Thews, Oliver and Schmid, Thomas and Kluttig, Alexander and Wienke, Andreas and Zinkhan, Melanie and Ahrens, Wolfgang and Baernighausen, Till and Brenner, Hermann and Castell, Stefanie and Lange, Berit and Lieb, Wolfgang and Greiser, Karin Halina and Doerr, Marcus and Krist, Lilian and Willich, Stefan N. and Harth, Volker and Obi, Nadia and Leitzmann, Michael and Peters, Annette and Schmidt, Boerge and Schulze, Matthias B. and Voelzke, Henry and Nauck, Matthias and Zylla, Stephanie and Hannemann, Anke and Pischon, Tobias and Velasquez, Ilais Moreno and Girndt, Matthias and Grossmann, Claudia and Gekle, Michael (2025) Physiological serum uric acid concentrations correlate with arterial stiffness in a sex-dependent manner. BMC MEDICINE, 23 (1): 356. ISSN 1741-7015,
Full text not available from this repository. (Request a copy)Abstract
BackgroundIn humans, uric acid is a product of purine metabolism that impacts the vascular system. In addition to effects on arterial vascular tone, associations between serum uric acid concentrations-even in the physiological range-and arterial hypertension and vascular-mediated end-organ damage due to an impact on vascular stiffness have been postulated.MethodsTherefore, we aim to investigate a possible cross-sectional association between serum uric acid concentrations in the physiological range and differences in arterial pulse wave velocity (PWV), an indicator of vascular remodeling, with a focus on possible differences between female and male individuals. We analyzed cross-sectional phenotypic and laboratory parameters, including PWV from 70,649 individuals in the population-based German National Cohort (NAKO) in a sex-specific manner. In parallel, we applied a machine learning approach to identify and quantify factors associated with PWV in a hypothesis-free manner.ResultsOur analysis uncovered a positive association between serum uric and PWV which was detected even if only individuals with urate values in the physiological range were included (n = 64,095). This correlation was more pronounced in women than in men. In multivariable linear regression models, we observed an association of uric acid (mmol/l) with PWV (m/s) of beta = 1.12 (95% confidence interval (CI): 0.78; 1.45) in males and beta = 1.35 (1.05; 1.66) in females, independent of other factors known to affect vascular stiffness. In addition, the machine learning approach identified uric acid as a major factor associated with PWV. The positive association was not restricted to hyperuricemia but evident even in the physiological concentration range. Based on the data from studies on the impact of aging on PWV, it is estimated that an increase in serum uric acid concentration by 0.1 mmol/l corresponds to an increase of approx. 7 years of age in females and of 4 years in males.ConclusionsAlready in the physiological concentration range, uric acid is positively associated with parameters of arterial stiffness. This association is more pronounced in females as compared to males. This finding provides a mechanistic explanation for the increased risk of vascular end-organ damage associated with higher serum uric acid concentrations and supports the observed greater benefit of therapeutic uric acid lowering in female. Future intervention studies have to address the mechanistic causality of the observed effect.
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | CHRONIC HEART-FAILURE; ALL-CAUSE MORTALITY; MIDDLE-AGED MEN; CARDIOVASCULAR MORTALITY; RISK-FACTOR; MOLECULAR-IDENTIFICATION; ESSENTIAL-HYPERTENSION; BLOOD-PRESSURE; HYPERURICEMIA; ALLOPURINOL; Urate; Vascular stiffness; Vascular damage; Pulse wave velocity; Hyperuricemia; Female health |
| Subjects: | 600 Technology > 610 Medical sciences Medicine |
| Divisions: | Medicine > Institut für Epidemiologie und Präventivmedizin |
| Depositing User: | Dr. Gernot Deinzer |
| Date Deposited: | 24 Mar 2026 13:00 |
| Last Modified: | 24 Mar 2026 13:00 |
| URI: | https://pred.uni-regensburg.de/id/eprint/68057 |
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