Feasibility and Safety of Drug-Coated Balloon for Treatment of De Novo Coronary Artery Lesions in Large Vessel Disease: A Large-Scale Multicenter Prospective Study.

Background: Drug-coated balloons (DCB) have been evaluated to be safe and practical in treating coronary small vessel disease (SVD). However, evidence about the practicality and safety of DCB in treating coronary lesions with diameters greater than 3.0 mm is limited. Methods: 1166 patients who received DCB angioplasty were enrolled and divided into groups of SVD or large vessel disease (LVD) according to the target vessel diameters ( < 3.0 mm for SVD; ≥ 3.0 mm for LVD). All participants received a 2-year follow-up. The two main outcomes were patient-oriented composite endpoint (patient-oriented composite endpoint (POCE), all-cause mortality, all myocardial infarctions [MI], or any revascularization), and target lesion failure (target lesion failure (TLF), cardiac death, target vessel MI, or ischemia-driven target lesion revascularization). Results: In these patients, a total of 30 (2.6%) TLF and 82 (7.0%) POCE were recorded. Patients in the LVD group showed statistically greater rates of lesion success compared to the SVD group (752 [96.0%] vs. 380 [99.2%], p = 0.004) and procedural success (751 [95.9%] vs. 380 [99.2%], p = 0.003). No significant difference was found in the 2-year risk of TLF (hazard ratio (HR) 1.41, 95% CI 0.58-3.44; p = 0.455), POCE (HR 1.29, 95% CI 0.76-2.20; p = 0.354), MI (HR 0.88, 95% CI 0.24-3.13; p = 0.837), revascularization (HR 1.22, 95% CI 0.68-2.21; p = 0.506), and stroke (HR 0.78, 95% CI 0.03-15.26; p = 0.784) between the SVD and LVD groups. Conclusions: There was no discernible inferiority of the DCB intervention in the LVD group as compared to the SVD group. The DCB intervention is practical for coronary lesions with diameters higher than 3.0 mm.

Clinical Characteristics of Borderzone Infarction in Egyptian Population.

OBJECTIVES: In this research we wanted to highlight the importance of defining Borderzone infarctions (BZI) as a separate subtype in stroke classifications. We thus studied cases of isolated BZI, small vessel disease (SVD), and large vessel disease (LVD), to identify their points of similarities and difference in a sample of Egyptian patients. METHODS: This is a cross-sectional (observational) study. Consecutive 637 acute ischemic stroke patients were recruited over a 2 year period, from 2 stroke units of Ain Shams University hospitals in Egypt. Medical history and laboratory investigations were done to identify risk factors. National Institute of Health Stroke Scale (NIHSS) was performed on admission, and modified Rankin scale (mRS) on admission, and after 3 months. MRI brain was done to identify stroke subtype; MRA and carotid duplex were used to define vascular status. RESULTS: Among the studied group of patients, 72 (11.3%) had BZI, 145 (22.8%) had SVD, 165 (26%) had LVD, and 255 were excluded as they had either undetermined, or mixed etiology. BZI showed significantly older age, early confluent lesions, more disease severity by NIHSS, and worst outcome by mRS (P < 0.05). SVD had more microbleeds than BZI and LVD. LVD showed lower prevalence of hypertension and lower high-density lipoprotein levels. CONCLUSIONS: Isolated BZI, SVD, and LVD infarctions have characteristic risk factors and clinical patterns. Further studies are needed to identify if they are different from cases with mixed pathology. This could have an impact on the selection of primary and secondary preventive measures appropriate to each type.

The many faces of IgG4-related disease: report of a case with inaugural recurrent aortic aneurism ruptures and literature review.

Vascular involvement in IgG4-related disease (IgG4-RD), is a well-recognized feature and large vessel commitment, especially the aorta, can be the only manifestation of the disease. Being a newly recognized disease, its diagnosis and workup still represents a challenge in clinical practice. A 47-year-old-man with two aortic aneurysms ruptures, one at abdominal and the other at thoracic level, was referred to our rheumatology department. The initial analysis of the surgical specimen obtained 3 years earlier revealed a nonspecific aortitis. Re-evaluation of the biopsy with immunohistology now demonstrated the presence of IgG4 deposits. Evidence-based recommendations regarding diagnosis, treatment and follow-up of IgG4-related large-vessel involvement are lacking. In this particular case, histopathology were crucial. The authors review and discuss vascular involvement in IgG4-RD and respective treatment options.

