{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,31]],"date-time":"2026-10-31T15:16:55Z","timestamp":1793459815822,"version":"4.5.0"},"reference-count":43,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2023,1,10]],"date-time":"2023-01-10T00:00:00Z","timestamp":1673308800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Cardiovasc. Med."],"abstract":"<jats:sec><jats:title>Background<\/jats:title><jats:p>The causal relationship between hyperuricemia and cardiovascular diseases is still unknown. We hypothesized that hyperuricemic patients after percutaneous coronary intervention (PCI) had a higher risk of major adverse cardiovascular events (MACE).<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>This was a large-scale multicenter cohort study. We enrolled patients with chronic coronary syndrome (CCS) after PCI between April 2013 and March 2019 using the database from the Clinical Deep Data Accumulation System (CLIDAS), and compared the incidence of MACE, defined as a composite of cardiovascular death, myocardial infarction, and hospitalization for heart failure, between hyperuricemia and non-hyperuricemia groups.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>In total, 9,936 patients underwent PCI during the study period. Of these, 5,138 patients with CCS after PCI were divided into two group (1,724 and 3,414 in the hyperuricemia and non-hyperuricemia groups, respectively). The hyperuricemia group had a higher prevalence of hypertension, atrial fibrillation, history of previous hospitalization for heart failure, and baseline creatinine, and a lower prevalence of diabetes than the non-hyperuricemia group, but the proportion of men and age were similar between the two groups. The incidence of MACE in the hyperuricemia group was significantly higher than that in the non-hyperuricemia group (13.1 vs. 6.4%, log-rank <jats:italic>P<\/jats:italic> &amp;lt; 0.001). Multivariable Cox regression analyses revealed that hyperuricemia was significantly associated with increased MACE [hazard ratio (HR), 1.52; 95% confidential interval (CI), 1.23\u20131.86] after multiple adjustments for age, sex, body mass index, estimated glomerular filtration rate, left main disease or three-vessel disease, hypertension, diabetes mellitus, dyslipidemia, history of myocardial infarction, and history of hospitalization for heart failure. Moreover, hyperuricemia was independently associated with increased hospitalization for heart failure (HR, 2.19; 95% CI, 1.69\u20132.83), but not cardiovascular death or myocardial infarction after multiple adjustments. Sensitive analyses by sex and diuretic use, B-type natriuretic peptide level, and left ventricular ejection fraction showed similar results.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>CLIDAS revealed that hyperuricemia was associated with increased MACE in patients with CCS after PCI. Further clinical trials are needed whether treating hyperuricemia could reduce cardiovascular events or not.<\/jats:p><\/jats:sec>","DOI":"10.3389\/fcvm.2022.1062894","type":"journal-article","created":{"date-parts":[[2023,1,10]],"date-time":"2023-01-10T21:05:57Z","timestamp":1673384757000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":26,"title":["Hyperuricemia predicts increased cardiovascular events in patients with chronic coronary syndrome after percutaneous coronary intervention: A nationwide cohort study from Japan"],"prefix":"10.3389","volume":"9","author":[{"given":"Naoyuki","family":"Akashi","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Masanari","family":"Kuwabara","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tetsuya","family":"Matoba","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Takahide","family":"Kohro","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yusuke","family":"Oba","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tomoyuki","family":"Kabutoya","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yasushi","family":"Imai","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kazuomi","family":"Kario","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Arihiro","family":"Kiyosue","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yoshiko","family":"Mizuno","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kotaro","family":"Nochioka","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Masaharu","family":"Nakayama","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Takamasa","family":"Iwai","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yoko","family":"Nakao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yoshitaka","family":"Iwanaga","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yoshihiro","family":"Miyamoto","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Masanobu","family":"Ishii","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Taishi","family":"Nakamura","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kenichi","family":"Tsujita","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hisahiko","family":"Sato","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hideo","family":"Fujita","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ryozo","family":"Nagai","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2023,1,10]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"2404","DOI":"10.1001\/jama.283.18.2404","article-title":"Serum