Systemic microvascular dysfunction in microvascular and vasospastic angina

Ford, T. J. et al. (2018) Systemic microvascular dysfunction in microvascular and vasospastic angina. European Heart Journal, 39(46), pp. 4086-4097. (doi:10.1093/eurheartj/ehy529) (PMID:30165438) (PMCID:PMC6284165)

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Abstract

Aims: Coronary microvascular dysfunction and/or vasospasm are potential causes of ischaemia in patients with no obstructive coronary artery disease (INOCA). We tested the hypothesis that these patients also have functional abnormalities in peripheral small arteries. Methods and results: Patients were prospectively enrolled and categorised as having microvascular angina (MVA), vasospastic angina (VSA) or normal control based on invasive coronary artery function tests incorporating probes of endothelial and endothelial-independent function (acetylcholine and adenosine). Gluteal biopsies of subcutaneous fat were performed in 81 subjects (62 years, 69% female, 59 MVA, 11 VSA, and 11 controls). Resistance arteries were dissected enabling study using wire myography. Maximum relaxation to ACh (endothelial function) was reduced in MVA vs. controls [median 77.6 vs. 98.7%; 95% confidence interval (CI) of difference 2.3–38%; P = 0.0047]. Endothelium-independent relaxation [sodium nitroprusside (SNP)] was similar between all groups. The maximum contractile response to endothelin-1 (ET-1) was greater in MVA (median 121%) vs. controls (100%; 95% CI of median difference 4.7–45%, P = 0.015). Response to the thromboxane agonist, U46619, was also greater in MVA (143%) vs. controls (109%; 95% CI of difference 13–57%, P = 0.003). Patients with VSA had similar abnormal patterns of peripheral vascular reactivity including reduced maximum relaxation to ACh (median 79.0% vs. 98.7%; P = 0.03) and increased response to constrictor agonists including ET-1 (median 125% vs. 100%; P = 0.02). In all groups, resistance arteries were ≈50-fold more sensitive to the constrictor effects of ET-1 compared with U46619. Conclusions: Systemic microvascular abnormalities are common in patients with MVA and VSA. These mechanisms may involve ET-1 and were characterized by endothelial dysfunction and enhanced vasoconstriction. Clinical trial registration: ClinicalTrials.gov registration is NCT03193294.

Item Type:Articles
Status:Published
Refereed:Yes
Glasgow Author(s) Enlighten ID:Berry, Professor Colin and Robertson, Dr Keith and Shaukat, Dr Aadil and Harvey, Dr Adam and Haddow, Mrs Laura and Beattie, Mrs Elisabeth and Eteiba, Dr Hany and Oldroyd, Dr Keith and Montezano, Dr Augusto and Sidik, Ms Novalia and Touyz, Professor Rhian and Hood, Dr Stuart
Authors: Ford, T. J., Rocchiccioli, P., Good, R., McEntegart, M., Eteiba, H., Watkins, S., Shaukat, A., Lindsay, M., Robertson, K., Hood, S., Yii, E., Sidik, N., Harvey, A., Montezano, A. C., Beattie, E., Haddow, L., Oldroyd, K. G., Touyz, R. M., and Berry, C.
College/School:College of Medical Veterinary and Life Sciences > Institute of Cardiovascular and Medical Sciences
College of Medical Veterinary and Life Sciences > School of Medicine, Dentistry & Nursing
Journal Name:European Heart Journal
Publisher:Oxford University Press
ISSN:0195-668X
ISSN (Online):1522-9645
Published Online:27 August 2018
Copyright Holders:Copyright © 2018 The Authors
First Published:First published in European Heart Journal 39(46): 4086-4097
Publisher Policy:Reproduced under a Creative Commons License

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Project CodeAward NoProject NamePrincipal InvestigatorFunder's NameFunder RefLead Dept
617771BHF centre of excellenceRhian TouyzBritish Heart Foundation (BHF)RE/13/5/30177RI CARDIOVASCULAR & MEDICAL SCIENCES