ACE Gene in Egyptian Ischemic Stroke Patients.

BACKGROUND: Angiotensin-1-converting enzyme (ACE) is a crucial player in vascular homeostasis and in the pathogenesis of atherosclerosis and hypertension. The present study was conducted to determine whether there is an association between the ACE insertion/deletion (I/D) polymorphism and ischemic stroke in Egyptian population. Also, we analyzed the ACE gene I/D polymorphism as a risk factor for small-vessel (SV) versus large-vessel (LV) disease. METHODS: Sixty patients with ischemic stroke were included: 30 with SV disease and 30 with LV disease. In addition, a control group of 30 apparent healthy subjects were studied. Clinical assessment, computed tomography, magnetic resonance imaging brain, and genetic study using the polymerase chain reaction of ACE gene were done for all subjects. RESULTS: We found that the distribution of ACE gene polymorphism frequency was significantly different between the 3 groups. The DD genotype was far more common in stroke patients compared to controls. It was also significantly more common in each of the patient groups compared to controls but rather similar in the 2 patient groups with SV and LV diseases. CONCLUSION: We found that the ACE gene deletion/deletion genotype is common in Egyptian patients with non-cardioembolic ischemic stroke but does not appear to be specific neither to SV nor to LV disease.

Drug-coated balloon versus drug-eluting stent for treating de novo large vessel coronary artery disease: a systematic review and meta-analysis of 13 studies involving 2888 patients.

INTRODUCTION: Drug-coated balloon (DCB) is an established treatment option for in-stent restenosis and small vessel, de novo, coronary artery disease (CAD). Although the use of this tool is increasing in everyday practice, data regarding performance in the treatment of de novo, large vessel CAD (LV-CAD) is still lacking. A systematic review and meta-analysis were conducted to evaluate the efficacy and safety of DCB versus drug-eluting stent (DES) in this setting. METHODS: A comprehensive literature search was performed including Medline, Embase, and Cochrane electronic databases up to January 24, 2024, for studies which compared the efficacy and safety of DCB versus DES in the treatment of de novo lesions in large vessels (≥ 2.5 mm), reporting at least one clinical outcome of interest (PROSPERO ID: CRD42023470417). The analyzed outcomes were cardiovascular death (CVD), myocardial infarction (MI), target lesion revascularization (TLR), all-cause death (ACD), and late lumen loss (LLL) at follow-up. The effect size was estimated using a random effects model as risk ratio (RR) and mean difference (MD) and relative 95% confidence interval (CI). RESULTS: A total of 13 studies (6 randomized controlled trials and 7 observational studies) involving 2888 patients (DCB n = 1334; DES n = 1533) with de novo LV-CAD were included in this meta-analysis following our inclusion criteria. No differences were observed between DCB and DES in terms of CVD (RR 0.49; 95% CI [0.23-1.03]; p = 0.06), MI (RR 0.48; 95% CI [0.16-1.45]; p = 0.89), TLR (RR 0.73; 95% CI [0.40-1.34]; p = 0.32), ACD (RR 0.78; 95% CI [0.57-1.07]; p = 0.12), and LLL (MD - 0.14; 95% CI [- 0.30 to 0.02]; p = 0.10) at follow-up. DES proved a higher mean acute gain versus DCB [1.94 (1.73, 2.14) vs 1.31 (1.02, 1.60); p = 0.0006]. CONCLUSION: Our meta-analysis showed that DCB PCI might provide a promising option for the management of selected, de novo LV-CAD compared to DES. However, more focused RCTs are needed to further prove the benefits of a "metal-free" strategy in this subset of CAD.

Linking peripheral atherosclerosis to blood-brain barrier disruption: elucidating its role as a manifestation of cerebral small vessel disease in vascular cognitive impairment.

