Abstract
The association between uric acid (UA) and hyperuricemia with 5-year hypertension incidence using different blood pressure (BP) diagnostic references in men and women without cardiometabolic diseases is unknown. We used the checkup data from Kagoshima Kouseiren Hospital. All participants with hypertension or on BP medication, diabetes, dyslipidemia, obesity, estimated glomerular filtration rate<60 ml/min/1.73m2, metabolic syndrome, history of gout, and UA-lowering medication were excluded. UA was categorized into sex-specific quartiles and hyperuricemia was defined as UA > 7 mg/dl in men and UA > 6 mg/dl in women. We performed multivariate logistic regression to assess the effects of UA on hypertension development. The 5-year hypertension incidence was defined as subsets of BP ≥ 140/90 mmHg in cohort 1 and BP ≥ 130/80 mmHg in cohort 2. The study enrolled 21,443 participants (39.8%, men) in cohort 1 and 15,245 participants (36.5%, men) in cohort 2. The incidence of hypertension in cohorts 1 and 2 over 5 years was 16.3% and 29.7% in men and 10.9% and 21.4% in women, respectively. When comparing the fourth to the first UA quartile, there was an association with hypertension in men in cohort 1, with odds ratio (OR): 1.36 (95% confidence interval [CI], 1.13–1.63, p < 0.01) and cohort 2, OR: 1.31 (95%CI, 1.09–1.57, p < 0.01), respectively, but not in women. Additionally, an association between hyperuricemia and hypertension was observed in men only in cohort 1, with OR: 1.23 (95%CI, 1.07–1.42, p = 0.02), and in women in cohort 2, OR: 1.57 (95%CI, 1.14–2.16, p < 0.01). The effect of UA on the development of hypertension is influenced by sex and incidence differs with the BP reference used.
This is a preview of subscription content, access via your institution
Access options
Subscribe to this journal
Receive 12 print issues and online access
$259.00 per year
only $21.58 per issue
Buy this article
- Purchase on Springer Link
- Instant access to full article PDF
Prices may be subject to local taxes which are calculated during checkout
Similar content being viewed by others
References
Roth GA, Mensah GA, Johnson CO, Addolorato G, Ammirati E, Baddour LM, et al. Global Burden of cardiovascular diseases and risk factors, 1990–2019: update from the GBD 2019 study. J Am Coll Cardiol. 2020;76:2982–3021.
Mills KT, Bundy JD, Kelly TN, Reed JE, Kearney PM, Reynolds K, et al. Global disparities of hypertension prevalence and control: a systematic analysis of population-based studies from 90 countries. Circulation. 2016;134:441–50.
NCD Risk Factor Collaboration (NCD-RisC). Worldwide trends in blood pressure from 1975 to 2015: a pooled analysis of 1479 population-based measurement studies with 19·1 million participants. Lancet. 2017;389:37–55.
Whelton PK, Carey RM, Aronow WS, Casey DE, Collins KJ, Dennison Himmelfarb C, et al. 2017 ACC/AHA/AAPA/ABC/ACPM/AGS/APhA/ASH/ASPC/NMA/PCNA guideline for the prevention, detection, evaluation, and management of high blood pressure in adults: executive summary: a report of the American college of cardiology/american heart association task force on clinical practice guidelines. Hypertension. 2018;71:1269–324.
Unger T, Borghi C, Charchar F, Khan NA, Poulter NR, Prabhakaran D, et al. 2020 International Society of Hypertension Global Hypertension Practice guidelines. Hypertension. 2020;75:1334–57.
Mancia G, Kreutz R, Brunström M, Burnier M, Grassi G, Januszewicz A, et al. 2023 ESH guidelines for the management of arterial hypertension The Task Force for the management of arterial hypertension of the European Society of Hypertension Endorsed by the European Renal Association (ERA) and the International Society of Hypertension (ISH). J Hypertens. 2023;41:1874–2071.
Umemura S, Arima H, Arima S, Asayama K, Dohi Y, Hirooka Y, et al. The Japanese Society of Hypertension Guidelines for the Management of Hypertension (JSH 2019). Hypertens Res. 2019;42:1235–481.
Feig DI, Kang DH, Johnson RJ. Uric acid and cardiovascular risk. N Engl J Med. 2008;359:1811–21.
Hisatome I, Li P, Miake J, Taufiq F, Mahati E, Maharani N, et al. Uric acid as a risk factor for chronic kidney disease and cardiovascular disease—Japanese guideline on the management of asymptomatic hyperuricemia. Circ J. 2021;85:130–8.
Yu W, Cheng JD. Uric acid and cardiovascular disease: an update from molecular mechanism to clinical perspective. Front Pharm. 2020;11:582680.
Lanaspa MA, Andres-Hernando A, Kuwabara M. Uric acid and hypertension. Hypertens Res. 2020;43:832–4.
Kuwabara M, Niwa K, Hisatome I, Nakagawa T, Roncal-Jimenez CA, Andres-Hernando A, et al. Asymptomatic hyperuricemia without comorbidities predicts cardiometabolic diseases: 5-year Japanese cohort study. Hypertension. 2017;69:1036–44.
