Implications of the dynamic nature of metabolic health status and obesity on risk of incident cardiovascular events and mortality: a nationwide population-based cohort study

Aims We hypothesized that transitions in metabolic health status and obesity affect the cardiovascular (CV) risk and mortality in population with metabolically healthy obesity (MHO). Methods This study enrolled 514,866 participants from the Korean National Health Insurance Service–National Sample Cohort. Changes in metabolic health status and obesity from the baseline examination in 2009–2010 to the next biannual health examination in 2011–2012 were determined. Study participants were categorized into four groups: (1) metabolically healthy, non-obese (MHNO), defined as BMI < 25 kg/m2 and no or one metabolic risk factor; (2) metabolically unhealthy, non-obese (MUNO), defined as BMI < 25 kg/m2 and ≥2 metabolic risk factors; (3) MHO, defined as BMI ≥ 25 kg/m2 and no or one metabolic risk factor; and (4) metabolically unhealthy, obese (MUO), defined as BMI ≥ 25 kg/m2 and ≥2 metabolic risk factors. The study subjects were followed-up from 2011 to 2015 for cardiovascular events, CV mortality and all-cause mortality. Results Among the subjects classified as MHO in 2009–2010, 45.6% were classified as MHO in 2011–2012, whereas 11.6%, 6.0%, and 36.8% were classified as MHNO, MUNO, and MUO, respectively. The risk of CV events was higher in baseline MHO group than MHNO group (HR, 1.14; 95% CI, 1.05–1.24). However, in baseline MHO group, CV mortality was not increased (HR, 0.85; 95% CI, 0.69–1.06) and all-cause mortality was even lower than that of MHNO group (HR, 0.86; 95% CI, 0.79–0.93). Compared to the stable MHO subjects, the risk of CV events was significantly higher in the subjects who transitioned from MHO to MUO with multivariate-adjusted HRs of 1.24 (95% CI: 1.00–1.54). When weight loss and progression to metabolic unhealthy phenotype occur simultaneously in the MHO population, the all-cause mortality was increased compared to the stable MHO group (HR, 1.96; 95% CI, 1.45–2.65). Conclusions Subjects with MHO constitute a heterogeneous group. Our finding supports that evolving to a metabolically unhealthy status and losing weight simultaneously is associated with the adverse outcome in the MHO population.