Aging plays a pivotal role in the pathogenesis of cerebral small vessel disease (CSVD), contributing to the onset and progression of vascular cognitive impairment and dementia (VCID). In older adults, CSVD often leads to significant pathological outcomes, including blood-brain barrier (BBB) disruption, which in turn triggers neuroinflammation and white matter damage. This damage is frequently observed as white matter hyperintensities (WMHs) in neuroimaging studies. There is mounting evidence that older adults with atherosclerotic vascular diseases, such as peripheral artery disease, ischemic heart disease, and carotid artery stenosis, face a heightened risk of developing CSVD and VCID. This review explores the complex relationship between peripheral atherosclerosis, the pathogenesis of CSVD, and BBB disruption. It explores the continuum of vascular aging, emphasizing the shared pathomechanisms that underlie atherosclerosis in large arteries and BBB disruption in the cerebral microcirculation, exacerbating both CSVD and VCID. By reviewing current evidence, this paper discusses the impact of endothelial dysfunction, cellular senescence, inflammation, and oxidative stress on vascular and neurovascular health. This review aims to enhance understanding of these complex interactions and advocate for integrated approaches to manage vascular health, thereby mitigating the risk and progression of CSVD and VCID.

Development and initial validation of the Indian Takayasu Clinical Activity Score (ITAS2010).

OBJECTIVES: There are no valid instruments to measure disease activity in Takayasu arteritis (TA). We aim to provide a valid measure to assess clinical disease activity with or without incorporating acute phase reactants. METHODS: The Indian Takayasu Clinical Activity Score (ITAS) was initially derived from disease manifestations scored in the Disease Extent Index (DEI.Tak). The ITAS was validated by a group of physicians scoring both live and paper cases for inter-rater reliability (IRR), convergence with BVAS, correlation with the Physician's Global Assessment (PGA) and ESR/CRP. It was further validated at a single centre in 177 patients for its ability to discriminate between active and inactive disease state at first visit and sensitivity to change in 132 active patients measured serially at two follow-up visits. ITAS-A also included graded scores for ESR/CRP. RESULTS: The final ITAS2010 contains 44 items with 33 features arising from the cardiovascular system. Seven key items are weighted to score 2 and all others score 1 only. Inter-observer variability was highly satisfactory (IRR 0.97). The ITAS showed superior inter-rater agreement compared with the BVAS (IRR 0.9) and PGA (IRR 0.82). In the single-centre study, median ITAS scores at first visit were significantly higher in active disease (5.62 ± 3.14) compared with grumbling (3.36 ± 1.96) and inactive disease (1.27 ± 1.26, P < 0.0001). The therapy induced a significant decrease in the ITAS2010 but the higher ITAS-A scores remained elevated. CONCLUSION: The ITAS2010, validated in over 300 TA patients and sensitive to change, is a useful measure of clinical disease activity for patient monitoring. Higher ITAS-A scores suggest poor control of active disease by current therapy.

Hyperhomocysteinemia associates with small vessel disease more closely than large vessel disease.

BACKGROUND: Hyperhomocysteinemia was believed to be an independent risk factor for stroke and associate with small vessel disease (SVD) related stroke and large vessel disease (LVD) related stroke differently. However it's still unclear which type of stroke associated with homocysteine (HCY) more strongly because the conclusions of previous studies were contradictory. In this study we focused on the subclinical angiopathies of stroke, i.e., SVD and LVD instead of stroke subtypes and sought to compare the associations between HCY level and different angiopathies. METHODS: 324 non-stroke patients were enrolled. Sex, age, HCY level and other vascular risk factors were collected. MRI and angiographies were used to determine the type of angiopathies and their severity, i.e., the scores of leukoaraiosis (LA), plaques and numbers of silent brain infarctions (SBI). LVD was defined as the presence of atherosclerotic plaques of cerebral arteries. SVD was defined as the presence of either LA or SBI. 230 patients were deemed to have LVD; 180 patients were deemed to have SVD. Spearman's correlation test and logistic regression were used to analyze the association between HCY level and different angiopathies. RESULTS: The correlation between HCY level and scores of plaques was weaker than that of the scores of LA and numbers of SBI. Hyperhomocysteinemia was an independent risk factor for SVD (OR = 1.315, P <0.001), whereas the association between HCY level and LVD was not that significant (OR = 1.058, P = 0.075). CONCLUSION: HCY level associated with SVD more strongly than LVD.

