@article {Chowdhurye002480, author = {Mahin Chowdhury and Sarah Nevitt and Aikaterini Eleftheriadou and Prathap Kanagala and Hani Esa and Daniel J Cuthbertson and Abd Tahrani and Uazman Alam}, title = {Cardiac autonomic neuropathy and risk of cardiovascular disease and mortality in type 1 and type 2 diabetes: a meta-analysis}, volume = {9}, number = {2}, elocation-id = {e002480}, year = {2021}, doi = {10.1136/bmjdrc-2021-002480}, publisher = {BMJ Specialist Journals}, 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.All data relevant to the study are included in the article or uploaded as supplementary information.}, URL = {https://drc.bmj.com/content/9/2/e002480}, eprint = {https://drc.bmj.com/content/9/2/e002480.full.pdf}, journal = {BMJ Open Diabetes Research and Care} }