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BMC Cardiovascular Disorders
Published in: BMC Cardiovascular Disorders 1/2019

Open Access 01-12-2019 | Research article

Serum uric acid and risk of cardiovascular mortality: a systematic review and dose-response meta-analysis of cohort studies of over a million participants

Authors: Fatemeh Rahimi-Sakak, Mahsa Maroofi, Jamal Rahmani, Nick Bellissimo, Azita Hekmatdoost

Published in: BMC Cardiovascular Disorders | Issue 1/2019

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Abstract

Background

Cardiovascular disease (CVD) is the leading cause of death worldwide. Some studies have suggested anassociation between serum uric acid levels and cardiovascular mortality; however, the results have not been summarized in a meta-analysis.

Methods

A comprehensive search of all related studies until April 2018was performed in MEDLINE/PubMed and Scopus databases DerSimonianand Laird random-effects models were used to combine hazard ratios (HRs) with 95% confidence intervals (CIs). Dose-response analysis was also carried out.

Results

Thirty-two studies containing forty-four arms with 1,134,073 participants reported association between uric acid and risk of CVD mortality were included in our analysis. Pooled results showed a significant positive association between uric acid levels and risk of CVD mortality (HR 1.45, 95% CI 1.33–1.58, I2 = 79%). Sub-group analysis showed this relationshipwasstronger in women compared to men. Moreover, there was a significant non-linear association between uric acid levels and the risk of CVD mortality (r = 0.0709, p = 0.001).

