Diastolic Dysfunction as a Positive Predictor of Recurrent Vascular Events in Patients With Noncardioembolic Stroke.

BACKGROUND: This study aimed to assess the effects of left ventricular diastolic dysfunction (LVDD) on vascular outcomes among patients with stroke of noncardioembolic origins. METHODS: This prospective observational study enrolled 563 patients with noncardioembolic stroke (mean age, 67.9 years; 66.7% men and 33.3% women individuals) registered in the Tokyo Women's Medical University Stroke Registry between 2013 and 2020. Then, patients were divided into the LVDD and non-LVDD groups. The primary outcome was a composite of major adverse cardiovascular events, including nonfatal stroke, nonfatal acute coronary syndrome, and vascular death 1 year after stroke onset. The effect of LVDD on vascular events was assessed using multivariable Cox regression analyses. RESULTS: A total of 130 (23.1%) patients had any grade of LVDD, and patients with LVDD had a higher risk of major adverse cardiovascular event at 1 year than those without LVDD (annual rate, 20.9% versus 10.8%; log-rank P=0.001). The multivariable Cox proportional hazards regression model demonstrated that the presence of LVDD was independently associated with the major adverse cardiovascular event risk (hazard ratio, 1.79 [95% CI, 1.02-3.12]; P=0.019). Furthermore, the LVDD grade was proportional to the risk of major adverse cardiovascular events and recurrent stroke. CONCLUSIONS: LVDD may be associated with further vascular events after a noncardioembolic stroke, suggesting the importance of LVDD evaluations in risk stratification and secondary prevention in patients with noncardioembolic stroke. REGISTRATION: URL: https://upload.umin.ac.jp; Unique identifier: UMIN000031913.

Motor function is associated with cerebral small vessel disease and can predict mortality and poor functional outcome.

INTRODUCTION: Primary outcome of this study is to elucidate the predictive role of subtle motor impairment evaluated using the Unified Parkinson's Disease Rating Scale (UPDRS) Part III on mortality and functional outcome. Secondary outcome is to evaluate the association of motor impairment with small vessel disease (SVD) severity. METHODS: We derived data from a Japanese cohort of patients with evidence of SVD who were enrolled from 2015 to 2019, and followed until 2023. The present study included 586 participants who agreed for UPDRS Part III evaluation. The severity of white matter hyperintensities (WMH) and the presence of lacunes were evaluated. Cox proportional hazard models and multiple logistic regression analysis were used to examine the association between UPDRS Part III score, and all-cause death and functional outcome defined by the modified Rankin Scale (mRS) score at last visit, respectively. RESULTS: The median age was 71 years, and the median UPDRS Part III score was 2. The UPDRS Part III score was associated with the severity of WMH (r=0.225, P<0.001) and the number (0, 1, >2) of lacunes (P<0.001). During a mean follow-up period of 4.8 years, 29 patients died. The Cox proportional hazard analysis revealed that high UPDRS Part III scores (>5) were associated with higher risk of all-cause death compared to low (score 0) and middle (score 1-4) scores (adjusted hazard ratio 3.04; 95% confidence interval, 1.50-7.34, P=0.005). In multivariate logistic analysis, high UPDRS Part III scores were associated with poor functional outcome (mRS of 3 or more) compared with low and middle scores after adjusting for confounding factors (adjusted odds ratio 1.86; 95% confidence interval 1.02-3.41, P=0.043). CONCLUSIONS: Subtle motor impairment was associated with the severity of WMH and numbers of lacunes, and could predict mortality and poor functional outcome independently of vascular risk factors and severity of WMH and lacunes.

Long-Term Outcome in Patients With Acute Ischemic Stroke and Heart Failure.

BACKGROUND: This study aimed to identify the association between long term functional outcomes and acute ischemic stroke (AIS) in patients with heart failure (HF) in Japan and whether 1-year event risks can be related to these patients.Methods and Results: This was a prospective observational study, and 651 patients registered in the Tokyo Women's Medical University Stroke Registry were classified into the HF and non-HF groups. Functional outcome at 1 year after stroke onset was defined as either good (modified Rankin Scale [mRS] score of 0-2) or poor (mRS score of 3-6). The primary outcome was a composite of major adverse cardiovascular events (MACE), including non-fatal stroke, non-fatal acute coronary syndrome, and vascular death. Patients with HF had a higher poor functional outcome rate at 1 year than those without HF (54.7% vs. 28.2%, P<0.001). Multivariate logistic regression analysis also demonstrated the prevalence of HF was an independent predictor of an mRS score of ≥3 at 1 year after stroke onset (odds ratio, 1.05; 95% confidence interval, 1.00-1.10; P=0.036). Furthermore, patients with HF tended to have a higher risk of MACE and all-cause mortality than those without HF. CONCLUSIONS: AIS patients with HF were associated with poor functional outcome at the 1-year follow up. Further multicenter studies involving a larger number of patients are warranted to verify these results.

