Resolved Proteinuria May Attenuate the Risk of Heart Failure: A Nationwide Population-Based Cohort Study.

Although proteinuria is a risk factor for heart failure (HF), proteinuria can be reversible or persistent. Our objective was to explore the link between changes in the proteinuria status and the risk of HF. We included participants from a Korean national health screening cohort who underwent health examinations in 2003-2004 and 2005-2006 and had no history of HF. Participants were categorized into four groups: proteinuria-free, proteinuria-resolved, proteinuria-developed, and proteinuria-persistent. The outcome of interest was the occurrence of HF. The study included 1,703,651 participants, among whom 17,543 (1.03%) were in the proteinuria-resolved group and 4585 (0.27%) were in the proteinuria-persistent group. After a median follow-up period of 14.04 years (interquartile range 14.19-15.07), HF occurred in 75,064 (4.41%) participants. A multivariable Cox proportional hazards regression analysis indicated that the proteinuria-persistent group had a higher risk of HF compared with the proteinuria-free group (hazard ratio (HR): 2.19, 95% confidence interval (CI): 2.03-2.36, p < 0.001). In a further pairwise comparison analysis, participants in the proteinuria-resolved group had a relatively low risk of HF compared with those in the proteinuria-persistent group (HR: 0.64, 95% CI: 0.58-0.70, p < 0.001). In conclusion, the risk of HF can change with alterations in the proteinuria status.

Better oral hygiene is associated with a reduced risk of osteoporotic fracture: a nationwide cohort study.

Background: The aim of this study was to examine the longitudinal association between oral health parameters and osteoporotic fracture. Methods: The study included participants who received oral health screening by dentists from the National Health Screening cohort database of Korea between 2003 and 2006. The primary outcome was osteoporotic fracture occurrence, which was defined using specific international classification of diseases-10 codes; vertebral fracture (S22.0, S22.1, S32.0, S32.7, T08, M48.4, M48.5, and M49.5), hip fracture (S72.0 and S72.1), distal radius fracture (S52.5 and S52.6), and humerus fracture (S42.2 and S42.3). The presence of periodontitis and various oral health examination findings, such as missing teeth, caries, frequency of tooth brushing, and dental scaling, were analyzed using a Cox proportional hazard model to assess their association with osteoporotic fracture occurrence. Results: The analysis included a total of 194,192 participants, among whom 16,683 (8.59%) developed osteoporotic fracture during a median follow-up of 10.3 years. Poor oral health status, including periodontitis (adjusted hazard ratio [aHR]: 1.09, 95% confidence interval [CI]: 1.01-1.18, p = 0.039), a higher number of missing teeth (≥15; aHR: 1.59, 95% CI: 1.45-1.75, p < 0.001), and dental caries (≥6; aHR: 1.17, 95% CI: 1.02-1.35, p = 0.030), was associated with an increased risk of osteoporotic fracture. On the other hand, better oral hygiene behaviors such as brushing teeth frequently (≥3 times per day; aHR: 0.82, 95% CI: 0.78-0.86, p < 0.001) and having dental scaling within 1 year (aHR: 0.87, 95% CI: 0.84-0.90, p < 0.001) were negatively associated with the occurrence of osteoporotic fracture. Conclusion: The study found that poor oral health, such as periodontitis, missing teeth, and dental caries, was associated with an increased risk of osteoporotic fracture. Conversely, good oral hygiene behaviors like frequent teeth brushing and dental scaling within 1 year were associated with a reduced risk. Further research is needed to confirm this association.

Prevalence of Mutations in Mendelian Stroke Genes in Early Onset Stroke Patients.

