Cross-sectional and longitudinal associations between serum uric acid and endothelial function in subjects with treated hypertension ☆ Atsushi Tanaka a, ⁎, Atsushi Kawaguchi b , Hirofumi Tomiyama c , Tomoko Ishizu d , Chisa Matsumoto c , Yukihito Higashi e , Bonpei Takase f , Toru Suzuki g , Shinichiro Ueda h , Tsutomu Yamazaki i , Tomoo Furumoto j , Kazuomi Kario k , Teruo Inoue l , Shinji Koba m , Yasuhiko Takemoto n , Takuzo Hano o , Masataka Sata p , Yutaka Ishibashi q , Koji Maemura r , Yusuke Ohya s , Taiji Furukawa t , Hiroshi Ito u , Akira Yamashina c , Koichi Node a, ⁎ a Department of Cardiovascular Medicine, Saga University, Saga, Japan b Clinical Research Center, Saga University Hospital, Saga, Japan c Department of Cardiology, Tokyo Medical University, Tokyo, Japan d Cardiovascular Division, Institute of Clinical Medicine, University of Tsukuba, Ibaraki, Japan e Department of Regeneration and Medicine, Research Center for Radiation Genome Medicine, Research Institute for Radiation Biology and Medicine, Hiroshima University, Hiroshima, Japan f Division of Biomedical Engineering, National Defense Medical College Research Institute, Saitama, Japan g Department of Cardiovascular Sciences, University of Leicester, Leicester, UK h Department of Clinical Pharmacology and Therapeutics, University of the Ryukyu School of Medicine, Okinawa, Japan i Clinical Research Support Center, The University of Tokyo Hospital, Tokyo, Japan j Department of Cardiovascular Medicine, Hokkaido University Graduate School of Medicine, Hokkaido, Japan k Division of Cardiovascular Medicine, Jichi Medical University School of Medicine, Tochigi, Japan l Department of Cardiovascular Medicine, Dokkyo Medical University, Mibu, Tochigi, Japan m Department of Medicine, Division of Cardiology, Showa University School of Medicine, Tokyo, Japan n Department of Medical Education and General Practice, Department of Internal Medicine and Cardiology, Osaka City University Graduate School of Medicine, Osaka, Japan o Satellite Clinic for Integrative and Anti-Aging Medicine, Wakayama Medical University, Wakayama, Japan p Department of Cardiovascular Medicine, Institute of Health Biosciences, The University of Tokushima Graduate School, Tokushima, Japan q Department of General Medicine, Shimane University Faculty of Medicine, Izumo, Japan r Department of Cardiovascular Medicine, Nagasaki University Graduate School of Biomedical Sciences, Nagasaki, Japan s Department of Cardiovascular Medicine, Nephrology and Neurology, University of the Ryukyus Graduate School of Medicine, Okinawa, Japan t Department of Internal Medicine, Teikyo University School of Medicine, Tokyo, Japan u Department of Cardiovascular Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama, Japan abstract article info Article history: Received 2 April 2018 Received in revised form 1 June 2018 Accepted 4 June 2018 Available online xxxx Objectives: The endothelial dysfunction-arterial stiffness-atherosclerosis continuum plays an important patho- physiological role in hypertension. The aim of this study was to investigate the cross-sectional association be- tween serum uric acid (SUA) and vascular markers related to this continuum, and to assess the longitudinal association between SUA and endothelial function that represents the initial step of the continuum. Methods: We evaluated the baseline associations between SUA levels and vascular markers that included flow- mediated vasodilatation (FMD), brachial-ankle pulse wave velocity (baPWV), and common carotid artery intima-media thickness (CCA-IMT) in 648 subjects receiving antihypertensive treatment. The longitudinal asso- ciation between baseline SUA levels and FMD measured at 1.5 and 3 yr of follow-up was also investigated. Results: At baseline, modest, but significant correlations were observed between SUA and FMD in females (r = -0.171), baPWV in males with SUA N368.78 μmol/L (r = -0.122) and in females with a SUA level ≤ 362.83 μmol/ L(r = 0.217), mean CCA-IMT in females with a SUA level ≤ 333.09 μmol/L (r = 0.139), and max CCA-IMT in females with SUA level ≤ 333.09 μmol/L (r = 0.138). A longitudinal association between SUA and FMD was less observed in males. In females, the baseline SUA was associated significantly with FMD values at 1.5 yr (r = -0.211), and SUA levels N237.92 μmol/L were associated significantly and independently with FMD values at 3 yr (r = -0.166). Conclusions: Lower SUA levels were associated with better vascular markers of the continuum, especially in females. Furthermore, we observed a longitudinal association between SUA and endothelial function, suggesting SUA level may be a potential marker of the continuum in hypertension. © 2017 Elsevier B.V. All rights reserved. Keywords: Uric acid Flow-mediated vasodilatation Endothelial function Atherosclerosis Vascular function International Journal of Cardiology xxx (2017) xxx–xxx ☆ All authors take responsibility for all aspects of the reliability and freedom from bias of the data presented and their discussed interpretation. ⁎ Corresponding authors at: Department of Cardiovascular Medicine, Saga University, 5-1-1 Nabeshima, Saga 849-8501, Japan. E-mail addresses: tanakaa2@cc.saga-u.ac.jp, (A. Tanaka), node@cc.saga-u.ac.jp (K. Node). IJCA-26566; No of Pages 6 https://doi.org/10.1016/j.ijcard.2018.06.017 0167-5273/© 2017 Elsevier B.V. All rights reserved. Contents lists available at ScienceDirect International Journal of Cardiology journal homepage: www.elsevier.com/locate/ijcard Please cite this article as: A. Tanaka, et al., Cross-sectional and longitudinal associations between serum uric acid and endothelial function in subjects with treated hypertensi..., Int J Cardiol (2017), https://doi.org/10.1016/j.ijcard.2018.06.017