Sex Differences in Perihematomal Edema Volume and Outcome After Intracerebral Hemorrhage.

BACKGROUND: Although larger hematoma volume is associated with worse outcome after intracerebral hemorrhage (ICH), the association between perihematomal edema (PHE) volume and outcome remains uncertain, as does the impact of sex on PHE and outcome. Here we aimed to determine whether larger PHE volume is associated with worse outcome and whether PHE volume trajectories differ by sex. METHODS: We conducted a post hoc analysis of the Factor VIIa for Acute Hemorrhagic Stroke Treatment (FAST) trial, which randomized patients with ICH to receive recombinant activated factor VIIa or placebo. Computerized planimetry calculated PHE and ICH volumes on serial computed tomography (CT) scans (at baseline [within 3 h of onset], at 24 h, and at 72 h). Generalized estimating equations examined interactions between sex, CT time points, and FAST treatment arm on PHE and ICH volumes. Mixed and multivariable logistic models examined associations between sex, PHE, and outcomes. RESULTS: A total of 781 patients with supratentorial ICH (mean age 65 years) were included. Compared to women (n = 296), men (n = 485) had similar median ICH (14.9 vs. 13.6 mL, p = 0.053) and PHE volumes (11.1 vs. 10.5 mL, p = 0.56) at baseline but larger ICH and PHE volumes at 24 h (19.0 vs. 14.0 mL, p < 0.001; 22.2 vs. 15.7 mL, p < 0.001) and 72 h (16.0 vs. 11.8 mL, p < 0.001; 28.7 vs. 19.9 mL, p < 0.001). Men had higher absolute early PHE expansion (p < 0.001) and more hematoma expansion (growth ≥ 33% or 6 mL at 24 h, 33% vs. 22%, p < 0.001). An interaction between sex and CT time points on PHE volume (p < 0.001), but not on ICH volume, confirmed a steeper PHE trajectory in men. PHE expansion (per 5 mL, odds radio 1.19, 95% confidence interval 1.10-1.28), but not sex, was associated with poor outcome. CONCLUSIONS: Early PHE expansion and trajectory in men were significantly higher. PHE expansion was associated with poor outcomes independent of sex. Mechanisms leading to sex differences in PHE trajectories merit further investigation.

Sex differences in perihematomal edema volume and outcome after intracerebral hemorrhage.

Objective: To determine whether in patients with intracerebral hemorrhage (ICH) perihematomal edema (PHE) volume trajectories differ by sex. Methods: We conducted a post-hoc analysis of the Factor-VII-for-Acute-Hemorrhagic-Stroke-Treatment (FAST) trial that randomized patients with ICH to receive recombinant activated Factor VIIa or placebo. Computerized planimetry calculated PHE and ICH volumes on serial CT scans (at baseline [within 3 hours of onset], at 24, and at 72 hours). Generalized estimating equations examined interactions between sex, CT-timepoints, and FAST treatment-arm on PHE and ICH volumes. Mixed and multivariate logistic models examined associations between sex, PHE, and outcomes. Results: 781 with supratentorial ICH (mean age 65 years) were included. Compared to women (n=296), men (n=485) had similar median ICH (14.9 versus 13.6 ml, p=0.053), and PHE volumes (11.1 versus 10.5 ml, p=0.56) at baseline but larger ICH and PHE at 24 hours (19.0 versus 14.0, p<0.001; 22.2 versus 15.7, p<0.001) and 72 hours (16.0 versus 11.8, p<0.001; 28.7 versus 19.9, p<0.001). Men had higher absolute PHE expansion (p<0.001), and more hematoma expansion (growth ≥33% or 6 mL at 24 hours, 33% versus 22%, p<0.001). An interaction between sex and CT-timepoints on PHE (p<0.001) but not on ICH volumes confirmed a steeper PHE trajectory in men. PHE expansion (per 5mL, odds radio, 1.19, 95%-confidence interval 1.10-1.28), but not sex, was associated with poor outcome. Conclusions: PHE expansion and trajectory in men were significantly higher. PHE expansion was associated with poor outcomes independent of sex. Mechanisms leading to sex differences in PHE trajectories merit further investigation. What is already known on this topic: Prior research has reported sex differences in intracerebral hemorrhage (ICH) characteristics and some studies suggest worse outcome after ICH in women. However, we do not have a good understanding whether there are sex differences in perihematomal edema (PHE) volume trajectories, or whether sex, independent of confounders, is associated with poor after ICH. What this study adds: In this post-hoc analysis of 781 patients with supratentorial ICH from the Factor-VII-for-Acute-Hemorrhagic-Stroke-Treatment (FAST) trial in which patients underwent brain CT imaging time-locked to symptom onset (within 3 hours of symptom onset, at 24 hours, and at 72 hours), men compared to women had similar ICH and PHE volumes at baseline, but larger ICH expansion and PHE expansion on follow up imaging. The PHE but not the ICH volume trajectory across scans was significantly higher in men than in women. While PHE expansion was associated with poor outcome at 90 days, outcome between the sexes was similar at 90 days, and sex was not associated with outcome. How this study might affect research practice or policy: The finding of heightened early PHE and ICH expansion in men may inform study design, patient recruitment strategies, and pre-specification of subgroup analyses in future interventional trials. The findings of this study also suggest that focusing on sex-specific factors may allow novel mechanistic insight into PHE, a major cause of secondary injury and poor outcome after ICH.