Stewart DJ, Langlois V, Noone D. Hyperuricemia and Hypertension: Links and Risks. Integr Blood Press Control. 2019;12:43–62.
Kanellis J, Kang DH. Uric acid as a mediator of endothelial dysfunction, inflammation, and vascular disease. Semin Nephrol. 2005;25:39–42.
Qu LH, Jiang H, Chen JH. Effect of uric acid-lowering therapy on blood pressure: systematic review and meta-analysis. Ann Med. 2017;49:142–56.
Gunawardhana L, McLean L, Punzi HA, Hunt B, Palmer RN, Whelton A, et al. Effect of febuxostat on ambulatory blood pressure in subjects with hyperuricemia and hypertension: a phase 2 randomized placebo‐controlled study. J Am Heart Assoc. 2017;6:e006683.
Feig DI, Soletsky B, Johnson RJ. Effect of allopurinol on blood pressure of adolescents with newly diagnosed essential hypertension: a randomized trial. JAMA. 2008;300:924.
Engel B, Hoffmann F, Freitag MH, Jacobs H. Should we be more aware of gender aspects in hyperuricemia? Analysis of the population-based German health interview and examination survey for adults (DEGS1). Maturitas. 2021;153:33–40.
Kuwabara M, Hisatome I, Niwa K, Bjornstad P, Roncal-Jimenez CA, Andres-Hernando A, et al. The optimal range of serum uric acid for cardiometabolic diseases: a 5-year Japanese cohort study. J Clin Med. 2020;9:942.
Cheng F, Li Y, Zheng H, Tian L, Jia H. Mediating effect of body mass index and dyslipidemia on the relation of uric acid and type 2 diabetes: results from China health and retirement longitudinal study. Front Public Health. 2021;9:823739.
Yang T, Chu CH, Bai CH, You SL, Chou YC, Chou WY, et al. Uric acid level as a risk marker for metabolic syndrome: a Chinese cohort study. Atherosclerosis. 2012;220:525–31.
Sumiyoshi H, Ohyama Y, Imai K, Kurabayashi M, Saito Y, Nakamura T. Association of uric acid with incident metabolic syndrome in a Japanese general population. Int Heart J. 2019;60:830–5.
Kawasoe S, Kubozono T, Yoshifuku S, Ojima S, Miyata M, Miyahara H, et al. Uric acid level and new-onset atrial fibrillation in the Japanese General population- longitudinal study. Circ J. 2018;83:156–63.
Nyrnes A, Toft I, Njølstad I, Mathiesen EB, Wilsgaard T, Hansen JB, et al. Uric acid is associated with future atrial fibrillation: an 11-year follow-up of 6308 men and women-the Tromso Study. Europace. 2014;16:320–6.
Shani M, Vinker S, Dinour D, Leiba M, Twig G, Holtzman EJ, et al. High normal uric acid levels are associated with an increased risk of diabetes in lean, normoglycemic healthy women. J Clin Endocrinol Metab. 2016;101:3772–8.
Kawai T, Ohishi M, Takeya Y, Onishi M, Ito N, Yamamoto K, et al. Serum uric acid is an independent risk factor for cardiovascular disease and mortality in hypertensive patients. Hypertens Res. 2012;35:1087–92.
Kikuchi A, Kawamoto R, Ninomiya D, Kumagi T. Hyperuricemia is associated with all-cause mortality among males and females: findings from a study on Japanese community-dwelling individuals. Metab Open. 2022;14:100186.
Antón FM, García Puig J, Ramos T, González P, Ordás J. Sex differences in uric acid metabolism in adults: evidence for a lack of influence of estradiol-17 beta (E2) on the renal handling of urate. Metabolism. 1986;35:343–8.
Guan S, Tang Z, Fang X, Wu X, Liu H, Wang C, et al. Prevalence of hyperuricemia among Beijing post-menopausal women in 10 years. Arch Gerontol Geriatr. 2016;64:162–6.
Grayson PC, Kim SY, LaValley M, Choi HK. Hyperuricemia and incident hypertension: a systematic review and meta-analysis. Arthritis Care Res. 2011;63:102–10.
Nagahama K, Inoue T, Iseki K, Touma T, Kinjo K, Ohya Y, et al. Hyperuricemia as a predictor of hypertension in a screened cohort in Okinawa, Japan. Hypertens Res. 2004;27:835–41.
Nishio S, Maruyama Y, Sugano N, Hosoya T, Yokoo T, Kuriyama S. Gender interaction of uric acid in the development of hypertension. Clin Exp Hypertens. 2018;40:446–51.
Kim W, Go TH, Kang DO, Lee J, Choi JY, Roh SY, et al. Age and sex-dependent association of uric acid and incident hypertension. Nutr Metab Cardiovasc Dis. 2021;31:1200–8.
Wang SF, Shu L, Wang S, Wang XQ, Mu M, Hu CQ, et al. Gender difference in the association of hyperuricemia with hypertension in a middle-aged Chinese population. Blood Press. 2014;23:339–44.
