Prestroke Statins Improve Prognosis of Atrial Fibrillation-Associated Stroke through Increasing Suppressor of Cytokine Signaling-3 Levels

Abstract

<b><i>Background:</i></b> Cerebral infarction associated with atrial fibrillation (AF) has relatively higher mortality and morbidity rates than other types of stroke. Statins are being commonly prescribed to patients with stoke. However, the use of statins in AF-related stroke, especially prestroke, has not been well studied. This study aimed to investigate whether the use of prestroke statins could improve clinical outcomes in patients with AF-related acute ischemic stroke (AIS) and its mechanism. <b><i>Methods:</i></b> This prospective study enrolled 453 AF-associated AIS patients from 4 medical centers and divided them into 2 groups based on the statin use before the stroke episode. All patients received comprehensive clinical examinations including 72-h Holter electrocardiogram monitoring and were followed up for 3 months. Plasma suppressor of cytokine signaling-3 (SOCS-3) and matrix metalloproteinase-9 (MMP-9) levels were measured by ELISA on admission and days 3 and 7 after enrollment. The endpoints were death, major disability (modified Rankin Scale score ≥3), and composite outcome (death/major disability) at 3 months after the AIS episode. <b><i>Results:</i></b> Plasma SOCS-3 levels were significantly increased and MMP-9 levels decreased in patients in the prestroke statin group on hospital admission and days 3 and 7 after enrollment (<i>p</i> &#x3c; 0.001). Furthermore, our data suggested that baseline plasma SOCS-3 levels were associated with increased risk of 3-month mortality (adjusted odds ratio [OR], 1.012; 95% confidence interval [CI], 1.006–1.018; <i>p</i> &#x3c; 0.001) and major disability (adjusted OR, 1.013; 95% CI, 1.007–1.02; <i>p</i> &#x3c; 0.001). Similarly, baseline plasma MMP-9 levels were also associated with increased risk of 3-month mortality (adjusted OR, 1.037; 95% CI, 1.022–1.053; <i>p</i> &#x3c; 0.001) and major disability (adjusted OR, 1.038; 95% CI, 1.022–1.55; <i>p</i> &#x3c; 0.001). <b><i>Conclusion:</i></b> Our data suggested that the prestroke use of statins improved the clinical outcomes in AIS patients with AF by upregulating the level of SOCS-3 and reducing the plasma MMP-9 level.