Pathophysiology, cellular and molecular mechanisms of large and small vessel diseases.

Cerebrovascular disease (CVD) is the second most common cause of cognitive impairment and dementia in aged population. CVD presents in a myriad number of clinical ways based on the functional location of pathology. While primary clinical emphasis has been placed on motor, speech and visual deficits, vascular cognitive decline is a vastly under recognized and devastating condition afflicting millions of Americans. CVD, a disease of the blood vessels that supply blood to brain involves an integration between small and large vessels. Cerebral large vessel diseases (LVD) are associated with atherosclerosis, artery-to-artery embolism, intracardiac embolism and a large vessel stroke leading to substantial functional disability. Cerebral small vessel disease (SVD) is critically involved in stroke, brain hemorrhages, cognitive decline and functional loss in elderly patients. An evolving understanding of cellular and molecular mechanisms emphasizes that inflammatory vascular changes contribute to systemic pathologic conditions of the central nervous systems (CNS), with specific clinical presentations including, cognitive decline. Advances in an understanding of pathophysiology of disease processes and therapeutic interventions may help improve outcomes. This review will focus on large and small vessels diseases and their relationship to vascular cognitive decline, atherosclerosis, stroke, and inflammatory neurodegeneration. We will also emphasize the molecular and cellular mechanisms, as well as genetic and epigenetic factors associated with LVD and SVD.

Predictors of Carotid Atherosclerosis Progression: Evidence from an Ultrasonography Laboratory.

BACKGROUND AND PURPOSE: The purpose of this study was to investigate the role of risk factors in predicting the variation in carotid atherosclerosis at ultrasonographic follow-up and, therefore, its role in the progression of large-vessel disease. METHODS: This retrospective population study included all the outpatients that underwent at least two carotid ultrasonographies at our laboratory from 2001 to 2017. Demographic data, vascular risk factors, and the results at follow-up were analysed to determine if correlations exist between these risk factors and variation in carotid atherosclerosis. RESULTS: Data from 600 patients (327 males and 273 females with a mean age of 67 years) were collected. The mean follow-up period was 49 months (range: 1-195). We analysed each demographic variable and risk factor to assess its correlation with a worsening of carotid atherosclerosis; previous myocardial infarction (2.594), previous carotid surgical treatment (2.368), and hypertension (1.85) were found to have the highest odds ratios, respectively. Furthermore, the sample was divided into specific subpopulations (diabetes, hypertension, and smoking), and an association was found between age and worsening stenosis. DISCUSSION AND CONCLUSIONS: Our results confirm the importance of carotid ultrasonographic follow-up in the monitoring and managing of large-vessel disease. Myocardial infarction, previous stroke, and previous surgical treatment were the strongest predictors of a worsening of carotid atherosclerosis. These findings suggest a strict follow-up is needed, even in the absence of significant carotid atherosclerosis at baseline.

Comparative Study of Risk Factors and Cognitive Profile of Small- and Large-Vessel Vascular Dementia - A Clinic Based Study.

