Metabolically healthy obesity and risk of cardiovascular disease, cancer, and all-cause and cause-specific mortality: a protocol for a systematic review and meta-analysis of prospective studies

INTRODUCTION: Metabolically healthy obese phenotype (MHO) refers to obese individuals with an adequate metabolic profile and absence of metabolic syndrome. Many prospective studies have reported the benign condition relating the MHO phenotype and its potential role in reducing risk of cardiovascular disease, total cancer, and all-cause and cause-specific mortality. However, inconsistent results were found and the question remains controversial. We aim to conduct a systematic review and meta-analysis to clarify the associations these associations from relevant prospective studies. METHODS AND ANALYSIS: The Preferred Reporting Items for Systematic Reviews and Meta-Analyses for Protocols 2015 statement was used to prepare this protocol. MEDLINE, Web of Science databases, EMBASE and Cochrane Database will be used for literature search from their inception up to December 2019 with restriction of published studies in English. Published prospective studies reporting adjusted relative risk (RR) estimates for the association between MHO phenotype and cardiovascular disease, total cancer, all-cause or cause-specific mortality will be included. The process of study screening, selection and data extraction will be performed independently by two reviewers, and the risk of bias for the studies included will be assessed using the Newcastle-Ottawa Quality Assessment Scale. HRs or RRs for disease events and mortality with 95% CIs will be considered as primary outcomes, and summary HRs/RRs will be pooled using random-effects models. The Cochrane’s Q and the I(2) statistics will be used to assess and quantify heterogeneity, respectively. Subgroup analysis will also be carried out according to study characteristics to investigate potential sources of heterogeneity. ETHICS AND DISSEMINATION: As this meta-analysis is performed based on the published studies, no ethical approval and patient safety considerations are required. The findings of the study will be reported and submitted to a peer-reviewed journals for publication. PROSPERO REGISTRATION NUMBER: CRD42019121766.