Conclusion

Our analysis indicates a positive dose-response association between SUA and CVD mortality risk.
Literature
1.
Dhindsa DS, Khambhati J, Sandesara PB, Eapen DJ, Quyyumi AA. Biomarkers to predict cardiovascular death. Card Electrophysiol Clin. 2017;9(4):651–64 PubMed PMID: 29173408. Epub 2017/11/28.PubMedCrossRef
2.
Mora-Ramirez M, Estevez-Garcia IO, Irigoyen-Camacho ME, Bojalil R, Gonzalez-Pacheco H, Amezcua-Guerra LM. Hyperuricemia on admission predicts short-term mortality due to myocardial infarction in a population with high prevalence of cardiovascular risk factors. Rev Investig Clin. 2017;69(5):247–53 PubMed PMID: 29077696. Epub 2017/10/28.
3.
Zhao G, Huang L, Song M, Song Y. Baseline serum uric acid level as a predictor of cardiovascular disease related mortality and all-cause mortality: a meta-analysis of prospective studies. Atherosclerosis. 2013;231(1):61–8 PubMed PMID: 24125412. Epub 2013/10/16. eng.PubMedCrossRef
4.
Vassalle C, Mazzone A, Sabatino L, Carpeggiani C. Uric Acid for Cardiovascular Risk: Dr. Jekyll or Mr. Hide? Diseases. 2016;4(1) PubMed PMID: 28933392. Pubmed Central PMCID: PMC5456305. Epub 2016/02/26.PubMedCentralCrossRef
5.
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;54(1):7–15 PubMed PMID: 26351943. Epub 2015/09/10.PubMedCrossRef
6.
Xu Q, Zhang M, Abeysekera IR, Wang X. High serum uric acid levels may increase mortality and major adverse cardiovascular events in patients with acute myocardial infarction. Saudi Med J. 2017;38(6):577–85 PubMed PMID: 28578435. Pubmed Central PMCID: PMC5541179. Epub 2017/06/05.PubMedPubMedCentralCrossRef
7.
Kanbay M, Segal M, Afsar B, Kang DH, Rodriguez-Iturbe B, Johnson RJ. The role of uric acid in the pathogenesis of human cardiovascular disease. Heart. 2013;99(11):759–66 PubMed PMID: 23343689. Epub 2013/01/25.PubMedCrossRef
8.
Kei A, Koutsouka F, Makri A, Elisaf M. Uric acid and cardiovascular risk: What genes can say. Int J Clin Pract. 2018;72(1) PubMed PMID: 29250870. Epub 2017/12/19.CrossRef
9.
Stroup DF, Berlin JA, Morton SC, Olkin I, Williamson GD, Rennie D, et al. Meta-analysis of observational studies in epidemiology: a proposal for reporting. JAMA. 2000;283(15):2008–12.PubMedCrossRef
10.
Jackson D, White IR, Thompson SG. Extending DerSimonian and Laird’s methodology to perform multivariate random effects meta-analyses. Stat Med. 2010;29(12):1282–97.PubMedCrossRef
11.
Beberashvili I, Sinuani I, Azar A, Shapiro G, Feldman L, Stav K, et al. Serum uric acid as a clinically useful nutritional marker and predictor of outcome in maintenance hemodialysis patients. Nutrition. 2015;31(1):138–47 English.PubMedCrossRef
12.
Chen JH, Chuang SY, Chen HJ, Yeh WT, Pan WH. Serum uric acid level as an independent risk factor for all-cause, cardiovascular, and ischemic stroke mortality: a Chinese cohort study. Arthritis Rheum. 2009;61(2):225–32 PubMed PMID: 19177541. Epub 2009/01/30. eng.PubMedCrossRef
13.
Hsu WL, Li SY, Liu JS, Huang PH, Lin SJ, Hsu CC, et al. High uric acid ameliorates Indoxyl sulfate-induced endothelial dysfunction and is associated with lower mortality among hemodialysis patients. Toxins. 2017;9(1) PubMed PMID: 28067806. Pubmed Central PMCID: PMC5308252. Epub 2017/01/10. eng.PubMedCentralCrossRef
14.
Hu SL, Liu CS, Lin CH, Davidson LE, Li CI, Lin CC, et al. Uric acid and mortality in elderly chinese: a 10-year population-based cohort study. J Am Geriatr Soc. 2012;60(9):1783–5 English.PubMedCrossRef
15.
Kamei K, Konta T, Ichikawa K, Sato H, Suzuki N, Kabasawa A, et al. Serum uric acid levels and mortality in the Japanese population: the Yamagata (Takahata) study. Clin Exp Nephrol. 2016;20(6):904–9 PubMed PMID: 26779905. Epub 2016/01/19. eng.PubMedCrossRef
16.
Li Q, Zhang Y, Ding D, Yang Y, Chen Q, Liu C, et al. Association between serum uric acid and mortality among Chinese patients with coronary artery disease. Cardiology. 2016;134(3):347–56 PubMed PMID: 26985667. Epub 2016/03/18. eng.PubMedCrossRef
17.
Lin GM, Li YH, Zheng NC, Lai CP, Lin CL, Wang JH, et al. Serum uric acid as an independent predictor of mortality in high-risk patients with obstructive coronary artery disease. A prospective observational cohort study from the ET-CHD registry, 1997-2003. J Cardiol. 2013;61(2):122–7 English.PubMedCrossRef