uric acid and cardiovascular mortality the NHANES I epidemiologic follow-up study, 1971\u20131992. National health and nutrition examination survey","volume":"283","author":"Fang","year":"2000","journal-title":"JAMA"},{"key":"B2","doi-asserted-by":"publisher","first-page":"1503","DOI":"10.1161\/01.STR.0000221716.55088.d4","article-title":"Uric acid is a risk factor for myocardial infarction and stroke: the Rotterdam study","volume":"37","author":"Bos","year":"2006","journal-title":"Stroke"},{"key":"B3","doi-asserted-by":"publisher","first-page":"229","DOI":"10.1016\/j.atherosclerosis.2018.01.017","article-title":"Hyperuricemia as a prognostic factor after acute coronary syndrome","volume":"269","author":"Lopez-Pineda","year":"2018","journal-title":"Atherosclerosis"},{"key":"B4","doi-asserted-by":"publisher","first-page":"150","DOI":"10.1016\/j.amjcard.2021.05.007","article-title":"Relation of serum uric acid and cardiovascular events in young adults aged 20\u201349 years","volume":"152","author":"Seki","year":"2021","journal-title":"Am J Cardiol"},{"key":"B5","doi-asserted-by":"publisher","first-page":"e114259","DOI":"10.1371\/journal.pone.0114259","article-title":"Hyperuricemia and risk of incident hypertension: a systematic review and meta-analysis of observational studies","volume":"9","author":"Wang","year":"2014","journal-title":"PLoS ONE"},{"key":"B6","doi-asserted-by":"publisher","first-page":"e56864","DOI":"10.1371\/journal.pone.0056864","article-title":"High serum uric acid and increased risk of type 2 diabetes: a systemic review and meta-analysis of prospective cohort studies","volume":"8","author":"Lv","year":"2013","journal-title":"PLoS ONE"},{"key":"B7","doi-asserted-by":"publisher","first-page":"715","DOI":"10.1007\/s40620-020-00702-7","article-title":"Uric acid in CKD: has the jury come to the verdict?","volume":"33","author":"Bonino","year":"2020","journal-title":"J Nephrol"},{"key":"B8","doi-asserted-by":"publisher","first-page":"851","DOI":"10.1053\/j.ajkd.2017.12.009","article-title":"Hyperuricemia, acute and chronic kidney disease, hypertension, and cardiovascular disease: report of a scientific workshop organized by the national kidney foundation","volume":"71","author":"Johnson","year":"2018","journal-title":"Am J Kidney Dis"},{"key":"B9","doi-asserted-by":"publisher","first-page":"885","DOI":"10.1253\/circj.CJ-08-0828","article-title":"Elevated serum uric acid is an independent predictor for cardiovascular events in patients with severe coronary artery stenosis: subanalysis of the Japanese Coronary Artery Disease (JCAD) study","volume":"73","author":"Okura","year":"2009","journal-title":"Circ J"},{"key":"B10","doi-asserted-by":"publisher","first-page":"7","DOI":"10.1515\/cclm-2015-0523","article-title":"Hyperuricemia as risk factor for coronary heart disease incidence and mortality in the general population: a systematic review and meta-analysis","volume":"54","author":"Braga","year":"2016","journal-title":"Clin Chem Lab Med"},{"key":"B11","doi-asserted-by":"publisher","first-page":"7","DOI":"10.7326\/0003-4819-131-1-199907060-00003","article-title":"Serum uric acid and risk for cardiovascular disease and death: the Framingham Heart Study","volume":"131","author":"Culleton","year":"1999","journal-title":"Ann Intern Med"},{"key":"B12","doi-asserted-by":"publisher","first-page":"136","DOI":"10.1016\/S1047-2797(99)00037-X","article-title":"Serum uric acid and risk of coronary heart disease: atherosclerosis risk in communities (ARIC) study","volume":"10","author":"Moriarity","year":"2000","journal-title":"Ann Epidemiol"},{"key":"B13","doi-asserted-by":"publisher","first-page":"242","DOI":"10.1159\/000443769","article-title":"Hyperuricemia, Cardiovascular Disease, and Hypertension","volume":"3","author":"Kuwabara","year":"2016","journal-title":"Pulse (Basel)"},{"key":"B14","doi-asserted-by":"publisher","first-page":"131","DOI":"10.3414\/ME10-01-0015","article-title":"SS-MIX: a ministry project to promote standardized healthcare information exchange","volume":"50","author":"Kimura","year":"2011","journal-title":"Methods Inf Med"},{"key":"B15","doi-asserted-by":"publisher","first-page":"264","DOI":"10.1536\/ihj.18-113","article-title":"Architecture of the