Background: Vascular dementia (VaD) is a clinically heterogeneous entity. There is a dearth of studies for comparison of the cognitive profile of cerebral small-vessel disease (SVD) with large-vessel disease. Objective: We planned to evaluate and compare the cognitive profile of SVD and large-vessel VaD and evaluate various risk factors associated with them. Materials and Methods: Patients of VaD were recruited after excluding mixed and ambiguous cases. Patients were classified into SVD and large-vessel VaD and analyzed for their clinic-epidemiological and cognitive profiles. Results: Among 76 patients, 48 (62.5%) have SVD and 28 (37.5%) have large-vessel disease. Hypertension (93.4%) was the commonest risk factor, followed by smoking (34.21%), hyperlipidemia (26.31%), and diabetes mellitus (DM, 22.36%). Hypertension (P < 0.05) and DM were common in SVD, whereas smoking, hyperlipidaemia, and cardiac diseases were common in large-vessel disease. Attention (77.1% vs 25%), executive function (68.8% vs 28.6%), and calculation (58.3% vs 32.1%) were significantly more impaired in SVD compared to large-vessel disease, whereas visuoperceptual (21.4% vs 6.3%), praxis (28.6% vs 4.2%), and gnosis (14.3% vs 2.1%) were significantly more impaired in large-vessel disease than in SVD. Disruption of frontal-subcortical connection was responsible for the cognitive profile in SVD, but in large-vessel disease, it resulted from the cumulative loss of function from different lesions. Conclusions: Despite having common vascular risk factors, few are more common in SVD than in large-vessel disease. The different clinical and cognitive profile is due to the diverse anatomical lesions in these two subclasses of VaD.

Failure of Therapeutic Anticoagulation in COVID-19 Patients With Acute Ischemic Stroke. A Retrospective Multicenter Study.

Background: Acute ischemic stroke (AIS) is a possible complication of coronavirus disease 2019 (COVID-19) infection. Although peculiar clinical features and underlying specific mechanisms of thrombogenesis have been suggested so far, there is no consensus on the appropriate vascular preventive drug regimen in patients with COVID-19. Aim and Methods: From a larger clinical series of consecutive acute ischemic strokes related to COVID-19 admitted to three cerebrovascular units in Northern Italy, herein, we describe the clinical features of a subgroup of patients in whom stroke occurred despite therapeutic anticoagulation. Results: A total of seventeen/80 AIS related to COVID-19 (21.2%) occurred in anticoagulated patients. Although no blood level was available for Direct Oral AntiCoagulant, the drug dosage was appropriate according to guidelines. Their National Institute of Health Stroke Scale (NIHSS) at admission was 12.0 (SD = 7.4) and 58.8% of them had evidence of large vessel occlusion. The case fatality rate was as high as 64.7%. Discussion and Conclusions: The occurrence of an anticoagulation failure seems to be increased in the setting of COVID-19 infection, with worse clinical outcomes if compared to non-COVID-19 related ischemic strokes. We discuss the diagnostic and therapeutic implications of such evidence, suggesting that some arterial thrombotic complications might be either resistant to or independent of the anticoagulation effect.

Is the TOAST Classification Suitable for Use in Personalized Medicine in Ischemic Stroke?

Pathophysiologic classification of ischemic stroke is essential to a personalized approach to stroke treatment. The Trial of Org 101072 in Acute Stroke Treatment (TOAST) classification is the most frequently used tool to classify index ischemic strokes. We aimed to assess presence of small and large vessel disease markers across the TOAST groups. In an observational study, 99 ischemic stroke patients were consecutively included and classified according to TOAST. The assessment was supplemented with cerebral small vessel disease (SVD) score, based on Magnetic Resonance Imaging (MRI), and tests for carotid atherosclerosis, ankle−brachial index (ABI), estimated glomerular filtration rate (eGFR), and peripheral reactive hyperemia index (RHI). Markers of small and large vessel disease were present in all TOAST groups. Carotid stenosis and atrial fibrillation were associated with their respective TOAST groups (p = 0.023 and p < 0.001, respectively). We found no association between the SVD score and the small vessel occlusion TOAST group (p = 0.59), and carotid atherosclerosis (p = 0.35), RHI (p = 0.39), ABI (p = 0.20), and eGFR (p = 0.79) were not associated with TOAST groups. The TOAST classification does not provide differential information on the pathophysiologies of the ischemic stroke. An operational classification that contains quantification of each vascular pathophysiology in the individual patient is pivotal for future research and development of personalized medicine.

Intracranial Atherosclerotic Burden and Cerebral Parenchymal Changes at 7T MRI in Patients With Transient Ischemic Attack or Ischemic Stroke.