Atherogenic Dyslipidemia and Residual Vascular Risk After Stroke or Transient Ischemic Attack.

BACKGROUND AND PURPOSE: Notwithstanding the current guideline-based management, patients with stroke retain a substantial risk of further vascular events. We aimed to assess the contribution of atherogenic dyslipidemia (AD) to this residual risk. METHODS: This was a prospective observational study, in which 792 patients (mean age, 70.1 years; male, 60.2%) with acute ischemic stroke (n=710) or transient ischemic attack (n=82) within 1 week of onset were consecutively enrolled and followed for 1 year. AD was defined as having both elevated levels of triglycerides ≥150 mg/dL and low HDL-C (high-density lipoprotein cholesterol) <40 mg/dL in men or <50 mg/dL in women, under fasting conditions. The primary outcome was a composite of major adverse cardiovascular events, including nonfatal stroke, nonfatal acute coronary syndrome, and vascular death. RESULTS: The prevalence of AD was 12.2%. Patients with AD more often had intracranial artery stenosis than those without (42.3% versus 24.1%; P=0.004), whereas no differences were observed in the prevalence of extracranial artery stenosis (17.7% versus 12.9%; P=0.62) or aortic plaques (33.3% versus 27.0%; P=0.87). At 1 year, patients with AD were at a greater risk of major adverse cardiovascular events (annual rate, 24.5% versus 10.6%; hazard ratio [95% CI], 2.33 [1.44-3.80]) and ischemic stroke (annual rate, 16.8% versus 8.6%; hazard ratio [95% CI], 1.84 [1.04-3.26]) than those without AD. When patients were stratified according to baseline LDL-C (low-density lipoprotein cholesterol) level, AD was predictive of major adverse cardiovascular events among those with LDL-C ≥100 mg/dL (n=509; annual rate, 20.5% versus 9.6%; P=0.036) as well as those with LDL-C <100 mg/dL (n=283; annual rate, 38.6% versus 12.4%; P<0.001). CONCLUSIONS: AD is associated with intracranial artery atherosclerosis and a high residual vascular risk after a stroke or transient ischemic attack. AD should be a promising modifiable target for secondary stroke prevention. Registration: URL: https://upload.umin.ac.jp; Unique identifier: UMIN000031913.

Triglyceride-glucose index as a prognostic marker after ischemic stroke or transient ischemic attack: a prospective observational study.

BACKGROUND: Triglyceride-glucose (TyG) index has been proposed as a simple and credible surrogate for insulin resistance and an independent predictor of cardiovascular outcomes. Due to lack of data on TyG index in stroke, we aimed to evaluate the predictive value of the index for recurrent vascular event risk among stroke patients. METHODS: This was a prospective observational study, in which 866 patients (mean age, 70.1 years; male, 60.9%) with ischemic stroke (n = 781) or transient ischemic attack (n = 85) within 1 week of onset were consecutively enrolled and followed up for 1 year. The TyG index was calculated as ln (fasting triglycerides [mg/dL] × fasting glucose [mg/dL]/2). Patients were divided into 3 groups according to the tertile of TyG index levels: tertile 1, < 8.48; tertile 2, 8.48-9.01; and tertile 3, > 9.01. The primary outcome was a composite of major adverse cardiovascular events (MACE), including nonfatal stroke, nonfatal acute coronary syndrome, and vascular death. RESULTS: The median TyG index was 8.74 (interquartile range, 8.34-9.16). Higher levels of TyG index were significantly associated with increased prevalence of ipsilateral extracranial carotid (P = 0.032) and intracranial (P = 0.003) atherosclerotic stenosis. There were significant differences in the MACE risk between the three groups (annual rate, 8.6%, 11.6%, and 17.3% in the tertile 1, tertile 2, tertile 3 groups, respectively; log-rank P = 0.005). After multivariable adjustments, the TyG index remains to be a significant predictor of MACE, with an adjusted hazard ratio for tertile 3 versus tertile 1 groups (95% confidence interval) of 2.01 (1.16-3.47). Similar results were also found for the risk of recurrent stroke. CONCLUSIONS: TyG index is associated with cervicocerebral atherosclerosis and the MACE risk after a stroke, suggesting the potential value of TyG index to optimize the risk stratification of stroke patients. Trial registration URL:  https://upload.umin.ac.jp . Unique identifier: UMIN000031913.

