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

Abstract

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.

Keywords: Cardiovascular disease risk; Cardiovascular mortality; Metabolic syndrome; Mortality; Obesity.