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: The MEDLINE, 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 studies with a total of 299,059 participants and 12,125 cases of incident CVD, 2130 cases of CVD death, and 7071 cases of all-cause death were included in the meta-analysis. Compared with 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 >15 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: Individuals with metabolic abnormality, although at normal-weight, had an increased risk of CVD and mortality. Healthy overweight and obese persons had higher risk, which refuted the notion that metabolically healthy obese phenotype is a benign condition.