Risk and protective factors for stroke and transient ischaemic attack in patients with atrial fibrillation: an umbrella review of meta-analyses.

Background: Atrial fibrillation (AF) is linked to significant morbidity and mortality, with ischaemic stroke being a leading cause of death. Identifying modifiable risk and protective factors may help reduce stroke incidence in patients with AF.

Methods: This umbrella review evaluated meta-analyses of observational studies and randomised controlled trials (RCTs) to assess the association of protective and risk factors with stroke and transient ischaemic attack (TIA) in patients with AF. Observational associations were graded with the Ioannidis framework. Associations from RCTs and non-randomised baseline factors in meta-analyses of RCTs were assessed with GRADE (Grading of Recommendations Assessment, Development and Evaluation). Composite risk scores were summarised separately as risk-stratification tools.

Results: 35 studies were included, comprising 23 meta-analyses of observational studies, reporting on 45 associations and 22 meta-analyses of RCTs on 24 associations based on data from over 7 276 000 participants. Among observational studies, only high levels of N-terminal pro-brain Natriuretic Peptide (NT-proBNP) provided convincing evidence of stroke risk. Previous stroke/TIA and age (65-74 years) were also associated with stroke, supported by a highly suggestive level of evidence. Among meta-analyses of non-randomised factors, female sex, kidney failure, non-paroxysmal AF and type 2 diabetes mellitus were risk factors with moderate to high evidence. However, other well-established risk factors, such as hypertension and vascular disease, were associated with stroke; however, they were supported with a weak level of evidence.

Conclusions: Despite stroke being the most severe complication of AF, this umbrella review reveals that few risk factors are supported by high-level evidence. Our findings confirm that elevated NT-proBNP, age and prior stroke are credible stroke risk factors in patients with AF. However, risk factors with weaker evidence, such as hypertension and vascular disease, require further investigation to clarify their actual impact.PROSPERO registration numberCRD42023471263.