Prediabetes Increases Risk for Stroke in Individuals With Nonvalvular Atrial Fibrillation

Brain in stroke. Magnetic resonance imaging (MRI) scan of an axial section through the brain of an 80-year-old male patient following a stroke. A stroke, or cerebrovascular accident (CVA), is the rapid loss of brain function due to a disturbance in the blood supply to the brain. An ischaemic stroke is caused by a reduction in the blood supply to an area of the brain.
Study authors evaluated whether prediabetes was associated with increased risk of stroke and death in patients with nonvalvular atrial fibrillation.

Prediabetes is associated with an increased risk for stroke in patients with nonvalvular atrial fibrillation (NVAF), according to the results of a study published in the Journal of the American College of Cardiology.

Although research has established diabetes as a risk factor for the development of atrial fibrillation (AF) and ischemic stroke, the association of prediabetes with an increased risk for ischemic stroke in the context of NVAF has not yet been determined.

To evaluate this, investigators analyzed data from 44,451 individuals (52.5% women). The median age of included individuals was 75 (interquartile range, 65-83) years. The researchers included individuals aged 25 years of age or older, with a new diagnosis of NVAF, no diagnosis of valvular disease, and no previous diagnosis of AF. They followed patients until December 31, 2017 (1-7 years after diagnosis) to assess the incidence of ischemic stroke.

The investigators established prediabetes as having:

· 2 fasting blood glucose (FBG) values of 100 mg/dL or greater within 6 months of each other, or

· 2 glycated hemoglobin (HbA1c) tests 5.7% or higher, or

· A combination of 1 FBG 100 mg/dL or higher and 1 HbA1c test 5.7% or higher, both at least 2 years prior to being diagnosed with AF.

They did not include transient ischemic attack data in ischemic stroke data.

After adjusting for various demographic covariates and comorbidities, individuals with prediabetes had a hazard ratio for stroke of 1.19 (95% CI, 1.01-1.4) compared with normoglycemic individuals. After adjusting for comorbidities, individuals with prediabetes were at similar risk for mortality compared with normoglycemic individuals.

The results of this study demonstrated that individuals with prediabetes have a 19% increased risk for stroke compared with normoglycemic individuals. This association was significant despite controlling for known risk factors as well as anticoagulation use. Researchers found a graded relationship between glycemic levels and risk for stroke, with individuals with prediabetes having greater risk than normoglycemic individuals but less risk than individuals with diabetes. These findings may be used to improve predictions for thromboembolic events in NVAF.

Limitations to this study include the higher incidence of comorbidities in the prediabetes group compared with the normoglycemic group, although multivariate analyses adjusted for these variables. Additional limitations include its observational and nonrandomized nature, which is inherent in studies of such a large scale.

Future research confirming these findings, evaluating potential differences between types of AF, and including time-sensitive analyses for the diagnosis of prediabetes and diabetes throughout the follow-up period is warranted.


Kezerle L, Tsadok MA, Akriv A, et al. Pre-diabetes increases stroke risk in patients with nonvalvular atrial fibrillation. J Am Coll Cardiol. 2021;77:875-884. doi:10.1016/j.jacc.2020.12.030