OBJECTIVE: Heritability of stroke is assumed not to be low, especially in the young stroke population. However, most genetic studies have been performed in highly selected patients with typical clinical or neuroimaging characteristics. We investigated the prevalence of 15 Mendelian stroke genes and explored the relationships between variants and the clinical and neuroimaging characteristics in a large, unselected, young stroke population. METHODS: We enrolled patients aged ≤55 years with stroke or transient ischemic attack from a prospective, nationwide, multicenter stroke registry. We identified clinically relevant genetic variants (CRGVs) in 15 Mendelian stroke genes (GLA, NOTCH3, HTRA1, RNF213, ACVRL1, ENG, CBS, TREX1, ABCC6, COL4A1, FBN1, NF1, COL3A1, MT-TL1, and APP) using a customized, targeted next generation sequencing panel. RESULTS: Among 1,033 patients, 131 (12.7%) had 28 CRGVs, most frequently in RNF213 (n = 59), followed by ABCC6 (n = 53) and NOTCH3 (n = 15). The frequency of CRGVs differed by ischemic stroke subtypes (p < 0.01): the highest in other determined etiology (20.1%), followed by large artery atherosclerosis (13.6%). It also differed between patients aged ≤35 years and those aged 51 to 55 years (17.1% vs 9.3%, p = 0.02). Only 27.1% and 26.7% of patients with RNF213 and NOTCH3 variants had typical neuroimaging features of the corresponding disorders, respectively. Variants of uncertain significance (VUSs) were found in 15.4% patients. INTERPRETATION: CRGVs in 15 Mendelian stroke genes may not be uncommon in the young stroke population. The majority of patients with CRGVs did not have typical features of the corresponding monogenic disorders. Clinical implications of having CRGVs or VUSs should be explored. ANN NEUROL 2023;93:768-782.

Association between CHADS2, CHA2DS2-VASc, ATRIA, and Essen Stroke Risk Scores and Functional Outcomes in Acute Ischemic Stroke Patients Who Received Endovascular Thrombectomy.

Background: CHADS2, CHA2DS2-VASc, ATRIA, and Essen stroke risk scores are used to estimate thromboembolism risk. We aimed to investigate the association between unfavorable outcomes and stroke risk scores in patients who received endovascular thrombectomy (EVT). Methods: This study was performed using data from a nationwide, multicenter registry to explore the selection criteria for patients who would benefit from reperfusion therapies. We calculated pre-admission CHADS2, CHA2DS2-VASc, ATRIA, and Essen scores for each patient who received EVT and compared the relationship between these scores and 3-month modified Rankin Scale (mRS) records. Results: Among the 404 patients who received EVT, 213 (52.7%) patients had unfavorable outcomes (mRS 3−6). All scores were significantly higher in patients with unfavorable outcomes than in those with favorable outcomes. Multivariable logistic regression analysis indicated that CHADS2 and the ATRIA score were positively correlated with unfavorable outcomes after adjusting for body mass index and variables with p < 0.1 in the univariable analysis (CHADS2 score: odds ratio [OR], 1.484; 95% confidence interval [CI], 1.290−1.950; p = 0.005, ATRIA score, OR, 1.128; 95% CI, 1.041−1.223; p = 0.004). Conclusions: The CHADS2 and ATRIA scores were positively correlated with unfavorable outcomes and could be used to predict unfavorable outcomes in patients who receive EVT.

Plasma osteoprotegerin level is associated with hemorrhagic transformation in stroke patients who underwent endovascular thrombectomy.

OBJECTIVE: Osteoprotegerin (OPG) is a component of the tumor necrosis factor receptor superfamily. Several studies have shown a relationship between OPG and cardiovascular disease. We investigated the association between plasma OPG levels and hemorrhagic transformation in stroke patients who received endovascular thrombectomy (EVT). METHODS: We prospectively enrolled 360 patients diagnosed with acute ischemic stroke and performed EVT from April 2014 to December 2020. Blood sampling for plasma OPG was performed after fasting for 12 h after EVT. Hemorrhagic transformation was defined using the definition and classification of the European Cooperative Acute Stroke Study-3 trial. RESULTS: Of all the included patients, 130 (36.1%) experienced hemorrhagic transformation. The mean ± standard deviation of the plasma OPG concentrations was 200.2 ± 74.4 pg/mL. In multivariable analysis, after adjusting for age, sex, body mass index (BMI), and variables with p < 0.1 in univariable analysis (diabetes mellitus, atrial fibrillation, coronary artery disease, alcohol intake, current smoking, NIHSS, ASPECT score, mass effect, hemoglobin, vitamin D 25(OH)D), increased plasma OPG concentration was independently related to any hemorrhagic transformation (highest tertile vs. lowest tertile of OPG; odds ratio [OR] 2.31, 95% confidence interval [CI] (1.29-4.14), p = 0.005) and severity of hemorrhagic transformation (OR 2.92, 95% CI (1.66-5.12), p = 0.001). CONCLUSIONS: Our results demonstrate that increased plasma OPG level is related to the occurrence and severity of hemorrhagic transformation in patients with cerebral infarction who receive EVT.

