Development and validation of cardiometabolic risk predictive models based on LDL oxidation and candidate geromarkers from the MARK-AGE data.

Journal: Mechanisms of ageing and development
PMID:

Abstract

The predictive value of the susceptibility to oxidation of LDL particles (LDLox) in cardiometabolic risk assessment is incompletely understood. The main objective of the current study was to assess its relationship with other relevant biomarkers and cardiometabolic risk factors from MARK-AGE data. A cross-sectional observational study was carried out on 1089 subjects (528 men and 561 women), aged 40-75 years old, randomly recruited age- and sex-stratified individuals from the general population. A correlation analysis exploring the relationships between LDLox and relevant biomarkers was undertaken, as well as the development and validation of several machine learning algorithms, for estimating the risk of the combined status of high blood pressure and obesity for the MARK-AGE subjects. The machine learning models yielded Area Under the Receiver Operating Characteristic Curve Score ranging 0.783-0.839 for the internal validation, while the external validation resulted in an Under the Receiver Operating Characteristic Curve Score between 0.648 and 0.787, with the variables based on LDLox reaching significant importance within the obtained predictions. The current study offers novel insights regarding the combined effects of LDL oxidation and other ageing markers on cardiometabolic risk. Future studies might be extended on larger patient cohorts, in order to obtain reproducible clinical assessment models.

