Background/Purpose: Blood pressure and hypertension are associated with uric acid, the end product of purine catabolism, but the underlying mechanism remainds unclear. During the final stage of purine metabolism, xanthine oxidase (XO) breaks down hypoxanthine to xanthine, and xanthine to uric acid, while reactive oxygen species (ROS) are formed. Accumulation of ROS by increased uric acid production has been suggested as a possible underlying mechanism for the association between uric acid and high blood pressure. We therefore investigated whether (i) serum uric acid concentration and/or (ii) 24h urinary uric acid excretion, as proxy for uric acid production, are associated with ambulatory blood pressure and hypertension.

Methods:  Cross-sectional analyses were conducted among 2660 individuals (52% men, mean age 60.0±8.2 years; 26.7% type 2 diabetes [by design]) from The Maastricht Study. Multivariable linear and logistic regression analyses were performed to investigate the association of serum uric acid concentration and 24h urinary uric acid excretion with 24h pulse pressure (PP), 24h mean arterial pressure (MAP) and hypertension. Hypertension was defined as mean 24h systolic BP of ≥ 135 mmHg, 24h DBP ≥ 85 mmHg, and/or the use of anti-hypertensive medication. Analyses were adjusted for sex, age, glucose metabolism status, and further for treatment of diabetes and hypertension, body mass index, smoking behavior, alcohol consumption, education, and eGFR (in the logistic analyses, no adjustment for anti-hypertensive medication). Analyses exploring the role of serum uric acid were additionally adjusted for 24h urine uric acid excretion, whereas analyses exploring the role of 24h urine uric acid excretion were additionally adjusted for serum uric acid concentration and fractional excretion of uric acid (FE_UA).

Results:  In fully adjusted analyses, serum uric acid concentration (per standard deviation [SD] of 330 µmol/L) was associated with higher MAP (β 0.50 mmHg (95% confidence [CI], 0.14 to 0.88; P­=0.01) and positively associated with hypertension (odds ratio 1.29; CI, 1.14 to 1.46; P­-value <0.001). Twenty-four-hour urinary uric acid excretion (per SD 141 mg/day/1.73m²) was associated with higher MAP (β 0.85 mmHg; CI, 0.30 to 1.40; P­-value <0.001). There was no significant association between serum and 24h urinary uric acid excretion with PP. There was no interaction for the aforementioned associations with sex or age.

Conclusion:  We found evidence of associations between serum uric acid concentration with MAP and hypertension. Additionally, 24h uric acid excretion was associated with MAP. This indicates that both serum uric acid concentration and uric acid production are, independent of each other, associated with blood pressure.

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ACR Meeting Abstracts - https://acrabstracts.org/abstract/uric-acid-production-and-blood-pressure-the-role-of-uric-acid-concentration-as-well-as-uric-acid-production/