Clinical Rheumatology

, Volume 37, Issue 7, pp 1903–1911 | Cite as

Impaired arterial responsiveness in untreated gout patients compared with healthy non-gout controls: association with serum urate and C-reactive protein

  • Svetlana Krasnokutsky
  • Aaron Garza Romero
  • Daisy Bang
  • Virginia C. Pike
  • Binita Shah
  • Talia F. Igel
  • Irina Dektiarev
  • Yu Guo
  • Judy Zhong
  • Stuart D. Katz
  • Michael H. PillingerEmail author
Original Article


To determine whether arterial responsiveness is impaired among patients with gout, and whether arterial responsiveness inversely correlates with serum urate and inflammatory measures. This is a cross-sectional study of untreated gout subjects (n = 34) and non-gout healthy controls (n = 64). High-resolution dynamic ultrasound-measured flow-mediated dilation (FMD) and nitroglycerin-mediated dilation (NMD) assessed endothelium-dependent and endothelium-independent arterial responsiveness respectively. Serum urate (sUA) and high-sensitivity C-reactive protein (hsCRP) were measured in the gout group, and correlated with FMD and NMD responses. Both FMD (2.20 ± 0.53 vs 3.56 ± 0.31, p = 0.021) and NMD (16.69 ± 1.54 vs 24.51 ± 0.90, p = 0.00002) were impaired in the gout versus control group. Stratification for individual comorbidities suggested that no single risk factor accounted for impaired FMD/NMD in the gout subjects. However, the degree of association between gout and FMD, but not NMD impairment, was dampened after multivariable adjustment (FMD unadjusted beta = − 1.36 (SE 0.58), p = 0.02; adjusted beta = − 1.16 (SE 0.78), p = 0.14 and NMD unadjusted beta = − 7.68 (SE 1.78), p < 0.0001; adjusted beta = − 5.33 (SE 2.46), p = 0.03). Within the gout group, there was an inverse correlation between FMD and sUA (R = − 0.5, p = 0.003), and between FMD and hsCRP (R = − 0.42, p = 0.017), but not between NMD and sUA or hsCRP. Compared with healthy controls, subjects with gout have reduced arterial function. Individual comorbidities are insufficient to account for differences between gout and control groups, but multiple comorbidities may collectively contribute to impairment in endothelium-dependent arterial responsiveness. Endothelial impairment is also related to sUA and hsCRP, markers of gout severity and inflammation respectively. Studies to determine whether gout therapy may improve arterial responsiveness are warranted.


Arterial function Endothelium Flow-mediated dilation Gout Hyperuricemia Inflammation 



The authors thank Drs. Jonathan Samuels, Cesar Fors, Stephen Bernstein, Adey Berhanu, and Sabina Sandigursky for referring their patients for the study, and Dr. Bruce Cronstein for helpful input.

Funding information

This work was supported by a New York State Empire Clinical Research Investigator Program (ECRIP) award, to S.D.K. and S.K. S.K. was also supported in part by an Investigator Award from the Rheumatology Research Foundation. B.S. was supported in part by the Biomedical Laboratory Research & Development Service of the VA Office of Research and Development (I01BX007080). M.H.P. and S.D.K. received support from a CTSA award (1UL1TR001445) to New York University from the National Center for the Advancement of Translational Science, National Institutes of Health.

Compliance with ethical standards

Approval and consent statement

The studies described in this manuscript were approved by the Institutional Review Boards of New York University School of Medicine and the New York Harbor Health Care System, United States Department of Veterans Affairs. All participating subjects gave their informed consent in writing prior to participation in the study.

Conflict of interest statement

None of the authors have any conflict of interest regarding this manuscript. For the purposes of full transparency, we acknowledge the following disclosures. S.K. has served as a consultant for Crealta, Horizon, and Ironwood. B.S. serves on the Philips Volcano Medical Education Steering Committee and has a research grant from Siemens Medical Solutions. M.H.P. serves and/or has served as a consultant for AstraZeneca, Crealta, Horizon, Ironwood, and SOBI, and has been an investigative site for a sponsored trial by Takeda.


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Copyright information

© International League of Associations for Rheumatology (ILAR) 2018

Authors and Affiliations

  • Svetlana Krasnokutsky
    • 1
    • 2
    • 3
  • Aaron Garza Romero
    • 1
    • 2
    • 3
  • Daisy Bang
    • 1
    • 2
    • 3
  • Virginia C. Pike
    • 1
    • 2
    • 3
  • Binita Shah
    • 3
    • 4
    • 5
  • Talia F. Igel
    • 1
    • 2
    • 3
  • Irina Dektiarev
    • 3
    • 4
    • 5
  • Yu Guo
    • 3
    • 5
    • 6
  • Judy Zhong
    • 3
    • 5
    • 6
  • Stuart D. Katz
    • 3
    • 5
  • Michael H. Pillinger
    • 1
    • 2
    • 3
    • 7
    Email author
  1. 1.Section of RheumatologyVA New York Harbor Health Care SystemNew YorkUSA
  2. 2.Division of Rheumatology (Crystal Diseases Study Group)New York University School of MedicineNew YorkUSA
  3. 3.TRIAD (Translational Research in Inflammation and Atherosclerotic Disease)New York University School of MedicineNew YorkUSA
  4. 4.Section of CardiologyVA New York Harbor Health Care SystemNew YorkUSA
  5. 5.Division of Cardiology, Department of MedicineNew York University School of MedicineNew YorkUSA
  6. 6.Division of Biostatistics, Department of Population HealthNew York University School of MedicineNew YorkUSA
  7. 7.Division of RheumatologyNYU Hospital for Joint DiseasesNew YorkUSA

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