Hemoglobin glycation index and the dynamic progression of cardiometabolic multimorbidity and mortality: a multi-state Markov analysis

Cardiometabolic multimorbidity (CMM) develops through the accumulation of cardiometabolic conditions but is often analyzed as a single endpoint. The hemoglobin glycation index (HGI) reflects interindividual variation in HbA1c relative to that predicted by fasting glucose, but its role in stage-specific CMM progression remains unclear. This prospective cohort study included 8,075 middle-aged and older adults from the China Health and Retirement Longitudinal Study with baseline HGI, covariates, and follow-up data from 2011 to 2018. HGI was calculated as observed HbA1c minus fasting plasma glucose–predicted HbA1c. Four states were defined: no cardiometabolic disease (NCMD), single cardiometabolic disease (SCMD), CMM (at least two of diabetes, heart disease, and stroke), and death. Continuous-time multistate Markov models estimated transition intensity ratios (TIRs) for six transitions. Each 1-SD increase in HGI was associated with higher transition intensities from NCMD to SCMD (TIR, 1.215; 95% CI 1.150–1.283), NCMD to CMM (1.596; 1.273–2.001), and SCMD to CMM (1.094; 1.019–1.174). HGI showed an association with the CMM-to-death transition in the primary analysis. Associations with NCMD-to-SCMD and SCMD-to-CMM were generally consistent across sensitivity analyses, and associations with cardiometabolic disease accumulation persisted after additional adjustment for fasting plasma glucose. Higher HGI was associated with stage-specific cardiometabolic disease progression, with the most consistent associations observed for cardiometabolic disease accumulation.