Aortic dimensions and distensibility are key risk factors for aortic aneurysms and dissections, as well as for other cardiovascular and cerebrovascular diseases. We present genome-wide associations ...of ascending and descending aortic distensibility and area derived from cardiac magnetic resonance imaging (MRI) data of up to 32,590 Caucasian individuals in UK Biobank. We identify 102 loci (including 27 novel associations) tagging genes related to cardiovascular development, extracellular matrix production, smooth muscle cell contraction and heritable aortic diseases. Functional analyses highlight four signalling pathways associated with aortic distensibility (TGF-β, IGF, VEGF and PDGF). We identify distinct sex-specific associations with aortic traits. We develop co-expression networks associated with aortic traits and apply phenome-wide Mendelian randomization (MR-PheWAS), generating evidence for a causal role for aortic distensibility in development of aortic aneurysms. Multivariable MR suggests a causal relationship between aortic distensibility and cerebral white matter hyperintensities, mechanistically linking aortic traits and brain small vessel disease.
OBJECTIVETo evaluate whether pretreatment with metformin (MET) is associated with less stroke severity and better outcome after IV thrombolysis (IVT), we analyzed a cohort of 1,919 patients with ...stroke with type 2 diabetes mellitus in a multicenter exploratory analysis.
METHODSData from patients with diabetes and ischemic stroke treated with IVT were collected within the European Thrombolysis in Ischemic Stroke Patients (TRISP) collaboration. We applied propensity score matching (PSM) to obtain balanced baseline characteristics of patients treated with and without MET.
RESULTSOf 1,919 patients with stroke with type 2 diabetes who underwent IVT, 757 (39%) had received MET before stroke (MET+), whereas 1,162 (61%) had not (MET−). MET+ patients were younger with a male preponderance. Hypercholesterolemia and pretreatment with statins, antiplatelets, or antihypertensives were more common in the MET+ group. After PSM, the 2 groups were well balanced with respect to demographic and clinical aspects. Stroke severity on admission (NIH Stroke Scale 10.0 ± 6.7 vs 11.3 ± 6.5), 3-month degree of independence on modified Rankin Scale (2 interquartile range (IQR) 1.0–4.0 vs 3 IQR 1.0–4.0), as well as mortality (12.5% vs 18%) were significantly lower in the MET+ group. The frequency of symptomatic intracerebral hemorrhages did not differ between groups. HbA1c levels were well-balanced between the groups.
CONCLUSIONSPatients with stroke and diabetes on treatment with MET receiving IVT had less severe strokes on admission and a better functional outcome at 3 months. This suggests a protective effect of MET resulting in less severe strokes as well as beneficial thrombolysis outcome.
Intravenous thrombolysis for acute ischemic stroke is usually based on clinical assessment, blood test results, and CT findings. Intravenous thrombolysis of stroke mimics may occur but has not been ...studied in detail.
We determined frequency, clinical characteristics, and outcome of mimic patients versus patients with stroke treated with intravenous thrombolysis using data of a prospective, single-center thrombolysis data bank.
Among 250 patients, 243 (97.2%) had strokes and 7 (2.8%) were mimics. Seizure was the most frequent diagnosis among mimics. There was a trend toward lower National Institutes of Health Stroke Scale scores in mimics (9.9+/-4.2) compared with strokes (13.7+/-5.4; P=0.06). Global aphasia without hemiparesis was the presenting symptom in 3 (42.9%) mimics versus 8 (3.3%) strokes (P=0.002). Orolingual angioedema, symptomatic intracranial hemorrhage, and asymptomatic intracranial hemorrhage occurred in 3 (1.2%), 13 (5.3%), and 30 (12.3%) patients with stroke, but were absent in mimics. After 3 months, 6 (85.7%) mimics and 86 (35.4%) strokes had a modified Rankin Scale score of 0 to 1 (P=0.01).
Only few patients receiving intravenous thrombolysis did eventually have a final diagnosis other than stroke, ie, mostly seizures. Their outcome was favorable. Although clinical features differed between the stroke and the mimic groups, the differences were not distinctive enough to allow assigning individual patients to either of the groups. Multimodal neuroimaging or electroencephalographic recordings may be helpful for this assignment. However, their potential benefit has to be weighed against the potential harm of delayed thrombolysis.