Authors

  • Andrei Valeanu
    Carol Davila University of Medicine and Pharmacy, Faculty of Pharmacy, 6 Traian Vuia St., Bucharest 020956, Romania. Electronic address: andrei.valeanu@umfcd.ro.
  • Denisa Margina
    Carol Davila University of Medicine and Pharmacy, Faculty of Pharmacy, 6 Traian Vuia St., Bucharest 020956, Romania. Electronic address: denisa.margina@umfcd.ro.
  • Daniela Weber
    Department of Molecular Toxicology, German Institute of Human Nutrition, Potsdam-Rehbrücke, Nuthetal 14558, Germany; NutriAct-Competence Cluster Nutrition Research Berlin-Potsdam, Nuthetal 14458, Germany. Electronic address: Daniela.Weber@dife.de.
  • Wolfgang Stuetz
    Department of Food Biofunctionality, Institute of Nutritional Sciences (140), University of Hohenheim, Stuttgart 70599, Germany. Electronic address: wolfgang.stuetz@uni-hohenheim.de.
  • María Moreno-Villanueva
    Molecular Toxicology Group, Department of Biology, University of Konstanz, Konstanz 78457, Germany; Human Performance Research Centre, Department of Sport Science, University of Konstanz, Konstanz 78457, Germany. Electronic address: maria.moreno-villanueva@uni-konstanz.de.
  • Martijn E T Dollé
    Centre for Health Protection, National Institute for Public Health and the Environment, PO Box 1, Bilthoven 3720 BA, the Netherlands. Electronic address: Martijn.Dolle@rivm.nl.
  • Eugène Hjm Jansen
    Centre for Health Protection, National Institute for Public Health and the Environment, PO Box 1, Bilthoven 3720 BA, the Netherlands. Electronic address: eugenejansen99@gmail.com.
  • Efstathios S Gonos
    National Hellenic Research Foundation, Institute of Biology, Medicinal Chemistry and Biotechnology, Athens, Greece. Electronic address: sgonos@eie.gr.
  • Jürgen Bernhardt
    BioTeSys GmbH, Schelztorstr. 54-56, Esslingen 73728, Germany. Electronic address: j.bernhardt@biotesys.de.
  • Beatrix Grubeck-Loebenstein
    Research Institute for Biomedical Aging Research, University of Innsbruck, Rennweg, 10, Innsbruck 6020, Austria. Electronic address: Beatrix.Grubeck-Loebenstein@uibk.ac.at.
  • Birgit Weinberger
    Research Institute for Biomedical Aging Research, University of Innsbruck, Rennweg, 10, Innsbruck 6020, Austria. Electronic address: birgit.weinberger@uibk.ac.at.
  • Simone Fiegl
    UMIT TIROL - Private University for Health Sciences, Medical Informatics and Technology, Hall in Tyrol 6060, Austria. Electronic address: simone.fiegl@umit-tirol.at.
  • Ewa Sikora
    Laboratory of the Molecular Bases of Ageing, Nencki Institute of Experimental Biology, Polish Academy of Sciences, 3 Pasteur street, Warsaw 02-093, Poland. Electronic address: e.sikora@nencki.edu.pl.
  • Grazyna Mosieniak
    Laboratory of the Molecular Bases of Ageing, Nencki Institute of Experimental Biology, Polish Academy of Sciences, 3 Pasteur street, Warsaw 02-093, Poland. Electronic address: g.mosieniak@nencki.edu.pl.
  • Olivier Toussaint
    URBC-NARILIS, University of Namur, Rue de Bruxelles, 61, Namur, Belgium.
  • Florence Debacq-Chainiaux
    URBC-NARILIS, University of Namur, Rue de Bruxelles, 61, Namur, Belgium. Electronic address: florence.chainiaux@unamur.be.
  • Miriam Capri
    Department of Medical and Surgical Science, University of Bologna, Bologna, Italy.
  • Paolo Garagnani
    Department of Medical and Surgical Sciences (DIMEC), Alma Mater Studiorum, University of Bologna, Bologna 40126, Italy; IRCCS Azienda Ospedaliero-Universitaria di Bologna, Bologna, Italy. Electronic address: paolo.garagnani2@unibo.it.
  • Chiara Pirazzini
    Department of Medical and Surgical Sciences (DIMEC), Alma Mater Studiorum, University of Bologna, Bologna 40126, Italy. Electronic address: chiara.pirazzini5@unibo.it.
  • Maria Giulia Bacalini
    IRCCS Istituto delle Scienze Neurologiche di Bologna, 40139 Bologna, Italy.
  • Antti Hervonen
    Medical School, University of Tampere, Tampere 33014, Finland. Electronic address: antti.hervonen@gmail.com.
  • P Eline Slagboom
    Section of Molecular Epidemiology, Leiden University Medical Centre, Leiden, the Netherlands. Electronic address: p.slagboom@lumc.nl.
  • Duncan Talbot
    Department of Unilever Science and Technology, Beauty and Personal Care, Sharnbrook, UK. Electronic address: scoutwell.supplies@btinternet.com.
  • Nicolle Breusing
    Department of Applied Nutritional Science/Dietetics, Institute of Nutritional Medicine, University of Hohenheim, Stuttgart 70599, Germany. Electronic address: nicolle_breusing@yahoo.de.
  • Jan Frank
    Department of Food Biofunctionality, Institute of Nutritional Sciences (140), University of Hohenheim, Stuttgart 70599, Germany. Electronic address: jan.frank@uni-hohenheim.de.
  • Alexander Bürkle
    Molecular Toxicology Group, Department of Biology, University of Konstanz, Konstanz 78457, Germany. Electronic address: alexander.buerkle@uni-konstanz.de.
  • Claudio Franceschi
    Institute of Information Technologies, Mathematics and Mechanics, Lobachevsky University, Nizhny, Russia.
  • Tilman Grune
    Department of Molecular Toxicology, German Institute of Human Nutrition, Potsdam-Rehbrücke, Nuthetal 14558, Germany; NutriAct-Competence Cluster Nutrition Research Berlin-Potsdam, Nuthetal 14458, Germany; German Center for Diabetes Research (DZD), München-Neuherberg 85764, Germany; German Center for Cardiovascular Research (DZHK), Partner Site Berlin, Berlin 13347, Germany; University of Potsdam, Institute of Nutritional Science, Nuthetal 14458, Germany; University of Vienna, Department of Physiological Chemistry, Faculty of Chemistry, Vienna 1090, Austria. Electronic address: scientific.director@dife.de.
  • Daniela Gradinaru
    Carol Davila University of Medicine and Pharmacy, Faculty of Pharmacy, 6 Traian Vuia St., Bucharest 020956, Romania; Ana Aslan National Institute of Gerontology and Geriatrics, Bucharest, Romania. Electronic address: daniela.gradinaru@umfcd.ro.