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We conducted a prospective observational study to assess whether initiating guideline-concordant gout therapy with colchicine and a urate-lowering xanthine oxidase inhibitor (XOI) improves arterial function and reduces inflammation.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>Thirty-eight untreated gout patients meeting American College of Rheumatology (ACR)\/European League Against Rheumatism classification criteria for gout and ACR guidelines for initiating urate-lowering therapy (ULT) received colchicine (0.6\u00a0mg twice daily, or once daily for tolerance) and an XOI (allopurinol or febuxostat) titrated to ACR guideline-defined serum urate (sU) target. Treatment was begun during intercritical periods. The initiation of colchicine and XOI was staggered to permit assessment of a potential independent effect of colchicine. Brachial artery flow-mediated dilation (FMD) and nitrate-mediated dilation (NMD) assessed endothelium-dependent and endothelium-independent (smooth muscle) arterial responsiveness, respectively. High-sensitivity C-reactive protein (hsCRP), IL-1\u03b2, IL-6, myeloperoxidase (MPO) concentrations, and erythrocyte sedimentation rate (ESR) assessed systemic inflammation.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Four weeks after achieving target sU concentration on colchicine plus an XOI, FMD was significantly improved (58% increase,\n                      <jats:italic>p<\/jats:italic>\n                      \u2009=\u20090.03). hsCRP, ESR, IL-1\u03b2, and IL-6 also all significantly improved (30%, 27%, 19.5%, and 18.8% decrease respectively; all\n                      <jats:italic>p<\/jats:italic>\n                      \u2009\u2264\u20090.03). Prior to addition of XOI, treatment with colchicine alone resulted in smaller numerical improvements in FMD, hsCRP, and ESR (20.7%, 8.9%, 13% reductions, respectively; all non-significant), but not IL-1\u03b2 or IL-6. MPO and NMD did not change with therapy. We observed a moderate inverse correlation between hsCRP concentration and FMD responsiveness (\n                      <jats:italic>R<\/jats:italic>\n                      \u2009=\u2009\u2212\u20090.41,\n                      <jats:italic>p<\/jats:italic>\n                      \u2009=\u20090.01). Subgroup analyses demonstrated improvement in FMD after achieving target sU concentration in patients without but not with established cardiovascular risk factors and comorbidities, particularly hypertension and hyperlipidemia.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>Initiating guideline-concordant gout treatment reduces intercritical systemic inflammation and improves endothelial-dependent arterial function, particularly in patients without established cardiovascular comorbidities.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1186\/s13075-020-02260-6","type":"journal-article","created":{"date-parts":[[2020,7,11]],"date-time":"2020-07-11T01:02:48Z","timestamp":1594429368000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":25,"title":["Initiating guideline-concordant gout treatment improves arterial endothelial function and reduces intercritical inflammation: a prospective observational study"],"prefix":"10.1186","volume":"22","author":[{"given":"Michael","family":"Toprover","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Binita","family":"Shah","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cheongeun","family":"Oh","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Talia F.","family":"Igel","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aaron Garza","family":"Romero","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Virginia C.","family":"Pike","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fatmira","family":"Curovic","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daisy","family":"Bang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Deana","family":"Lazaro","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Svetlana","family":"Krasnokutsky","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stuart D.","family":"Katz","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3168-1542","authenticated-orcid":false,"given":"Michael H.","family":"Pillinger","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2020,7,11]]},"reference":[{"issue":"6","key":"2260_CR1","doi-asserted-by":"publisher","first-page":"991","DOI":"10.1002\/art.40807","volume":"71","author":"M Chen-Xu","year":"2019","unstructured":"Chen-Xu M, Yokose C, Rai SK, Pillinger MH, Choi HK. 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All subjects provided signed consent for participation.","order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethics approval and consent to participate"}},{"value":"Not applicable.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Consent for publication"}},{"value":"The authors declare that they have no direct competing interests relating to this study. For the purposes of full transparency, they offer the following disclosures. MT: nothing to disclose. BS: Philips Volcano Advisory Board; Radux Medical Advisory Board; Terumo Medical Consultant. CO. nothing to disclose. TFI: nothing to disclose. AGR: nothing to disclose. VCP: nothing to disclose. FC: nothing to disclose. DB: nothing to disclose. DL: nothing to disclose. SK: Investigator-initiated grant from Hikma Pharmaceuticals. SDK: nothing to disclose. MHP: Consultancies for Horizon Pharma, and Sobi, and investigator-initiated grants from Horizon Pharma and Hikma Pharmaceuticals.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"169"}}