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Original article
Failure to reach uric acid target of <0.36 mmol/L in hyperuricaemia of gout is associated with elevated total and cardiovascular mortality
  1. Fernando Pérez Ruiz1,
  2. Pascal Richette2,3,
  3. Austin G Stack4,5,
  4. Ravichandra Karra Gurunath6,
  5. Ma Jesus García de Yébenes7 and
  6. Loreto Carmona7
  1. 1Department of Rheumatolgy, Hospital Universitario Cruces, Barakaldo, Spain
  2. 2Service de Rhumatologie, Hopital Lariboisiere Centre Viggo Petersen, Paris, France
  3. 3Inserm UMR1132 Bioscar, Universite Paris Diderot UFR de Medecine, Paris, France
  4. 4Division of Nephrology, University Hospital Limerick, Limerick, Ireland
  5. 5Graduate Entry Medical School, University of Limerick, Limerick, Ireland
  6. 6Grünenthal GMBH, Aachen, Germany
  7. 7Instituto de Salud Musculoesquelética, Madrid, Spain
  1. Correspondence to Dr Fernando Pérez Ruiz; fernando.perezruiz{at}osakidetza.eus

Abstract

Objective To determine the impact of achieving serum uric acid (sUA) of <0.36 mmol/L on overall and cardiovascular (CV) mortality in patients with gout.

Methods Prospective cohort of patients with gout recruited from 1992 to 2017. Exposure was defined as the average sUA recorded during the first year of follow-up, dichotomised as ≤ or >0.36 mmol/L. Bivariate and multivariate Cox proportional hazards models were used to determine mortality risks, expressed HRs and 95% CIs.

Results Of 1193 patients, 92% were men with a mean age of 60 years, 6.8 years’ disease duration, an average of three to four flares in the previous year, a mean sUA of 9.1 mg/dL at baseline and a mean follow-up 48 months; and 158 died. Crude mortality rates were significantly higher for an sUA of ≥0.36 mmol/L, 80.9 per 1000 patient-years (95% CI 59.4 to 110.3), than for an sUA of <0.36 mmol/L, 25.7 per 1000 patient-years (95% CI 21.3 to 30.9). After adjustment for age, sex, CV risk factors, previous CV events, observation period and baseline sUA concentration, an sUA of ≥0.36 mmol/L was associated with elevated overall mortality (HR=2.33, 95% CI 1.60 to 3.41) and CV mortality (HR=2.05, 95% CI 1.21 to 3.45).

Conclusions Failure to reach a target sUA level of 0.36 mmol/L in patients with hyperuricaemia of gout is an independent predictor of overall and CV-related mortality. Targeting sUA levels of <0.36 mmol/L should be a principal goal in these high-risk patients in order to reduce CV events and to extend patient survival.

  • gout
  • hyperuricaemia
  • mortality
  • risk factors

This is an open access article distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited, appropriate credit is given, any changes made indicated, and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/.

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Footnotes

  • Contributors FPR: study design, analysis, verification, interpretation and writing. PR, AGS and RKG: interpretation and writing. MJGdY and LC: analysis, verification, interpretation and writing.

  • Funding The authors have not declared a specific grant for this research from any funding agency in the public, commercial or not-for-profit sectors.

  • Competing interests FPR: grants from Ministerio de Sanidad, Gobierno de España, Fundación Española de Reumatología and Asociación de Reumatólogos del Hospital de Cruces; consultancies for Menarini, Grünenthal, Horizon, Syneos and Dyve; speakers' bureau for Menarini, Astella, Grünenthal, Logarithm and Fundación Española de Reumatología. PR: fees from Ipsen, Menarini, Grünenthal and Savient. AGS: grants from the Irish Heart Foundation, Midwest Kidney Disease Research and Education Foundation, Limerick and the Health Research Institute, University of Limerick; advisory fees from AstraZeneca, Grünenthal and Menarini; unrestricted grant from the Menarini Foundation. RK: employee of Grunenthal GmbH, Aachen, Germany. MJGdY and LC work for an institution that receives payment for research services from companies interested in gout, concretely, Grünenthal and Novartis. A brother and the mother of LC have gout.

  • Patient consent for publication Not required.

  • Provenance and peer review Not commissioned; externally peer reviewed.

  • Data availability statement Data are available upon reasonable request.

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