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Publications

Journal Article Epublish 8 citations

PubMed: 40597154 DOI: 10.1186/s12916-025-04195-8

Physiological serum uric acid concentrations correlate with arterial stiffness in a sex-dependent manner.

BMC Med 23(1):356

Authors: Oliver Thews, Thomas Schmid, Alexander Kluttig, Andreas Wienke, Melanie Zinkhan, Wolfgang Ahrens, Till Bärnighausen, Hermann Brenner, Stefanie Castell, Berit Lange, Wolfgang Lieb, Karin Halina Greiser, Marcus Dörr, Lilian Krist, Stefan N Willich, Volker Harth, Nadia Obi, Michael Leitzmann, Annette Peters, Börge Schmidt, Matthias B Schulze, Henry Völzke, Matthias Nauck, Stephanie Zylla, Anke Hannemann, Tobias Pischon, Ilais Moreno Velásquez, Matthias Girndt, Claudia Grossmann, Michael Gekle

Affiliations

  • Julius-Bernstein-Institut für Physiologie, Martin-Luther-Universität Halle-Wittenberg, Halle (Saale), Germany.
  • AG Digitale Forschungsmethoden in der Medizin, Martin-Luther-Universität Halle-Wittenberg, Medizinische Fakultät, Halle (Saale), Germany.
  • Studienzentrumder, NAKO Gesundheitsstudie , Halle (Saale), Germany.
  • Institute for Medical Epidemiology, Biometrics and Informatics, Martin Luther University Halle-Wittenberg, Halle (Saale), Germany.
  • Biobank der Universitätsmedizin Halle, Martin-Luther-Universität Halle-Wittenberg, Halle (Saale), Germany.
  • Department Epidemiological Methods and Etiological Research, Leibniz Institute for Prevention Research and Epidemiology-BIPS , Bremen, Germany.
  • Medical Faculty and University Hospital, Heidelberg Institute of Global Health (HIGH), Heidelberg University, Heidelberg, Germany.
  • Department of Global Health and Population, Harvard T.H. Chan School of Public Health, Boston, USA.
  • Harvard Centre for Population and Development Studies, Cambridge, MA, USA.
  • Division of Clinical Epidemiology and Aging Research, German Cancer Research Center (DKFZ), Heidelberg, Germany.
  • Department for Epidemiology, Helmholtz Centre for Infection Research, Brunswick, Germany.
  • Institute of Epidemiology, Kiel University, Kiel, Germany.
  • Division of Cancer Epidemiology, German Cancer Research Centre, Heidelberg, Germany.
  • Department of Internal Medicine B, Angiology & Pneumology, University Medicine Greifswald, CardiologyGreifswald, Germany.
  • German Centre for Cardiovascular Research (DZHK), Partner Site Greifswald, Greifswald, Germany.
  • Institute of Social Medicine, Epidemiology and Health Economics, Charité-Universitätsmedizin Berlin, Berlin, Germany.
  • Institute for Occupational and Maritime Medicine (ZfAM), University Medical Center Hamburg-Eppendorf, Hamburg, Germany.
  • Institut für Epidemiologie Und Präventivmedizin, Universität Regensburg, Regensburg, Germany.
  • Institute of Epidemiology, Helmholtz Zentrum München-German Research Center for Environmental Health (GmbH) , Neuherberg, Germany.
  • Institute for Medical Information Processing, Biometry and Epidemiology, Medical Faculty, Ludwig-Maximilians-Universität München, Munich, Germany.
  • DZHK (German Centre for Cardiovascular Research), Partner Site Munich Heart Alliance, Munich, Germany.
  • Institute for Medical Informatics, Biometry and Epidemiology, University Hospital of Essen, University of Duisburg-Essen, Essen, Germany.
  • Department of Molecular Epidemiology, German Institute of Human Nutrition Potsdam-Rehbruecke, Nuthetal, Germany.
  • Institute of Nutritional Science, University of Potsdam, Nuthetal, Germany.
  • Institut für Community Medicine, Abteilung SHIP/Klinisch-Epidemiologische Forschung, University Medicine Greifswald, Greifswald, Germany.
  • Institut für Klinische Chemie Und Laboratoriumsmedizin, University Medicine Greifswald, Greifswald, Germany.
  • Max-Delbrueck-Center for Molecular Medicinein the, Molecular Epidemiology Research Group , Helmholtz Association (MDC), Berlin, Germany.
  • Max-Delbrueck-Center for Molecular Medicinein the , Helmholtz Association (MDC), Biobank Technology Platform, Berlin, Germany.
  • Charité - Universitätsmedizin Berlin, Freie Universität Berlin and Humboldt-Universität zu Berlin, Berlin, Germany.
  • Universitätsklinik für Innere Medizin II, Martin-Luther-Universität Halle-Wittenberg, Halle (Saale), Germany.
  • Julius-Bernstein-Institut für Physiologie, Martin-Luther-Universität Halle-Wittenberg, Halle (Saale), Germany.

Abstract

BACKGROUND

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.

METHODS

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.

RESULTS

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.

CONCLUSIONS

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.

MeSH

Uric Acid, Serum, Machine Learning, Sex, Learning, Vascular Stiffness