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Associations between serum uric acid levels and the incidence of nonfatal stroke: a nationwide community-based cohort study

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Abstract

Background

Hyperuricemia is an established risk factor for cardiovascular events and mortality. This study investigated the association between serum uric acid and the incidence of nonfatal stroke in a Japanese community-based population.

Methods

We used a nationwide database of 155,322 subjects (aged 40–73, male 39 %) who participated in the annual “Specific Health Check and Guidance in Japan” checkup from 2008 to 2010. We examined the relationship between the quintiles of serum uric acid levels at baseline and the incidence of nonfatal stroke during a 2-year study period using self-reported data.

Results

The crude incidence of nonfatal stroke was significantly associated with serum uric acid levels at baseline, showing the lowest values in subjects with the 3rd quintile (Q3: men, 5.0–5.6; women, 3.8–4.3) of uric acid levels (mg/dL) and the highest values in subjects with the highest quintile (Q5: men ≥7.1, women ≥5.5) both in men and women (P < 0.05). In multivariate-adjusted logistic regression analysis, the odds ratio (OR) of the Q5 group was significantly higher than for the Q3 group in both men and women [men: OR 1.26, 95 % confidence interval (CI) 1.04–1.54, women: OR 1.24, 95 % CI 1.00–1.48]. In the subgroup analysis, the OR of the Q5 group of uric acid levels for incident stroke was high, irrespective of characteristics such as age, sex, and renal function.

Conclusions

This study has shown that serum uric acid is independently associated with the incidence of nonfatal stroke in the general Japanese population.

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References

  1. Holme I, Aastveit AH, Hammar N, Jungner I, Walldius G. Uric acid and risk of myocardial infarction, stroke and congestive heart failure in 417,734 men and women in the Apolipoprotein MOrtality RISk study (AMORIS). J Intern Med. 2009;266:558–70.

    Article  CAS  PubMed  Google Scholar 

  2. Bos MJ, Koudstaal PJ, Hofman A, Witteman JC, Breteler MM. Uric acid is a risk factor for myocardial infarction and stroke: the Rotterdam study. Stroke. 2006;37:1503–7.

    Article  CAS  PubMed  Google Scholar 

  3. Wang JG, Staessen JA, Fagard RH, Birkenhäger WH, Gong L, Liu L. Prognostic significance of serum creatinine and uric acid in older Chinese patients with isolated systolic hypertension. Hypertension. 2001;37:1069–74.

    Article  CAS  PubMed  Google Scholar 

  4. Chen JH, Chuang SY, Chen HJ, Yeh WT, Pan WH. Serum uric acid level as an independent risk factor for all-cause, cardiovascular, and ischemic stroke mortality: a Chinese cohort study. Arthritis Rheum. 2009;61:225–32.

    Article  CAS  PubMed  Google Scholar 

  5. Storhaug HM, Norvik JV, Toft I, et al. Uric acid is a risk factor for ischemic stroke and all-cause mortality in the general population: a gender specific analysis from The Tromsø Study. BMC Cardiovasc Disord. 2013;13:115.

    Article  PubMed  PubMed Central  Google Scholar 

  6. Fang J, Alderman MH. Serum uric acid and cardiovascular mortality: the NHANES I epidemiologic follow-up study, 1971–1992. National Health and Nutrition Examination Survey. JAMA. 2000;283:2404–10.

    Article  CAS  PubMed  Google Scholar 

  7. Kamei K, Konta T, Ichikawa K, et al. Serum uric acid levels and mortality in the Japanese population: the Yamagata (Takahata) study. Clin Exp Nephrol. 2016. doi:10.1007/s10157-016-1228-1

    Google Scholar 

  8. Lehto S, Niskanen L, Rönnemaa T, Laakso M. Serum uric acid is a strong predictor of stroke in patients with non-insulin-dependent diabetes mellitus. Stroke. 1998;29:635–59.

    Article  CAS  PubMed  Google Scholar 

  9. Kim SY, Guevara JP, Kim KM, Choi HK, Heitjan DF, Albert DA. Hyperuricemia and risk of stroke: a systematic review and meta-analysis. Arthritis Rheum. 2009;61:885–92.

    Article  PubMed  PubMed Central  Google Scholar 

  10. Gerber Y, Tanne D, Medalie JH, Goldbourt U. Serum uric acid and long-term mortality from stroke, coronary heart disease and all causes. Eur J Cardiovasc Prev Rehabil. 2006;13:193–8.

    Article  PubMed  Google Scholar 

  11. Kuo CF, See LC, Yu KH, Chou IJ, Chiou MJ, Luo SF. Significance of serum uric acid levels on the risk of all-cause and cardiovascular mortality. Rheumatology (Oxford). 2013;52:127–34.

    Article  CAS  Google Scholar 

  12. Sakata K, Hashimoto T, Ueshima H, Okayama A, NIPPON DATA 80 Research Group. Absence of an association between serum uric acid and mortality from cardiovascular disease: NIPPON DATA 80, 1980–1994. National Integrated Projects for prospective observation of non-communicable diseases and its trend in the aged. Eur J Epidemiol. 2001;17:461–8.

    Article  CAS  PubMed  Google Scholar 

  13. Kawai T, Ohishi M, Takeya Y, et al. Serum uric acid is an independent risk factor for cardiovascular disease and mortality in hypertensive patients. Hypertens Res. 2012;35:1087–92.

