Peer Review #2 of "Association of metabolically healthy obesity and elevated risk of coronary artery calcification: a systematic review and meta-analysis (v0.3)"

Background: Metabolically healthy obesity (MHO) is defined as obesity with less than 2 parameters of metabolic abnormalities.Some studies report that MHO individuals show similar risk of cardiovascular disease(CVD) compared with metabolically healthy non-obese(MHNO) individuals, but the results are conflicting.Coronary artery calcium (CAC) reflects the extent of coronary atherosclerosis and is a useful tool to predict future risk of CVD.The objective of this meta-analysis was to investigate whether MHO is associated with elevated risk of CAC. Method:We searched Cochrane, PubMed, and Embase up to April 19, 2019.Prospective cohort and cross-sectional studies examining the association between MHO subjects and CAC were included with MHNO as the reference.Pooled odds ratio (OR) and 95% confidence interval (CI) were calculated using random-effect models.Subgroup analysis and meta-regression were applied to define possible sources of heterogeneity.We conducted this research following a pre-established protocol registered on PROSPERO (CRD 42019135006).Results: A total of nine studies were included in this review and six studies with 23,543 participants were eligible for the meta-analysis.Compared with MHNO subjects, MHO had a higher odds of CAC (OR 1.36, 95% CI [1.11 to 1.66]; I 2 =39%).In the subgroup analysis, the risk associated with MHO participants was significant in cohort studies (OR =1.47, 95% CI [1.15,1.87],I 2 =0%), and borderline significant in cross-sectional studies.The risk of CAC was also significant in MHO participants defined by Adult Treatment Panel III (ATP III) (OR =1.55, 95% CI [1.25,1.93],I 2 =0%).The univariate meta-regression model showed that age and smoking status were possible effect modifiers for MHO and CAC risk. Conclusion:Our meta-analysis showed that MHO phenotypes were associated with elevated risk of CAC compared with MHNO, which reflects the extent of coronary atherosclerosis.People with obesity should strive to achieve normal weight even when only one metabolic abnormality is present.