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000302868 1001_ $$aThews, Oliver$$b0
000302868 245__ $$aPhysiological serum uric acid concentrations correlate with arterial stiffness in a sex-dependent manner.
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000302868 520__ $$aIn 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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000302868 650_7 $$2Other$$aFemale health
000302868 650_7 $$2Other$$aHyperuricemia
000302868 650_7 $$2Other$$aPulse wave velocity
000302868 650_7 $$2Other$$aUrate
000302868 650_7 $$2Other$$aVascular damage
000302868 650_7 $$2Other$$aVascular stiffness
000302868 650_7 $$0268B43MJ25$$2NLM Chemicals$$aUric Acid
000302868 650_2 $$2MeSH$$aHumans
000302868 650_2 $$2MeSH$$aVascular Stiffness: physiology
000302868 650_2 $$2MeSH$$aUric Acid: blood
000302868 650_2 $$2MeSH$$aMale
000302868 650_2 $$2MeSH$$aFemale
000302868 650_2 $$2MeSH$$aCross-Sectional Studies
000302868 650_2 $$2MeSH$$aMiddle Aged
000302868 650_2 $$2MeSH$$aPulse Wave Analysis
000302868 650_2 $$2MeSH$$aAdult
000302868 650_2 $$2MeSH$$aSex Factors
000302868 650_2 $$2MeSH$$aAged
000302868 650_2 $$2MeSH$$aGermany
000302868 7001_ $$aSchmid, Thomas$$b1
000302868 7001_ $$aKluttig, Alexander$$b2
000302868 7001_ $$aWienke, Andreas$$b3
000302868 7001_ $$aZinkhan, Melanie$$b4
000302868 7001_ $$aAhrens, Wolfgang$$b5
000302868 7001_ $$aBärnighausen, Till$$b6
000302868 7001_ $$0P:(DE-He78)90d5535ff896e70eed81f4a4f6f22ae2$$aBrenner, Hermann$$b7$$udkfz
000302868 7001_ $$aCastell, Stefanie$$b8
000302868 7001_ $$aLange, Berit$$b9
000302868 7001_ $$aLieb, Wolfgang$$b10
000302868 7001_ $$0P:(DE-He78)e0ac0d57cdb66d87f2d95ae5f6178c1b$$aGreiser, Karin-Halina$$b11$$udkfz
000302868 7001_ $$aDörr, Marcus$$b12
000302868 7001_ $$aKrist, Lilian$$b13
000302868 7001_ $$aWillich, Stefan N$$b14
000302868 7001_ $$aHarth, Volker$$b15
000302868 7001_ $$aObi, Nadia$$b16
000302868 7001_ $$aLeitzmann, Michael$$b17
000302868 7001_ $$aPeters, Annette$$b18
000302868 7001_ $$aSchmidt, Börge$$b19
000302868 7001_ $$aSchulze, Matthias B$$b20
000302868 7001_ $$aVölzke, Henry$$b21
000302868 7001_ $$aNauck, Matthias$$b22
000302868 7001_ $$aZylla, Stephanie$$b23
000302868 7001_ $$aHannemann, Anke$$b24
000302868 7001_ $$aPischon, Tobias$$b25
000302868 7001_ $$aVelásquez, Ilais Moreno$$b26
000302868 7001_ $$aGirndt, Matthias$$b27
000302868 7001_ $$aGrossmann, Claudia$$b28
000302868 7001_ $$aGekle, Michael$$b29
000302868 773__ $$0PERI:(DE-600)2131669-7$$a10.1186/s12916-025-04195-8$$gVol. 23, no. 1, p. 356$$n1$$p356$$tBMC medicine$$v23$$x1741-7015$$y2025
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