The association of plasma osteoprotegerin levels and functional outcomes post endovascular thrombectomy in acute ischemic stroke patients: a retrospective observational study.

Background: Osteoprotegerin (OPG), also known as osteoclastogenesis inhibitory factor, is a tumor necrosis factor receptor superfamily component. There is an established relationship between OPG and cardiovascular disease. We hypothesized that plasma OPG levels are associated with functional outcomes in acute ischemic stroke patients who have undergone endovascular thrombectomy (EVT). Methods: From April 2014 through December 2020, a total of 360 acute ischemic stroke patients who underwent EVT were prospectively included in this retrospective observational study. Plasma OPG was measured after fasting for 12 postoperative hours after EVT. A modified Rankin Scale (mRS) was used to assess functional outcomes 3 months after index stroke occurrence. Univariate and multivariate binary logistic regression and ordinal logistic regression analyses were performed to investigate the association of plasma OPG levels with poor functional outcomes. Results: Overall, 145 (40.2%) patients had poor (mRS > 2) outcomes. The mean ± standard deviation plasma OPG level was 200.2 ± 74.4 pg/mL. Multivariate analysis after adjusting for sex, body mass index, and variables with p < 0.1 in the preceding univariate analysis revealed high plasma OPG levels were independently associated with poor functional outcomes (highest tertile vs. lowest tertile of OPG; odds ratios (OR) 2.121, 95% confidence interval (CI) [1.089-4.191], p = 0.037 in binary logistic regression, OR 2.102, 95% CI [1.301-3.412], p = 0.002 in ordinal logistic regression analysis). Conclusions: This study demonstrated that higher plasma OPG levels were associated with poor functional outcomes in acute ischemic stroke patients who underwent EVT.

Association of Cerebral Venous Thrombosis with mRNA COVID-19 Vaccines: A Disproportionality Analysis of the World Health Organization Pharmacovigilance Database.

Cerebral venous thrombosis (CVT), a rare thrombotic event that can cause serious neurologic deficits, has been reported after some ChAdOx1 nCoV-19 vaccinations against coronavirus disease 2019 (COVID-19). However, there are few reports of associations between COVID-19 mRNA vaccination and CVT. We retrospectively analyzed CVT occurrence, time of onset after vaccination, outcomes (recovered/not recovered), and death after COVID-19 vaccination from adverse drug reactions (ADR) reports in VigiBase. A disproportionality analysis was performed regarding COVID-19 mRNA vaccines (BNT162b2 and mRNA-1273) and the ChAdOx1 nCoV-19 vaccine. We identified 756 (0.07%) CVT cases (620 (0.05%) after BNT162b2 and 136 (0.01%) after mRNA-1273) of 1,154,023 mRNA vaccine-related ADRs. Significant positive safety signals were noted for COVID-19 mRNA vaccines (95% lower end of information component = 1.56; reporting odds ratio with 95% confidence interval (CI) = 3.27). The median days to CVT onset differed significantly between the BNT162b2 and ChAdOx1 nCoV-19 vaccines (12 (interquartile range, 3−22) and 11 (interquartile range, 7−16), respectively; p = 0.02). Fewer CVT patients died after receiving mRNA vaccines than after receiving the ChAdOx1 nCoV-19 vaccine (odds ratio, 0.32; 95% CI, 0.22−0.45; p < 0.001). We noted a potential safety signal for CVT occurrence after COVID-19 mRNA vaccination. Therefore, awareness about the risk of CVT, even after COVID-19 mRNA vaccination, is necessary.

Clinical Implications of Atrial Fibrillation Detection Using Wearable Devices in Patients With Cryptogenic Stroke (CANDLE-AF) Trial: Design and Rationale.

