Identification and management of polyvascular disease in patients with noncardioembolic ischaemic stroke

Recent registry results have shown that polyvascular disease (PolyVD), usually manifested as coronary heart disease or peripheral arterial disease (PAD), is a marker of increased morbidity and mortality in patients with noncardioembolic ischaemic stroke, but is often inadequately assessed. This Personal View Paper advocates routine examination for PolyVD in such patients. Peripheral arterial disease can be readily detected in routine practice by measurement of the ankle-brachial index. This paper makes recommendations for risk stratification, discharge documentation and, where possible, management of ischaemic stroke patients with PolyVD

Carotid plaque and intima-media thickness and the incidence of ischemic events in patients with atherosclerotic vascular disease

We aimed to evaluate whether carotid intima-media thickness (CIMT) or the presence of plaque can confer additional predictive value of future cardiovascular (CV) ischemic events in patients with pre-existing atherosclerotic vascular disease. We identified 2317 patients enrolled in the REduction of Atherothrombosis for Continued Health (REACH) registry who had atherosclerotic vascular disease and baseline CIMT measurements. The entire range of CIMT was divided into quartiles and the fourth quartile (? 1.5 mm) was defined as carotid plaque. Mean ± standard deviation baseline CIMT was 1.31 ± 0.65 mm. Associated CV ischemic events and vascular-related hospitalizations were evaluated over a 2-year follow-up. There was a positive increase in adjusted hazard ratios (HRs) for all-cause mortality (p = 0.04 for trend) and the quadruple endpoint (CV death, myocardial infarction (MI), stroke, hospitalization for CV events) with increasing quartiles of CIMT (p = 0.0008 for trend), which was mainly driven by the fourth quartile (carotid plaque). HRs for all-cause mortality, CV death, CV death/MI/stroke and the quadruple endpoint comparing the highest (carotid plaque) with the lowest CIMT quartile were 2.09 (95% CI, 1.07-4.10; p = 0.03); 2.49 (1.10-5.67; p = 0.03); 1.71 (1.10-2.67; p = 0.02); and 1.73 (1.31-2.27; p = 0.0001). In conclusion, our analyses suggest that the presence of carotid plaque, rather than the thickness of intima-media, appears to be associated with increased risk of CV morbidity and mortality, but confirmation of these findings in other population and prospective studies is required

Randomized, Placebo-Controlled, Dose-Ranging Clinical Trial of Intravenous Microplasmin in Patients With Acute Ischemic Stroke

Background and Purpose-Microplasmin is a recombinant truncated form of human plasmin. It has demonstrated efficacy in experimental animal models of stroke and tolerability in healthy volunteers. We tested the tolerability of microplasmin in patients with acute ischemic stroke. Methods-In a multicenter, double-blind, randomized, placebo-controlled Phase II trial, 40 patients with ischemic stroke were treated with either placebo or active drug between 3 and 12 hours after symptom onset in a dose-finding design. Ten patients received placebo, 6 patients received a total dose of 2 mg/kg, 12 patients received a total dose of 3 mg/kg, and 12 patients received a total dose of 4 mg/kg. We studied the pharmacodynamics of microplasmin and its effect on the clinical and hemodynamic parameters of the patients. MRI was used as a surrogate marker and matrix metalloproteinases serum concentrations were used as markers of neurovascular integrity. The study was underpowered to detect clinical efficacy. Results-Microplasmin induced reversible effects on markers of systemic thrombolysis and neutralized alpha(2)-antiplasmin by up to 80%. It was well tolerated with one of 30 treated patients developing a fatal symptomatic intracerebral hemorrhage. No significant effect on reperfusion rate or on clinical outcome was observed. Matrix metalloproteinase-2 levels were reduced in microplasmin-treated patients. Conclusions-Microplasmin was well tolerated and achieved neutralization of alpha(2)-antiplasmin. Further studies are warranted to determine whether microplasmin is an effective therapeutic agent for ischemic stroke. (Stroke. 2009; 40: 3789-3795.

