Stroke—can it be predicted from the condition of the blood vessels?

Aim of the study: Asymptomatic embolic signals (ES) detected using transcranial Doppler have been reported in patients with potential cerebral embolic sources. They may be useful in risk stratification and in assessing therapies. First, it is essential to show whether they predict stroke risk.

Results: ES are most frequent in large artery disease, less frequent in cardioembolic stroke, and infrequent in lacunar stroke. Data relating ES to future stroke risk were available for acute stroke, large artery disease, and the perioperative period of carotid endarterectomy. For symptomatic carotid stenosis, ES predicted stroke alone (OR, 9.57; 95%CI, 1.54 to 59.38; P=0.02) and stroke/TIA (OR, 6.36; 95% CI, 2.90-13.96; P<0.00001). For asymptomatic carotid stenosis, ES predicted stroke alone (OR, 7.46; 95% CI, 2.24-24.89; P=0.001) and stroke/TIA (OR, 12.00; 95% CI, 2.43-59.34; P=0.002) but with heterogeneity (P=0.004). In acute stroke ES predicted stroke alone (OR, 2.44; 95% CI, 1.17-5.08; P=0.02) and stroke/TIA (OR, 3.71; 95% CI, 1.64-8.38; P=0.002). A high frequency of ES immediately after carotid endarterectomy predicted stroke alone (OR, 24.54; 95% CI, 7.88-76.43; P<0.00001) and stroke/TIA (OR, 32.04; 95% CI, 11.36-90.39; P<0.00001).

Aim of the study: Stroke is a leading cause of morbidity and mortality. Retinal imaging allows non-invasive assessment of the microvasculature. Consequently, retinal imaging is a technology which is garnering increasing attention as a means of assessing cardiovascular health and stroke risk.

Results: Twenty-four studies were included in this systematic review. The available evidence suggests that wider retinal venules, lower fractal dimension, increased arteriolar tortuosity, presence of retinopathy, and presence of retinal emboli are associated with increased likelihood of stroke. There is weaker evidence to suggest that narrower arterioles and the presence of individual retinopathy traits such as microaneurysms and arteriovenous nicking indicate increased stroke risk. Our review identified three models utilizing artificial intelligence algorithms for the analysis of retinal images to predict stroke. Two of these focused on fundus photographs, whilst one also utilized optical coherence tomography (OCT) technology images. The constructed models performed similarly to conventional risk scores but did not significantly exceed their performance. Only two studies identified in this review used OCT imaging, despite the higher dimensionality of this data.

Aim of the study: To review the evidence for an association of white matter hyperintensities with risk of stroke, cognitive decline, dementia, and death.

Results: White matter hyperintensities predict an increased risk of stroke, dementia, and death. Therefore white matter hyperintensities indicate an increased risk of cerebrovascular events when identified as part of diagnostic investigations, and support their use as an intermediate marker in a research setting. Their discovery should prompt detailed screening for risk factors of stroke and dementia.

Aim of the study: Vascular aging is the accumulation of functional and structural changes of vessels throughout life.

Results: Vascular aging manifestations were evaluated non-invasively by carotid ultrasound methods. The main and the validation analysis were conducted on 8360 and 2086 participants in two separate prospective cohorts. We find that arteriosclerosis and atherosclerosis compared to HVA clusters are independent predictors of CVD, and improve risk stratification for stroke among those at intermediate risk. Vascular aging evaluation may help identify those at increased risk of CVD.

Aim of the study: Approximately half of all cerebral infarctions are caused by artery-to-artery emboli from atherosclerotic plaques in the aorta and pre- or intracranial arteries. This review article presents an update on the development of atherosclerotic plaques, and discusses the diagnostic and therapeutic implications of new pathophysiological knowledge of atherosclerosis in relation to cerebral infarction.

Results: Unstable plaques have a thin and vulnerable capsule, inflammatory cells, high fat content and often intra-plaque bleeding. Calcium deposition and organized fibrous tissue have a stabilizing effect. The development of atherosclerosis and biological characteristics of plaques can be explained by known vascular risk factors and genetic disposition. Ultrasound examination of the aorta and pre-cerebral arteries can be used to assess the degree of atherosclerosis and to provide important information regarding patients' risk of cerebrovascular disease. New knowledge regarding the pathophysiology of atherosclerosis can improve prediction of a patient's risk for ischemic stroke. This forms the basis for a better and more individualized prophylactic treatment of cerebrovascular disease.

Aim of the study: Retinal vessels may provide information on cerebral vascular pathology, because they share many features with cerebral vessels. A smaller ratio of the retinal arteriolar-to-venular diameters reportedly predicts the risk of stroke. It is unclear if this is due to arteriolar narrowing or venular dilation. To investigate whether smaller arteriolar or larger venular diameters are related to the risk of stroke and cerebral infarction.

Results: After a mean follow-up of 8.5 years, 411 participants had a stroke, of whom 259 had cerebral infarction. Larger venular diameters were associated with an increased risk of stroke (hazard ratio [HR] adjusted for age and sex per SD increase: 1.12 [95% CI: 1.02 to 1.24]) and cerebral infarction (HR: 1.15 [95% CI: 1.02 to 1.29]). Smaller arteriolar diameters were neither related to the risk of stroke (HR per SD decrease: 1.02 [95% CI: 0.93 to 1.13]) nor to the risk of cerebral infarction (HR: 1.02 [95% CI: 0.90 to 1.15]). After additional adjustment for other cardiovascular risk factors, the results did not change. Larger retinal venular diameters are associated with an increased risk of stroke and cerebral infarction. The role of venules in cerebrovascular disease warrants further exploration.

Aim of the study: Recently, a standardized classification system for carotid atherosclerotic plaques, known as Carotid Plaque-RADS (Reporting and Data System), has been introduced. However, its capacity to improve stroke risk stratification beyond traditional stenosis degree assessment has not been extensively explored. This study aimed to determine the incremental prognostic value of Carotid Plaque-RADS over stenosis degree for stroke risk.

Results: The study enrolled 1,378 subjects. During a follow-up period of 57 ± 25 months, 4.6% of 987 asymptomatic individuals and 16.9% of 391 subjects with stroke history experienced initial and recurrent strokes, respectively. Significant differences in DFS and RFS rates were found between subjects with mild/moderate and severe stenosis (P < 0.001). Significant differences in DFS rates were observed across Carotid Plaque-RADS categories (P < 0.001), with a notable decrease in DFS rates as Carotid Plaque-RADS categories increased from 1 to 4. This trend was similar in subjects with a history of stroke (P < 0.001). For patients with mild/moderate stenosis, significant differences in DFS and RFS rates were found between those with Carotid Plaque-RADS of ≥3 vs <3 (P < 0.001). Correct reclassification was achieved for 3.3% (32 of 979) of asymptomatic individuals and 9.7% (37 of 381) of subjects with a stroke history initially identified with mild/moderate stenosis.