Cardiac autonomic neuropathy and risk of cardiovascular disease and mortality in type 1 and type 2 diabetes: a meta-analysis

Mahin Chowdhury; Sarah Nevitt; Aikaterini Eleftheriadou; Prathap Kanagala; Hani Esa; Daniel J Cuthbertson; Abd Tahrani; Uazman Alam

doi:10.1136/bmjdrc-2021-002480

Cardiac autonomic neuropathy and risk of cardiovascular disease and mortality in type 1 and type 2 diabetes: a meta-analysis

BMJ Open Diabetes Res Care. 2021 Dec;9(2):e002480. doi: 10.1136/bmjdrc-2021-002480.

Authors

Mahin Chowdhury¹, Sarah Nevitt², Aikaterini Eleftheriadou¹, Prathap Kanagala^{1

3}, Hani Esa^{1

3}, Daniel J Cuthbertson^{1

3}, Abd Tahrani^{4

5

6}, Uazman Alam^{7

3

8

9}

Affiliations

¹ Department of Cardiovascular and Metabolic Medicine, University of Liverpool, Liverpool, UK.
² Department of Health Data Science, University of Liverpool, Liverpool, UK.
³ Department of Medicine, University Hospital Aintree, Liverpool University NHS Foundation Trust, Liverpool, UK.
⁴ Centre of Endocrinology, Diabetes and Metabolism, University of Birmingham, Birmingham, UK.
⁵ Institute of Metabolism and Systems Research, University of Birmingham, Birmingham, UK.
⁶ Department of Diabetes and Endocrinology, University Hospitals Birmingham NHS Foundation Trust, Birmingham, UK.
⁷ Department of Cardiovascular and Metabolic Medicine, University of Liverpool, Liverpool, UK Uazman.Alam@liverpool.ac.uk.
⁸ Division of Diabetes, Endocrinology and Gastroenterology, Institute of Human Development, University of Manchester, Manchester, UK.
⁹ Department of Cardiovascular & Metabolic Medicine, Institute of Life Course and Medical Sciences and Pain Research Institute, University of Liverpool and Liverpool University Hospital NHS Foundation Trust, Liverpool, UK.

Abstract

We aimed to determine the prognostic association between cardiac autonomic neuropathy (CAN) and cardiovascular disease events (CVE) and mortality in type 1 and type 2 diabetes through a systematic review and meta-analysis. This systematic review and meta-analysis was registered with PROSPERO (CRD42020216305) and was conducted with Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) methodological criteria. CAN was defined on the basis of 1 (early/possible CAN) or ≥2 (definite CAN) positive autonomic function tests as per the Toronto Consensus guidelines. Studies included those with prospective CVE or mortality data. Methodological variables/risk of bias were assessed using ROBINS-I (Risk Of Bias In Non-randomized Studies - of Interventions) and RoB-2 (Risk-Of-Bias tool for randomized trials) appraisal tools. Electronic database searches yielded 18 467 articles; 84 articles were screened full-text, 26 articles fulfilled the inclusion criteria for quantitative synthesis. Sixteen studies from patients with (n=2875) and without (n=11 722) CAN demonstrated a pooled relative risk (RR) of 3.16 (95%CI 2.42 to 4.13; p<0.0001) of future CVE in favour of CAN. Nineteen studies provided all-cause mortality data from patients with (n=3679) and without (n=12 420) CAN, with a pooled RR of 3.17 (95%CI 2.11 to 4.78; p<0.0001) in favour of CAN. The risk of both future CVE and mortality was higher in type 1 compared with type 2 diabetes and with a definite CAN (vs possible CAN) diagnosis. Three studies were considered to have risk of serious bias. This study confirms the significant association between CAN and CVE and all-cause mortality. The implementation of population-based CAN screening will identify a subgroup with disproportionately higher cardiovascular and mortality risk that will allow for earlier targeted intervention.

Keywords: cardiac autonomic neuropathy; cardiovascular system; diabetes complications; mortality.

Publication types

Meta-Analysis
Review
Systematic Review

MeSH terms

Cardiovascular Diseases* / etiology
Cardiovascular Diseases* / mortality
Diabetes Mellitus, Type 1* / complications
Diabetes Mellitus, Type 2* / complications
Diabetic Neuropathies* / complications
Humans
Mass Screening
Prognosis