Roles of general and central adiposity in cardiometabolic multimorbidity: revisiting the obesity paradox using a multistate model

OBJECTIVE: The objective of this study was to evaluate the associations of general and central obesity with risk of first cardiometabolic disease (FCMD), cardiometabolic multimorbidity (CMM), and death. METHODS: A total of 86,169 participants who were CMD-free were included from the Kailuan cohort and categorized into four groups by quartiles of BMI, waist to hip ratio (WHR), weight-adjusted waist index, and waist to height ratio. We defined FCMD as the first onset of diabetes, stroke, or myocardial infarction and CMM as co-occurrence of at least two CMDs. Multistate models were used to estimate hazard ratios and 95% CI. RESULTS: A total of 18,461 participants developed FCMD, of whom 1476 progressed to CMM, and 10,009 died during follow-ups. Both general and central adiposity indices increased the risk of transition from baseline to FCMD and from FCMD to CMM. However, compared with the first quartile, the hazard ratio (95% CI) of the fourth quartile of BMI was 0.86 (95% CI: 0.80-0.91) for transition from health to death and 0.66 (95% CI: 0.59-0.74) from FCMD to death, whereas the corresponding estimates of WHR were 1.22 (95% CI: 1.14-1.31) and 1.16 (95% CI: 1.02-1.32), respectively. CONCLUSIONS: Central adiposity indices such as WHR were associated with an increased risk of CMD and mortality, showing no evidence for the obesity paradox and thereby supporting a shift of public focus from BMI only to both general obesity and adiposity distribution.