Intravenous tissue plasminogen activator (tPA) remains the cornerstone of recanalization therapy for acute ischemic stroke (AIS), albeit with varying degrees of response. The triglyceride-glucose (TyG) index is a novel marker of insulin resistance, but association with outcomes among AIS patients who have received tPA has not been well elucidated. We studied 698 patients with AIS who received tPA from 2006 to 2018 in a comprehensive stroke centre. TyG index was calculated using the formula: ln[fasting triglycerides (mg/dL) × fasting glucose (mg/dL)/2]. TyG index was significantly lower in patients that survived at 90-days than those who died (8.61 [Interquartile Range: 8.27–8.99] vs 8.76 [interquartile range: 8.39–9.40], p = 0.007). In multivariate analysis, TyG index was significantly associated with 90-day mortality (OR: 2.12, 95% CI: 1.39–3.23, p = 0.001), poor functional outcome (OR: 1.41 95% CI: 1.05–1.90, p = 0.022), and negatively associated with early neurological improvement (ENI) (OR: 0.68, 95% CI: 0.52–0.89, p = 0.004). There was no association between TyG index and symptomatic intracranial hemorrhage. ‘High TyG’ (defined by TyG index ≥ 9.15) was associated with mortality, poor functional outcomes and no ENI. In conclusion, the TyG index, a measure of insulin resistance, was significantly associated with poorer clinical outcomes in AIS patients who received tPA.

Contradicting evidence exists regarding the role of lipids in outcomes following intravenous (IV) thrombolysis with tissue plasminogen activator (tPA). Restricted cubic spline curves and adjusted logistic regression were used to evaluate associations of low-density lipoprotein cholesterol (LDL-C), non-high-density lipoprotein cholesterol (non-HDL-C), total cholesterol (TC), high-density lipoprotein cholesterol (HDL-C) and LDL-C/HDL-C ratio with poor functional outcome, symptomatic intracranial hemorrhage (SICH) and 90-day mortality, among 1004 acute ischemic stroke (AIS) patients who received IV tPA in a comprehensive stroke center. Quartile (Q) 1, Q2 and Q3 of HDL-C were associated with increased odds of poor functional outcome (adjusted odds ratio (adjOR) 1.66, 95% CI 1.06–2.60, p = 0.028, adjOR 1.63, 95% CI 1.05–2.53, p = 0.027, adjOR 1.56, 95% CI 1.01–2.44, p = 0.048) compared to Q4. Q2 and Q4 of non-HDL-C were associated with increased odds of SICH (adjOR 4.28, 95% CI 1.36–18.90, p = 0.025, adjOR 5.17, 95% CI 1.64–22.81, p = 0.011) compared to Q3. Q1 and Q2 of LDL-C was associated with increased odds of mortality (adjOR 2.57, 95% CI 1.27–5.57, p = 0.011 and adjOR 2.28, 95% CI 1.10–5.02, p = 0.032) compared to Q3. In AIS patients who received IV tPA, low LDL-C was associated with increased odds of mortality while HDL-C may be protective against poor functional outcome.

The Fibrosis (FIB)-4 index is an established non-invasive test to detect liver fibrosis. Liver fibrosis is postulated to be one of the predictors of the risk of symptomatic Intracranial Haemorrhage (SICH) after intravenous tissue plasminogen activator (IV tPA) therapy, the mainstay of treatment following acute ischemic stroke (AIS). However, SICH is a feared complication of thrombolytic therapy. We aimed to evaluate the association of FIB-4 with outcomes of AIS after IV tPA. Consecutive AIS patients receiving IV tPA from 2006 to 2018 at a single stroke centre were studied in a retrospective cohort study. Multivariable adjusted logistic regression was performed to assess associations of FIB-4 with outcomes. The primary outcome was SICH, and secondary outcomes included functional independence (mRS of 0–2) and mortality measured at 90 days. Among 887 patients (median age: 67 (IQR: 57–77)), 342 had FIB-4 < 1.3 and 161 had FIB-4 > 2.67. A greater proportion of moderate to severe strokes (NIHSS ≥10) occurred in the FIB-4 > 2.67 group (n = 142, 88.8%) compared to the FIB-4 < 1.3 group (n = 208, 61.2%). Amongst the different stroke subtypes, median FIB-4 was highest in cardioembolic stroke (CES) compared to the 3 other non-CES stroke subtypes (1.90 (IQR: 1.41–2.69)). Following IV tPA, having FIB-4 > 2.67 was associated with an increased rate of SICH (adjusted OR: 4.09, 95% CI: 1.04–16.16, p = 0.045) and increased mortality (adjusted OR 3.05, 95% CI: 1.28–7.26, p = 0.012). Advanced liver fibrosis was associated with an increased rate of SICH and increased 90-day mortality after IV tPA. The FIB-4 score may be useful for prognostication after IV tPA.

