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J Am Heart Assoc. Publish New Findings on Subcutaneous Small Arteries Linked to Cardiac Dysfunction

J Am Heart Assoc. 2017 Apr 11;6(4). pii: e004603. doi: 10.1161/JAHA.116.004603. Abnormal Remodeling of Subcutaneous Small Arteries Is Associated With Early Diastolic Impairment in Metabolic Syndrome. Khavandi K1,2, Aghamohammadzadeh R1, Luckie M3, Brownrigg J4, Alam U1, Khattar R5, Malik RA6, Heagerty AM1, Greenstein AS7. Author information 1Division of Cardiovascular Sciences, Manchester Academic Health Sciences Centre, University of Manchester, United Kingdom.2British Heart Foundation Centre of Excellence, The Rayne Institute, King’s College London, London, United Kingdom.3Manchester Heart Centre, Central Manchester Teaching Hospitals Foundation Trust, Manchester, United Kingdom.4St. George’s Vascular Institute, St George’s, University of London, United Kingdom.5Department of Cardiology, Royal Brompton Hospital, National Heart and Lung Institute, Imperial College, London, United Kingdom.6Department of Medicine, Weill Cornell Medical College, Doha, Qatar.7Division of Cardiovascular Sciences, Manchester Academic Health Sciences Centre, University of Manchester, United Kingdom Abstract BACKGROUND: Small artery pathophysiology is frequently invoked as a cause of obesity-related diastolic heart failure. However, evidence to support this hypothesis is scant, particularly in humans. METHODS AND RESULTS: To address this, we studied human small artery structure and function in obesity and looked for correlations between vascular parameters and diastolic function. Seventeen obese patients with metabolic syndrome and 5 control participants underwent echocardiography and subcutaneous gluteal fat biopsy. Small arteries were isolated from the biopsy and pressure myography was used to study endothelial function and wall structure. In comparison with the control group, small arteries from obese participants exhibited significant endothelialdysfunction, assessed as the vasodilatory response to acetylcholine and also pathological growth of the wall. For the obese participants, multiple regression analysis revealed an association between left atrial volume and both the small artery wall thickness (β=0.718, P=0.02) and wall-to-lumen ratio (β=0.605, P=0.02). Furthermore, the E:E’ ratio was associated with wall-to-lumen ratio (β=0.596, P=0.02) and inversely associated with interleukin-6 (β=-0.868, P=0.03). By contrast, endothelial function did not correlate with any of the echocardiographic parameters studied. CONCLUSIONS: Although the small arteries studied were not cardiac in origin, our results support a role for small artery remodeling in the development of diastolic dysfunction in humans. Further direct examination of the structure and function of the myocardial resistance vasculature is now warranted, to elucidate the temporal association between metabolic risk factors, small artery injury, and diastolic impairment. © 2017 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley. KEYWORDS: diastolic dysfunction; endothelial dysfunction; heart failure; obesity; vascular remodeling

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