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041 _ _ |a English
082 _ _ |a 610
100 1 _ |a Thews, Oliver
|b 0
245 _ _ |a Physiological serum uric acid concentrations correlate with arterial stiffness in a sex-dependent manner.
260 _ _ |a London
|c 2025
|b BioMed Central
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520 _ _ |a In 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.Therefore, 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.Our 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 β = 1.12 (95% confidence interval (CI): 0.78; 1.45) in males and β = 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.Already 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.
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650 _ 7 |a Female health
|2 Other
650 _ 7 |a Hyperuricemia
|2 Other
650 _ 7 |a Pulse wave velocity
|2 Other
650 _ 7 |a Urate
|2 Other
650 _ 7 |a Vascular damage
|2 Other
650 _ 7 |a Vascular stiffness
|2 Other
650 _ 7 |a Uric Acid
|0 268B43MJ25
|2 NLM Chemicals
650 _ 2 |a Humans
|2 MeSH
650 _ 2 |a Vascular Stiffness: physiology
|2 MeSH
650 _ 2 |a Uric Acid: blood
|2 MeSH
650 _ 2 |a Male
|2 MeSH
650 _ 2 |a Female
|2 MeSH
650 _ 2 |a Cross-Sectional Studies
|2 MeSH
650 _ 2 |a Middle Aged
|2 MeSH
650 _ 2 |a Pulse Wave Analysis
|2 MeSH
650 _ 2 |a Adult
|2 MeSH
650 _ 2 |a Sex Factors
|2 MeSH
650 _ 2 |a Aged
|2 MeSH
650 _ 2 |a Germany
|2 MeSH
700 1 _ |a Schmid, Thomas
|b 1
700 1 _ |a Kluttig, Alexander
|b 2
700 1 _ |a Wienke, Andreas
|b 3
700 1 _ |a Zinkhan, Melanie
|b 4
700 1 _ |a Ahrens, Wolfgang
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700 1 _ |a Bärnighausen, Till
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700 1 _ |a Brenner, Hermann
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700 1 _ |a Castell, Stefanie
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700 1 _ |a Lange, Berit
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700 1 _ |a Lieb, Wolfgang
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700 1 _ |a Greiser, Karin-Halina
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700 1 _ |a Dörr, Marcus
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700 1 _ |a Krist, Lilian
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700 1 _ |a Willich, Stefan N
|b 14
700 1 _ |a Harth, Volker
|b 15
700 1 _ |a Obi, Nadia
|b 16
700 1 _ |a Leitzmann, Michael
|b 17
700 1 _ |a Peters, Annette
|b 18
700 1 _ |a Schmidt, Börge
|b 19
700 1 _ |a Schulze, Matthias B
|b 20
700 1 _ |a Völzke, Henry
|b 21
700 1 _ |a Nauck, Matthias
|b 22
700 1 _ |a Zylla, Stephanie
|b 23
700 1 _ |a Hannemann, Anke
|b 24
700 1 _ |a Pischon, Tobias
|b 25
700 1 _ |a Velásquez, Ilais Moreno
|b 26
700 1 _ |a Girndt, Matthias
|b 27
700 1 _ |a Grossmann, Claudia
|b 28
700 1 _ |a Gekle, Michael
|b 29
773 _ _ |a 10.1186/s12916-025-04195-8
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