Pre-diabetes increases the risk of heart failure among patients with nonvalvular atrial fibrillation

Abstract

Type of funding sources: None. Heart failure (HF) is common in patients with nonvalvular atrial fibrillation (NVAF) which is associated with excess morbidity and mortality. Notably, the presence of diabetes increases risk of HF in patients with NVAF. The association between pre-diabetes and risk of HF was nonetheless unexplored in this population. The present study aimed to evaluate whether pre-diabetes was associated with an increased risk of HF in patients with NVAF. Using a previously validated territory-wide electronic health record database, patients with newly diagnosed NVAF from 2010 to 2018 were included to evaluate for risk of HF upon competing risk regression with Cox proportional-hazard model adjustment. Patients were divided into 3 groups according to their baseline glycemic status: (1) type 2 diabetes, (2) pre-diabetes, and (3) normoglycemia. In the pre-diabetes group, the subsequent risk of HF was further evaluated according to the changes of glycemic status at two years following index date. Among 65,994 NVAF patients (mean age 75.7 years, 48.5% female), 27,706 (42.0%) were normoglycemic, 10,926 (16.6%) had pre-diabetes, and 27,312 (41.4%) had diabetes at baseline. Over a median follow-up of 7.1 years, 7,203 (26%) normoglycemic patients, 3,168 (29%) pre-diabetic patients, and 8,745 (32%) diabetic patients developed HF (Log rank test, P<0.001). Pre-diabetes was associated with an increased risk of HF compared with normoglycemic patients (subdistribution Hazard Ratio (SHR) = 1.09, 95% confidence interval (CI): 1.04-1.14) and diabetes conferred the highest risk amongst three groups (SHR=1.19, 95%CI: 1.15-1.24). In patients with pre-diabetes at baseline, 873 (8.0%) progressed to diabetes and 1204 (11%) resolved to normoglycemia at 2 years. Compared to those who remained pre-diabetic, patients who progressed to diabetes had a higher risk of HF (SHR = 1.23, 95% CI :1.05-1.44), whereas those who resolved to normoglycemia incurred a lower risk (SHR = 0.80, 95% CI :0.68-0.94). Pre-diabetes was independently associated with an increased risk of HF in patients with NVAF. Pre-diabetic patients who progressed to diabetes at 2 years experienced an increased risk of HF, whereas those who resolved to normoglycemia reduced risk of HF, as compared to those who remained pre-diabetic. These findings highlight the importance of strict blood glucose control in reducing the risk of HF in patients with atrial fibrillation.