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Associations of plasma uric acid and purine metabolites with blood pressure in children: the KOALA Birth Cohort Study

Scheepers, Lieke E.J.M.a,b; Boonen, Anneliesa,b; Pijnenburg, Wiekec; Bierau, Jörgend; Staessen, Jan A.c,e; Stehouwer, Coen D.A.f,g; Thijs, Carelb,c; Arts, Ilja C.W.c,h

doi: 10.1097/HJH.0000000000001270

Objective: Elevated serum uric acid concentration has been associated with high blood pressure (BP) and hypertension. A putative underlying mechanism is the accumulation of reactive oxygen species when uric acid is generated by an increased enzyme activity of xanthine oxidase (XO). The aims of the present study were to investigate the associations between plasma uric acid concentration, purine metabolite ratios, as proxies for increased XO activity, and SBP and DBP in school-age children.

Methods: Cross-sectional analyses were performed in 246 children (46% boys; mean age 7.1 years) from the Dutch KOALA Birth Cohort Study. Purine metabolites were determined with ultra-performance liquid chromatography–tandem mass spectrometry. During a home visit, a nurse collected a blood sample and measured BP three times; in addition, parents measured their child's BP on three consecutive days, in the morning and evening. Generalized estimating equations were used for analyses while controlling for variables such as sex, age, BMI, physical activity, and dietary intake.

Results: In multivariable analysis, uric acid (per SD of 38 μmol/l) was associated with DBP z-scores [sβ 0.07; confidence interval (CI), 0.01–1.14], but not with SBP z-scores. Higher ratios of uric acid/xanthine (per SD of 138) (sβ 0.09; CI, 0.01–0.17) and xanthine/hypoxanthine (per SD of 321) (sβ 0.08; CI, 0.02–0.17) were associated with higher DBP z-scores, but not with SBP z-scores.

Conclusion: In school-age children, uric acid and the ratios of uric acid/xanthine and xanthine/hypoxanthine were significantly associated with DBP z-scores. Suggesting that, both uric acid concentration and increased XO activity are associated with BP.

aDivision of Rheumatology, Department of Internal Medicine, Maastricht University Medical Centre

bCAPHRI School for Public Health and Primary Care

cDepartment of Epidemiology, Maastricht University

dDepartment of Clinical Genetics, Maastricht University Medical Centre, Maastricht, The Netherlands

eResearch Unit Hypertension and Cardiovascular Epidemiology, KU Leuven Department of Cardiovascular Diseases, Studies Coordinating Centre, University of Leuven, Leuven, Belgium

fDepartment of Internal Medicine, Maasticht University Medical Center

gCARIM School for Cardiovascular Diseases, Maastricht University Medical Centre

hCARIM School for Cardiovascular Diseases, and MaCSBio Maastricht Centre for Systems Biology, Maastricht University, Maastricht, The Netherlands

Correspondence to Lieke E.J.M. Scheepers, MSc, Ing., Department of Rheumatology, Maastricht University Medical Centre+, Postbus 5800, 6202 AZ Maastricht, The Netherlands. Tel: +0031 6 18984522; fax: +0031 433 875006; e-mail:

Abbreviations: BP, blood pressure; CI, confidence interval; eNOS, endothelial nitric oxide synthase; FFQ, food frequency questionnaire; GEE, generalized estimating equations; HGPRT, hypoxanthine–guanine phosphoribosyltransferase; IMP, inosine monophosphate; IQR, interquartile range; KOALA, Kind, Ouders en gezondheid: Aandacht voor Leefstijl en Aanleg (A Dutch acronym for child, parents and health: lifestyle and genetic constitution); NAD(P)H, nicotinamide adenine dinucleotide (phosphate) (reduced form); NHBPEP, National High Blood Pressure Education Program; NO, nitric oxide; PPGP, pregnancy-related pelvic girdle pain; ROS, reactive oxygen species; UA, uric acid; XO, xanthine oxidase; XOR, xanthine oxidoreductase

Received 25 October, 2016

Revised 2 December, 2016

Accepted 30 December, 2016

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