Background: Although many electrocardiography wearable devices have been released recently for the detection of atrial fibrillation (AF), there are few studies reporting prospective data for wearable devices compared to the strategy of the existing guidelines in the detection of atrial fibrillation (AF) after cryptogenic stroke. A tiny single-patch monitor is more convenient than a conventional Holter monitor recording device and, therefore, longer duration of monitoring may be acceptable. Methods and Design: The CANDLE-AF study is a multicenter, prospective, randomized controlled trial. Patients with transient ischemic attack or ischemic stroke without any history of AF will be enrolled. The superiority of the 72-h single-patch monitor to standard strategy and non-inferiority of the 72-h single-patch monitor to an event-recorder-type device will be investigated. Single-patch monitor arm will repeat monitoring at 1, 3, 6, and 12 months, event-recorder-type arm will repeat monitoring twice daily for 12 months. The enrollment goal is a total of 600 patients, and the primary outcome is the detection of AF which continues at least 30 s during study period. The secondary outcome is the rate of changes from antiplatelet to anticoagulant and major adverse cardiac and cerebrovascular events within 1 year. Conclusions: The results of CANDLE-AF will clarify the role of a single-lead patch ECG for the early detection of AF in patients with acute ischemic stroke. In addition, the secondary outcome will be analyzed to determine whether more sensitive AF detection can affect the prognosis and if further device development is meaningful. (cris.nih.go.kr KCT0005592).

Association of periodontitis with microvascular complications of diabetes mellitus: A nationwide cohort study.

BACKGROUND: Periodontitis is a common chronic inflammatory disease and one of oral complications in diabetes. Diabetes-related microvascular complications and periodontitis are also closely related to systemic inflammation. We hypothesized that periodontitis and oral hygiene markers might increase the risk of microvascular complications in diabetes mellitus. METHODS: We enrolled 11,353 diabetes participants without prior microvascular complications who received complete oral health checkups in the National Health Insurance Service-National Health Screening Cohort in 2003-2004. The primary outcome was the first development of diabetes-related microvascular complications, including nephropathy, neuropathy, and retinopathy. RESULTS: The age of all participants was 55.27 ± 9.46 years, and 7833 (68.99%) participants were male. Periodontitis was noted in 8.37%. During the 7.03 ± 4.30 year of the mean follow-up period, 7227 patients experienced diabetes-related microvascular complications (2645 with nephropathy, 2513 with neuropathy, 2069 with retinopathy). Multivariable Cox regression analyses revealed that periodontitis was an independent risk factor for diabetes-related microvascular complications (adjusted hazard ratio (HR):1.13; 95% confidence interval (CI):1.04-1.23; p = 0.004). In the secondary analysis for individual microvascular complications, periodontitis was an independent risk factor for retinopathy (adjusted HR: 1.21; 95% CI: 1.04-1.40; p = 0.013). CONCLUSIONS: The presence of periodontitis was associated with an increased risk of microvascular complications in diabetes patients.

Association between CHADS2, CHA2DS2-VASc, ATRIA, and Essen Stroke Risk Scores and Unsuccessful Recanalization after Endovascular Thrombectomy in Acute Ischemic Stroke Patients.

BACKGROUND: The CHADS2, CHA2DS2-VASc, ATRIA, and Essen scores have been developed for predicting vascular outcomes in stroke patients. We investigated the association between these stroke risk scores and unsuccessful recanalization after endovascular thrombectomy (EVT). METHODS: From the nationwide multicenter registry (Selection Criteria in Endovascular Thrombectomy and Thrombolytic therapy (SECRET)) (Clinicaltrials.gov NCT02964052), we consecutively included 501 patients who underwent EVT. We identified pre-admission stroke risk scores in each included patient. RESULTS: Among 501 patients who underwent EVT, 410 (81.8%) patients achieved successful recanalization (mTICI ≥ 2b). Adjusting for body mass index and p < 0.1 in univariable analysis revealed the association between all stroke risk scores and unsuccessful recanalization (CHADS2 score: odds ratio (OR) 1.551, 95% confidence interval (CI) 1.198-2.009, p = 0.001; CHA2DS2VASc score: OR 1.269, 95% CI 1.080-1.492, p = 0.004; ATRIA score: OR 1.089, 95% CI 1.011-1.174, p = 0.024; and Essen score: OR 1.469, 95% CI 1.167-1.849, p = 0.001). The CHADS2 score had the highest AUC value and differed significantly only from the Essen score (AUC of CHADS2 score; 0.618, 95% CI 0.554-0.681). CONCLUSION: All stroke risk scores were associated with unsuccessful recanalization after EVT. Our study suggests that these stroke risk scores could be used to predict recanalization in stroke patients undergoing EVT.