Mori K, Furuhashi M, Tanaka M, Higashiura Y, Koyama M, Hanawa N, et al. Serum uric acid level is associated with an increase in systolic blood pressure over time in female subjects: linear mixed-effects model analyses. Hypertens Res. 2022;45:344–53.
Lin X, Wang X, Li X, Song L, Meng Z, Yang Q, et al. Gender- and age-specific differences in the association of hyperuricemia and hypertension: a cross-sectional study. Int J Endocrinol. 2019;2019:7545137.
Teramoto T, Sasaki J, Ueshima H, Egusa G, Kinoshita M, Shimamoto K, et al. Metabolic syndrome. J Atheroscler Thromb. 2008;15:1–5.
World Health Organization: Waist circumference and waist-hip ratio: report of a WHO expert consultation [Internet]. WHO Press, Geneva, Switzerland, 2011; 2008. Available from: https://www.who.int/publications/i/item/9789241501491.
Matsuo S, Imai E, Horio M, Yasuda Y, Tomita K, Nitta K, et al. Revised equations for estimated GFR from serum creatinine in Japan. Am J Kidney Dis. 2009;53:982–92.
Risk NCD. Factor Collaboration (NCD-RisC). Worldwide trends in hypertension prevalence and progress in treatment and control from 1990 to 2019: a pooled analysis of 1201 population-representative studies with 104 million participants. Lancet 2021;398:957–80.
Mills KT, Stefanescu A, He J. The global epidemiology of hypertension. Nat Rev Nephrol. 2020;16:223–37.
Bundy JD, Mills KT, He J. Comparison of the 2017 ACC/AHA hypertension guideline with earlier guidelines on estimated reductions in cardiovascular disease. Curr Hypertens Rep. 2019;21:76.
Wilson PWF, D’Agostino RB, Sullivan L, Parise H, Kannel WB. Overweight and obesity as determinants of cardiovascular risk: the Framingham experience. Arch Intern Med. 2002;162:1867–72.
Aronow WS. Association of obesity with hypertension. Ann Transl Med. 2017;5:350.
Salim AA, Kawasoe S, Kubozono T, Ojima S, Kawabata T, Ikeda Y, et al. Assessment of future hypertension risk by sex using combined body mass index and waist-to-height ratio. Circ Rep. 2022;4:9–16.
Rahman MA, Halder HR, Yadav UN, Mistry SK. Prevalence of and factors associated with hypertension according to JNC 7 and ACC/AHA 2017 guidelines in Bangladesh. Sci Rep. 2021;11:15420.
Liu C-W, Ke S-R, Tseng G-S, Wu Y-W, Hwang J-J. Elevated serum uric acid is associated with incident hypertension in the health according to various contemporary blood pressure guidelines. Nutr, Metab Cardiovasc Dis. 2021;31:1209–18.
Wang J, Qin T, Chen J, Li Y, Wang L, Huang H, et al. Hyperuricemia and risk of incident hypertension: a systematic review and meta-analysis of observational studies. PLoS One. 2014;9:e114259.
Borghi C, Agnoletti D, Cicero AFG, Lurbe E, Virdis A. Uric acid and hypertension: a review of evidence and future perspectives for the management of cardiovascular risk. Hypertension. 2022;79:1927–36.
Yokokawa H, Fukuda H, Suzuki A, Fujibayashi K, Naito T, Uehara Y, et al. Association between serum uric acid levels/hyperuricemia and hypertension among 85,286 Japanese workers. J Clin Hypertens. 2016;18:53–59.
Nagahama K, Inoue T, Kohagura K, Kinjo K, Ohya Y. Associations between serum uric acid levels and the incidence of hypertension and metabolic syndrome: a 4-year follow-up study of a large screened cohort in Okinawa, Japan. Hypertens Res. 2015;38:213–8.
Ohyama Y, Imai K, Obokata M, Araki M, Sumiyoshi H, Koitabashi N, et al. Impact of uric acid on incident hypertension: sex-specific analysis in different age groups. Int J Cardiol Hypertens. 2019;2:100009.
Hoshide S, Yamamoto K, Katsurada K, Yano Y, Nishiyama A, Wang JG, et al. Agreement regarding overcoming hypertension in the Asian hypertension society network 2022. Hypertens Res. 2023;46:3–8.
Acknowledgements
We thank the medical staff at Kagoshima Kouseiren Hospital for their support with data collection.
Author information
Authors and Affiliations
Contributions
All authors made substantial contribution to this work.
Corresponding author
Ethics declarations
Conflict of interest
The authors declare no competing interests.
Additional information
Publisher’s note Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.
Supplementary information
Rights and permissions
Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.
About this article
Cite this article
Salim, A.A., Kawasoe, S., Kubozono, T. et al. Sex-specific associations between serum uric acid levels and risk of hypertension for different diagnostic reference values of high blood pressure. Hypertens Res 47, 1120–1132 (2024). https://doi.org/10.1038/s41440-023-01535-0
Received:
Revised:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1038/s41440-023-01535-0