Treatment and Outcomes of Patients With Ischemic Stroke During COVID-19: An Analysis From Get With The Guidelines-Stroke.

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Acute Ischemic Stroke in Patients With COVID-19: An Analysis From Get With The Guidelines-Stroke.

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Timing of Initiation of Oral Anticoagulation after Acute Ischemic Stroke in Patients with Atrial Fibrillation.

Patients with atrial fibrillation (AF) who suffer an acute ischemic stroke are at risk for both hemorrhagic transformation and recurrent ischemic stroke in the acute post-stroke period. Oral anticoagulants are recommended for secondary stroke prevention in patients with AF. The optimal time to initiate anticoagulant therapy after acute ischemic stroke in patients with AF is uncertain. There is concern that early initiation increases the risk of hemorrhagic transformation, whereas delayed initiation leaves the patient at risk for recurrent ischemic stroke. In this article, we provide a review of the risk of hemorrhagic transformation of acute ischemic stroke as well as review the literature and major guidelines addressing the timing of anticoagulation initiation after an acute ischemic stroke in patients with AF. Relevant articles published from 1990 to the present were identified using the PubMed and Embase databases. The majority of available literature is observational data. Large ischemic lesions, cerebral microbleeds, thrombolytic therapy, and other clinical factors may increase the risk of hemorrhagic transformation of an acute ischemic stroke. Parenteral anticoagulation within 48 hours is associated with an increased risk of hemorrhagic transformation and is not recommended. Insufficient data exist to support the safety of routine oral anticoagulant (direct oral anticoagulants or warfarin) initiation within 48 hours of an acute ischemic stroke. Direct oral anticoagulant initiation within 2 days of an acute ischemic stroke is associated with a 5% rate of hemorrhagic transformation. Infarct size and presence of hemorrhage are important factors in identifying the optimal time to initiation and should guide decisions when available. A recommended framework for patient decision making is provided. Randomized controlled trials in this area are needed to identify the optimal timing of anticoagulation initiation, and such trials are under way.

D-dimer, magnetic resonance imaging diffusion-weighted imaging, and ABCD2 score for transient ischemic attack risk stratification.

BACKGROUND: We sought to determine whether measurement of D-dimer (DD) would improve risk stratification after transient ischemic attack (TIA). METHODS: We enrolled 167 patients with acute TIA in a prospective observational study. DD was measured using rapid enzyme-linked immunosorbent assay. The primary outcome measure was a composite end point consisting of stroke or death within 90 days or the identification of a high-risk stroke mechanism requiring specific early intervention (defined as > or =50% stenosis in a vessel referable to symptoms or a cardioembolic source warranting anticoagulation). RESULTS: The composite end point occurred in 41 patients (25%). A 50% or greater stenosis was found in 25 patients (15%), a cardioembolic source in 14 (8%), and clinical events in 8 (5 strokes, 3 deaths), 6 of whom also had a high-risk cause of TIA. ABCD(2) score was associated with outcome (P for trend = .017, c-statistic 0.63). DD levels did not differ based on outcome status (geometric mean 0.75 v 0.82 microg fibrinogen equivalent unit/mL, P = .56), and DD had little use for predicting outcome (c-statistic 0.57), even when combined with ABCD(2) score. Of 96 patients with early magnetic resonance imaging (MRI), 23% had diffusion-weighted imaging (DWI) abnormalities, and MRI DWI was predictive of outcome (c-statistic 0.76). The addition of MRI DWI to ABCD(2) improved predictive accuracy (c-statistic 0.83) compared with either alone. CONCLUSIONS: Many patients with TIA have a high-risk mechanism (large vessel stenosis or cardioembolism) or will experience stroke/death within 90 days. Increasing ABCD(2) scores were associated with this composite end point. Measurement of DD did not provide additional prognostic information.