Analysis of microRNA signatures in ischemic stroke thrombus.

BACKGROUND: We investigated the microRNA expression pattern from thrombus retrieved by mechanical thrombectomy in acute stroke patients to understand the stroke mechanism. METHODS: This study included acute ischemic stroke patients who had undergone intra-arterial thrombectomy at Chung-Ang University Hospital in Seoul, Korea between February 2016 and March 2019. The thrombus was retrieved and stored at -70℃ after obtaining informed consent. MicroRNA microarray analysis was performed for the patients with identified stroke mechanisms including (1) large artery atherosclerosis, (2) cardioembolism with atrial fibrillation, and (3) cardioembolism with valvular heart disease. The microRNAs derived from microarray analysis were validated by quantitative real-time polymerase chain reaction (qRT-PCR) from different patient populations. The correlation analysis was performed between microRNA levels and laboratory data to understand the functional relevance of the altered microRNA. RESULTS: In total, 55 thrombi were obtained from 74 patients, and the microRNAs were analyzed in 45 samples. Microarray analysis of 2578 microRNAs revealed that 50 microRNAs were significantly altered among the three groups. Validation using qRT-PCR showed that miR-378f and miR-450b-5p were significantly elevated among the cardioembolic thrombi; both microRNAs were inversely correlated with the ejection fraction from echocardiography. Thrombi from patients with early neurological deterioration exhibited higher levels of miR-93-5p and lower levels of miR-629-5p than those from neurologically stable patients. CONCLUSIONS: The microRNA expression pattern can provide information regarding the mechanism of stroke by reflecting the underlying pathological status of the organ from which the thrombus was derived.

Plasma osteoprotegerin levels are associated with the presence and burden of cerebral small vessel disease in patients with acute ischemic stroke.

BACKGROUND AND PURPOSE: Osteoprotegerin (OPG) is a component of the tumor necrosis factor receptor superfamily. Several studies have shown a relationship between OPG and cardiovascular diseases. We hypothesized that there is a relationship between plasma OPG levels and cerebral small vessel disease (SVD). METHODS: Patients diagnosed with their first cerebral ischemic infarction between April 2014 and March 2017 were enrolled. All the enrolled patients were evaluated through the hospital stroke protocol, including routine blood tests, brain imaging, and measuring the plasma OPG levels. The presence and burden of cerebral SVD [cerebral microbleeds (CMBs), asymptomatic lacunar infarction (ALI), high-grade perivascular space (HPVS), high-grade white matter hyperintensity (HWMH)], and total SVD score were assessed through brain magnetic resonance imaging. RESULTS: Of the 270 patients included in our study, 158 (58.5%) were men. The mean age of the patients was 63.8 ± 11.6 years. In multivariable analysis, plasma OPG levels were positively associated with the presence and burden of each cerebral SVD. The odds ratios (OR) of CMBs, ALI, HPVS, and HWMH for the association of OPG per standard deviation (SD) increase were 1.58 [95% confidence interval (CI), 1.09-2.27], 1.40 (95% CI, 1.04-1.88), 1.88 (95% CI, 1.27-2.78), and 1.47 (95% CI, 1.04-2.08), respectively. Plasma OPG levels were positively correlated with total SVD score (beta = 0.211, standard error = 0.061, p-value = 0.009, R2 = 0.275). CONCLUSIONS: Plasma OPG levels correlate with the presence and burden of cerebral SVD in patients with acute ischemic stroke.

Association of Bone Mineral Density to Cerebral Small Vessel Disease Burden.

