Review Article

The Relationship between Uric Acid and the Development, Complication, and Prognosis of Atrial Fibrillation: The Views from a Clinical Study

Table 1

Details of the literature.

TitleTypeAreaPopulationSample sizeConclusion

Kuwabara et al. International Journal of Cardiology, 2017 [10]Single-center cross-sectional study.Tokyo, Japan.People underwent annual regular health checkup.90117 people were included.Hyperuricemia is an independent competing risk factor for AF.
Chen et al. BMJ Open, 2017 [11]Population-based cross-sectional study from health checkups.Tangshan, China.Residents ≥18 years participated in the study with informed consent.8937 people.SUA levels were significantly associated with AF prevalence. Females (but not males) with higher SUA levels had an increased prevalence of AF, suggesting a sex-specific mechanism.
Ding et al. QJM, 2015 [12]Population-based cross-sectional study from health checkups.Tangshan, China.Workers with diabetes from the Kailuan Coal Mine Group Corporation.9050 people were included, of which 60 had AF.UA is independent predictive factor of AF in both male and female diabetic patients.
Lin et al. BMJ Open, 2019 [13]Population-based cross-sectional study using randomized multistage cluster sampling.Guangdong, China.Residents aged 35 or older.A total of 11488 residents were included, of which 4547 had hyperuricemia.Hyperuricemia was highly prevalent among citizens of southern China and was a predictor of nonvalvular AF among women.
Huang et al. Scientific reports, 2018 [14]Population-based cross-sectional study by using of a stratified three-stage cluster-sampling design.Chengdu, China.Very elderly (≥80 years old) people.1038 participants were enrolled in analysis (55 had AF).Hyperuricemia is associated with the prevalence of AF in the general very elderly.
Krittayaphong et al. BMC Cardiovascular Disorders, 2016 [15]Population-based cross-sectional study using a two-stage tstratified cluster-sampling technique.Thailand.Hypertensive patients visiting public hospitals.71440 patients with hypertension were enrolled.UA level is one of the factors associated with increased risk of AF.
Kawasoe et al. Circulation Journal, 2016 [16]Single-center cross-sectional study.Kagoshima, Japan.People underwent routine health checkups.285882 people were included.The UA level was significantly associated with AF, independently of other cardiovascular risk factors.
Sun et al. BMC Cardiovascular Disorders, 2015 [17]Population-based cross-sectional study using a multistage, randomly stratified, cluster-sampling scheme.Liaoning, China.A representative sample of people ≥35 years of age from rural areas.A total of 11338 people, of which 104 of 9909 with normal SUA levels had AF, and 35 of 1429 with hyperuricemia had AF.SUA is positively associated with the prevalence of AF in rural China.
Suzuki et al. Circulation Journal [18]Single-center cross-sectional study.Tokyo, Japan.All patients with SUA measurements.7155 patients were included.The SUA level was apparently associated with AF prevalence. The independent association in women might imply some sex-specific mechanisms.
Liu Y, et al. Acta Cardiologica, 2010 [19]Single-center cross-sectional study.Beijing, China.Patients over 40 years.A total of 3489 patients were included, of which 1253 had AF.An independent relationship between high SUA and AF was confirmed.
Hu et al. Acta Cardiologica, 2010 [20]Multicenter cross-sectional study.Taiwan, China.Aged 55–80 years, diagnosed with hypertension.3472 patients, of whom 125 had AF.The level of UA in AF patients is increased, but UA is not an independent predictor for AF.
Mantovani et al. Journal of endocrinological investigation, 2015 [21]Single-center cross-sectional study.Verona, Italy.Patients with type 2 diabetes, who were discharged from endocrinology.Of the 842 hospitalized patients included, 243 had hyperuricemia and 91 had AF.Hyperuricemia is associated with an increased prevalence of AF in hospitalized patients with type 2 diabetes, independently of multiple risk factors and potential confounders.
Mantovani et al. Journal of endocrinological investigation, 2017 [22]Single-center cross-sectional study.Verona, Italy.Outpatients with established T2DM, who regularly attended diabetes clinic.Of the 245 patients with T2DM, 59 had hyperuricemia.Hyperuricemia is independently associated with an approximately fourfold increased risk of prevalent paroxysmal AF in patients with T2DM.
Memetoglu et al. European review for medical and pharmacological sciences, 2015 [23]Single-center cross-sectional study.Istanbul, Turkey.Patients undergoing their first CABG surgery.174 patients were included.The SUA level can increase the sensitivity and specificity in predicting AF in patients after CABG operation.
Karatas et al. Coronary artery Aisease, 2016 [24]Single-center cross-sectional study.Istanbul, Turkey.Patients who were hospitalized with a diagnosis of STEMI and treated with primary PCI.A total of 621 patients, of whom 40 were diagnosed with new-onset AF after PCI.SUA levels were found to be correlated independently with new-onset AF after primary PCI.