Little is known about the risk factors for cervical artery dissection (CEAD), a major cause of ischemic stroke (IS) in young adults. Hypertension, diabetes mellitus, smoking, hypercholesterolemia, ...and obesity are important risk factors for IS. However, their specific role in CEAD is poorly investigated. Our aim was to compare the prevalence of vascular risk factors in CEAD patients versus referents and patients who suffered an IS of a cause other than CEAD (non-CEAD IS) in the multicenter Cervical Artery Dissection and Ischemic Stroke Patients (CADISP) study.
The study sample comprised 690 CEAD patients (mean age, 44.2 ± 9.9 years; 43.9% women), 556 patients with a non-CEAD IS (44.7 ± 10.5 years; 39.9% women), and 1170 referents (45.9 ± 8.1 years; 44.1% women). We compared the prevalence of hypertension, diabetes mellitus, hypercholesterolemia, smoking, and obesity (body mass index ≥ 30 kg/m²) or overweightness (body mass index ≥ 25 kg/m² and <30 kg/m²) between the 3 groups using a multinomial logistic regression adjusted for country of inclusion, age, and gender. Compared with referents, CEAD patients had a lower prevalence of hypercholesterolemia (odds ratio 0.55; 95% confidence interval, 0.42 to 0.71; P<0.0001), obesity (odds ratio 0.37; 95% confidence interval, 0.26 to 0.52; P<0.0001), and overweightness (odds ratio 0.70; 95% confidence interval, 0.57 to 0.88; P=0.002) but were more frequently hypertensive (odds ratio 1.67; 95% confidence interval, 1.32 to 2.1; P<0.0001). All vascular risk factors were less frequent in CEAD patients compared with young patients with a non-CEAD IS. The latter were more frequently hypertensive, diabetic, and current smokers compared with referents.
These results, from the largest series to date, suggest that hypertension, although less prevalent than in patients with a non-CEAD IS, could be a risk factor of CEAD, whereas hypercholesterolemia, obesity, and overweightness are inversely associated with CEAD.
Ischaemic stroke (IS) in young adults has been increasingly recognized as a serious health condition. Stroke aetiology is different in young adults than in the older population. This study aimed to ...investigate aetiology and risk factors, and to search for predictors of outcome and recurrence in young IS patients. We conducted a prospective multicentre study of consecutive IS patients aged 16–55 years. Baseline demographic data, risk factors, stroke aetiology including systematic genetic screening for Fabry disease and severity were assessed and related to functional neurological outcome (modified Rankin Scale, mRS), case fatality, employment status, place of residence, and recurrent cerebrovascular events at 3 months. In 624 IS patients (60 % men), median age was 46 (IQR 39–51) years and median NIHSS on admission 3 (IQR 1–8). Modifiable vascular risk factors were found in 73 %. Stroke aetiology was mostly cardioembolism (32 %) and of other defined origin (24 %), including cervicocerebral artery dissection (17 %). Fabry disease was diagnosed in 2 patients (0.3 %). Aetiology remained unknown in 20 %. Outcome at 3 months was favourable (mRS 0–1) in 61 % and fatal in 2.9 %. Stroke severity (
p
< 0.001) and diabetes mellitus (
p
= 0.023) predicted unfavourable outcome. Stroke recurrence rate at 3 months was 2.7 %. Previous stroke or TIA predicted recurrent cerebrovascular events (
p
= 0.012). In conclusion, most young adults with IS had modifiable vascular risk factors, emphasizing the importance of prevention strategies. Outcome was unfavourable in more than a third of patients and was associated with initial stroke severity and diabetes mellitus. Previous cerebrovascular events predicted recurrent ones.
The safety and efficacy of thrombolysis in cervical artery dissection (CAD) are controversial. The aim of this meta-analysis was to pool all individual patient data and provide a valid estimate of ...safety and outcome of thrombolysis in CAD.
We performed a systematic literature search on intravenous and intra-arterial thrombolysis in CAD. We calculated the rates of pooled symptomatic intracranial hemorrhage and mortality and indirectly compared them with matched controls from the Safe Implementation of Thrombolysis in Stroke-International Stroke Thrombolysis Register. We applied multivariate regression models to identify predictors of excellent (modified Rankin Scale=0 to 1) and favorable (modified Rankin Scale=0 to 2) outcome.
