==== Front Korean J AnesthesiolKorean J AnesthesiolKJAEKorean Journal of Anesthesiology2005-64192005-7563Korean Society of Anesthesiologists 10.4097/kja.d.18.00046kja-d-18-00046Letter to the EditorPerioperative stroke and hyperhomocysteinemia: a possible pathogenic link http://orcid.org/0000-0003-4149-1785Acampa Maurizio 1http://orcid.org/0000-0001-6721-1214Lazzerini Pietro Enea 2http://orcid.org/0000-0002-1176-3463Martini Giuseppe 1 1 Department of Neurological and Sensorineural Sciences, University Hospital of Siena, “Santa Maria alle Scotte” General Hospital, Siena, Italy 2 Department of Medical Sciences, Surgery and Neurosciences, University of Siena, Siena, ItalyCorresponding author: Maurizio Acampa, M.D., Ph.D. Department of Neurological and Sensorineural Sciences, University Hospital of Siena, “Santa Maria alle Scotte” General Hospital, 17, Viale Bracci, Siena 53100, Italy Tel: 39-0577585408, Fax: 39-0577586294, Email: m.acampa@ao-siena.toscana.it8 2018 9 5 2018 71 4 332 333 19 2 2018 27 2 2018 Copyright © The Korean Society of Anesthesiologists, 20182018This is an open-access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/4.0/) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited. ==== Body We have read with interest the review by Ko [1], focused on pathophysiologic mechanisms of perioperative stroke. The author examined different risk factors for perioperative stroke, including conventional vascular risk factors and specific mechanisms related to the type of surgery. In addition to these mechanisms, we suggest that hyperhomocysteinemia (HHcy) may represent a relevant pathogenic factor in the development of perioperative stroke, especially in specific cardiac surgical procedures [2,3]. High homocysteine levels can lead to an ischemic stroke through multiple mechanisms and are associated with the occurrence of atrial fibrillation (AF) and a prothrombotic state [3]. HHcy has an acute and direct effect on atrial ionic channels (inhibition of the transient outward potassium current and ultra-rapid delayed-rectifier K+ currents, increase of inward-rectifier K+-current, increased Na+ currents) that produce early after depolarization and cause focal ectopic/triggered activity [3]. Moreover, HHcy may promote atrial fibrosis (atrial structural remodeling) that causes slow and heterogeneous atrial conduction (with increased P wave dispersion on the electrocardiogram), favoring the appearance of a vulnerable reentrant substrate [4]. These atrial electrical and structural alterations represent a wellknown substrate for AF, resulting in an increased risk of cardioembolic stroke. HHcy may also contribute to a prothrombotic state through different mechanisms (increased tissue factor expression, attenuated anticoagulant processes, enhanced platelet reactivity, increased thrombin generation, augmented Factor V activity, impaired fibrinolytic potential), resulting in increased risk of atrial thrombosis and possible subsequent ischemic embolic stroke [3]. In patients undergoing cardiac surgery who develop HHcy, an appropriate homocysteine-lowering treatment [5] could represent a preventive strategy to prevent the occurrence of AF and reduce the risk of ischemic stroke. ==== Refs References 1 Ko SB Perioperative stroke: pathophysiology and management Korean J Anesthesiol 2018 71 3 11 29441169 2 Acampa M Lazzerini PE Martini G Postoperative atrial fibrillation and ischemic stroke: the role of homocysteine Eur Stroke J 2018 3 92 3 3 Acampa M Lazzerini PE Guideri F Tassi R Martini G Ischemic stroke after heart transplantation J Stroke 2016 18 157 68 26915504 4 Acampa M Lazzerini PE Guideri F Rechichi S Capecchi PL Maccherini M Homocysteine and P wave dispersion in patients with heart transplantation Clin Transplant 2011 25 119 25 19878513 5 Spence JD Yi Q Hankey GJ B vitamins in stroke prevention: time to reconsider Lancet Neurol 2017 16 750 60 28816120