Combined effect of obesity and cardio-metabolic abnormality on the risk of cardiovascular disease: A meta-analysis of prospective cohort studies

Background: Cardiovascular risk is inconsistent in the normal-weight, overweight, and obese individuals due to metabolic abnormality. We aimed to investigate combined effects of obesity and metabolic abnormality on the risk of cardiovascular disease and mortality. Methods: TheMEDLINE, EMBASE, Cochrane library, and references of relevant original articles prior to May 2013 were searched for prospective studies investigating cardiovascular risk and death associated with combined effects of obesity and metabolic syndrome or insulin resistance. Pooled relative risks (RR) and 95% confidence intervals (CI) were calculated using random-effects or fixed-effect models when appropriate. Results: Fourteen perspective studieswith a total of 299,059 participants and 12,125 cases of incident CVD, 2130 cases of CVD death, and 7071 cases of all-cause deathwere included in themeta-analysis. Comparedwith healthy normal-weight individuals, metabolically healthy overweight (MHOW) and obese (MHOB) individuals showed increased risk for CVD events, which appeared much stronger during the long-term follow-up period of N15 years, with pooled RR of 1.47 (95% CI 1.37-1.58) in MHOW and 2.00 (95% CI 1.79-2.24) in MHOB. Normal-weight but metabolically abnormal individuals were at increased risk for CVD (pooled RR 1.81, 95% CI 1.56-2.10), CVD-related death (pooled RR 1.55, 95% CI 1.16-2.08), and all-cause death (pooled RR 1.27, 95% CI 1.10-1.47). Metabolically abnormal obese individuals were at the highest risk for CVD and mortality. Conclusion: Individualswithmetabolic abnormality, although at normal-weight, had an increased risk of CVDand mortality. Healthy overweight and obese persons had higher risk, which refuted the notion that metabolically healthy obese phenotype is a benign condition. (C) 2013 Elsevier Ireland Ltd. All rights reserved.