Associations of glycemic status with dynamic disease trajectories of atrial fibrillation and dementia

BACKGROUND: Atrial fibrillation (AF) has been associated with elevated dementia risk, while few studies have examined the role of the optimal glycemic status in disease trajectories of AF and dementia. OBJECTIVES: We aim to evaluate associations between glycemic status with disease trajectories of AF and dementia, as well as major dementia subtypes, including Alzheimer's disease and vascular dementia. DESIGN: Population-based cohort study. SETTING: UK Biobank. PARTICIPANTS: A total of 458 368 participants who were free of prevalent dementia and AF at baseline, with complete glycemic status assessment. MEASUREMENTS: Based on clinical recommendations, we categorized glycemic status as low-normal (glycated hemoglobin [HbA1c] <5.5 %), normal (HbA1c 5.5 to 5.9 %), pre-diabetes (HbA1c 6.0 to 6.4 %), diabetes with HbA1c<7 %, and diabetes with HbA1c≥7 %. Outcomes including AF, dementia (all-cause and sub-type dementia), and death were ascertained via linkage to external registry databases. A multi-state survival analysis was conducted to evaluate disease trajectories of AF and dementia. RESULTS: Better glycemic status was consistently associated with decreased hazards of trajectories of AF and dementia, including progression from AF to the comorbidity of AF and dementia. Among people with diabetes, those with HbA1c<7 % had a 31 % lower hazard (hazard ratio [HR], 0.69; 95 % confidence intervals [CI], 0.51-0.93) of progression from incident AF to dementia comorbidity, compared to those with HbA1c≥7 %. Similar risk reductions were found in individuals with pre-diabetes, normal HbA1c, and low-normal HbA1c, respectively. Strong dose-response associations were observed, with each 1 % increment in HbA1c related to a 28 % higher hazard of progression from AF to dementia comorbidity (HR,1.28; 95 % CI, 1.19-1.37). The glycemic status was most relevant for associations with disease trajectories of AF and vascular dementia, compared to trajectories of AF and Alzheimer's disease. CONCLUSIONS: The better glycemic status was consistently associated with lower hazards of disease trajectories of AF and dementia, including the reduced risk of progression from incident AF to comorbidity of AF and dementia. These findings support the significance of reaching optimal glycemic status to alleviate the huge disease burden of both AF and dementia simultaneously.