Prevalence of Microembolic Signals in Embolic Stroke of Undetermined Source and Other Subtypes of Ischemic Stroke.

Background and Purpose- Embolic stroke of undetermined source (ESUS) has been proposed to cause thromboembolic infarction from unknown but potential embolic sources. However, an embolus remains undetected in ESUS. The goal of this study was to characterize the prevalence and risk factors of microembolic signals (MESs) in ESUS. Methods- We examined 108 patients with acute ischemic stroke in the internal carotid artery territory or transient ischemic attack within 14 days of symptom onset and who were admitted to our hospital between April 2017 and March 2019. MESs were monitored in the middle cerebral artery on transcranial Doppler for 60 minutes. We examined the prevalence and number of MES in ESUS and other stroke subtypes, such as cardioembolism, large artery atherosclerosis, cerebral small vessel disease, and transient ischemic attack. The present study was registered in University Hospital Medical Information Network Clinical Trials Registry (UMIN000031913). Results- MESs were detected in 33 (31%) of 108 patients. ESUS showed the highest proportion (12/24 [50%]), followed by large artery atherosclerosis (8/20 [40%]), cardioembolism (6/18 [33%]), transient ischemic attack (4/24 [17%]), and cerebral small vessel disease (3/21 [14%]). Univariate analysis showed that higher systolic blood pressure, body mass index, hemoglobin A1c, and ESUS were significantly associated with MES. In multiple logistic regression analysis, ESUS remained significantly associated with MES after adjustment for described covariates from univariate analysis (odds ratio, 2.86 [95% CI, 1.01-8.08]). Conclusions- This study demonstrated significant association of ESUS with MES, supporting the embolic nature of this stroke subtype. Registration- URL: https://upload.umin.ac.jp. Unique identifier: UMIN000031913.

Leptomeningeal anastomosis and early ischemic lesions on diffusion-weighted imaging in male murine focal cerebral ischemia.

Leptomeningeal anastomosis is a key factor for determining early ischemic lesions on diffusion-weighted imaging (DWI) in human stroke. However, few studies have validated this relationship in an experimental model. This study sought to clarify the involvement of leptomeningeal anastomosis in early ischemic lesions using a murine model. Adult male C57BL/6 mice were subjected to unilateral common carotid artery (CCA) occlusion or sham surgery. Seven or 14 days later, the middle cerebral artery (MCA) was occluded for 45 min. In the first experiment, the leptomeningeal collaterals were visualized using magnetic resonance imaging (MRI) DWI. In the second experiment, DWI was performed immediately after MCA occlusion, and the infarct sizes were determined 24 hr after recirculation. Unilateral CCA occlusion reduced the size of early ischemic lesions, enlarged the pial vessel diameter, and mitigated infarct size. The relationship between the DWI lesion size and pial vessel diameter was significant (r = 0.84, p < 0.01). The association between infarct size and DWI lesion size was also significant (r = 0.96, p < 0.01). In conclusion, involvement of the collateral circulation in early ischemic lesions was evident in the murine model. Both MRI and evaluation of leptomeningeal anastomosis could be used to develop a novel strategy targeting enhancement of the collateral circulation.

Ischemic Stroke due to Virologically-Confirmed Varicella Zoster Virus Vasculopathy: A Case Series.

BACKGROUND: Limited data are available regarding the characteristics and prognosis of patients with stroke due to varicella zoster virus (VZV) vasculopathy. METHODS: We studied 4 patients (2 men and 2 women; age, 38-63 years) from a single center who developed acute ischemic stroke due to VZV vasculopathy. The virological diagnosis was confirmed by detecting VZV DNA and/or the IgG antibody to VZV in the cerebrospinal fluid. RESULTS: Three patients were taking immunosuppressive agents, including prednisolone and/or methotrexate, at baseline. Each patient had a characteristic skin rash prior to stroke, with the interval from rash to stroke onset ranging from 13 to 122 days. Two patients experienced antecedent cranial nerve palsies; one had the third, seventh, ninth, and 10th nerve palsies and the other had the fourth nerve palsy before stroke. Cerebral infarctions were located in the anterior circulation lesion (n = 1), in the posterior circulation lesion (n = 2), and in both lesions (n = 1). Intracranial arterial stenosis was only identified in one patient on magnetic resonance angiography. A high plasma d-dimer level was detected in 1 patient, whereas high ß-thromboglobulin and platelet factor 4 levels were detected in 2 patients. As a result of combined therapies with acyclovir, steroid, and antithrombotic agents, neurological symptoms markedly improved in 3 patients, whereas 1 patient was left with moderate hemiplegia. CONCLUSIONS: Cranial nerve palsies may be prodromal symptoms of VZV-associated stroke. Increased levels of thrombotic markers may support the use of antithrombotic agents, although the benefit of combined treatment should be determined through larger studies.

