Risk Factors

Studies investigating risk factors for intracranial atherosclerosis (ICAS) have been infrequent. However, due to recent availability of non-invasive vascular imaging techniques that can assess intracranial cerebral arteries, there are a growing number of studies on risk factors for ICAS. Conventional vascular risk factors such as hypertension, diabetes, hypercholesterolemia and cigarette smoking are risk factors for ICAS. However, it remains uncertain whether there is a difference in risk factors between ICAS and extracranial atherosclerosis (ECAS). It also remains unclear why ICAS is more common in Asians and Blacks than in Caucasians. Although we reviewed available evidences on these differences, the review was limited because studies were heterogeneous in the definition of risk factors, diagnostic method, and characteristics of study subjects (hospitalized vs. community) or cerebral vessels (symptomatic vs. asymptomatic). Nevertheless, it seems that hypercholesterolemia is more closely associated with ECAS than ICAS. The difference in hypercholesterolemia prevalence is one of the main reasons for racial differences in the location of cerebral atherosclerosis. Intracranial arteries contain higher antioxidant level than extracranial arteries and may be more vulnerable to risk factors that deplete antioxidants (e.g., metabolic syndrome and diabetes mellitus). Intracranial arteries may be more vulnerable to factors associated with hemodynamic stress (e.g., advanced, salt-retaining hypertension and arterial tortuosity) because of a smaller diameter, thinner media and adventitia, and fewer elastic medial fibers than extracranial arteries. Additionally, non-atherosclerotic arterial diseases (e.g., moyamoya disease) that commonly occur in the intracranial arteries of East Asians may contaminate the reports of ICAS cases. Various genes, including RNF 213, might also explain racial differences in atherosclerotic location. Prospective, well-designed risk factor and genetic studies should be performed in a homogeneous group of patients with diverse ethnicities. These efforts are essential in the prevention of atherosclerotic diseases based on adequate knowledge of the risk factors and pathogenesis

Supplementary Material for: Is Atrial Fibrillation Always a Culprit of Stroke in Patients with Atrial Fibrillation plus Stroke?

<b><i>Background:</i></b> Some ischemic strokes in patients with atrial fibrillation (AF) are caused by noncardioembolic etiologies (AF-unrelated stroke), but not AF itself (AF-related stroke). However, most clinical trials on the risk of stroke in AF have not distinguished between these. We investigated the frequency and features of AF-unrelated versus AF-related strokes in patients with AF plus ischemic stroke. We hypothesized that certain clinical factors, including chronicity of AF, treatment at the time of stroke onset and echocardiographic findings, may help to discriminate between AF-related and AF-unrelated strokes. The mechanisms and antithrombotic medications at the time of stroke recurrence in the two groups were also examined. <b><i>Methods:</i></b> Consecutive patients with ischemic stroke within 7 days of symptom onset and with AF were included. Patients were classified according to the previously published criteria. Clinical factors including CHADS₂ and CHA₂DS₂-VASc scores and transthoracic echocardiographic (TTE) findings were evaluated. <b><i>Results:</i></b> Of 522 patients, 424 (81.2%) were grouped as AF-related stroke and the remaining 90 (17.2%) were classified as AF-unrelated stroke. Among the patients with AF-unrelated stroke, 51 (9.8%) were categorized as possible large artery atherosclerosis and 38 (7.3%) as possible small artery occlusion; 1 patient (0.2%) was assigned to miscellaneous cause. The AF-related and AF-unrelated strokes had similar CHADS₂ and CHA₂DS₂-VASc scores. However, compared to AF-unrelated stroke, AF-related stroke was independently associated with female sex (odds ratio, OR, 2.19; 95% confidence interval, CI, 1.18-4.05), sustained AF (OR, 2.09; 95% CI, 1.21-3.59), inadequate anticoagulation at stroke onset (OR, 3.21; 95% CI, 1.33-7.75) and left ventricular dysfunction on TTE (OR, 2.84; 95% CI, 1.40-5.74). We identified 26 patients who experienced 2 strokes during the study period. The initial stroke subtype was a strong predictor of the recurrent stroke mechanism (p < 0.001). Among 17 events of AF-related recurrent stroke in these subpopulation, only 2 strokes (11.8%) occurred in a setting of adequate anticoagulation, whereas 4 out of 9 patients (44.4%) who had AF-unrelated strokes at recurrence were sufficiently anticoagulated at the time of admission (p = 0.138). <b><i>Conclusion:</i></b> AF is not always a culprit of stroke in patients with AF plus ischemic stroke; approximately one sixth of these cases are unrelated to AF and have distinct characteristics compared to AF-related stroke. There are significant differences in terms of some clinical and TTE parameters between AF-related and AF-unrelated stroke. Future studies are warranted to optimize strategies for risk stratification, treatment and prevention of stroke in these patients

Supplementary Material for: Free Fatty Acid Is Associated with Thrombogenicity in Cardioembolic Stroke

