{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,7]],"date-time":"2026-09-07T15:40:43Z","timestamp":1788795643461,"version":"build-2803163510"},"reference-count":14,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2017,11,26]],"date-time":"2017-11-26T00:00:00Z","timestamp":1511654400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/501100000274","name":"British Heart Foundation","doi-asserted-by":"publisher","award":["PG\/07\/051\/23063"],"award-info":[{"award-number":["PG\/07\/051\/23063"]}],"id":[{"id":"10.13039\/501100000274","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cardiovascular Therapeutics"],"published-print":{"date-parts":[[2018,2]]},"abstract":"Summary<\/jats:title>The role of endothelial dysfunction and oxidative stress in the pathogenesis of cardiac syndrome X has recently been recognized. Allopurinol has previously been shown to improve endothelial dysfunction, reduce oxidative stress burden, and improve myocardial efficiency. In this \u201cproof of concept\u201d study, we investigated the effect of allopurinol on exercise capacity, coronary and peripheral endothelial function, and serum B\u2010type natriuretic peptide (BNP<\/jats:styled-content>: a marker of cardiac function and myocardial ischemia) in patients with cardiac syndrome X.<\/jats:p><\/jats:sec>Methods and Results<\/jats:title>This study was a randomized, double\u2010blind, placebo\u2010control crossover trial. Nineteen patients (mean age 59\u00a0\u00b1\u00a010\u00a0years, 11 women and 8 men) with cardiac syndrome X were randomized to a 6\u2010week treatment with either allopurinol (600\u00a0mg\/day) or placebo. After 4\u00a0weeks of washout period, they were crossed over to the other arm. Outcomes measured at baseline and after treatment were maximum exercise time (ET<\/jats:styled-content>) derived from Bruce protocol exercise treadmill test, serum BNP<\/jats:styled-content> measurement, coronary flow reserve (CFR<\/jats:styled-content>) as assessed by measuring the response of flow velocity in the left anterior descending artery to adenosine, and flow\u2010mediated vasodilatation of the brachial artery (FMD<\/jats:styled-content>). Allopurinol significantly reduced serum uric acid levels when compared with placebo (\u221248\u00a0\u00b1\u00a024% vs 1.9\u00a0\u00b1\u00a011%, P<\/jats:italic>\u00a0<\u00a0.001). There was no significant difference in maximum ET<\/jats:styled-content>, CFR<\/jats:styled-content>, and FMD<\/jats:styled-content> between allopurinol and placebo. However, there was a trend that allopurinol reduced serum BNP<\/jats:styled-content> when compared to placebo (\u22128% [interquartile range \u221222% to 65%] vs 44% [interquartile range \u221218% to 140%]; P<\/jats:italic>\u00a0=\u00a0.07).<\/jats:p><\/jats:sec>Conclusion<\/jats:title>In patients with cardiac syndrome X, high\u2010dose allopurinol did not improve exercise capacity, and coronary or peripheral endothelial function.<\/jats:p><\/jats:sec>","DOI":"10.1111\/1755-5922.12311","type":"journal-article","created":{"date-parts":[[2017,10,28]],"date-time":"2017-10-28T15:32:39Z","timestamp":1509204759000},"source":"Crossref","is-referenced-by-count":13,"title":["The APEX<\/scp> trial: Effects of allopurinol on exercise capacity, coronary and peripheral endothelial function, and natriuretic peptides in patients with cardiac syndrome X"],"prefix":"10.1111","volume":"36","author":[{"given":"Tiong Keng","family":"Lim","sequence":"first","affiliation":[{"name":"National Heart Centre Singapore Singapore Singapore"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Awson","family":"Noman","sequence":"additional","affiliation":[{"name":"Aberdeen Royal Infirmary Aberdeen Scotland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anna Maria J","family":"Choy","sequence":"additional","affiliation":[{"name":"Division of Molecular and Clinical Medicine Ninewells Hospital and Medical School University of Dundee Dundee UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Faisel","family":"Khan","sequence":"additional","affiliation":[{"name":"Division of Molecular and Clinical Medicine Ninewells Hospital and Medical School University of Dundee Dundee UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Allan D","family":"Struthers","sequence":"additional","affiliation":[{"name":"Division of Molecular and Clinical Medicine Ninewells Hospital and Medical School University of Dundee Dundee UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4530-3078","authenticated-orcid":false,"given":"Chim C","family":"Lang","sequence":"additional","affiliation":[{"name":"Division of Molecular and Clinical Medicine Ninewells Hospital and Medical School University of Dundee Dundee UK"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2017,11,26]]},"reference":[{"key":"e_1_2_9_2_1","doi-asserted-by":"publisher","DOI":"10.2165\/00129784-200404030-00005"},{"key":"e_1_2_9_3_1","first-page":"1385","article-title":"Comparison of angiographic with myocardial perfusion scintigraphy findings in cardiac syndrome X (CSX)","volume":"15","author":"Yaghoubi M","year":"2011","journal-title":"Eur Rev Med Pharmacol 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