Japanese Versus Non-Japanese Patients with Transient Ischemic Attack or Minor Stroke: Subanalysis of TIA registry.org.

BACKGROUND: TIAregistry.org is an international cohort of patients with transient ischemic attack (TIA) or minor stroke within 7 days before enrollment in the registry. Main analyses of 1-year follow-up data have been reported.5 We conducted subanalysis on the baseline and 1-year follow-up data of Japanese patients. METHODS: The patients were classified into 2 groups based on Japanese ethnicity, Japanese (345) and non-Japanese (3238), and their baseline data and 1-year event rates were compared. We also determined risk factors and predictors of 1-year stroke. RESULTS: Current smoking, regular alcohol drinking, intracranial arterial stenosis, and small vessel occlusion; and hypertension, dyslipidemia, coronary artery disease, and extracranial arterial stenosis were more and less common among Japanese patients, respectively. Stroke risk was higher and TIA risk was lower at 1-year follow-up among Japanese patients. The baseline risk factors for recurrent stroke were diabetes, alcohol drinking, and large artery atherosclerosis. Independent predictors of 1-year stroke risk were prior congestive heart failure and alcohol consumption. CONCLUSIONS: The two populations of patients featured differences in risk factors, stroke subtypes, and outcome events. Predictors of recurrent stroke among Japanese patients included congestive heart failure and regular alcohol drinking. Strategies to attenuate residual risk of stroke aside from adherence to current guidelines should take our Japanese-patient specific findings into account.

Associations of Mitral and Aortic Valve Calcifications with Complex Aortic Atheroma in Patients with Embolic Stroke of Undetermined Source.

BACKGROUND: This study investigated the associations of mitral and aortic valve calcification with complex aortic atheroma among patients with embolic stroke of undetermined source. METHODS: We included 52 consecutive patients (mean age 58.1 years; 75.0% male) with embolic stroke of undetermined source. Mitral annular calcification, aortic annular calcification, and aortic valve sclerosis were assessed by transthoracic echocardiography. Complex aortic atheroma was assessed by transesophageal echocardiography and was defined as plaque protruding greater than or equal to 4 mm into the lumen or with ulcerated or mobile components. RESULTS: Ten patients (19.2%) had complex aortic atheroma. Patients with and without complex aortic atheroma showed significant differences in terms of hypertension (80.0% versus 38.1%, P = .017), dyslipidemia (90.0% versus 31.0%, P <.01), chronic kidney disease (60.0% versus 14.3%, P <.01), previous coronary artery disease (30.0% versus 4.8%, P = .013), prior stroke (40.0% versus 7.1%, P <.01), left atrial dimension (4.0 cm versus 3.6 cm, P = .023), aortic valve sclerosis (80.0% versus 26.2%, P <.01), aortic valve calcification (aortic annular calcification or aortic valve sclerosis) (80.0% versus 26.0%, P <.01), and left-sided valve calcification (mitral annular calcification or aortic annular calcification or aortic valve sclerosis) (80.0% versus 28.6%, P <.01). In multivariate analysis, left-sided valve calcification was independently associated with complex aortic atheroma (odds ratio 4.1, 95% confidence interval 1.3-26.1, P = .049). CONCLUSIONS: Mitral or aortic valve calcification detected by transthoracic echocardiography can be a useful marker for predicting complex aortic atheroma in patients with embolic stroke of undetermined source.

Differences in Characteristics and Outcomes Between Asian and Non-Asian Patients in the TIAregistry.org.