The relevance of intracranial vessel wall lesions detected with MRI is not fully established. In this study (trial identification number: NTR2119; www.trialregister.nl), 7T MRI was used to investigate if a higher vessel wall lesion burden is associated with more cerebral parenchymal changes in patients with ischemic stroke or transient ischemic attack (TIA). MR images of 82 patients were assessed for the number of vessel wall lesions of the large intracranial arteries and for cerebral parenchymal changes, including the presence and number of cortical, small subcortical, and deep gray matter infarcts; lacunes of presumed vascular origin; cortical microinfarcts; and periventricular and deep white matter hyperintensities (WMHs). Regression analyses showed that a higher vessel wall lesion burden was associated with the presence of small subcortical infarcts, lacunes of presumed vascular origin, and deep gray matter infarcts (relative risk 1.18; 95% CI, 1.03-1.35) and presence of moderate-to-severe periventricular WMHs (1.21; 95% CI, 1.03-1.42), which are all manifestations of small vessel disease (SVD). The burden of enhancing vessel wall lesions was associated with the number of cortical microinfarcts only (1.48; 95% CI, 1.04-2.11). These results suggest an interrelationship between large vessel wall lesion burden and cerebral parenchymal manifestations often linked to SVD or, alternatively, that vascular changes occur in both large and small intracranial arteries simultaneously.

Symptomatic carotid near-occlusion causes a high risk of recurrent ipsilateral ischemic stroke.

OBJECTIVE: To assess the risk of recurrent ipsilateral ischemic stroke in patients with symptomatic near-occlusion with and without full collapse. METHODS: Included were consecutive patients eligible for revascularization, grouped into symptomatic conventional ≥ 50% carotid stenosis (n = 266), near-occlusion without full collapse (n = 57) and near-occlusion with full collapse (n = 42). The risk of preoperative recurrent ipsilateral ischemic stroke was analyzed, or, for cases not revascularized within 90 days, 90-day risk was analyzed. RESULTS: The risk of a preoperative recurrent ipsilateral ischemic stroke or ipsilateral retinal artery occlusion was 15% (95% CI 9-20%) for conventional ≥ 50% stenosis, 22% (95% CI 6-38%) among near-occlusion without full collapse and 30% (95% CI 16-44%) among near-occlusion with full collapse (p = 0.01, log rank test). In multivariate analysis, near-occlusion with full collapse had a higher risk of recurrent ipsilateral ischemic stroke (adjusted HR 2.6, 95% CI 1.3-5.3) and near-occlusion without full collapse tended to have a higher risk (adjusted HR 2.0, 95% CI 0.9-4.5) than conventional ≥ 50% stenosis. Only 24% of near-occlusion with full collapse underwent revascularization, common causes for abstaining were misdiagnosis as occlusion (31%), deemed surgically unfeasible (21%) and low perceived benefit (10%). CONCLUSIONS: Symptomatic carotid near-occlusion has a high short-term risk of recurrent ipsilateral ischemic stroke, especially near-occlusion with full collapse.

The Prognostic Value of High Platelet Reactivity in Ischemic Stroke Depends on the Etiology: A Pilot Study.

BACKGROUND: Reduced aspirin response may result in a worse prognosis and a poor clinical outcome in ischemic stroke. The aim of this prospective pilot study was to assess the relationship between platelet reactivity and early and late prognosis, and the clinical and functional status in ischemic stroke, with the role of stroke etiology. METHODS: The study involved 69 subjects with ischemic stroke, divided into large and small vessel etiological subgroups. Platelet function testing was performed with two aggregometric methods-impedance and optical-while the clinical condition was assessed using the National Institute of Health Stroke Scale (NIHSS) and the functional status was assessed using the modified Rankin Scale (mRS) on the first and eighth day (early prognosis) and the 90th day of stroke (late prognosis). RESULTS: The initial platelet reactivity was found to be higher in patients with severe neurological deficits on the 90th day after stroke, than in the group with mild neurological deficits (median, respectively, 40 area under the curve (AUC) units vs. 25 AUC units, p = 0.033). In the large vessel disease group, a significant correlation between the platelet reactivity and the functional status on the first day of stroke was found (correlation coefficient (R) = 0.4526; p = 0.0451), the platelet reactivity was higher in the subgroup with a severe clinical condition compared to a mild clinical condition on the first day of stroke (p = 0.0372), and patients resistant to acetylsalicylic acid (aspirin) had a significantly greater possibility of a severe neurological deficit on the first day of stroke compared to those who were sensitive to aspirin (odds ratio (OR) = 14.00, 95% confidence interval (CI) 1.25-156.12, p = 0.0322). CONCLUSION: High on-treatment platelet reactivity in ischemic stroke was associated with a worse late prognosis regardless of the etiology. We demonstrated a significant relationship between high platelet reactivity and worse early prognosis and poor clinical and functional condition in the large vessel etiologic subgroup. However, due to the pilot nature of this study, its results should be interpreted with caution and further validation on a larger cohort is required.