OBJECTIVE: To test the hypothesis that bone mineral loss is mechanistically related to cerebral small vessel disease (SVD), we investigated the relationship between bone mineral density and the prevalence and intensity of SVD among patients with stroke. METHODS: We analyzed data of 1,190 consecutive patients with stroke who were >50 years of age and underwent both brain MRI and dual-energy x-ray absorptiometry from the stroke registry of Chung-Ang University Hospital in Seoul, Korea. The patients were categorized into 3 groups according to their bone mineral density (normal, osteopenia, and osteoporosis). White matter hyperintensities, silent lacunes, cerebral microbleeds, and extensive perivascular space were assessed from brain MRI. Multinomial logistic regression model was used to examine the association between osteoporosis and total SVD score. We also recruited 70 patients with stroke to study serum bone turnover markers and microRNAs related to both cerebral atherosclerosis and bone metabolism to understand bone and brain interaction. RESULTS: Osteoporosis was determined among 284 patients (23.9%), and 450 patients (37.8%) had osteopenia. As bone mineral density decreased, total SVD score and the incidence of every SVD phenotype increased except strictly lobar cerebral microbleeds. Multinomial logistic regression analysis showed that osteoporosis was independently associated with severe SVD burden. The levels of microRNA-378f were significantly increased among the patients with osteoporosis and maximal total SVD score and positively correlated with parathyroid hormone and osteocalcin. CONCLUSIONS: These findings suggest a pathophysiologic link between bone mineral loss and hypertensive cerebral arteriolar degeneration, possibly mediated by circulating microRNA.

White matter hyperintensity determines ischemic stroke severity in symptomatic carotid artery stenosis.

INTRODUCTION: The aim of this study is to investigate the influence of white matter hyperintensity (WMH) on stroke severity and prognosis in patients with symptomatic carotid artery stenosis. METHODS: Patients with symptomatic carotid artery stenosis were retrieved from the Samsung Medical Center stroke registry from January 2011 to December 2016. Stroke severity was categorized into three levels according to National Institutes of Health Stroke Scale (NIHSS): transient ischemic attack (TIA) or transient symptoms with infarction (TSI), mild stroke, and moderate to severe stroke. WMH volume was measured with medical image processing and visualization. The clinical outcome was assessed using the modified Rankin scale on the 90th day from which the latest onset of the neurological symptom. Logistic regression was used to predict stroke severity, and ordinal regression was used to compare the clinical outcome. RESULTS: Among 158 patients, the numbers of patients with TIA or TSI, mild stroke, and moderate to severe stroke were 48 (30.4%), 59 (37.3%), and 51 (32.3%), respectively. The larger WMH volume was associated with moderate to severe strokes (TIA/TSI vs. moderate to severe strokes, odds ratio (OR) 2.318, 95% confidence interval (CI) 1.194-4.502, p = 0.007; mild vs. moderate to severe strokes, OR 1.972, 95% CI 1.118-3.479, p = 0.013). Patients with larger volume of WMH showed poorer clinical outcome (cutoff value: 9.71 cm3, OR 2.099, 95% CI 1.030-4.311, p = 0.042). CONCLUSION: Our study showed that larger WMH volume is associated with more severe stroke and poorer prognosis in patients with symptomatic carotid artery stenosis.

Five-Year Risk of Acute Myocardial Infarction After Acute Ischemic Stroke in Korea.

Background The long-term incidence of acute myocardial infarction (AMI) in patients with acute ischemic stroke (AIS) has not been well defined in large cohort studies of various race-ethnic groups. Methods and Results A prospective cohort of patients with AIS who were registered in a multicenter nationwide stroke registry (CRCS-K [Clinical Research Collaboration for Stroke in Korea] registry) was followed up for the occurrence of AMI through a linkage with the National Health Insurance Service claims database. The 5-year cumulative incidence and annual risk were estimated according to predefined demographic subgroups, stroke subtypes, a history of coronary heart disease (CHD), and known risk factors of CHD. A total of 11 720 patients with AIS were studied. The 5-year cumulative incidence of AMI was 2.0%. The annual risk was highest in the first year after the index event (1.1%), followed by a much lower annual risk in the second to fifth years (between 0.16% and 0.27%). Among subgroups, annual risk in the first year was highest in those with a history of CHD (4.1%) compared with those without a history of CHD (0.8%). The small-vessel occlusion subtype had a much lower incidence (0.8%) compared with large-vessel occlusion (2.2%) or cardioembolism (2.4%) subtypes. In the multivariable analysis, history of CHD (hazard ratio, 2.84; 95% CI, 2.01-3.93) was the strongest independent predictor of AMI after AIS. Conclusions The incidence of AMI after AIS in South Korea was relatively low and unexpectedly highest during the first year after stroke. CHD was the most substantial risk factor for AMI after stroke and conferred an approximate 5-fold greater risk.