Topolyanskaya et al. SN Comprehensive Clinical Medicine, 2020 [25]Single-center cross-sectional study.Moscow, Russia.Patients with coronary heart disease over the age of 75.312 patients, of whom 123 had hyperuricemia.The diagnosis of AF was significantly increased in patients with hyperuricemia.
Murakami et al. Open Heart, 2017 [26]Multicenter cross-sectional study.Japan.Patients who have undergone coronary angiography.A total of 1150 patients were included, of which 574 had coronary heart disease and 576 had no coronary heart disease.Major risk factors of AF are different in patients with or without coronary artery disease. Patients with coronary artery disease are more likely to develop AF when the SUA level is high.
Wan et al. Archives of Medical Research, 2014 [27]Single-center cross-sectional study.Xuzhou, China.Obstructive sleep apnea patients.516 patients were included while 106 had AF.The occurrence of AF in obstructive sleep apnea patients is strongly related to SUA level.
Liu et al. Internal Medicine, 2011 [28]Single-center cross-sectional study.Tianjin, China.Patients with essential hypertension.451 patients were included while 50 had AF.SUA levels are associated with AF in hypertensive patients.
Shi D et al. Aging Clinical and Experimental Research, 2016 [29]Single-center cross-sectional study.Sichuan, China.Patients with hypertension.A total of 268 patients, 132 of whom had AF (48 cases of paroxysmal AF and 84 cases of persistent AF).In patients with hypertension, the presence of AF was associated with arterial stiffness. SUA levels may reflect mechanisms behind this association.
Tekin et al. Angiology, 2013 [30]Single-center cross-sectional study.Turkey.Patients with ischemic heart failure from the outpatient cardiology clinic.363 patients were included while 78 had AF.Patients with AF have significantly higher SUA and this was independently associated with AF in patients with ischemic heart failure.
Aghaali et al. Shiraz E-Med J, 2016 [31]Single-center case-control study.Qom, Iran.Consecutive patients with persistent, permanent, or paroxysmal AF who attended the outpatient cardiology clinic or the emergency department were recruited.32 patients with AF and 32 healthy controls.Serum uric acid can be considered a risk factor for AF.
Minami et al. Int Heart J, 2009 [32]Single-center nested cased-control study based on routine annual medical checkups.Ishikawa prefecture, Japan.Cases consisted of male workers newly diagnosed with AF based on ECG. Each of these cases had 3 prior annual checkups during which ECGs were negative for AF. Controls, which were matched for age and time period were randomly selected from those never diagnosed with AF over the same 4 yearly evaluations as cases.69 cases of new-onset AF and 138 controls were included.New-onset AF was associated with systolic blood pressure and drinking habits, while uric acid is not an independent risk factor.
Tamariz et al. The American Journal of Cardiology, 2011 [33]Longitudinal community-based cohort study.United States.Participants from atherosclerosis risk in communities (ARIC) study.15382 adults free of AF were enrolled in the analysis with a median follow-up of 16.8 years.Elevated SUA is associated with a greater risk of AF, particularly among blacks and women.
Singh et al. RMD Open, 2018 [34]Cohort study based on data from the 5% random sample of medicare claims.United States.People older than 64 and younger than 110.1647812 were observed from 2006 to 2012.A diagnosis of gout almost doubled the risk of incident AF in the elderly.
Kuo et al. Sci Rep, 2016 [35]Cohort study using population-based health databases.Taiwan, China.Patients diagnosed with gout for the first time between 2000 and 2007 were enrolled for gout group, and 1 : 1 matched patients for control group.63264 : 63264 patients were enrolled with the mean follow-up duration as 6.1 ± 2.1 years.Gout was found to be associated with an increased risk of developing AF after adjusting for potential confounders.
Chao et al. International Journal of Cardiology, 2013 [36]Health insurance-based cohort study.Taiwan, China.Patients with hyperuricemia and without AF. For each study patient, an age-, sex- and underlying disease-matched subject without hyperuricemia and history of AF was selected to be the control.61262 study patients and 61262 controls were enrolled with a mean follow-up duration of 6.3 ± 3.0 years.Hyperuricemia may be a novel risk factor for the development of AF.
Kawasoe et al. Circulation Journal, 2018 [37]Cohort study based on data from annual health checkups.Kagoshima, Japan.Subjects who underwent annual health checkups at least twice.111566 subjects were observed during the median period of 4.1 years.Higher baseline UA was significantly associated with higher AF incidence in women.
