Elevated LPS is largely driven by time since symptom onset in acute ischemic stroke: the impact on clinical outcomes.

ABSTRACT

BACKGROUND: Gut dysbiosis leading to increased intestinal barrier permeability and translocation of lipopolysaccharide (LPS) in the circulation has been demonstrated in patients with acute myocardial infarction and pulmonary embolism. OBJECTIVES: We investigated changes in circulating LPS concentrations in acute ischemic stroke (AIS) and their consequences, including prognosis. PATIENTS/METHODS: We studied 98 AIS patients, aged 74±12 years, including 74 (75.5%) thrombolysed individuals. We determined serum LPS and zonulin, a marker of gut permeability, along with protein carbonylation (PC), fibrin clot properties, and thrombin generation on admission, at 24 hours and 3 months. Stroke severity was assessed using the NIH Stroke Scale (NIHSS). Stroke functional outcome using modified Rankin Scale (mRS) and stroke-related mortality were evaluated at 3 months. RESULTS: Serum LPS and zonulin on admission were associated with time since symptom onset (r=0.57, p<0.0001 and r=0.40, p<0.0001). Baseline LPS correlated with PC (r=0.51, p<0.0001) but not with coagulation and fibrinolysis markers. LPS levels increased at 24 hours in thrombolysed patients (p<0.001) and correlated with the NIHSS score (r=0.31, p=0.002) and PC (r=0.32, p=0.0057). Both LPS and zonulin levels measured at 24 hours increased the odds of having unfavorable mRS (OR=1.22, 95%CI, 1.04-1.42 and 2.36, 95%CI, 1.24-4.49 per unit). Elevated LPS, but not zonulin, was associated with stroke-related mortality (OR=1.26, 95%CI, 1.02-1.55 per unit). CONCLUSIONS: In AIS patients intestinal permeability is mainly driven by increasing time since the symptom onset. Our findings suggest that LPS with a trend toward its further rise following thrombolysis adversely affect neurological functional outcomes and 3-month mortality.