Hypoxia-inducible factor-1α in acute ischemic stroke: neuroprotection for better clinical outcome.

BACKGROUND: Hypoxia-inducible factor-1α (HIF-1α) is a transcription factor which maintains cellular homeostasis in response to hypoxia. It can trigger apoptosis while stimulating angiogenesis process and decrease neurological deficit after an ischemic stroke. Up until now, this protein complex has not been widely investigated especially in stroke patient. OBJECTIVE: Here, we examined the potential of HIF-1α as a marker for neuroplasticity process after ischemic stroke. METHODS: Serum HIF-1α were measured in acute ischemic stroke patients. National Institute of Health Stroke Scale (NIHSS) were assessed on the admission and discharge day (between days 7 and 14). Ischemic stroke divided into 2 groups: large vessel disease (LVD, n = 31) and small vessel disease (SVD, n = 27). Statistical significances were calculated with Spearman rank test. RESULTS: A total of 58 patients, 31 with large artery atherosclerosis LVD and 27 with small vessel disease (SVD) were included in this study. HIF-1α level in LVD group was 0.5225 ± 0.2459 ng/mL and in SVD group was 0.3815 ± 0.121 ng/mL. HIF-1α was higher (p = 0.004) in LVD group than in SVD group. The initial NIHSS score in LVD group was 15.46 ± 2.61 and discharge NIHSS score was 13.31 ± 3.449. Initial NIHSS score in SVD group was 6.07 ± 1.82 and the discharge NIHSS was 5.703 ± 1.7055. In both SVD and LVD group, HIF-1α were significantly correlated with initial NIHSS (both p < 0.001) and discharge NIHSS (p < 0.0383 r = 0.94, p < 0.001, r = 0.93, respectively). CONCLUSIONS: HIF-1α has a strong correlation with NIHSS and it may be used as predictor in acute ischemic stroke outcome.

Perfusion imaging and recurrent cerebrovascular events in intracranial atherosclerotic disease or carotid occlusion.

Background Large vessel disease stroke subtype carries the highest risk of early recurrent stroke. In this study we aim to look at the association between impaired perfusion and early stroke recurrence in patients with intracranial atherosclerotic disease or total cervical carotid occlusion. Methods This is a retrospective study from a comprehensive stroke center where we included consecutive patients 18 years or older with intracranial atherosclerotic disease or total cervical carotid occlusion admitted with a diagnosis of ischemic stroke within 24 h from symptom onset with National Institute Health Stroke Scale < 15, between 1 December 2016 and 30 June 2017. Patients with (1) evidence of ≥ 50% stenosis of a large intracranial artery or total carotid artery occlusion, (2) symptoms referable to the territory of the affected artery, and (3) perfusion imaging data using the RAPID processing software were included. The primary predictor was unfavorable perfusion imaging defined as Tmax > 6 s mismatch volume (penumbra volume-infarct volume) of 15 ml or more. The outcome was recurrent cerebrovascular events at 90 days defined as worsening or new neurological symptoms in the absence of a nonvascular cause attributable to the decline, or new infarct or infarct extension in the territory of the affected artery. We used Cox proportional hazards models to determine the association between impaired perfusion and recurrent cerebrovascular events. Results Sixty-two patients met our inclusion criteria; mean age 66.4 ± 13.1 years, 64.5% male (40/62) and 50.0% (31/62) with intracranial atherosclerotic disease. When compared to patients with favorable perfusion pattern, patients with unfavorable perfusion pattern were more likely to have recurrent cerebrovascular events (55.6% (10/18) versus 9.1% (4/44), p < 0.001). This association persisted after adjusting for potential confounders (adjusted hazard ratio 10.44, 95% confidence interval 2.30-47.42, p = 0.002). Conclusion Perfusion mismatch predicts recurrent cerebrovascular events in patients with ischemic stroke due to intracranial atherosclerotic disease or total cervical carotid occlusion. Studies are needed to determine the utility of revascularization strategies in this patient population.

