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Assessment and pathophysiology of microvascular disease: recent progress and clinical implications.

  • Masi, Stefano1, 2
  • Rizzoni, Damiano3, 4
  • Taddei, Stefano1
  • Widmer, Robert Jay5
  • Montezano, Augusto C6
  • Lüscher, Thomas F7, 8
  • Schiffrin, Ernesto L9
  • Touyz, Rhian M6
  • Paneni, Francesco8, 10, 11
  • Lerman, Amir5
  • Lanza, Gaetano A12
  • Virdis, Agostino1
  • 1 Department of Clinical and Experimental Medicine, University of Pisa, Pisa, Italy. , (Italy)
  • 2 Institute of Cardiovascular Science, University College London, London, UK.
  • 3 Clinica Medica, Department of Clinical and Experimental Sciences, University of Brescia, Brescia, Italy. , (Italy)
  • 4 Division of Medicine, Istituto Clinico Città di Brescia, Brescia, Italy. , (Italy)
  • 5 Division of Cardiovascular Diseases, Mayo Clinic College of Medicine, Rochester, MN, USA.
  • 6 Institute of Cardiovascular & Medical Sciences, BHF Glasgow Cardiovascular Research Centre, University of Glasgow, Glasgow, UK.
  • 7 Heart Division, Royal Brompton and Harefield Hospital and Imperial College, London, UK.
  • 8 Center for Molecular Cardiology, University of Zürich, Zürich, Switzerland. , (Switzerland)
  • 9 Department of Medicine and Lady Davis Institute, Sir Mortimer B. Davis-Jewish General Hospital, McGill University, Montreal, QC, Canada. , (Canada)
  • 10 Department of Cardiology, University Heart Center, University Hospital Zurich, Zürich, Switzerland. , (Switzerland)
  • 11 Department of Research and Education, University Hospital Zurich, Zürich, Switzerland. , (Switzerland)
  • 12 Department of Cardiovascular and Thoracic Medicine, Fondazione Policlinico Universitario A. Gemelli IRCCS, Università Cattolica del Sacro Cuore, Rome, Italy. , (Italy)
Published Article
European Heart Journal
Oxford University Press
Publication Date
Jul 08, 2021
DOI: 10.1093/eurheartj/ehaa857
PMID: 33257973


The development of novel, non-invasive techniques and standardization of protocols to assess microvascular dysfunction have elucidated the key role of microvascular changes in the evolution of cardiovascular (CV) damage, and their capacity to predict an increased risk of adverse events. These technical advances parallel with the development of novel biological assays that enabled the ex vivo identification of pathways promoting microvascular dysfunction, providing novel potential treatment targets for preventing cerebral-CV disease. In this article, we provide an update of diagnostic testing strategies to detect and characterize microvascular dysfunction and suggestions on how to standardize and maximize the information obtained from each microvascular assay. We examine emerging data highlighting the significance of microvascular dysfunction in the development CV disease manifestations. Finally, we summarize the pathophysiology of microvascular dysfunction emphasizing the role of oxidative stress and its regulation by epigenetic mechanisms, which might represent potential targets for novel interventions beyond conventional approaches, representing a new frontier in CV disease reduction. © The Author(s) 2020. Published by Oxford University Press on behalf of the European Society of Cardiology.

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