Japan ischemic heart disease multimodal prospective data acquisition for precision treatment (J-IMPACT) System","volume":"60","author":"Matoba","year":"2019","journal-title":"Int Heart J"},{"key":"B16","doi-asserted-by":"publisher","first-page":"1492","DOI":"10.3233\/SHTI190500","article-title":"Development of patient state model to overview clinical registry database","volume":"264","author":"Ishii","year":"2019","journal-title":"Stud Health Technol Inform"},{"key":"B17","doi-asserted-by":"publisher","first-page":"7351","DOI":"10.1038\/s41598-020-64123-z","article-title":"J-CKD-DB: a nationwide multicentre electronic health record-based chronic kidney disease database in Japan","volume":"10","author":"Nakagawa","year":"2020","journal-title":"Sci Rep"},{"key":"B18","doi-asserted-by":"publisher","first-page":"149","DOI":"10.1620\/tjem.209.149","article-title":"G-protein beta3 subunit gene variant is unlikely to have a significant influence on serum uric acid level in Japanese workers","volume":"209","author":"Suwazono","year":"2006","journal-title":"Tohoku J Exp Med"},{"key":"B19","doi-asserted-by":"publisher","first-page":"e0176786","DOI":"10.1371\/journal.pone.0176786","article-title":"Early onset hyperuricemia is a prognostic marker for kidney graft failure: propensity score matching analysis in a Korean multicenter cohort","volume":"12","author":"Han","year":"2017","journal-title":"PLoS ONE"},{"key":"B20","doi-asserted-by":"publisher","first-page":"391","DOI":"10.1007\/s10157-011-0420-6","article-title":"Risk of macrovascular disease stratified by stage of chronic kidney disease in type 2 diabetic patients: critical level of the estimated glomerular filtration rate and the significance of hyperuricemia","volume":"15","author":"Tanaka","year":"2011","journal-title":"Clin Exp Nephrol"},{"key":"B21","doi-asserted-by":"publisher","first-page":"98","DOI":"10.1111\/jdi.12243","article-title":"Role of elevated serum uric acid levels at the onset of overt nephropathy in the risk for renal function decline in patients with type 2 diabetes","volume":"6","author":"Tanaka","year":"2015","journal-title":"J Diabetes Investig"},{"key":"B22","doi-asserted-by":"publisher","DOI":"10.1253\/circj.CJ-22-0314.","article-title":"Relationships among heart rate, \u03b2-blocker dosage, and prognosis in patients with coronary artery disease in a real-world database using a multimodal data acquisition system","author":"Oba","year":"2022","journal-title":"Circ J"},{"key":"B23","doi-asserted-by":"publisher","first-page":"982","DOI":"10.1053\/j.ajkd.2008.12.034","article-title":"Revised equations for estimated GFR from serum creatinine in Japan","volume":"53","author":"Matsuo","year":"2009","journal-title":"Am J Kidney Dis"},{"key":"B24","doi-asserted-by":"publisher","first-page":"e263","DOI":"10.1016\/j.jacc.2021.12.012","article-title":"2022 AHA\/ACC\/HFSA guideline for the management of heart failure: a report of the American college of cardiology\/American heart association joint committee on clinical practice guidelines","volume":"79","author":"Heidenreich","year":"2022","journal-title":"J Am Coll Cardiol"},{"key":"B25","doi-asserted-by":"publisher","first-page":"3599","DOI":"10.1093\/eurheartj\/ehab368","article-title":"2021 ESC Guidelines for the diagnosis and treatment of acute and chronic heart failure","volume":"42","author":"McDonagh","year":"2021","journal-title":"Eur Heart J"},{"key":"B26","doi-asserted-by":"publisher","first-page":"241","DOI":"10.1016\/j.atherosclerosis.2015.03.030","article-title":"Impact of sex on uric acid levels and its relationship with the extent of coronary artery disease: a single-centre study","volume":"241","author":"Barbieri","year":"2015","journal-title":"Atherosclerosis"},{"key":"B27","doi-asserted-by":"publisher","first-page":"122","DOI":"10.1016\/j.jjcc.2012.09.004","article-title":"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\u20132003","volume":"61","author":"Lin","year":"2013","journal-title":"J Cardiol"},{"key":"B28","doi-asserted-by":"publisher","first-page":"800414","DOI":"10.3389\/fcvm.2022.800414","article-title":"Effect of asymptomatic hyperuricemia on mortality of elderly patients after elective percutaneous coronary intervention","volume":"9","author":"Chen","year":"2022","journal-title":"Front Cardiovasc Med"},{"key":"B29","doi-asserted-by":"publisher","first-page":"558","DOI":"10.1016\/j.amjcard.2018.11.027","article-title":"Implications of hyperuricemia in severe coronary artery disease","volume":"123","author":"Zhang","year":"2019","journal-title":"Am J Cardiol"},{"key":"B30","doi-asserted-by":"publisher","first-page":"393","DOI":"10.1016\/j.numecd.2021.09.034","article-title":"Impact of serum uric acid levels on cardiovascular events and quality of life in patients with chronic coronary