Background Elevated uric acid concentrations have been associated with high blood pressure (BP) in adults and children. An increased production of uric acid by the enzyme xanthine oxidoreductase (XOR), which is accompanied by the generation of reactive oxygen species, is a putative underlying mechanism that has so far scarcely been studied. We hypothesize that a higher XOR activity leads to increased concentrations of downstream purine metabolites, resulting in higher ratios of xanthine/hypoxanthine, uric acid/xanthine, and uric acid/hypoxanthine (figure 1).
Objectives The objectives were therefore to study the association between (i) the purine metabolites uric acid, hypoxanthine, and xanthine and (ii) the ratios of the three different purine metabolites as proxy measures for uric acid production, with systolic (SBP) and diastolic blood pressure (DBP).
Methods Cross-sectional analyses were performed in a subset of 246 children from the Dutch Koala Birth Cohort Study. This cohort originates from two recruitment groups: pregnant women with either a conventional lifestyle or recruited through alternative channels. During a home visit, a nurse collected a venous blood sample and measured BP three times after a 5-minute rest, with an automated BP monitor. Furthermore, parents were in instructed to measure their child's BP on three consecutive days, in the morning and evening, using the same monitor. Purine metabolites were determined with UPLC-MS/MS. Data were analysed using a multivariable generalized estimating equations model, including repeated BP measurements, with an exchangeable correlation structure. Analyses were adjusted for sex, age, BMI, recruitment group, place and mode of delivery (hospital vs. at home; natural vs. caesarean section), maternal smoking during pregnancy (active and passive), total physical activity, and dietary intake at four years of age (total energy intake [kcal], energy from carbohydrates and protein [%] and fibre intake [grams]).
Results At a mean age of 7.1 yrs, mean plasma concentrations were 202.8 μmol/L (SD 37.7) for uric acid, 4.60 μmol/L (SD 6.93) for hypoxanthine, and 0.53 μmol/L (SD 0.17) for xanthine. Average BP was 104.3 mm Hg (SD 10.0) systolic and 63.4 mm Hg (SD 10.6) diastolic. Higher ratios of uric acid/xanthine and xanthine/hypoxanthine were associated with higher DBP (adj. β 0.01 mm Hg; 95%CI 0.00 to 0.02; P=0.03; and adj. β 0.11 mm Hg; 95%CI 0.01 to 0.21; P=0.03), respectively, but not with SBP. Uric acid, xanthine, and hypoxanthine concentrations and the ratio uric acid/hypoxanthine were not associated with SBP nor DBP (P≥0.05).
Conclusions In multivariable-adjusted analyses, DBP in children was significantly associated with the ratios of uric acid/xanthine and xanthine/hypoxanthine, and might, as hypothesized, be proxies for uric acid production. The ratio uric acid/hypoxanthine was not associated with BP, may be explained by differential excretion or autofeedback (of non XOR metabolism).
Disclosure of Interest None declared
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