BACKGROUND AND PURPOSE: This study provides the contemporary causes and prognosis of transient ischemic attack (TIA) and minor stroke in Asians and the direct comparisons with non-Asians. METHODS: The TIAregistry.org enrolled 4789 patients (1149 Asians and 3640 non-Asians) with a TIA or minor ischemic stroke within 7 days of onset. Every participating facility had systems dedicated to urgent intervention of TIA/stroke patients by specialists. The primary outcome was a composite of cardiovascular death, nonfatal stroke, and nonfatal acute coronary syndrome. RESULTS: Approximately 80% of patients were evaluated within 24 hours of symptom onset. At 1 year, there were no differences in the rates of composite cardiovascular events (6.8% versus 6.0%; P=0.38) and stroke (6.0% versus 4.8%; P=0.11) between Asians and non-Asians. Asians had a lower risk of cerebrovascular disease (stroke or TIA) than non-Asians (adjusted hazard ratio, 0.79; 95% confidence interval, 0.63-0.98; P=0.03); the difference was primarily driven by a lower rate of TIA in Asians (4.2% versus 8.3%; P<0.001). Moderately severe bleeding was more frequent in Asians (0.8% versus 0.3%; P=0.02). In multivariable analysis, multiple acute infarcts (P=0.005) and alcohol consumption (P=0.02) were independent predictors of stroke recurrence in Asians, whereas intracranial stenosis (P<0.001), ABCD2 score (P<0.001), atrial fibrillation (P=0.008), extracranial stenosis (P=0.03), and previous stroke or TIA (P=0.03) were independent predictors in non-Asians. CONCLUSIONS: The short-term stroke risk after a TIA or minor stroke was lower than expected when urgent evidence-based care was delivered, irrespective of race/ethnicity or region. However, the predictors of stroke were different for Asians and non-Asians.

Prolonged QTc interval predicts poststroke paroxysmal atrial fibrillation.

BACKGROUND AND PURPOSE: Paroxysmal atrial fibrillation (PAF) is often difficult to detect in patients with acute ischemic stroke. We aimed to assess the predictive value of a prolonged QT interval corrected for heart rate (QTc) in PAF detection after acute ischemic stroke. METHODS: We enrolled 972 patients with acute ischemic stroke consecutively extracted from our observational stroke registry system. Exclusion criteria were as follows: (1) AF on the initial 12-lead ECG (n=171); (2) previously diagnosed PAF (n=47); and (3) the use of a cardiac pacemaker (n=10). Of the 972 patients, 744 (mean age, 67.6 years; men, 62.6%) were eligible for analysis. The clinical characteristics and 12-lead ECG findings of the patients with and without PAF were compared, and multiple logistic regression analysis was performed to identify predictors of poststroke PAF. RESULTS: The poststroke cardiac work-up yielded 69 (9.3%) de novo PAF cases among the 744 patients. The QTc interval was significantly longer in patients with PAF than in those without PAF (436 versus 417 ms; P<0.001). Each 10-ms increase in the QTc interval was associated with an increased risk of PAF after multivariate adjustments (odds ratio, 1.41; 95% confidence interval, 1.24-1.61; P<0.001). The optimal threshold value of QTc interval calculated by a receiver-operating characteristic curve was 438 ms, and the area under the curve was 0.73 in this data set. CONCLUSIONS: The QTc interval prolongation is potentially a strong and useful predictor for poststroke PAF.

CHADS2, CHA2DS2-VASc, and R2CHADS2 scores are associated with 3-month functional outcome of stroke in patients with prior coronary artery disease.

BACKGROUND: Recent reports have shown that CHADS2 score can be applied to stroke risk in coronary artery disease (CAD) patients. This study evaluated the efficacy of CHADS2, CHA2DS2-VASc and R2CHADS2 scores as prognostic tools for stroke subsequent to CAD. METHODS AND RESULTS: We enrolled 159 consecutive patients with acute ischemic stroke who were (1) living independently before stroke; and (2) diagnosed with CAD before stroke. Comparisons were made between patients with poor and good 3-month functional outcome (modified Rankin scale ≥3 and <3, respectively) with regard to clinical characteristics and pre-stroke CHADS2, CHA2DS2-VASc and R2CHADS2 scores. Multivariate analysis was used to assess the predictive value of each of the 3 scores for poor outcome. The patients with poor and good outcomes had significant differences in intracranial artery stenosis (31.4% vs. 14.9%; P=0.016), carotid artery stenosis (41.9% vs. 23.9%; P=0.019), atrial fibrillation (37.2% vs. 17.9%; P=0.008), NIHSS (11 vs. 5; P<0.001), CHADS2 (3 vs. 2; P=0.004), CHA2DS2-VASc (5 vs. 4; P=0.003), and R2CHADS2 (3 vs. 3; P=0.005). Multivariate analysis showed that CHADS2 >2 (OR, 1.65; 95% CI: 1.05-2.65; P=0.032), CHA2DS2-VASc >4 (OR, 1.60; 95% CI: 1.02-1.78; P=0.042), and R2CHADS2 >3 (OR, 1.57; 95% CI: 1.01-2.49; P=0.049) positively predicted poor outcome. CONCLUSIONS: CHADS2, CHA2DS2-VASc and R2CHADS2 are useful in predicting functional status after stroke in CAD patients.