Cardiological evaluation after cerebral ischaemia

The cardiological evaluation of patients with cerebral ischaemia is of great clinical importance because diseases of the heart and aorta represent important sources of embolism, because ischaemic stroke is an index event that can lead to the diagnosis of cardiovascular diseases and because the mortality and morbidity of stroke patients are determined by concomitant cardiac diseases. Despite the importance of cardiological examinations for patients with ischaemic strokes, the topic is only addressed by few prospective clinical studies. Therefore, this interdisciplinary consensus document was developed to summarise the available information and to make expert recommendations for the evaluation of cardiovascular risk markers, electrocardiographic examinations, echocardiography and the indications for further investigations of a cardiac disease

Evaluation of Fibroblasts Adhesion and Proliferation on Alginate-Gelatin Crosslinked Hydrogel

<div><p>Due to the relatively poor cell-material interaction of alginate hydrogel, alginate-gelatin crosslinked (ADA-GEL) hydrogel was synthesized through covalent crosslinking of alginate di-aldehyde (ADA) with gelatin that supported cell attachment, spreading and proliferation. This study highlights the evaluation of the physico-chemical properties of synthesized ADA-GEL hydrogels of different compositions compared to alginate in the form of films. Moreover, <i>in vitro</i> cell-material interaction on ADA-GEL hydrogels of different compositions compared to alginate was investigated by using normal human dermal fibroblasts. Viability, attachment, spreading and proliferation of fibroblasts were significantly increased on ADA-GEL hydrogels compared to alginate. Moreover, <i>in vitro</i> cytocompatibility of ADA-GEL hydrogels was found to be increased with increasing gelatin content. These findings indicate that ADA-GEL hydrogel is a promising material for the biomedical applications in tissue-engineering and regeneration.</p></div

Ischemic Benefit and Hemorrhage Risk of Ticagrelor-Aspirin Versus Aspirin in Patients With Acute Ischemic Stroke or Transient Ischemic Attack

Background and Purpose: In patients with acute mild-moderate ischemic stroke or high-risk transient ischemic attack, the THALES trial (Acute Stroke or Transient Ischemic Attack Treated With Ticagrelor and Aspirin for Prevention of Stroke and Death) demonstrated that when added to aspirin, ticagrelor reduced stroke or death but increased risk of severe hemorrhage compared with placebo. The primary efficacy outcome of THALES included hemorrhagic stroke and death, events also counted in the primary safety outcome. We sought to disentangle risk and benefit, assess their relative impact, and attempt to identify subgroups with disproportionate risk or benefit. Methods: In a randomized, placebo-controlled, double-blind trial of patients with mild-to-moderate acute noncardioembolic ischemic stroke or high-risk transient ischemic attack, patients were randomized within 24 hours after symptom onset to a 30-day regimen of either ticagrelor plus aspirin or matching placebo plus aspirin. For the present analyses, we defined the efficacy outcome, major ischemic events, as the composite of ischemic stroke or nonhemorrhagic death, and defined the safety outcome, major hemorrhage, as intracranial hemorrhage or hemorrhagic death. Net clinical impact was defined as the combination of these 2 end points. Results: In 11 016 patients (5523 ticagrelor-aspirin and 5493 aspirin), a major ischemic event occurred in 294 patients (5.3%) in the ticagrelor-aspirin group and in 359 patients (6.5%) in the aspirin group (absolute risk reduction 1.19% [95% CI, 0.31%-2.07%]). Major hemorrhage occurred in 22 patients (0.4%) in the ticagrelor-aspirin group and 6 patients (0.1%) in the aspirin group (absolute risk increase 0.29% [95% CI, 0.10%-0.48%]). Net clinical impact favored ticagrelor-aspirin (absolute risk reduction 0.97% [95% CI, 0.08%-1.87%]). Findings were similar when different thresholds for disability were applied and over a range of predefined subgroups. Conclusions: In patients with mild-moderate ischemic stroke or high-risk transient ischemic attack, ischemic benefits of 30-day treatment with ticagrelor-aspirin outweigh risks of hemorrhage. REGISTRATION: URL: https://www.clinicaltrials.gov; Unique identifier: NCT03354429