syndromes: insights from a contemporary, prospective, nationwide registry","volume":"32","author":"De Luca","year":"2022","journal-title":"Nutr Metab Cardiovasc Dis"},{"key":"B31","first-page":"605","article-title":"Uric Acid is not an independent predictor of cardiovascular death in patients with angiographically proven coronary artery disease","volume":"32","author":"Tsai","year":"2009","journal-title":"Chang Gung Med J"},{"key":"B32","doi-asserted-by":"publisher","first-page":"1811","DOI":"10.1056\/NEJMra0800885","article-title":"Uric acid and cardiovascular risk","volume":"359","author":"Feig","year":"2008","journal-title":"N Engl J Med"},{"key":"B33","doi-asserted-by":"publisher","first-page":"594","DOI":"10.1111\/joim.12120","article-title":"Longitudinal association between serum urate and subclinical atherosclerosis: the Coronary Artery Risk Development in Young Adults (CARDIA) study","volume":"274","author":"Wang","year":"2013","journal-title":"J Intern Med"},{"key":"B34","doi-asserted-by":"publisher","first-page":"856","DOI":"10.1097\/RCT.0000000000001222","article-title":"Monosodium urate crystal deposition in coronary artery plaque by 128-slice dual-energy computed tomography: an ex vivo phantom and in vivo study","volume":"45","author":"Feuchtner","year":"2021","journal-title":"J Comput Assist Tomogr"},{"key":"B35","doi-asserted-by":"publisher","first-page":"15","DOI":"10.1093\/eurjhf\/hft132","article-title":"Uric acid and risk of heart failure: a systematic review and meta-analysis","volume":"16","author":"Huang","year":"2014","journal-title":"Eur J Heart Fail"},{"key":"B36","doi-asserted-by":"publisher","first-page":"110","DOI":"10.1002\/clc.22083","article-title":"Is serum uric acid level an independent predictor of heart failure among patients with coronary artery disease?","volume":"36","author":"Eisen","year":"2013","journal-title":"Clin Cardiol"},{"key":"B37","doi-asserted-by":"publisher","first-page":"40","DOI":"10.1016\/j.atherosclerosis.2020.01.025","article-title":"Association of variability in uric acid and future clinical outcomes of patient with coronary artery disease undergoing percutaneous coronary intervention","volume":"297","author":"Lim","year":"2020","journal-title":"Atherosclerosis"},{"key":"B38","doi-asserted-by":"publisher","first-page":"1951","DOI":"10.1161\/01.CIR.0000066420.36123.35","article-title":"Uric acid predicts clinical outcomes in heart failure: insights regarding the role of xanthine oxidase and uric acid in disease pathophysiology","volume":"107","author":"Hare","year":"2003","journal-title":"Circulation"},{"key":"B39","doi-asserted-by":"publisher","first-page":"51","DOI":"10.1016\/j.jjcc.2020.12.013","article-title":"Uric acid and cardiovascular disease: a clinical review","volume":"78","author":"Saito","year":"2021","journal-title":"J Cardiol"},{"key":"B40","doi-asserted-by":"publisher","first-page":"e026677","DOI":"10.1136\/bmjopen-2018-026677","article-title":"Diagnosis and treatment for hyperuricemia and gout: a systematic review of clinical practice guidelines and consensus statements","volume":"9","author":"Li","year":"2019","journal-title":"BMJ Open"},{"key":"B41","doi-asserted-by":"publisher","first-page":"2301","DOI":"10.1016\/j.jacc.2008.01.068","article-title":"Impact of oxypurinol in patients with symptomatic heart failure. Results of the OPT-CHF study","volume":"51","author":"Hare","year":"2008","journal-title":"J Am Coll Cardiol"},{"key":"B42","doi-asserted-by":"publisher","first-page":"1763","DOI":"10.1161\/CIRCULATIONAHA.114.014536","article-title":"Effects of xanthine oxidase inhibition in hyperuricemic heart failure patients: the xanthine oxidase inhibition for hyperuricemic heart failure patients (EXACT-HF) Study","volume":"131","author":"Givertz","year":"2015","journal-title":"Circulation"},{"key":"B43","doi-asserted-by":"publisher","first-page":"533","DOI":"10.1002\/ccd.21447","article-title":"Unprotected left main disease managed with drug-eluting stents: long-term outcome of 100 patients with increased surgical risk","volume":"71","author":"Wood","year":"2008","journal-title":"Catheter Cardiovasc Interv"}],"container-title":["Frontiers in Cardiovascular Medicine"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fcvm.2022.1062894\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,1,10]],"date-time":"2023-01-10T21:06:03Z","timestamp":1673384763000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fcvm.2022.1062894\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,1,10]]},"references-count":43,"alternative-id":["10.3389\/fcvm.2022.1062894"],"URL":"https:\/\/doi.org\/10.3389\/fcvm.2022.1062894","relation":{},"ISSN":["2297-055X"],"issn-type":[{"value":"2297-055X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,1,10]]},"article-number":"1062894"}}