Initiating guideline-concordant gout treatment improves arterial endothelial function and reduces intercritical inflammation: a prospective observational study

• Published in: Arthritis research & therapy Vol. 22; no. 1; pp. 1 - 169
• Main Authors: Toprover, Michael, Shah, Binita, Oh, Cheongeun, Igel, Talia F, Romero, Aaron Garza, Pike, Virginia C, Curovic, Fatmira, Bang, Daisy, Lazaro, Deana, Krasnokutsky, Svetlana, Katz, Stuart D, Pillinger, Michael H
• Format: Journal Article
• Language: English
• Published: London BioMed Central Ltd 11.07.2020; BioMed Central; BMC
• Subjects: Ambulatory care; Arthritis; Blood pressure; Blood tests; Canakinumab; Cardiac patients; Cardiovascular disease; Colchicine; Cytokines; Drug therapy; Endothelium; Gout; Gout suppressants; Hypertension; Hyperuricemia; Inflammation; Iron compounds; Laboratories; Monte Carlo simulation; Observational studies; Oxidases; Physicians; Practice guidelines (Medicine); Primary care; Rheumatism; Risk factors; Subclinical cardiovascular disease; Urate-lowering therapy; Veins & arteries
• ISSN: 1478-6362; 1478-6354; 1478-6362
• DOI: 10.1186/s13075-020-02260-6

Background Patients with gout have arterial dysfunction and systemic inflammation, even during intercritical episodes, which may be markers of future adverse cardiovascular outcomes. 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. Methods 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 mg 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[beta], IL-6, myeloperoxidase (MPO) concentrations, and erythrocyte sedimentation rate (ESR) assessed systemic inflammation. Results Four weeks after achieving target sU concentration on colchicine plus an XOI, FMD was significantly improved (58% increase, p = 0.03). hsCRP, ESR, IL-1[beta], and IL-6 also all significantly improved (30%, 27%, 19.5%, and 18.8% decrease respectively; all p [less than or equai to] 0.03). 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[beta] or IL-6. MPO and NMD did not change with therapy. We observed a moderate inverse correlation between hsCRP concentration and FMD responsiveness (R = - 0.41, p = 0.01). 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. Conclusions Initiating guideline-concordant gout treatment reduces intercritical systemic inflammation and improves endothelial-dependent arterial function, particularly in patients without established cardiovascular comorbidities. Keywords: Gout, Hyperuricemia, Subclinical cardiovascular disease, Inflammation, Urate-lowering therapy, Colchicine, Xanthine oxidase inhibitor, Allopurinol, Flow-mediated dilation, C-reactive protein