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@ARTICLE{Thews:302868,
      author       = {O. Thews and T. Schmid and A. Kluttig and A. Wienke and M.
                      Zinkhan and W. Ahrens and T. Bärnighausen and H.
                      Brenner$^*$ and S. Castell and B. Lange and W. Lieb and
                      K.-H. Greiser$^*$ and M. Dörr and L. Krist and S. N.
                      Willich and V. Harth and N. Obi and M. Leitzmann and A.
                      Peters and B. Schmidt and M. B. Schulze and H. Völzke and
                      M. Nauck and S. Zylla and A. Hannemann and T. Pischon and I.
                      M. Velásquez and M. Girndt and C. Grossmann and M. Gekle},
      title        = {{P}hysiological serum uric acid concentrations correlate
                      with arterial stiffness in a sex-dependent manner.},
      journal      = {BMC medicine},
      volume       = {23},
      number       = {1},
      issn         = {1741-7015},
      address      = {London},
      publisher    = {BioMed Central},
      reportid     = {DKFZ-2025-01408},
      pages        = {356},
      year         = {2025},
      abstract     = {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.},
      keywords     = {Humans / Vascular Stiffness: physiology / Uric Acid: blood
                      / Male / Female / Cross-Sectional Studies / Middle Aged /
                      Pulse Wave Analysis / Adult / Sex Factors / Aged / Germany /
                      Female health (Other) / Hyperuricemia (Other) / Pulse wave
                      velocity (Other) / Urate (Other) / Vascular damage (Other) /
                      Vascular stiffness (Other) / Uric Acid (NLM Chemicals)},
      cin          = {C070 / C020},
      ddc          = {610},
      cid          = {I:(DE-He78)C070-20160331 / I:(DE-He78)C020-20160331},
      pnm          = {313 - Krebsrisikofaktoren und Prävention (POF4-313)},
      pid          = {G:(DE-HGF)POF4-313},
      typ          = {PUB:(DE-HGF)16},
      pubmed       = {pmid:40597154},
      pmc          = {pmc:PMC12211650},
      doi          = {10.1186/s12916-025-04195-8},
      url          = {https://inrepo02.dkfz.de/record/302868},
}