We obtained individual patient data of 180 patients from 14 retrospective series and 22 case reports. Patients were predominantly female (68%), with a mean±SD age of 46±11 years. Most patients presented with severe stroke (median National Institutes of Health Stroke Scale score=16). Treatment was intravenous thrombolysis in 67% and intra-arterial thrombolysis in 33%. Median follow-up was 3 months. The pooled symptomatic intracranial hemorrhage rate was 3.1% (95% CI, 1.3 to 7.2). Overall mortality was 8.1% (95% CI, 4.9 to 13.2), and 41.0% (95% CI, 31.4 to 51.4) had an excellent outcome. Stroke severity was a strong predictor of outcome. Overlapping confidence intervals of end points indicated no relevant differences with matched controls from the Safe Implementation of Thrombolysis in Stroke-International Stroke Thrombolysis Register.
Safety and outcome of thrombolysis in patients with CAD-related stroke appear similar to those for stroke from all causes. Based on our findings, thrombolysis should not be withheld in patients with CAD.
Introduction: Measures of cerebral small vessel disease (cSVD), such as white matter hyperintensities (WMH) and cerebral microbleeds (CMB), are associated with an unfavorable clinical course in ...stroke patients on oral anticoagulation (OAC) for atrial fibrillation (AF). Here, we investigated whether similar findings can be observed for global cortical atrophy (GCA). Methods: Registry-based prospective observational study of 320 patients treated with OAC following AF stroke. Patients underwent magnetic resonance imaging (MRI) allowing assessment of GCA. Using the simplified visual Pasquier scale, the severity of GCA was categorized as follows: 0: no atrophy, 1: mild atrophy; 2: moderate atrophy, and 3: severe atrophy. Using adjusted logistic and Cox regression analysis, we investigated the association of GCA using a composite outcome measure, comprising: (i) recurrent acute ischemic stroke (IS); (ii) intracranial hemorrhage (ICH); and (iii) death. Results: In our time to event analysis after adjusting for potential confounders (i.e., WMH, CMB, age, sex, diabetes, arterial hypertension, coronary heart disease, hyperlipidemia, and antiplatelet use), GCA was associated with an increased risk for the composite outcome in all three degrees of atrophy (grade 1: aHR 3.95, 95% CI 1.34–11.63, p = 0.013; grade 2: aHR 3.89, 95% CI 1.23–12.30, p = 0.021; grade 3: aHR 4.16, 95% CI 1.17–14.84, p = 0.028). Conclusion: GCA was associated with our composite outcome also after adjusting for other cSVD markers (i.e., CMB, WMH) and age, indicating that GCA may potentially serve as a prognostic marker for stroke patients with atrial fibrillation on oral anticoagulation.
The aim of our study was to assess whether statins have dose-dependent effects on risk of symptomatic intracerebral hemorrhage (sICH) and outcome after intravenous thrombolysis for ischemic stroke.
...We pooled data from 2 European intravenous thrombolysis registries. Statin doses were stratified in 3 groups according to the attainable lowering of cholesterol levels (low dose: simvastatin 20 mg or equivalent; medium dose: simvastatin 40 mg or equivalent; and high dose: simvastatin 80 mg or equivalent). sICH was defined according to the European Cooperative Acute Stroke Study. Modified Rankin Scale score 0 to 2 at 3 months was considered a favorable outcome.
Among 1446 patients analyzed (median age, 75 years; median initial National Institutes of Health Stroke Scale score, 11; 54% men), 317 (22%) used statins before intravenous thrombolysis. Of them, 120 patients had low-dose, 134 medium-dose, and 63 high-dose statin therapy. sICH occurred in 4% of patients (n=53). Frequency of sICH was 2%, 6%, and 13% in patients with low-, medium-, and high-dose statin treatment, respectively (P<0.01). Adjusted odds ratio (OR) for sICH was 2.4 (95% confidence interval CI, 1.1-5.3) and 5.3 (95% CI, 2.3-12.3) for patients with medium- and high-dose statins compared with non-statin users. Statin users more often achieved favorable outcome compared with non-statin users (58% versus 51%; P=0.03). An independent association of statin use with favorable outcome was detected (adjusted OR, 1.8; 95% CI, 1.3-2.5). The association was maintained when stratifying for statin dose, although it was not significant in the high-dose group anymore (OR, 1.7; 95% CI, 0.9-3.2).