Ankle-brachial index and neurologic deterioration in acute ischemic stroke.

BACKGROUND: Few studies have examined the relationship between abnormal ankle-brachial index (ABI) and short-term outcome in patients with acute ischemic stroke (AIS). METHODS: We included 209 consecutive patients with AIS admitted to our hospital and divided them into abnormal ABI (≤.9) and normal ABI (>.9) groups. We defined neurologic deterioration (ND) as an increase of 1 or more points in the National Institutes of Health Stroke Scale score within 7 days of stroke onset. Clinical characteristics were compared between the 2 groups. Then, we performed a multiple logistic regression analysis to identify independent predictors of ND. In the multivariate analysis, the ABI values were used separately as binary variables in different cutoff thresholds (.9, 1.0, and 1.1). RESULTS: Of the 209 patients, 24 (11.5%) had an abnormal ABI. The patients in abnormal and normal ABI groups showed significant differences in carotid arterial stenosis (37.5% versus 18.9%; P = .040), intracranial artery stenosis (54.2% versus 18.9%; P < .001), and previous use of antiplatelet drugs (58.3% versus 29.2%; P = .004). According to the multivariate analysis, ABIs of .9 or less and 1.0 or less were positively associated with ND (odds ratio [OR], 1.74; 95% confidence interval [CI], 1.03-2.89; P = .034 and OR, 1.63; 95% CI, 1.05-2.54; P = .027, respectively), whereas an ABI value of 1.1 or less was not an independent predictor of ND (OR, 1.17; 95% CI, 0.79-1.74; P = .43). CONCLUSIONS: Not only an ABI of .9 or less but also an ABI of 1.0 or less can be a predictor of ND in patients with AIS.

Association of circulating CD34+ cells level and prognosis after ischemic stroke.

BACKGROUND: CD34 is a transmembrane phosphoglycoprotein and a marker of hematopoietic and nonhematopoietic stem/progenitor cells. In experimental studies, CD34+ cells are rich sources of endothelial progenitor cells and can promote neovascularization and endothelial repair. The potential role of CD34+ cells in stroke patients remains unclear. AIMS: We aimed to assess the prognostic effect of circulating CD34+ cell levels on the risk of vascular events and functional prognosis in stroke patients. PATIENTS AND METHODS: In this prospective observational study, patients with ischemic stroke were consecutively enrolled within 1 week of onset and followed up for 1 year. Patients were divided into three groups according to tertiles of the level of circulating CD34+ cells (Tertile 1, <0.51/µL; Tertile 2, 0.51-0.96/µL; and Tertile 3, >0.96/µL). The primary outcome was a composite of major adverse cardiovascular events (MACEs), including nonfatal stroke, nonfatal acute coronary syndrome, major peripheral artery disease, and vascular death. The secondary outcomes included the modified Rankin scale (mRS) scores. RESULTS: A total of 524 patients (mean age, 71.3 years; male, 60.1%) were included. High CD34+ cell levels were associated with younger age (p < 0.001) and low National Institutes of Health Stroke Scale scores at admission (p = 0.010). No significant differences were found in the risk of MACEs among the three groups (annual rates: 15.0%, 13.4%, and 12.6% in Tertiles 1, 2, and 3, respectively; log-rank p = 0.70). However, there were significant differences in the mRS scores at 3 months (median (interquartile range); 2 (1-4), 1 (1-3), and 1 (0-2) in Tertiles 1, 2, and 3, respectively; p = 0.010) and 1 year (3 (1-4), 2 (1-4), and 1 (0-3); p < 0.001) among these groups. After multivariable adjustments, a higher CD34+ cell level was independently associated with good functional outcomes (mRS score of 0-2) at 3 months (adjusted odds ratio (OR), 1.43; 95% confidence interval (CI), 1.01-2.05) and 1 year (adjusted OR, 1.53; 95% CI, 1.09-2.16). CONCLUSION: Although no correlations were found between circulating CD34+ cell levels and vascular event risk, elevated CD34+ cell levels were associated with favorable functional recovery in stroke patients. DATA ACCESS STATEMENT: Data supporting the findings of this study are available from the corresponding author on reasonable request. CLINICAL TRIAL REGISTRATION: The TWMU Stroke Registry is registered at https://upload.umin.ac.jp as UMIN000031913.