Li et al. Journal of the American Heart Association, 2019 [38]Community-based cohort study.Tangshan, China.All residents in the Kailuan community were invited based on Kailuan I and II studies.123238 participants were included with median follow-up of 6.7 years (interquartile range: 5.3–8.3 years).High SUA levels and increases in SUA over time were associated with increased risk of incident AF.
Nyrnes et al. Europace, 2014 [39]Cohort study based on participants from the Tromso study.Europe.White Europeans with 25 years and older.6308 persons were observed during a mean follow-up of 10.8 years.Baseline SUA was associated with an increased risk for future AF in both sexes.
Kwon et al. Circulation Journal, 2018 [40]Cohort study based on health screening program.Seoul, Korea.Working individuals who participated annual or biennial health examination based on the Korean industrial safety and health law.282473 subjects were enrolled with a mean follow-up duration of 5.4 ± 3.6 years.SUA is significantly and positively associated with incident AF in the Korean general population.
Kim et al. Ann Rheum Dis, 2016 [41]Cohort study using claims data from United HealthCare.United States.Adult patients aged ≥40 years who were diagnosed for gout were eligible for the gout group. Two comparison groups were defined ‘osteoarthritis group’ and ‘nongout group’.70015 gout patients with mean (SD) follow-up time as 2.1 (0.8) years and 210045 osteoarthritis patients with 2.0 (1.8). For the comparison between gout and nongout group, 91976 : 275928 patients with 2.0 (1.8) follow-up time were enrolled.Gout was associated with a modestly increased risk of incident AF compared with osteoarthritis and nongout after adjusting for other risk factors.
Kuo et al. Rheumatology (Oxford), 2016 [42]Cohort study based on the clinical practice research data-link (CPRD).United Kingdom.All incident gout patients diagnosed between 1997 and 2005, and 1 : 1 matched control patients.90756 patients with a median follow-up of 9 years.Gout is independently associated with a higher risk of AF at diagnosis and the risk is also higher after the diagnosis.
Peters et al. Heart, 2019 [43]Cohort study based on multiple overlapping studies.Scotland.Participants from Scottish Heart Health Extended Cohort.15737 participants with a median follow-up of 22.6 years.UA is strongly associated with the risk of AF in women.
Chuang et al. Nutr Metab Cardiovasc Dis, 2014 [44]Cohort study based on the elderly nutrition and health survey in taiwan.Taiwan, China.People aged 65 years and over in Taiwan.1485 people were included and the median follow-up time was 9.16 years.Hyperuricemia is associated with the development of AF in older persons with normal blood pressure.
Valbusa et al. Am J Cardiol, 2013 [45]Single-center cohort study.Verona, Italy.Patients with type 2 diabetes.400 Caucasian patients with followed for 10 years.Elevated SUA levels are strongly associated with an increased incidence of AF in patients with type 2 diabetes mellitus even after adjustment for multiple clinical risk factors for AF.
Zhao et al. Chin Med J (Engl), 2012 [46]Multicenter cohort study.Hubei, China.Patients with chronic systolic heart failure.20259 patients were enrolled with an undeclared follow-up period.Higher SUA level is associated strongly with AF in patients with chronic heart failure. SUA level can increase int sensitivity and specificity in predicting AF.
Tang et al. Can J Cardiol, 2014 [48]Single-center cross-sectional study.Beijing, China.Consecutive AF patients underwent TEE before the first-time ablation were included.1359 patients were included and 61 had LAT and another 50 patients had spontaneous echocardiographic contrast (SEC).Hyperuricemia was a modest risk factor for LAT, which might refine stratification of LAT in patients with nonvalvular AF.
Zhang et al. Eur J Prev Cardiol, 2020 [49]Single-center cross-sectional study.Hangzhou, China.Consecutive patients with nonvalvular AF who underwent transesophageal echocardiography (TEE) before ablation.2246 patients were included in the study and 30 of them had left atrial thrombosis (LAT).Abnormal uric acid metabolism is an independent risk marker for LAT.
Liao et al. J Geriatr Cardiol, 2015 [51]Single-center cross-sectional study.Guangdong, China.Consecutive hospitalized AF patients who underwent TEE prior to ablation.1419 patients with nonvalvular AF were included. 65 had LAT and 57 had SEC.SUA level is an independent risk factor and has a moderate predictive value for LA-SEC among nonvalvular AF patients in southern China.
Celik et al. Med Princ Pract, 2015 [52]Single-center cross-sectional study.Turkey.Patients with AF, who were admitted to the department of cardiology and in whom TEE was performed before cardioversion, were retrospectively screened.153 patients were included. Patients with a low left atrial appendage (LAA) peak flow velocity were identified as group 1, and patients with a normal LAA peak flow velocity were identified as group 2.High SUA levels are associated with a low contractile function of the LAA and could provide additional prognostic information on future thromboembolic events in patients with AF.
