Review
Copyright ©The Author(s) 2018. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Diabetes. Jan 15, 2018; 9(1): 1-24
Published online Jan 15, 2018. doi: 10.4239/wjd.v9.i1.1
Cardiac autonomic neuropathy: Risk factors, diagnosis and treatment
Victoria A Serhiyenko, Alexandr A Serhiyenko
Victoria A Serhiyenko, Alexandr A Serhiyenko, Department of Endocrinology, Lviv National Medical University Named by Danylo Halitsky, Lviv 79010, Ukraine
Author contributions: Serhiyenko VA and Serhiyenko AA contributed equally to this work, they have conceptualized, designed, performed and wrote the review.
Conflict-of-interest statement: All authors declare no conflict of interest.
Open-Access: This article is an open-access article which was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/
Correspondence to: Victoria A Serhiyenko, MD, PhD, Department of Endocrinology, Lviv National Medical University Named by Danylo Halitsky, Pekarska 69 Str., Lviv 79010, Ukraine. serhiyenko@inbox.ru
Telephone: +380-322-769496 Fax: +380-322-769496
Received: October 28, 2017
Peer-review started: October 29, 2017
First decision: November 23, 2017
Revised: December 9, 2017
Accepted: December 29, 2017
Article in press: December 29, 2017
Published online: January 15, 2018
Processing time: 73 Days and 12.1 Hours
Abstract

Cardiac autonomic neuropathy (CAN) is a serious complication of diabetes mellitus (DM) that is strongly associated with approximately five-fold increased risk of cardiovascular mortality. CAN manifests in a spectrum of things, ranging from resting tachycardia and fixed heart rate (HR) to development of “silent” myocardial infarction. Clinical correlates or risk markers for CAN are age, DM duration, glycemic control, hypertension, and dyslipidemia (DLP), development of other microvascular complications. Established risk factors for CAN are poor glycemic control in type 1 DM and a combination of hypertension, DLP, obesity, and unsatisfactory glycemic control in type 2 DM. Symptomatic manifestations of CAN include sinus tachycardia, exercise intolerance, orthostatic hypotension (OH), abnormal blood pressure (BP) regulation, dizziness, presyncope and syncope, intraoperative cardiovascular instability, asymptomatic myocardial ischemia and infarction. Methods of CAN assessment in clinical practice include assessment of symptoms and signs, cardiovascular reflex tests based on HR and BP, short-term electrocardiography (ECG), QT interval prolongation, HR variability (24 h, classic 24 h Holter ECG), ambulatory BP monitoring, HR turbulence, baroreflex sensitivity, muscle sympathetic nerve activity, catecholamine assessment and cardiovascular sympathetic tests, heart sympathetic imaging. Although it is common complication, the significance of CAN has not been fully appreciated and there are no unified treatment algorithms for today. Treatment is based on early diagnosis, life style changes, optimization of glycemic control and management of cardiovascular risk factors. Pathogenetic treatment of CAN includes: Balanced diet and physical activity; optimization of glycemic control; treatment of DLP; antioxidants, first of all α-lipoic acid (ALA), aldose reductase inhibitors, acetyl-L-carnitine; vitamins, first of all fat-soluble vitamin B1; correction of vascular endothelial dysfunction; prevention and treatment of thrombosis; in severe cases-treatment of OH. The promising methods include prescription of prostacyclin analogues, thromboxane A2 blockers and drugs that contribute into strengthening and/or normalization of Na+, K+-ATPase (phosphodiesterase inhibitor), ALA, dihomo-γ-linolenic acid (DGLA), ω-3 polyunsaturated fatty acids (ω-3 PUFAs), and the simultaneous prescription of ALA, ω-3 PUFAs and DGLA, but the future investigations are needed. Development of OH is associated with severe or advanced CAN and prescription of nonpharmacological and pharmacological, in the foreground midodrine and fludrocortisone acetate, treatment methods are necessary.

Keywords: Diabetes mellitus; Risk factors; Cardiac autonomic neuropathy; Screening for cardiac autonomic neuropathy; Cardiovascular reflex tests; Orthostatic hypotension; Heart rate variability; Prophylaxis; Treatment

Core tip: Cardiac autonomic neuropathy (CAN) is a serious complication of diabetes mellitus, which is strongly associated with increased risk of cardiovascular mortality. Although it is common complication, the significance of CAN has not been fully appreciated and there are no unified treatment algorithms for today. In this review we have analyzed the existing data about the known risk factors, screening and diagnostic algorithm, staging of CAN and possible treatment, including effectiveness of lifestyle modification, intensive glycemic control; treatment of diabetic dyslipidemia; antioxidants; vitamins; correction of vascular endothelial dysfunction; prevention and treatment of thrombosis; treatment of orthostatic hypotension.