Relationship between Factor V Leiden Gene Variant and Risk of Ischemic Stroke: A Case-Control Study.

BACKGROUND: Factor V Leiden is the most common genetic variation among the blood coagulation pathway which leads to prothrombotic state, therefore, is considered an important gene for understating the stroke mechanism. AIM: The aim of the present study is to determine the relationship between single nucleotide polymorphism at G1691A position of Factor V gene and risk of ischemic stroke (IS) in North Indian population. MATERIALS AND METHODS: In a retrospective case-control study, 250 patients with IS and 250 age- and gender-matched controls were enrolled in the period of October 2012 to September 2014 from in- and out-patient department of Neurology, All India Institute of Medical Sciences, New Delhi, India. Deoxyribonucleic acid for each case and control was isolated from peripheral blood using phenol-chloroform extraction method. Polymerase chain reaction-restriction fragment length polymorphism method was used to determine the polymorphism. Data were analyzed using STATA Software Version 13. RESULTS: The mean age of IS patient was 52.8 ± 12.5 years and in control group was 50.97 ± 12.7 years. Genotypic frequency distributions were in accordance with Hardy-Weinberg equilibrium in both cases and controls. As expected hypertension, diabetes, dyslipidemia, smoking, heavy alcohol intake, family history of stroke, and poor economic status were significantly associated with the risk of IS. Multivariate analysis revealed 5.17 times higher odds for developing the risk of large vessel subtype of IS in patients carrying Factor V Leiden G1691A gene variation as compared to control subjects (OR, 5.17; 95% CI, 1.32-20.3, P = 0.01). CONCLUSION: The present study suggests that Factor V Leiden G1691A polymorphism may be significantly associated with the risk of large vessel subtype of IS. Large sample size studies using prospective cohort designs are required to corroborate the present findings.

Association between infectious burden, socioeconomic status, and ischemic stroke.

BACKGROUND AND AIMS: Infectious diseases contribute to stroke risk, and are associated with socioeconomic status (SES). We tested the hypotheses that the aggregate burden of infections increases the risk of ischemic stroke (IS) and partly explains the association between low SES and ischemic stroke. METHODS: In a case-control study with 470 ischemic stroke patients and 809 age- and sex-matched controls, randomly selected from the population, antibodies against the periodontal microbial agents Aggregatibacter actinomycetemcomitans and Porphyromonas gingivalis, against Chlamydia pneumonia, Mycoplasma pneumoniae (IgA and IgG), and CagA-positive Helicobacter pylori (IgG) were assessed. RESULTS: IgA seropositivity to two microbial agents was significantly associated with IS after adjustment for SES (OR 1.45 95% CI 1.01-2.08), but not in the fully adjusted model (OR 1.32 95% CI 0.86-2.02). By trend, cumulative IgA seropositivity was associated with stroke due to large vessel disease (LVD) after full adjustment (OR 1.88, 95% CI 0.96-3.69). Disadvantageous childhood SES was associated with higher cumulative seropositivity in univariable analyses, however, its strong impact on stroke risk was not influenced by seroepidemiological data in the multivariable model. The strong association between adulthood SES and stroke was rendered nonsignificant when factors of dental care were adjusted for. CONCLUSIONS: Infectious burden assessed with five microbial agents did not independently contribute to ischemic stroke consistently, but may contribute to stroke due to LVD. High infectious burden may not explain the association between childhood SES and stroke risk. Lifestyle factors that include dental negligence may contribute to the association between disadvantageous adulthood SES and stroke.