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Serum uric acid levels and cardiovascular mortality in a general Japanese population: the Hisayama Study

Hypertension Research volume 43, pages 560–568 (2020)Cite this article

Abstract

Studies on the association between serum uric acid levels and the risk of cardiovascular disease have yielded inconsistent results. We investigated the association of serum uric acid levels with cardiovascular disease mortality in a Japanese community. A total of 2633 community-dwelling Japanese people aged ≥40 years without a history of cardiovascular disease were followed up for 19 years. Serum uric acid levels were categorized into quintiles (Q1, lowest; Q5, highest). The hazard ratios for mortality from cardiovascular disease, stroke, and coronary heart disease were computed using a Cox proportional hazards model. During the follow-up, 235 subjects died from cardiovascular disease (including 84 from stroke and 53 from coronary heart disease). Risks for cardiovascular disease mortality were higher in both the Q1 and Q5 groups than in the Q3 group after adjustment for confounding factors (Q1, hazard ratio 1.50 [95% confidence interval 0.94–2.39]; Q2, 1.06 [0.66–1.72]; Q3, 1.00 [reference]; Q4, 1.44 [0.93–2.23]; and Q5, 1.89 [1.23–2.91]). A similar U-shaped association was observed for stroke mortality (Q1, 3.26 [1.29–8.25]; Q2, 2.21 [0.85–5.73]; Q3, 1.00 [reference]; Q4, 2.65 [1.07–6.58]; and Q5, 3.77 [1.54–9.24]), while coronary heart disease mortality was increased only in the Q5 group (Q1, 1.27 [0.46–3.50]; Q2, 0.85 [0.29–2.48]; Q3, 1.00 [reference]; Q4, 1.57 [0.63–3.92]; and Q5, 2.53 [1.03–6.18]). Elevated serum uric acid was suggested to be a significant risk factor for stroke or coronary heart disease mortality in a Japanese community. Conversely, the excess risk of stroke mortality in individuals with lower serum uric acid levels may indicate a possible cerebroprotective role of uric acid.

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Acknowledgements

We would like to express our sincere gratitude to Professor Yoshinao Oda, Professor Toru Iwaki, and their colleagues in the Department of Anatomic Pathology and Department of Neuropathology, Graduate School of Medical Sciences, Kyushu University, who provided insight and expertize regarding the autopsy findings that greatly assisted our research. We also thank the staff of the Division of Health and Welfare of Hisayama for their cooperation in this study.

Funding

This study was supported in part by Grants-in-Aid for Scientific Research (A) (JP16H02692), (B) (JP16H05850, JP17H04126, and JP18H02737) and (C) (JP17K09114, JP17K09113, JP17K01853, JP18K07565, JP18K09412, and JP19K07890) and for Early-Career Scientists (JP18K17925 and JP18K17382) from the Ministry of Education, Culture, Sports, Science and Technology of Japan; by Health and Labour Sciences Research Grants of the Ministry of Health, Labour and Welfare of Japan (H29-Junkankitou-Ippan-003 and H30-Shokuhin-[Sitei]-005); and by the Japan Agency for Medical Research and Development (JP19dk0207025, JP19ek0210082, JP19ek0210083, JP19km0405202, JP19ek0210080, and JP19fk0108075). This study was sponsored by Teijin Pharma Limited (Tokyo, Japan). The sponsor of the study had no role in the study design, conduct of the study, data collection, data interpretation, or preparation of the report.

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Authors and Affiliations

  1. Department of Epidemiology and Public Health, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan

    Satoko Sakata, Jun Hata, Takanori Honda, Yoichiro Hirakawa, Emi Oishi, Mao Shibata, Daigo Yoshida & Toshiharu Ninomiya

  2. Center for Cohort Studies, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan

    Satoko Sakata, Jun Hata, Mao Shibata, Takanari Kitazono & Toshiharu Ninomiya

  3. Department of Medicine and Clinical Science, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan

    Satoko Sakata, Jun Hata, Yoichiro Hirakawa, Emi Oishi, Kenichi Goto & Takanari Kitazono

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  1. Satoko Sakata
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Correspondence to Jun Hata.

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The study protocol was approved by the Kyushu University Institutional Review Board for Clinical Research, and the procedures followed were in accordance with national guidelines. Written informed consent was obtained from the study subjects.

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Sakata, S., Hata, J., Honda, T. et al. Serum uric acid levels and cardiovascular mortality in a general Japanese population: the Hisayama Study. Hypertens Res 43, 560–568 (2020). https://doi.org/10.1038/s41440-019-0390-8

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