    Article  CAS  PubMed  Google Scholar 

  14. Skak-Nielsen H, Torp-Pedersen C, Finer N, et al. Uric acid as a risk factor for cardiovascular disease and mortality in overweight/obese individuals. PLoS One. 2013;8:e59121.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  15. Hozawa A, Folsom AR, Ibrahim H, Nieto FJ, Rosamond WD, Shahar E. Serum uric acid and risk of ischemic stroke: the ARIC Study. Atherosclerosis. 2006;187:401–7.

    Article  CAS  PubMed  Google Scholar 

  16. Kamei K, Konta T, Hirayama A, et al. A slight increase within the normal range of serum uric acid and the decline in renal function: associations in a community-based population. Nephrol Dial Transplant. 2014;29:2286–92.

    Article  CAS  PubMed  Google Scholar 

  17. WHO/IASO/IOTF. The Asia-Pacific perspective: redefining obesity and its treatment. Australia: Health Communications; 2000.

  18. Iseki K, Ikemiya Y, Inoue T, Iseki C, Kinjo K, Takishita S. Significance of hyperuricemia as a risk factor for developing ESRD in a screened cohort. Am J Kidney Dis. 2004;44:642–50.

    Article  PubMed  Google Scholar 

  19. Horio M, Imai E, Yasuda Y, Watanabe T, Matsuo S. Modification of the CKD epidemiology collaboration (CKD-EPI) equation for Japanese: accuracy and use for population estimates. Am J Kidney Dis. 2010;56:32–8.

    Article  PubMed  Google Scholar 

  20. Huang J, Hu D, Wang Y, Zhang D, Qu Y. Dose-response relationship of serum uric acid levels with risk of stroke mortality. Atherosclerosis. 2014;234:1–3.

    Article  CAS  PubMed  Google Scholar 

  21. Waring WS, Webb DJ, Maxwell SR. Systemic uric acid administration increases serum antioxidant capacity in healthy volunteers. J Cardiovasc Pharmacol. 2001;38:365–71.

    Article  CAS  PubMed  Google Scholar 

  22. Ishikawa I. Acute renal failure with severe loin pain and patchy renal ischemia after anaerobic exercise in patients with or without renal hypouricemia. Nephron. 2002;91:559–70.

    Article  PubMed  Google Scholar 

  23. Kang DH, Park SK, Lee IK, Johnson RJ. Uric acid-induced C-reactive protein expression: implication on cell proliferation and nitric oxide production of human vascular cells. J Am Soc Nephrol. 2005;16:3553–62.

    Article  CAS  PubMed  Google Scholar 

  24. Kohagura K, Kochi M, Miyagi T, et al. An association between uric acid levels and renal arteriolopathy in chronic kidney disease: a biopsy-based study. Hypertens Res. 2013;36:43–9.

    Article  CAS  PubMed  Google Scholar 

  25. Suzuki K, Konta T, Kudo K, et al. The association between serum uric acid and renal damage in a community-based population: the Takahata study. Clin Exp Nephrol. 2013;17:541–8.

    Article  CAS  PubMed  Google Scholar 

  26. Kuriyama S, Maruyama Y, Nishio S, et al. Serum uric acid and the incidence of CKD and hypertension. Clin Exp Nephrol. 2015;19:1127–34.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  27. Iseki K, Iseki C, Kinjo K. Changes in serum uric acid have a reciprocal effect on eGFR change: a 10-year follow-up study of community-based screening in Okinawa, Japan. Hypertens Res. 2013;36:650–4.

    Article  CAS  PubMed  Google Scholar 

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Acknowledgments

This study was supported by a Health and Labour Sciences Research Grant for “Design of the comprehensive health care system for chronic kidney disease (CKD) based on the individual risk assessment by Specific Health Checkup” from the Ministry of Health, Labour and Welfare of Japan and a Grant-in-Aid for “Research on Advanced Chronic Kidney Disease (REACH-J), Practical Research Project for Renal Disease” from Japan Agency for Medical Research and Development, AMED.

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Authors and Affiliations

  1. Department of Cardiology, Pulmonology, and Nephrology, Yamagata University School of Medicine, 2-2-2, Iida-Nishi, Yamagata, 990-9585, Japan

    Keita Kamei, Tsuneo Konta, Atsushi Hirayama, Kazunobu Ichikawa & Isao Kubota

  2. Steering Committee of Research on Design of the Comprehensive Health Care System for Chronic Kidney Disease (CKD) Based on the Individual Risk Assessment by Specific Health Checkup, Fukushima, Japan

    Tsuneo Konta, Shouichi Fujimoto, Kunitoshi Iseki, Toshiki Moriyama, Kunihiro Yamagata, Kazuhiko Tsuruya, Ichiei Narita, Masahide Kondo, Yugo Shibagaki, Masato Kasahara, Koichi Asahi & Tsuyoshi Watanabe

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  1. Keita Kamei
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  2. Tsuneo Konta
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  3. Atsushi Hirayama
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  14. Masato Kasahara
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  15. Koichi Asahi
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  16. Tsuyoshi Watanabe
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Corresponding author

Correspondence to Tsuneo Konta.

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Kamei, K., Konta, T., Hirayama, A. et al. Associations between serum uric acid levels and the incidence of nonfatal stroke: a nationwide community-based cohort study. Clin Exp Nephrol 21, 497–503 (2017). https://doi.org/10.1007/s10157-016-1311-7

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  • DOI: https://doi.org/10.1007/s10157-016-1311-7

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