pp. 977–982, 2011.
[26]
Y. Nozari and B. Geraiely, “Correlation between the serum levels of uric acid and HS-CRP with the occurrence of early systolic failure of left ventricle following acute myocardial infarction,” Acta Medica Iranica, vol. 49, no. 8, pp. 531–535, 2011.
[27]
W. Doehner and U. Landmesser, “Xanthine oxidase and uric acid in cardiovascular disease: clinical impact and therapeutic options,” Seminars in Nephrology, vol. 31, no. 5, pp. 433–440, 2011.
[28]
D. Misra, Y. Zhu, Y. Zhang, and H. K. Choi, “The independent impact of congestive heart failure status and diuretic use on serum uric acid among men with a high cardiovascular risk profile: a prospective longitudinal study,” Seminars in Arthritis and Rheumatism, vol. 41, no. 3, pp. 471–476, 2011.
[29]
L. Tamariz, A. Harzand, A. Palacio, S. Verma, J. Jones, and J. Hare, “Uric acid as a predictor of all-cause mortality in heart failure: a meta-analysis,” Congestive Heart Failure, vol. 17, no. 1, pp. 25–30, 2011.
[30]
G. S. Filippatos, M. I. Ahmed, J. D. Gladden et al., “Hyperuricaemia, chronic kidney disease, and outcomes in heart failure: potential mechanistic insights from epidemiological data,” European Heart Journal, vol. 32, no. 6, pp. 712–720, 2011.
[31]
P. E. Puddu, L. Iannetta, and M. Schiariti, “Age- and gender-normalized coronary incidence and mortality risks in primary and secondary prevention,” Cardiology Research, vol. 3, pp. 193–204, 2012.
[32]
P. E. Puddu, M. Lanti, A. Menotti et al., “Serum uric acid for short-term prediction of cardiovascular disease incidence in the Gubbio population study,” Acta Cardiologica, vol. 56, no. 4, pp. 243–251, 2001.
[33]
A. Strasak, E. Ruttmann, L. Brant et al., “Serum uric acid and risk of cardiovascular mortality: a prospective long-term study of 83 683 Austrian men,” Clinical Chemistry, vol. 54, no. 2, pp. 273–284, 2008.
[34]
A. M. Strasak, C. C. Kelleher, L. J. Brant et al., “Serum uric acid is an independent predictor for all major forms of cardiovascular death in 28,613 elderly women: a prospective 21-year follow-up study,” International Journal of Cardiology, vol. 125, no. 2, pp. 232–239, 2008.
[35]
H. Alcaíno, D. Greig, P. Castro et al., “The role of uric acid in heart failure,” Revista Medica de Chile, vol. 139, no. 4, pp. 505–515, 2011.
[36]
R. J. Johnson, M. A. Lanaspa, and E. A. Gaucher, “Uric acid: a danger signal from the RNA world that may have a role in the epidemic of obesity, metabolic syndrome, and cardiorenal disease: evolutionary considerations,” Seminars in Nephrology, vol. 31, no. 5, pp. 394–399, 2011.