18.
Nossent J, Raymond W, Divitini M, Knuiman M. Asymptomatic hyperuricemia is not an independent risk factor for cardiovascular events or overall mortality in the general population of the Busselton health study. BMC Cardiovasc Disord. 2016;16(1):256 PubMed PMID: 27978810. Pubmed Central PMCID: PMC5160002. Epub 2016/12/17. eng.PubMedPubMedCentralCrossRef
19.
Shimizu T, Yoshihisa A, Kanno Y, Takiguchi M, Sato A, Miura S, et al. Relationship of hyperuricemia with mortality in heart failure patients with preserved ejection fraction. Am J Physiol Heart Circ Physiol. 2015;309(7):H1123–9 PubMed PMID: 26297226. Epub 2015/08/25. eng.PubMedCrossRef
20.
Tomita M, Mizuno S, Yamanaka H, Hosoda Y, Sakuma K, Matuoka Y, et al. Does hyperuricemia aeffect mortality? A prospective cohort study of japanese male workers. J Epidemiol. 2000;10(6):403–9 English.PubMedCrossRef
21.
Tseng WC, Chen YT, Ou SM, Shih CJ, Tarng DC, Yang CY, et al. U-shaped association between serum uric acid levels with cardiovascular and all-cause mortality in the elderly: The role of malnourishment. J Am Heart Assoc. 2018;7(4) English.
22.
Wang J, Wang Y, Zhao D, Guo X, Zhong JQ. Association between serum uric acid and mortality in a Chinese population of hypertensive patients. Ren Fail. 2015;37(1):73–6 PubMed PMID: 25260057. Epub 2014/09/27. eng.PubMedCrossRef
23.
Wen CP, David Cheng TY, Chan HT, Tsai MK, Chung WS, Tsai SP, et al. Is high serum uric acid a risk marker or a target for treatment? Examination of its independent effect in a large cohort with low cardiovascular risk. Am J kidney Dis. 2010;56(2):273–88 PubMed PMID: 20605302. Epub 2010/07/08. eng.PubMedCrossRef
24.
Wu CY, Hu HY, Chou YJ, Huang N, Chou YC, Lee MS, et al. High serum uric acid levels are associated with all-cause and cardiovascular, but not Cancer, mortality in elderly adults. J Am Geriatr Soc. 2015;63(9):1829–36 PubMed PMID: 26277576. Epub 2015/08/19. eng.PubMedCrossRef
25.
Xia X, He F, Wu X, Peng F, Huang F, Yu X. Relationship between serum uric acid and all-cause and cardiovascular mortality in patients treated with peritoneal dialysis. Am J Kidney Dis. 2014;64(2):257–64 PubMed PMID: 24176223. Epub 2013/11/02. eng.PubMedCrossRef
26.
Zhang W, Iso H, Murakami Y, Miura K, Nagai M, Sugiyama D, et al. Serum uric acid and mortality form cardiovascular disease: EPOCH-JAPAN study. J Atheroscler Thromb. 2016;23(6):692–703 PubMed PMID: 26887218. Epub 2016/02/19. eng.PubMedCrossRef
27.
Zhu L, Wang J, Wang Y, Jia L, Sun K, Wang H, et al. Plasma uric acid as a prognostic marker in patients with hypertrophic cardiomyopathy. Can J Cardiol. 2015;31(10):1252–8 English.PubMedCrossRef
28.
Dawson J, Jeemon P, Hetherington L, Judd C, Hastie C, Schulz C, et al. Serum uric acid level, longitudinal blood pressure, renal function, and long-term mortality in treated hypertensive patients. Hypertension. 2013;62(1):105–11 PubMed PMID: 23690348. Epub 2013/05/22. eng.PubMedCrossRef
29.
Fang J, Alderman MH. Serum uric acid and cardiovascular mortality the NHANES I epidemiologic follow-up study, 1971-1992. National Health and nutrition examination survey. JAMA. 2000;283(18):2404–10 PubMed PMID: 10815083. Epub 2000/05/18. eng.PubMedCrossRef
30.
Ford ES. Uric acid and mortality from all-causes and cardiovascular disease among adults with and without diagnosed diabetes: findings from the National Health and nutrition examination survey III linked mortality study. Diabetes Res Clin Pract. 2011;93(2):e84–e6 English.PubMedCrossRef
31.
Kleber ME, Delgado G, Grammer TB, Silbernagel G, Huang J, Krämer BK, et al. Uric acid and cardiovascular events: a Mendelian randomization study. J Am Soc Nephrol. 2015;26(11):2831–8 English.PubMedPubMedCentralCrossRef
32.
Lopez-Pineda A, Cordero A, Carratala-Munuera C, Orozco-Beltran D, Quesada JA, Bertomeu-Gonzalez V, et al. Hyperuricemia as a prognostic factor after acute coronary syndrome. Atherosclerosis. 2018;269:229–35 PubMed PMID: 29407598. Epub 2018/02/07. eng.PubMedCrossRef
33.
Mayer FJ, Mannhalter C, Minar E, Schillinger M, Chavakis T, Siegert G, et al. The impact of uric acid on long-term mortality in patients with asymptomatic carotid atherosclerotic disease. J Stroke Cerebrovasc Dis. 2015;24(2):354–61 English.PubMedCrossRef