We observed an association between increasing dose of statin use and risk of sICH after intravenous thrombolysis. Nevertheless, there was an overall beneficial effect of previous statin use on favorable 3-month outcome.
Uncertainty remains regarding antithrombotic treatment in cervical artery dissection. This analysis aimed to explore whether certain patient profiles influence the effects of different types of ...antithrombotic treatment.
This was a post hoc exploratory analysis based on the per-protocol dataset from TREAT-CAD (NCT02046460), a randomized controlled trial comparing aspirin to anticoagulation in patients with cervical artery dissection. We explored the potential effects of distinct patient profiles on outcomes in participants treated with either aspirin or anticoagulation. Profiles included (1) presenting with ischemia (no/yes), (2) occlusion of the dissected artery (no/yes), (3) early versus delayed treatment start (</>median), and (4) intracranial extension of the dissection (no/yes). Outcomes included clinical (stroke, major hemorrhage, death) and magnetic resonance imaging outcomes (new ischemic or hemorrhagic brain lesions) and were assessed for each subgroup in separate logistic models without adjustment for multiple testing.
All 173 (100%) per-protocol participants were eligible for the analyses. Participants without occlusion had decreased odds of events when treated with anticoagulation (odds ratio OR = 0.28, 95% confidence interval CI = 0.07-0.86). This effect was more pronounced in participants presenting with cerebral ischemia (n = 118; OR = 0.16, 95% CI = 0.04-0.55). In the latter, those with early treatment (OR = 0.26, 95% CI = 0.07-0.85) or without intracranial extension of the dissection (OR = 0.34, 95% CI = 0.11-0.97) had decreased odds of events when treated with anticoagulation.
Anticoagulation might be preferable in patients with cervical artery dissection presenting with ischemia and no occlusion or no intracranial extension of the dissection. These findings need confirmation. ANN NEUROL 2024;95:886-897.
Data on the effectiveness and safety of direct oral anticoagulants (DOACs) versus vitamin K antagonists (VKAs) in patients with stroke attributable to atrial fibrillation (AF) who were dependent on ...the daily help of others at hospital discharge are scarce.
Based on prospectively obtained data from the observational Novel-Oral-Anticoagulants-in-Ischemic-Stroke-Patients-longterm registry from Basel, Switzerland, we compared the occurrence of the primary outcome—the composite of recurrent ischemic stroke, major bleeding, and all-cause death—among consecutive patients with AF-stroke treated with either VKAs or DOACs between patients dependent (defined as modified Rankin Scale score, 3–5) and patients independent at discharge. We used simple, adjusted, and weighted Cox proportional hazards regression to account for potential confounders.
We analyzed 801 patients (median age 80 years, 46% female), of whom 391 (49%) were dependent at discharge and 680 (85%) received DOACs. Over a total follow-up of 1216 patient-years, DOAC- compared to VKA-treated patients had a lower hazard for the composite outcome (hazard ratio HR, 0.58 95% CI, 0.42–0.81), as did independent compared to dependent patients (HR, 0.54 95% CI, 0.40–0.71). There was no evidence that the effect of anticoagulant type (DOAC versus VKA) on the hazard for the composite outcome differed between dependent (HRdependent, 0.68 95% CI, 0.45–1.01) and independent patients (HRindependent, 0.44 95% CI, 0.26–0.75) in the simple model (Pinteraction=0.212). Adjusted (HRdependent, 0.74 95% CI, 0.49–1.11 and HRindependent, 0.51 95% CI, 0.30–0.87; Pinteraction=0.284) and weighted models (HRdependent, 0.79 95% CI, 0.48–1.31 and HRindependent, 0.46 95% CI, 0.26–0.81; Pinteraction=0.163) yielded concordant results. Secondary analyses focusing on the individual components of the composite outcome were consistent to the primary analyses.
The benefits of DOACs in patients with atrial fibrillation with a recent stroke were maintained among patients who were dependent on the help of others at discharge.
URL: https://www.clinicaltrials.gov; Unique identifier: NCT03826927.
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