Metabolically unhealthy phenotype in normal weight population and risk of mortality and major adverse cardiac events: A meta-analysis of 41 prospective cohort studies

It is still debatable whether metabolic status in normal weight population increases the risk of mortality (all-cause mortality (ACM), cardiovascular mortality (CVM)) and major adverse cardiac events (MACE) as compared to the obese population. Therefore, this meta-analysis aims to evaluate the association of the metabolically unhealthy normal weight (MUH-NW) phenotype with all-cause mortality, cardiovascular mortality, and MACE in comparison to metabolically healthy obesity (MH-O), along with the association of metabolically unhealthy obesity (MUH-O) phenotype regarding the same outcomes compared to MUH-NW.A systematic literature search was conducted using online databases from inception to June 20, 2022, to comprehensively search all prospective cohort studies comprising three variables including adults aged ≥18 years, obesity and four metabolic phenotypes, and interest outcomes (ACM, CVM, and MACE).Forty-one prospective cohort studies with a total of 4,028,750 participants was included in this study. Compared to MH-O, MUH-NW had a substantially higher risk of ACM (RR = 1.47 (95%CI = 1.32-1.64); P < 0.001; I2 = 89.8%,P-heterogeneity<0.001), CVM (RR = 2.37 (95%CI = 1.97-2.86); P < 0.001; I2 = 83.7%,P-heterogeneity<0.001), and MACE (RR = 1.73 (95%CI = 1.49-2.00); P < 0.001; I2 = 74.3%,P-heterogeneity<0.001). Moreover, MUH-O did not have a significantly elevated risk of ACM (RR = 0.97 (95%CI = 0.82-1.15); P = 0.736; I2 = 98.3%,P-heterogeneity<0.001), CVM (RR = 0.96 (95%CI = 0.88-1.05); P = 0.394; I2 = 77.0%,P-heterogeneity<0.001), and MACE (RR = 0.95 (95%CI = 0.80-1.13); P = 0.570; I2 = 92.2%,P-heterogeneity<0.001) compared to MUH-NW.In conclusion, MUH-NW was superior but not inferior to MH-O and MUH-O in terms of increased risk of interest outcomes, refuting the notion that normal weight population is a benign condition. Hence, in normal weight population, metabolic screening is highly suggested to measure the baseline of obesity and metabolic phenotypes, thus preventing the risk of CVD and mortality in the future.