Specific inflammatory profile of acute ischemic stroke patients with left atrial enlargement

Abstract

Background: The inflammatory process underlying atrial myopathy may affect the inflammatory response activated in acute ischemic stroke (AIS).

Objectives: We aimed to assess whether left atrial enlargement (LAE) as a marker of atrial myopathy is associated with a different profile of circulating inflammatory markers in AIS patients.

Methods: HIBISCUS-STROKE is a cohort study including anterior circulation AIS patients treated with mechanical thrombectomy following MRI. Ten circulating inflammatory markers were measured at admission and 6, 24, and 48 h after admission. LAE was defined as a left atrial volume index (LAVi) ≥34 ml/m². A multiple logistic regression model was performed to detect an independent association between the area under the curve (AUC) of these markers and LAE.

Results: We included 143 patients. Of them, 85 (59.4%) had LAE. On univariable analysis, we found that patients with LAE had higher soluble form suppression of tumorigenicity 2 (sST2), soluble tumor necrosis factor receptor I (sTNFR1), and vascular cellular adhesion molecule-1 (VCAM-1) AUC, were older, mostly female, had a higher National Institutes of Health Stroke Scale (NIHSS) score and blood glucose level at admission, had more often hypertension, and a cardioembolic source of AIS, such as atrial fibrillation, while they were less frequently current smokers and had a lower rate of tandem occlusion than patients without LAE. On multivariable analysis, we found that among circulating inflammatory markers, only high VCAM-1 (OR: 9.13, 95% CI: 3.21-25.9) and sST2 (OR: 3.40, 95% CI: 1.68-6.86) AUC remained associated with LAE.

Conclusions: High VCAM-1 and sST2 levels within the first 48 h are associated with LAE in AIS patients.

Keywords: SST2; VCAM-1; inflammatory; ischemic stroke; left atrial enlargement.

Figure 1

Study flowchart.

Figure 2

Proportion of patients with atrial fibrillation (AF) according to the presence of left atrial enlargement (LAE) (Fisher's exact test, ***p < 0.001).

Figure 3

Scatter plot showing levels of circulating inflammatory markers according to the presence of left atrial enlargement (LAE): (A,C) reactive protein (CRP), (B) interleukin-6 (IL-6), (C) interleukin-8 (IL-8), (D) interleukin-10 (IL-10), (E) monocyte chemoattractant protein-1 (MCP-1), (F) soluble P-selectin (sP-selectin), (G) soluble form suppression of tumorigenicity 2 (sST2), (H) soluble tumor necrosis factor receptor I (sTNFR1), (I) vascular cellular adhesion molecule-1 (VCAM-1), (J) matrix metalloproteinase-9 [Whitney test, *p < 0.05, **p < 0.01, ****p < 0.0001, error bar (mean ± standard deviation) in black].

Figure 4

Kinetics of (A) vascular cellular adhesion molecule-1 (VCAM-1), (B) soluble form suppression of tumorigenicity 2 (sST2), and (C) soluble tumor necrosis factor receptor I (sTNFR1) according to the presence of left atrial enlargement (LAE) (Mann–Whitney test, *p < 0.05, **p < 0.01, ***p < 0.001, ****p < 0.0001).

Figure 5

Schematic summarizing the main link between atrial fibrillation, left atrial enlargement, and acute ischemic stroke: known circulating inflammatory markers associated with these conditions and the main results of our study (CRP, C-reactive protein; sICAM-1, soluble intercellular adhesion molecule-1; IL-6, interleukin-6; IL-8, interleukin-8; IL-10, interleukin-10; MMP-9, matrix metalloproteinase-9; MCP-1, monocyte chemoattractant protein-1; S100B, S100 calcium binding protein B; sP-selectin, soluble P-selectin; sST2, soluble form suppression of tumorigenicity 2; sTNFR1, soluble tumor necrosis factor receptor I; TGF-β, transforming growth factor-β; TNF-α, tumor necrosis factor-α; VCAM-1, vascular cellular adhesion molecule-1).