Background: Contradicting evidence exists regarding the role of lipids in intravenous (IV) thrombolysis with tissue plasminogen activator (tPA), with some studies suggesting low lipid levels are paradoxically associated with poorer post-thrombolysis outcomes. Methods: Restricted cubic spline regression, multivariable-adjusted logistic regression and risk score models evaluated associations of five lipid parameters with poor functional outcome (90-day modified Rankin Scale >2), symptomatic intracranial hemorrhage (SICH), and mortality among 1004 acute ischemic stroke (AIS) patients who received IV tPA in a comprehensive stroke center. Results: There was a U-shaped relationship of low-density lipoprotein cholesterol (LDL-C) and non-high-density lipoprotein cholesterol (non-HDL-C) with all three outcomes using spline regression. Quartile (Q) 2 and Q4 of non-HDL-C were associated with increased odds of SICH (OR 4.2, 95% CI 1.2-15.0, p=0.026 and OR 5.1, 95% CI 1.4-18.2, p=0.011) compared to Q3. Similar quartile associations were found for total cholesterol (TC), and for LDL-C/HDL-C ratio with poor functional outcome. Q1 and Q2 of HDL-C were associated with increased odds of poor functional outcome (OR 1.6, 95% CI 1.0-2.5, p=0.043 and OR 1.6, 95% CI 1.0-2.4, p=0.042) compared to Q4. Only Q3 of LDL-C/HDL-C ratio was associated with increased odds of large-artery atherosclerotic stroke (OR 1.9, 95% CI 1.0-3.7, p=0.039) compared to Q1. Conclusion: In AIS patients who received IV tPA, a U-shaped relationship was found between non-HDL-C and SICH. Low LDL-C was associated with increased odds of mortality, while HDL-C may be protective against poor functional outcome.

Introduction: It could be theorised that liver fibrosis and acute ischemic stroke (AIS) are related by inflammatory changes, but few studied this link, let alone in patients receiving intravenous thrombolysis (IVT). The Fibrosis (FIB)-4 index is an established rapid score to detect liver fibrosis. We aimed to understand the role of FIB-4 in predicting AIS subtype, severity and outcomes after IVT. Methods: AIS patients receiving IVT without severe liver derangement from 2006 to 2018 at a stroke centre were studied. Stroke subtype was defined using Trial of Org 10172 in Acute Stroke Treatment. Moderate and severe stroke was defined as National Institutes of Health Stroke Scale (NIHSS) ≥10. FIB-4 index was stratified into no advanced fibrosis (FIB-4 <1.45) and advanced fibrosis (FIB-4 >3.25). The primary outcome - functional outcome at 90-days using the modified Rankin Scale (mRS) - was analysed by ordinal shift analysis. Multivariable adjusted logistic regression evaluated associations of FIB-4 with stroke severity, functional independence (90-day mRS 0-2 vs 3-6), 90-day mortality, and symptomatic intracranial hemorrhage (SICH). Results: Among 900 patients, higher median FIB-4 was seen in cardioembolic stroke (CES) than non-CES (1.93 [IQR: 1.39-2.81] vs 1.27 [IQR: 0.92-1.90], p<0.001). On multivariate analysis, higher FIB-4 predicted moderate and severe stroke (OR: 1.33, 95% CI: 1.08-1.68, p=0.012). On ordinal shift analysis, advanced fibrosis was associated with an unfavourable shift in 90-day mRS compared to no advanced fibrosis (OR: 1.75, 95% CI: 1.06-2.89, p=0.028). Advanced fibrosis was also associated with increased mortality (OR: 3.07, 95% CI: 1.47-6.48, p=0.003) and SICH (OR: 3.65, 95% CI: 1.21-11.17, p=0.022), but not functional independence (OR: 0.80, 95% CI: 0.40-1.55, p=0.512). Conclusion: Liver fibrosis was associated with higher rates of CES, more severe AIS, and poorer outcomes after IVT. This is a novel marker that could prognosticate IVT use in AIS.