Small vessel disease burden predicts incident stroke and all-cause death, but not acute coronary event.

Total small vessel disease (SVD) score is used to measure the burden of SVD by incorporating four established neuroimaging markers; white matter hyperintensity, lacune, cerebral microbleed, and enlarged perivascular space, ranging from 0 to 4. Whether total SVD scores predict all vascular outcomes remains unclear. This study aimed to clarify the predictive value of the total SVD score for incident stroke, mortality, and acute coronary syndrome in independent outpatients with vascular risk factors. We derived data from The Tokyo Women's Medical University Cerebrovascular Disease registry, a prospective observational registry in which 1011 patients with evidence of cerebral vessel disease on magnetic resonance imaging were enrolled. They were followed up until March 2023. The primary outcomes were stroke, all-cause death, and acute coronary syndrome (ACS). After excluding those with a modified Rankin scale score >1, Mini-mental State Examination score <24, and missing T2* images, 692 patients were included. During a median follow-up period of 4.6 years, stroke, ACS, and all-cause death occurred in 52, 24, and 45 patients, respectively. In multivariate analysis, the total SVD score was independently associated with stroke, and all-cause death but not with acute coronary syndrome. Both cutoff values of the total SVD score for stroke, and all-cause death were 1. In conclusion, the total SVD score could predict stroke and mortality but not acute coronary syndrome. Our results suggest intensive management of patients with a total SVD score ≥1 to prevent stroke and all-cause death. Patients with higher total SVD scores were significantly more likely to have a stroke (A; P = 0.012) than those with lower total SVD scores. However, no association was observed between total SVD scores and acute coronary syndrome (B, P = 0.604). For incident stroke, total SVD scores of 1 and 2 were the cutoff levels.

Small Vessel Disease Burden Predicts Incident Dementia and Poor Functional Outcome in Independent Outpatients.

Background: Total small vessel disease (SVD) score is used to measure the burden of SVD. Objective: This study aimed to clarify the predictive value of total SVD score for incident dementia and functional outcomes in independent outpatients with vascular risk factors. Methods: We derived data from a Japanese cohort in which patients underwent magnetic resonance imaging and cognitive examinations. They were followed up until March 2023. The primary outcomes was dementia. Secondary outcome was functional outcomes. We measured a modified Rankin scale (mRS) score at the last visit and defined poor functional outcomes as mRS score ≥3. Results: After excluding those with a mRS score ≥2, Mini-Mental State Examination score in Japanese version < 24, and missing T2* images, 692 patients were included. During a median follow-up period of 4.6 years, dementia occurred in 31 patients. In multivariate analysis, the score 4 group showed a significantly higher risk of incident dementia than the score 0-3 groups (adjusted hazard ratio, 6.25; 95% CI, 1.83-21.40, p = 0.003). The total SVD score was also independently related to poor functional outcome. Conclusions: The total SVD score of 4, and ≥1 could predict dementia and poor functional outcomes, respectively. Our results suggest intensive management of patients with SVD to prevent dementia and to maintain independent activities of daily living.

Association of Transcranial Doppler Microembolic Signal With Short-Term Mortality in Acute Ischemic Stroke and Active Cancer.

BACKGROUND: This study aimed to clarify the characteristics and survival prediction value of transcranial Doppler microembolic signals (MES) in patients with acute cerebral infarction and active cancer. METHODS AND RESULTS: Between 2017 and 2022, 1089 cases of acute cerebral infarction were recorded within 7 days of disease onset. Among them, transcranial Doppler was successful in 33 patients who had active cancer, and these data were analyzed in this study. The primary outcomes were stroke recurrence and mortality at 3 months. The study population had the following characteristics [median (interquartile range)]: age, 70 years (63-78); body mass index, 21.6 (20-24), National Institutes of Health Stroke Scale 3 (1-6), and modified Rankin Scale score at discharge 1 (1-4). The most common cancer types were lung (24%), pancreatic (24%), and intestinal (18%). MES was present in 16 of 33 patients (48.5%). The presence and number of MES were significantly associated with the levels of D-dimer (P <0.001) and C-reactive protein (P=0.012). Moreover, the presence of MES was associated with multiple ischemic lesions and the 3-territory sign on magnetic resonance imaging. Of the 33 patients, 9 died at 3 months, and 1 had stroke recurrence. On Cox multivariate analysis, using the MES-negative group as a reference, the presence of MES was significantly associated with all-cause death (adjusted hazard ratio, 12.19 [95% CI, 1.45-216.85]; P=0.020). CONCLUSIONS: In patients with acute ischemic stroke and active cancer, the presence of MES was associated with D-dimer and C-reactive protein levels and multiple and 3-territory ischemic lesions, and was predictive of short-term survival.