34.
Meisinger C, Koenig W, Baumert J, Döring A. Uric acid levels are associated with all-cause and cardiovascular disease mortality independent of systemic inflammation in men from the general population the MONICA ORA cohort study. Arterioscler Thromb Vasc Biol. 2008;28(6):1186–92 English.PubMedCrossRef
35.
Niskanen LK, Laaksonen DE, Nyyssonen K, Alfthan G, Lakka HM, Lakka TA, et al. Uric acid level as a risk factor for cardiovascular and all-cause mortality in middle-aged men: a prospective cohort study. Arch Intern Med. 2004;164(14):1546–51 PubMed PMID: 15277287. Epub 2004/07/28. eng.PubMedCrossRef
36.
Silbernagel G, Hoffmann MM, Grammer TB, Boehm BO, Marz W. Uric acid is predictive of cardiovascular mortality and sudden cardiac death in subjects referred for coronary angiography. Nutr Metab Cardiovasc Dis. 2013;23(1):46–52 PubMed PMID: 21703834. Epub 2011/06/28. eng.PubMedCrossRef
37.
Spoon DB, Lerman A, Rule AD, Prasad A, Lennon RJ, Holmes DR, et al. The association of serum uric acid levels with outcomes following percutaneous coronary intervention. J Interv Cardiol. 2010;23(3):277–83 English.PubMedCrossRef
38.
Strasak A, Ruttmann E, Brant L, Kelleher C, Klenk J, Concin H, et al. Serum uric acid and risk of cardiovascular mortality: a prospective long-term study of 83,683 Austrian men. Clin Chem. 2008;54(2):273–84 PubMed PMID: 18039719. Epub 2007/11/28. eng.PubMedCrossRef
39.
Strasak AM, Kelleher CC, Brant LJ, Rapp K, Ruttmann E, Concin H, 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. Int J Cardiol. 2008;125(2):232–9 English.PubMedCrossRef
40.
Tscharre M, Herman R, Rohla M, Hauser C, Farhan S, Freynhofer MK, et al. Uric acid is associated with long-term adverse cardiovascular outcomes in patients with acute coronary syndrome undergoing percutaneous coronary intervention. Atherosclerosis. 2018;270:173–9 English.PubMedCrossRef
41.
Von Lueder TG, Girerd N, Atar D, Agewall S, Lamiral Z, Kanbay M, et al. Serum uric acid is associated with mortality and heart failure hospitalizations in patients with complicated myocardial infarction: findings from the high-risk myocardial infarction database initiative. Eur J Heart Fail. 2015;17(11):1144–51 English.CrossRef
42.
Zalawadiya SK, Veeranna V, Mallikethi-Reddy S, Bavishi C, Lunagaria A, Kottam A, et al. Uric acid and cardiovascular disease risk reclassification: findings from NHANES III. Eur J Prev Cardiol. 2015;22(4):513–8 PubMed PMID: 24431384. Epub 2014/01/17. eng.PubMedCrossRef
43.
Mazzali M, Kanellis J, Han L, Feng L, Xia Y-Y, Chen Q, et al. Hyperuricemia induces a primary renal arteriolopathy in rats by a blood pressure-independent mechanism. Am J Physiology Renal Physiol. 2002;282(6):F991–F7.CrossRef
44.
Tavil Y, Kaya MG, Oktar SÖ, Sen N, Okyay K, Yazıcı HU, et al. Uric acid level and its association with carotid intima–media thickness in patients with hypertension. Atherosclerosis. 2008;197(1):159–63.PubMedCrossRef
45.
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;26(5):480–6 PubMed PMID: 21207039. Epub 2011/01/06. eng.CrossRef
46.
Kaya EB, Yorgun H, Canpolat U, Hazirolan T, Sunman H, Ulgen A, et al. Serum uric acid levels predict the severity and morphology of coronary atherosclerosis detected by multidetector computed tomography. Atherosclerosis. 2010;213(1):178–83 PubMed PMID: 20863499. Epub 2010/09/25. eng.PubMedCrossRef
47.
Patetsios P, Song M, Shutze WP, Pappas C, Rodino W, Ramirez JA, et al. Identification of uric acid and xanthine oxidase in atherosclerotic plaque. Am J Cardiol 2001;88(2):188–191, a6. PubMed PMID: 11448423. Epub 2001/07/13. eng.
48.
Gordon T, Terkeltaub R, Ginsberg M. Gout: crystal-induced inflammation. Inflammation: Basic Principles and Clinical Correlates New York, NY, Raven 1988:775–83.
Metadata
Title
Serum uric acid and risk of cardiovascular mortality: a systematic review and dose-response meta-analysis of cohort studies of over a million participants
Authors
Fatemeh Rahimi-Sakak
Mahsa Maroofi
Jamal Rahmani
Nick Bellissimo
Azita Hekmatdoost
Publication date
01-12-2019
Publisher
BioMed Central
Published in
BMC Cardiovascular Disorders / Issue 1/2019
Electronic ISSN: 1471-2261
DOI
https://doi.org/10.1186/s12872-019-1215-z

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