Liu et al. Int J Cardiol, 2018 [53]Single-center cross-sectional study.Guangdong, China.Consecutive hospitalized AF patients who underwent TEE prior to ablation.1198 patients with nonvalvular AF were included. 49 had LAT and 49 had SEC.Hyperuricemia might independently predict and refine LA stasis risk among nonvalvular patients, especially in those with CHA2DS2-VASc score < 2.
Numa et al. Circ J, 2014 [54]Single-center cross-sectional study.Japan.Consecutive patients with nonvalvular AF who underwent TEE to determine their potential embolic risk.470 patients were enrolled.The SUA level was associated with thromboembolic risk on TEE in patients with nonvalvular AF at low-intermediate risk stratified by clinical risk factors.
Ning et al. Int Heart J, 2017 [55]Single-center cross-sectional study.Liaoning, China.Consecutive patients with NVAF who have not accepted anticoagulant therapy.The study population consisted of 284 patients, and 61 had LAT/SEC.SUA and left atrial diameter enhanced the predictive ability of CHADS2 and CHA2DS2-VASc for LAT/SEC as additional factors. For patients in moderate risk group, is SUA or LAD was higher than cut-off values, the risk of thromboembolism events would rise accompanied by the elevated risk of LAT/SEC.
Yang et al. J Neurol Sci, 2016 [58]Single-center cross-sectional study.Korea.Consecutive acute ischemic stroke patients.1489 patients were included. 412 of them were cardioembolic stroke (CES) and 268 of 412 had AF.SUA level is associated with the risk of CES in acute ischemic stroke patients of both sexes.
Liang et al. Nutr Metab Cardiovasc Dis, 2016 [59]Single-center cross-sectional study.Beijing, China.Consecutive elderly patients (age>60) with nonvalvular AF.577 patients were included, and 168 of them had left ventricular hypertrophy (LVH).SUA was independently associated with LVH in elderly male patients with nonvalvular AF.
Chao et al. Int J Cardiol, 2014 [60]Cohort study based on health insurance database.Taiwan, China.Patients 18 years of age or older with newly diagnosed AF were included. Patients who received antithrombotic therapy with either antiplatelet agents or oral anticoagulants were excluded.A total of 7601 patients who were selected as the study population. The mean follow-up duration was 3.0 ± 2.7 years, and there were 1116 patients who experienced ischemic stroke with an annual stroke rate of around 4.9%.Hyperuricemia was a significant risk factor of stroke which could potentially refine the clinical risk stratification in AF.
Su et al. Int J Cardiol, 2014 [61]Single-center prospective cohort study.Taiwan, China.Patients with persistent AF referred for echocardiographic examination were enrolled.160 AF patients were included. The follow-up period to cardiac events was 22 ± 10 months. 40 cardiac events were documented during the follow-up period.Hyperuricemia was independently associated with an increase in adverse cardiac events and could add significant incremental prognostic value beyond conventional clinical and echocardiographic parameters. Hence, SUA should be measured in AF patients for additional prognostication.
He et al. Chin Med J (Engl), 2013 [65]Single-center retrospective cohort study.Beijing, China.Consecutive patients underwent pulmonary vein isolation as a treatment for paroxysmal AF.303 patients diagnosed with paroxysmal AF with a mean follow-up of 9.341 ± 3.667 months were analyzed.In this retrospective study of patients with paroxysmal AF undergoing catheter ablation, elevated preoperative SUA levels were associated with a higher rate of recurrence of AF.
Canpolat et al. Europace, 2014 [66]Single-center prospective cohort study.Ankara, Turkey.Consecutive patients who underwent pulmonary vein isolation with cryoballoon technique for documented AF.363 patients were enrolled. After a mean follow-up period of 19.2 ± 6.1 months, early recurrence was developed in 33 patients and recurrence after blanking period was observed in 68 patients.In this prospective study of patients with paroxysmal AF undergoing cryoablation, increased preablation SUA levels were associated with a higher rate of AF recurrence.
Kok et al. PLoS One, 2014 [68]Population-based retrospective matched-cohort study using health insurance database.Taiwan, China.Every individual diagnosed with gout in the years 1999 to 2008 were included. Patients with or without allopurinol treatment were divided and matched.2483 treated and 2483 nontreated patients were included. The median follow-up time for the allopurinol group was 5.25 years, whereas it was 5.04 years for the nonallopurinol group.The current population-based matched-cohort study did not support the association between allopurinol therapy in gout patients with normal risk for cardiovascular sequels and beneficial future cardiovascular outcomes. Several important risk factors for cardiovascular diseases, such as smoking, alcohol consumption, body mass index, and blood pressure, were not obtainable in the current retrospective cohort study, which could potentially bias the effect estimate.