Partitioning risk factors for embolic stroke of undetermined source using exploratory factor analysis

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Partitioning risk factors for embolic stroke of undetermined source using exploratory factor analysis

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Jon D Perkins, Naveed Akhtar, Rajvir Singh, ...

First Published April 26, 2021 Research Article Find in PubMed 

https://doi.org/10.1177/17474930211009847

Article information

Abstract

Background

Embolic stroke of undetermined source (ESUS) accounts for up to 25% of strokes. Understanding risk factors associated with ESUS is important in reducing stroke burden worldwide. However, ESUS patients are younger and present with fewer traditional risk factors. Significant global variation in ESUS populations also exists making the clinical picture of this type of stroke unclear.

Methods and results

ESUS patients were pair matched for age, sex, and ethnicity with a group of all other strokes (both n = 331). Exploratory factor analysis was applied in both groups to 14 risk and clinical factors to identify latent factors. In ESUS patients, two latent factors emerged consisting primarily of heart-related variables such as left ventricular wall motion abnormalities, reduced ejection fraction, and increased left atrial volume index, as well as aortic arch atherosclerosis. This is in comparison to the all other strokes group, which was dominated by traditional stroke risk factors.

Conclusions

Our findings support the existence of a unique pattern of risk factors specific to ESUS. We show that LVWMA and corresponding changes in left heart function are a potential source of emboli in these patients. In addition, the clustering of aortic arch atherosclerosis with left heart factors suggests a causal link. Through the application of exploratory factor analysis, this work contributes to a further understanding of stroke mechanisms in ESUS.

Keywords Stroke, ESUS, exploratory factor analysis, cardiac dysfunction, risk model

Introduction

Since its formal characterization,¹ embolic stroke of undetermined source (ESUS) has generated much interest. Several risk factors have been associated with an ESUS diagnosis, such as aortic arch atherosclerosis,² hypertension,³ and left ventricular wall motion abnormalities (LVWMA).⁴ However, the clinical picture of ESUS remains unclear with covert atrial fibrillation the most widely speculated upon cause.^5,6

One of the difficulties in identifying risk profiles for ESUS patients is the consistent finding that they are younger and carry fewer traditional risk factors than other forms of stroke diagnosis.⁷ Another difficulty is the global variation in ESUS populations, likely stemming from genetic and culturally determined factors.^8,9 In addition, the majority of work on this topic uses multivariate statistics to show how risk factors differ from other forms of stroke diagnoses (or normal populations) but not how they manifest in ESUS only populations.

To address these issues, this study applies exploratory factor analysis to investigate the interactions between risk factors for ESUS while controlling for age, sex, and ethnicity. Exploratory factor analysis assesses underlying interactions between variables and specifies latent factors.¹⁰ Latent (meaning “hidden”) variables are unobserved but identified through shared features of observed variables. The usefulness of understanding risk factor interactions in this way is highlighted by metabolic syndrome, whereby vascular risk and metabolic abnormalities combine to confer increased cerebro- and cardiovascular hazard.¹¹ To our knowledge, no studies have explored similar clustering of risk factors in ESUS patients and this work is the first to do so.