Overlap of Diseases Underlying Ischemic Stroke

Abstract

Stroke classification is crucial to perform clinical trials, epidemiological studies, phenotyping for genetic studies, and classify patients to evaluate best treatment strategy. Precise analysis of stroke subtypes requires the integration of clinical features, diagnostic test findings, and knowledge about potential etiologic factors. With improvement of noninvasive brain and cardiovascular imaging, as well as biological tests, the amount of available information is fast increasing. Current classifications only consider the most likely cause, neglecting the overlap between diseases.1,2 Therefore, a patient classified in the atherosclerosis group is rigidly analyzed with this group even if there are MRI or clinical evidence of presence of small vessel disease (SVD) deemed to be not causally related with the index stroke. 3 In this example, any genetic analysis with this kind of classification would, therefore, be biased by neglecting the SVD presence. Furthermore, current diagnostic tools often identify several coexisting causes resulting in ≈40% of ischemic strokes classified as undetermined in causative system. 4,5 The ASCO (atherosclerosis, SVD, cardiac pathology, and other uncommon causes) phenotyping assigned a degree of likelihood on potential causality of all 4 main underlying diseases commonly encountered in ischemic stroke patients. 6 Therefore, the purpose of the ASCO phenotyping is not to reduce the rate of undetermined cause as in causative classifications, 7 because there is no undetermined category in ASCO, but to describe the overlap degree between the diseases.We investigated the overlap of underlying vascular diseases of ischemic stroke in the Asymptomatic Myocardial Ischemia Background and Purpose-ASCOD phenotyping (A, atherosclerosis; S, small vessel disease; C, cardiac pathology; O, other causes; and D, dissection) assigns a degree of likelihood to every potential cause (1 for potentially causal, 2 for causality is uncertain, 3 for unlikely causal but disease is present, 0 for absence of disease, and 9 for insufficient workup to rule out the disease) commonly encountered in ischemic stroke. We used ASCOD to investigate the overlap of underlying vascular diseases and their prognostic implication. Methods-A single rater applied ASCOD in 405 patients enrolled in the Asymptomatic Myocardial Ischemia in Stroke and Atherosclerotic Disease study. Results-A was present in 90% of patients (A1=43% and A2=15%), C in 52% (C1=23% and C2=14%), and S in 66% (S1=11% and S2=2%). On the basis of grades 1 and 2, 25% of patients had multiple underlying diseases, and 80% when all 3 grades were considered. The main overlap was found between A and C; among C1 patients, A was present in 92% of cases (A1=28%, A2=20%, and A3=44%). Conversely, among A1 patients, C was present in 47% of cases (C1=15%, C2=15%, and C3=17%). Grades for C were associated with gradual increase in the 3-year risk of vascular events, whereas risks were similar across A grades, meaning that the mere presence of atherosclerotic disease qualifies f...

Phenotypic ASCO Characterisation of Young Patients with Ischemic Stroke in the Prospective Multicentre Observational sifap1 Study

“…A recent study of 405 patients with ischemic stroke assessed using the updated version of ASCO [13] found concomitant aetiologies (grade 1 + 2) in 25% of the study population [21] . This number is higher than in our study, where approximately 10% had at least one concomitant aetiology.…”

Ticagrelor Added to Aspirin in Acute Nonsevere Ischemic Stroke or Transient Ischemic Attack of Atherosclerotic Origin

“…Among patients with ischemic stroke, 40% present with ipsilateral stenosis of the cervicocranial vasculature and have the highest risk of recurrence among ischemic stroke etiologic subtypes. 1 , 2 In the SOCRATES trial (Acute Stroke or Transient Ischemic Attack Treated With Aspirin or Ticagrelor and Patient Outcomes), patients with transient ischemic attack (TIA) or minor ischemic strokes, ticagrelor resulted in a 32% relative risk reduction in recurrent stroke and cardiovascular events compared with aspirin among the subgroup of patients with ipsilateral atherosclerotic stenosis of cervicocranial vasculature. 3 Because the main trial did not meet its primary hypothesis of a superiority of ticagrelor over aspirin, 3 the result in the atherosclerotic subgroup was considered hypothesis generating.…”

Cardiovascular diseases in patients 65 years and younger with non-cardiogenic stroke

“…The coexistence of several potential causes of cerebral ischaemia is observed in 1/4 of patients with stroke [ 41 ]. Most often these are heart diseases, carotid atherosclerosis and/or small vessel disease, and factors related to lifestyle in young patients [ 1 , 41 ]. In the present study, in 1/5 of the patients stroke was attributed to large artery atherosclerosis and small vessel disease.…”