Lipoprotein-associated phospholipase A2 and C-reactive protein for risk-stratification of patients with TIA.

BACKGROUND AND PURPOSE: Lipoprotein-associated phospholipase A(2) (Lp-PLA(2)) is a marker of unstable atherosclerotic plaque, and is predictive of both primary and secondary stroke in population-based studies. METHODS: We conducted a prospective study of patients with acute TIA who presented to the ED. Clinical risk scoring using the ABCD(2) score was determined and Lp-PLA(2) mass (LpPLA(2)-M) and activity (LpPLA(2)-A) and high-sensitivity C-reactive protein (CRP) were measured. The primary outcome measure was a composite end point consisting of stroke or death within 90 days or identification of a high-risk stroke mechanism requiring specific early intervention (defined as >or=50% stenosis in a vessel referable to symptoms or a cardioembolic source warranting anticoagulation). RESULTS: The composite outcome end point occurred in 41/167 (25%) patients. LpPLA(2)-M levels were higher in end point-positive compared to -negative patients (mean, 192+/-48 ng/mL versus 175+/-44 ng/mL, P=0.04). LpPLA(2)-A levels showed similar results (geometric mean, 132 nmol/min/mL, 95% CI 119 to 146 versus 114 nmol/min/mL, 95% CI 108 to 121, P=0.01). There was no relationship between CRP and outcome (P=0.82). Subgroup analysis showed that both LpPLA(2)-M (P=0.04) and LpPLA(2)-A (P=0.06) but not CRP (P=0.36) were elevated in patients with >50% stenosis. In multivariate analysis using cut-off points defined by the top quartile of each marker, predictors of outcome included LpPLA(2)-A (OR 3.75, 95% CI 1.58 to 8.86, P=0.003) and ABCD(2) score (OR 1.30 per point, 95% CI 0.97 to 1.75, P=0.08). CONCLUSIONS: Many patients with TIA have a high-risk mechanism (large vessel stenosis or cardioembolism) or will experience stroke/death within 90 days. In contrast to CRP, both Lp-PLA(2) mass and activity were associated with this composite end point, and LpPLA(2)-A appears to provide additional prognostic information beyond the ABCD(2) clinical risk score alone.

Is the ABCD score useful for risk stratification of patients with acute transient ischemic attack?

BACKGROUND AND PURPOSE: A 6-point scoring system (ABCD) was described recently for stratifying risk after transient ischemic attack (TIA). This score incorporates age (A), blood pressure (B), clinical features (C), and duration (D) of TIA. A score <4 reportedly indicates minimal short-term stroke risk. We evaluated this scoring system in an independent population. METHODS: This was a prospective study of TIA patients (diagnosed by a neurologist using the classic <24-hour definition) hospitalized <48 hours from symptom onset. The primary outcome assessment consisted of dichotomization of patients into 2 groups. The high-risk group included patients with stroke or death within 90 days, > or =50% stenosis in a relevant artery, or a cardioembolic source warranting anticoagulation. All others were classified as low risk. Findings on diffusion-weighted MRI (DWI) were also evaluated when performed and patients classified as DWI+ or DWI-. RESULTS: Over 3 years, 117 patients were enrolled. Median time from symptom onset to enrollment was 25.2 hours (interquartile range 19.8 to 30.2). Overall, 26 patients (22%) were classified as high risk, including 2 strokes, 2 deaths, 15 with > or =50% stenosis, and 10 with cardioembolic source. The frequency of high-risk patients increased with ABCD score (0 to 1 13%; 2 8%; 3 17%; 4 27%; 5 26%; 6 30%; P for trend=0.11). ABCD scores in the 2 patients with stroke were 3 and 6. Of those who underwent MRI, 15 of 61 (25%) were DWI+, but this correlated poorly with ABCD score (0 to 1 17%; 2 10%; 3 36%; 4 24%; 5 13%; 6 60%; P for trend=0.24). CONCLUSIONS: Although the ABCD score has some predictive value, patients with a score <4 still have a substantial probability of having a high-risk cause of cerebral ischemia or radiographic evidence of acute infarction despite transient symptoms.