<i>Background:</i> Recently, the role of free fatty acids (FFAs) in thromboembolism has re-emerged in the context of cardioembolic stroke. Therefore, we attempted to determine the role of FFAs in embolic risk in various potential sources of cardioembolism (PSCE). We hypothesized that if elevated FFA levels in stroke patients are associated with thrombogenesis, then patients with a well-known high risk of embolic sources would have high FFA levels. <i>Methods:</i> Data collected from 2 hospital-based stroke registries were analyzed to investigate the association between FFA and PSCE. <i>Results:</i> A total of 2,770 acute stroke patients, including 539 with cardioembolic stroke, were selected for analysis. FFA was an independent predictor for cardioembolism (OR 2.755, 95% CI 2.221-3.417, <i>p</i> < 0.001). Among the PSCE, FFA levels were significantly associated with high risk of atrial fibrillation (AF), valvular heart disease, congestive heart failure with low ejection fraction, left atrial thrombus, left ventricular thrombus, left atrial smoke, and ventricular wall motion abnormality. FFA levels increased with the number of PSCE per patient without interaction with the presence of AF. <i>Conclusions:</i> Among acute stroke patients, FFA levels increased in groups with higher risk of cardioembolic stroke irrespective of the presence of AF. These results suggest that enhanced thrombogenicity could be the main mechanism to explain the elevated FFA levels in patients with cardioembolic stroke

The effect of intensive statin therapy in non-symptomatic intracranial arteries: The STAMINA-MRI sub-study

Background and aims: Pleiotropic effects of statins result in the stabilization of symptomatic intracranial arterial plaque. However, little is known about the effect of statins in non-symptomatic cerebral arteries. We hypothesized that intensive statin therapy could produce a change in the non-symptomatic cerebral arteries. Methods: This is a sub-study of a prospective observational study under the title of “Intensive Statin Treatment in Acute Ischemic Stroke Patients with Intracranial Atherosclerosis: a High-Resolution Magnetic Resonance Imaging (HR-MRI) study.” Patients with statin-naive acute ischemic stroke who had symptomatic intracranial artery stenosis (above 50%) were recruited for this study. HR-MRI was performed to assess the patients’ cerebral arterial status before and 6 months after the statin therapy. To demonstrate the effect of statins in the non-symptomatic segment of intracranial cerebral arteries, we excluded symptomatic segments from the data to be analyzed. We compared the morphological changes using cerebrovascular morphometry. Results: A total of 54 patients (mean age: 62.9 ± 14.4 years, 59.3% women) were included in this study. Intensive statin therapy produced significant morphological changes of overall cerebral arteries. Among the morphological features, the arterial luminal area showed the highest number of significant changes with a range from 5.7 and 6.7%. Systolic blood pressure (SBP) was an independent factor associated with relative changes in posterior circulation bed maximal diameter percentage change (beta −0.21, 95% confidence interval −0.36 to −0.07, p = 0.005). Conclusion: Intensive statin therapy produced a favorable morphological change in cerebral arteries of not only the target arterial segment but also non-symptomatic arterial segments. The change in cerebral arterial luminal diameter was influenced by the baseline SBP and was dependent on the topographic distribution of the cerebral arteries. Clinical Trial Registration: ClinicalTrials.gov, identifier NCT02458755. Copyright © 2023 Sim, Song, Choi, Lee, Baek, Cho, Kim, Chung, Kim, Park, Bang and Seo.11Nsciescopu

Association of statin pretreatment with collateral circulation and final infarct volume in acute ischemic stroke patients: A meta-analysis

Background and aims: Statin pretreatment (SP) is associated with improved outcomes in acute ischemic stroke (AIS) patients. Collateral circulation status and final infarct volume (FIV) are independent predictors of functional outcome in AIS. Methods: We sought to evaluate the association of SP with collateral circulation and FIV in AIS patients. We used a random-effects model for all the analyses, and pooled standardized mean differences (SMDs) and odds ratios (OR) on the FIV and collateral status according to SP history, respectively. Results: We identified 9 eligible studies (1186 AIS patients). History of SP was associated with lower FIV (SMD = 0.25, 95%CI: 0.07–0.42, p = 0.005) compared to negative history of SP. A trend towards good collateral scores was observed in the SP group (OR = 1.45; 95% CI, 0.92–2.29, p = 0.11). Subgroup analysis demonstrated reduced FIV among atherosclerotic stroke patients with history of SP (SMD = 0.49; 95% CI, 0.19–0.80, p = 0.001). Conclusions: SP appears to be associated with decreased FIV, especially in atherosclerotic AIS. © 2019 Elsevier B.V

Supplementary Material for: Determinants of Basal Collaterals in Moyamoya Disease: Clinical and Genetic Factors

<b><i>Background/Aims:</i></b> To enable the diagnosis of moyamoya disease (MMD), detection of distal internal carotid artery stenosis and hazy network of basal collaterals (BCs) are required. This study aimed at evaluating the factors that could determine the degree of BCs in patients with angiographically confirmed MMD. <b><i>Methods:</i></b> We analyzed 146 consecutive patients with MMD (age 26.2 ± 19.6, range 1-75). The degree of BCs (%) was measured based on conventional angiography. Factors associated with the degree of BCs, including clinico-radiological and genetic factors (p.Arg4810Lys variant), were analyzed. <b><i>Results:</i></b> The degree of BCs varied among MMD patients and significantly decreased with an increase in the age of diagnosis of MMD (coefficient -1.55; p < 0.001). Although the degree of BC development depends on the MMD stage (Suzuki stage), it is less prominent in adult-onset (>18 years) MMD compared to childhood MMD. The presence of p.Arg4810Lys variant, types of MMD (bilateral vs. unilateral) and stroke (ischemic, hemorrhagic, or asymptomatic), shrinkage (outer diameter) of intracranial vessels, external carotid collateral status, and cortical neovascularization were not associated with the degree of BCs. <b><i>Conclusion:</i></b> Although prominent BCs are required for diagnosis of MMD, BCs are decreased with aging, suggesting that angiogenic capacity is altered in adult onset MMD compared to childhood MMD