Is microvascular dysfunction a systemic disorder with common biomarkers found in the heart, brain, and kidneys? — A scoping review

Although microvascular dysfunction (MVD) has been well characterized in individual organs as different disease entities, clinical evidence is mounting in support of an underlying systemic process. To address this hypothesis, we systematically searched PubMed and Medline for studies in adults published between 2014 and 2019 that measured blood biomarkers of MVD in three vital organs i.e. brain, heart, and the kidney. Of the 9706 unique articles 321 met the criteria, reporting 49 biomarkers of which 16 were common to the three organs. Endothelial dysfunction, inflammation including reactive oxidation, immune activation, and coagulation were the commonly recognized pathways. Triglyceride, C-reactive protein, Cystatin C, homocysteine, uric acid, IL-6, NT-proBNP, thrombomodulin, von Willebrand Factor, and uric acid were increased in MVD of all three organs. In contrast, vitamin D was decreased. Adiponectin, asymmetric dimethylarginine, total cholesterol, high-density and low-density cholesterol were found to be variably increased or decreased in studies. We review the pathways underlying MVD in the three organs and summarize evidence supporting its systemic nature. This scoping review informs clinicians and researchers in the multi-system manifestation of MVD. Future work should focus on longitudinal investigations to evaluate the multi-system involvement of this disease. • Microvascular dysfunction appears to be a systemic process as evidenced by changes in 16 biomarkers common to all three end organs. • Pathways underlying systemic microvascular dysfunction include endothelial dysfunction, inflammation including reactive oxidation, immune activation, and coagulation. • Markers are either uniformly increased (e.g. C-reactive protein), decreased (e.g. Vitamin D) or variably altered (e.g. adiponectin). • Future research and clinical care should employ a systematic holistic approach to multi-organ microvascular dysfunction.