Abstract

Background: Atrial fibrillation (AF) is a major substrate for ischemic stroke, but cerebrovascular risk is heterogeneous and influenced by AF phenotype, comorbidities, anticoagulant exposure, renal function, and metabolic risk. The triglyceride–glucose index (TyG index) is a simple surrogate marker of insulin resistance calculated from fasting triglycerides and fasting plasma glucose. Whether the TyG index is associated with ischemic stroke burden and recurrent cerebrovascular events in patients with different AF phenotypes remains insufficiently characterized. Objective: This study aimed to evaluate the association between the TyG index and ischemic stroke burden in patients with paroxysmal and permanent AF, with particular focus on recurrent ischemic stroke. Methods: We performed a retrospective observational analysis of patients with AF divided according to AF phenotype: paroxysmal AF and permanent AF. Clinical, biological, therapeutic, and cerebrovascular variables were extracted from an existing real-world clinical database. The TyG index was calculated as ln [fasting triglycerides (mg/dL) × fasting plasma glucose (mg/dL)/2]. Triglycerides and fasting plasma glucose were measured during hospitalization; therefore, the analysis was framed as a retrospective cross-sectional association with recorded ischemic stroke burden, not as a prospective prediction study. The main outcome was any ischemic stroke. Secondary outcomes included recurrent ischemic stroke, defined as ≥2 recorded ischemic stroke events, and stroke burden categorized as no stroke, single stroke, or recurrent stroke. Continuous variables were reported as mean ± standard deviation and compared using independent samples t-tests or one-way analysis of variance, as appropriate. Results: After patient-level de-duplication, 1031 unique patients with AF were identified: 310 with paroxysmal AF and 721 with permanent AF. The strict TyG-eligible analytical cohort included 941 patients: 295 with paroxysmal AF and 646 with permanent AF. Permanent AF was associated with a higher ischemic stroke burden than paroxysmal AF. Any ischemic stroke was recorded in 325/646 patients with permanent AF compared with 79/295 patients with paroxysmal AF (50.3% vs. 26.8%, p < 0.001). Recurrent ischemic stroke was also more frequent in permanent AF (7.7% vs. 4.1%, p = 0.035). Among stroke-positive patients, the proportion with recurrent stroke was similar between permanent and paroxysmal AF (15.4% vs. 15.2%, p = 0.966). The TyG index was significantly higher in paroxysmal AF than in permanent AF (8.93 ± 0.69 vs. 8.73 ± 0.61, p < 0.001), but it did not differ significantly across stroke burden categories. In logistic regression, the TyG index was not associated with any ischemic stroke or recurrent ischemic stroke in unadjusted, age/sex-adjusted, AF phenotype-adjusted, or clinically adjusted models. Conclusions: In this real-world retrospective cohort, permanent AF was associated with a substantially higher ischemic stroke burden than paroxysmal AF. However, the TyG index was not independently associated with ischemic stroke occurrence or recurrence. Although patients with paroxysmal AF had a more adverse lipid metabolic profile and higher TyG index values, this did not translate into a higher TyG-related cerebrovascular burden. These findings suggest that the TyG index alone has limited utility as a marker of ischemic stroke burden in heterogeneous AF cohorts and that its prognostic value may depend on cardiometabolic phenotype, adiposity distribution, AF substrate, anticoagulant exposure, and the clinical context in which it is applied.

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