Abstract P576: Plasma Bacterial Lipopolysaccharide Associates With Carotid Atherosclerosis, a Cause of Large Vessel Stroke

Abstract

Introduction: Inflammation and infection are associated with cerebrovascular diseases including stroke due to carotid atherosclerotic plaques. C-reactive protein (CRP), an acute-phase protein, is upregulated in the plasma of patients with carotid atherosclerotic plaques. However, little is known about whether bacterial molecules trigger inflammation or play a role in patients with carotid atherosclerotic plaques. Recently, it has been recognized that inflammation associated with atherosclerosis and morbidity and mortality in cardiovascular diseases may be due to lipopolysaccharide (LPS) that is found in the outer wall of all Gram-negative bacteria. These findings prompted this study to explore whether plasma levels of LPS and LPS-binding protein (LBP) are elevated and correlated with CRP levels in patients with asymptomatic carotid plaques (ACP). We also compared LBP levels in patients with ACP to large vessel (LV) strokes due to carotid plaques and to matched controls. Methods: Patients (n = 30) with ACP, LV stroke due to carotid atherosclerosis and age-, sex- matched healthy controls gave consent and had their blood drawn. Plasma was processed for LPS, LBP and CRP detection using separate ELISA for each. Results: Plasma LBP level in ACP (22.7 ± 2.92 μg/ml) was similar to LV stroke (21.6 ± 1.56 μg/ml, p = 0.74, ACP vs LV) but greater than controls (13.6 ± 1.43 μg/ml, p = 0.011, ACP vs controls). In ACP patients, plasma LPS level (159.5 ± 30.5 μg/ml) was greater than controls (42.6 ± 11.7 μg/ml, p = 0.001); plasma CRP levels (20.2 ± 6.2 μg/ml) was higher than controls (5.3 ± 2.1 μg/ml, p = 0.011). There was a positive correlation between LPS levels and LBP levels (r = 0.86, p < 0.00001), LPS levels and CRP levels (r = 0.82, p = 0.00001), and LBP levels and CRP levels (r = 0.89, p < 0.00001) in ACP cases. Conclusions: Plasma LPS, LBP and CRP associate with asymptomatic carotid plaques suggesting a pro-inflammatory state exists in patients with asymptomatic carotid plaques, a cause of large vessel stroke. LPS is postulated to directly upregulate both CRP and LBP. Elevated LBP in large vessel stroke patients suggests a Gram-negative bacteria associated post-stroke inflammatory state.