The association between HbA1c/HDL-C ratio and cardiometabolic multimorbidity among middle-aged and older adults: data from two national prospective cohorts in the United Kingdom and United States.

OBJECTIVE: This study aims to investigate the association between the hemoglobin A1c (HbA1c)/high-density lipoprotein cholesterol (HDL-C) ratio and incident cardiometabolic multimorbidity (CMM) among adults aged 50 years and older.

METHODS: This study analyzed data from wave 2 (2004) to wave 11 (2022) of the English Longitudinal Study of Ageing (ELSA) and wave 8 (2006) to wave 16 (2022) of the Health and Retirement Study (HRS). The independent variables included cumulative HbA1c/HDL-C ratio, its value at first visit, and its trajectory identified by group-based trajectory modeling (GBTM). The association between the HbA1c/HDL-C ratio and the risk of CMM was assessed using Kaplan-Meier curves, multivariable Cox regression analysis, and restricted cubic spline (RCS) models. Its incremental predictive value was also evaluated. Additionally, mediation analyses, subgroup analyses, and sensitivity analyses were further employed.

RESULTS: Among the 5,226 participants included, CMM developed in 303 of 1,918 participants (15.8%) in ELSA and in 283 of 3,308 participants (8.8%) in HRS. After adjusting for confounders, each 1-standard deviation (SD) increase in the cumulative HbA1c/HDL-C ratio and the value at first visit HbA1c/HDL-C ratio was significantly associated with a higher risk of CMM [pooled hazard ratio (HR): 1.33, 95% confidence interval (CI): 1.19-1.47,  < 0.001; pooled HR: 1.24, 95% CI: 1.07-1.43,  = 0.004]. Individuals in the persistently high HbA1c/HDL-C ratio group had a 100% higher risk of developing CMM than those in the persistently low group (pooled HR: 2.00, 95% CI: 1.45-2.74,  < 0.001). Linear associations were identified between the cumulative HbA1c/HDL-C ratio and incident CMM in ELSA and HRS, as well as between the HbA1c/HDL-C ratio and incident CMM at first visit in HRS (all for overall <0.05 and for non-linearity >0.05). The addition of the HbA1c/HDL-C ratio significantly improves the predictive ability of the basic model. The relationship between the trajectory of the HbA1c/HDL-C ratio and incident CMM was partially mediated by BMI in HRS. The results from sensitivity analyses and subgroup analyses aligned with the main findings.

CONCLUSION: Significant linear associations were identified between increases in the HbA1c/HDL-C ratio and the risk of incident CMM among middle-aged and older adults from the United Kingdom (UK) and the United States (US). Persistent monitoring and maintenance of favorable levels of HbA1c/HDL-C ratio may contribute to the early detection and effective prevention of CMM development.