Helicobacter pylori Eradication Does Not Adversely Affect the Clinical Course of Gastric Cancer: A Multicenter Study on Screening Endoscopic Examination in Japan.

BACKGROUND: Since gastric cancers (GCs) detected after Helicobacter pylori (HP) eradication present with different morphological characteristics from conventional HP-positive GCs, delayed detection of early-stage GCs may be observed. This study aimed to investigate the clinical impact of HP eradication on diagnosing GC during screening endoscopy. METHODS: Eleven health checkup institutions in Japan participated in the present study. All GC cases newly diagnosed by screening endoscopy between January 2016 and December 2020 were included. After propensity score matching, multivariable regression analysis was performed to estimate the effect of HP eradication on deep tumor invasion among HP-eradicated and HP-positive GC cases. RESULTS: A total of 231 patients with GCs (134 HP-eradicated and 97 HP-positive cases) were enrolled. After propensity score matching, there were 81 cases in each group. The distribution of the depth of tumor invasion (pT1a, pT1b1, pT1b2, and pT2) between the HP-eradicated group and HP-positive group was similar (p = 0.82). In the propensity analysis, with HP-positive as the reference value, HP eradication was not significantly associated with T1b-T4-GCs and T1b2-T4-GCs, with odds ratios (95% confidence intervals) of 1.16 (0.48-2.81) and 1.16 (0.42-3.19), respectively. CONCLUSIONS: HP eradication does not adversely affect the clinical course of GCs, supporting the recommendation of HP eradication in screening programs to reduce the total number of GC cases without delaying diagnosis.

Slow sinus heart rate as a potential predictive factor of paroxysmal atrial fibrillation in stroke patients.

BACKGROUND: Paroxysmal atrial fibrillation (PAF) is a strong independent risk factor for ischemic stroke and is also associated with stroke severity and mortality. However, the detection rate of PAF in patients with ischemic stroke is limited because they are often asymptomatic or present with sinus rhythm on electrocardiograms (ECGs). In the present study, we aimed to identify predictors of PAF in stroke patients by continuous ECG monitoring of the heart rate in sinus rhythm. METHODS: We enrolled 741 consecutive patients with acute symptomatic ischemic stroke who were admitted to our hospital. Exclusion criteria were the following: (1) patients with persistent AF, (2) cardiac pacemaker users and (3) incomplete clinical investigations. Each patient was subject to 24-hour Holter ECG, cardiac monitoring by inpatient telemetry and routine transthoracic echocardiography. The minimum and mean sinus heart rates (SHRs) on 24-hour Holter ECGs were recorded. The presence of PAF was judged on the basis of previous history and cardiac studies during hospitalization. Clinical characteristics of the patients with and without PAF were compared, and multiple logistic regression analysis was performed to identify the predictors of PAF. RESULTS: Of all enrolled patients, 606 (mean age 68.2 years, 63.4% male) were eligible for analysis, and the presence of PAF was confirmed in 116 subjects (19.1%). In the univariate analysis, the patients with and without PAF showed significant differences in age (74.3 vs. 66.7 years, p < 0.001), dyslipidemia (32.8 vs. 50.4%, p = 0.001), chronic heart failure (16.4 vs. 4.7%, p < 0.001), admission National Institute of Health Stroke Scale score (8.5 vs. 6, p < 0.001) and absence of vascular etiology (80.2 vs. 54.1%, p < 0.001). Furthermore, the minimum and mean SHRs were slower in the patients with than in those without PAF (46.5 vs. 54.0 bpm, p < 0.001 and 70.7 vs. 73.8 bpm, p = 0.009, respectively). In 501 (82.7%) out of 606 patients, minimum SHRs were detected at night (from 9:00 p.m. to 7:00 a.m.). A minimum SHR was an independent predictive factor of PAF in the multivariate analysis (odds ratio 1.08, 95% confidence interval 1.05 - 1.12, p < 0.001). CONCLUSIONS: A slow SHR on monitoring ECG is a potential predictive factor of PAF in patients with ischemic stroke.