Correlation Between Hippocampal Enlarged Perivascular Spaces and Cognition in Non-dementic Elderly Population.

Background and aims: The pathophysiology of hippocampal enlarged perivascular spaces (H-EPVS) and its relationship to cognitive impairment is largely unknown. This study aimed to investigate the relationship between H-EPVS and cognition in non-dementic elderly population. Methods: A total of 109 subjects were prospectively enrolled. The eligibilities for inclusion were age from 55 to 85 years and Mini-Mental Status Examination score of ≥26. The Alzheimer's Disease Assessment Scale-Cognitive Subscale (ADAS-Cog), Montreal Cognitive Assessment, transcranial Doppler (TCD), and brain magnetic resonance imaging results were evaluated. H-EPVS was categorized in a three-degree scale: degree 0 (no), degree 1 (1,2), and degree 2 (>2). The associations between H-EPVS and TCD parameters/cognitive test profiles were analyzed. Results: The mean age was 65.2 years, and 52.3% subjects were men. H-EPVS was found to be associated with age (degree 2 vs. degree 1 vs. degree 0, 69.20 ± 6.93 vs. 65.70 ± 5.75 vs. 63.80 ± 5.43; p = 0.030) and ADAS-Cog memory score (degree 2 vs. degree 1 vs. degree 0, 14.88 ± 4.27 vs. 12.49 ± 4.56 vs. 11.4 ± 4.23; p = 0.037). However, the pulsatility index was not related to the degree of H-EPVS. Multivariate analysis revealed medial temporal atrophy (MTA) scale score was independently associated with ADAS-Cog memory score (MTA scale sum ≥4, p = 0.011) but not with the degree of H-EPVS. MTA scale score showed correlation with H-EPVS (r = 0.273, p = 0.004). Conclusions: Aging was associated with the development of H-EPVS in non-dementic elderly population. Memory function was found to be associated with MTA but not with the degree of H-EPVS.

Neurologic deterioration in patients with acute ischemic stroke or transient ischemic attack.

OBJECTIVE: To improve epidemiologic knowledge of neurologic deterioration (ND) in patients with acute ischemic stroke (AIS). METHODS: In this prospective observational study, we captured ND prospectively in 29,446 patients with AIS admitted to 15 hospitals in Korea within 7 days of stroke onset. ND was defined as an increase in NIH Stroke Scale (NIHSS) score ≥2 (total), or ≥1 (motor or consciousness), or any new neurologic symptoms. Change in incidence rate after stroke onset, causes, factors associated with ND, modified Rankin Scale (mRS) score at 3 months and 1 year, and a composite of stroke, myocardial infarction, and all-cause death at 1 year were assessed. RESULTS: ND occurred in 4,299 (14.6%) patients. The highest rate, 6.95 per 1,000 person-hours incidence, was within the first 6 hours, which decreased to 2.09 within 24-48 hours, and 0.66 within 72-96 hours after stroke onset. Old age, female sex, diabetes, early arrival, large artery atherosclerosis as a stroke subtype, high NIHSS scores, glucose level, systolic blood pressure, leukocytosis at admission, recanalization therapy, TIA without a relevant lesion, and steno-occlusion of relevant arteries were associated with ND. The causes were stroke progression (71.8%) followed by recurrence (8.5%). Adjusted relative risks (95% CI) for poor outcome (mRS 3-6) at 3 months and 1 year were 1.75 (1.70-1.80) and 1.70 (1.65-1.75), respectively. The adjusted hazard ratio (95% CI) for the composite event was 1.59 (1.45-1.74). CONCLUSIONS: ND should be taken into consideration as a factor that may influence the outcome in acute ischemic stroke.

Development of stroke identification algorithm for claims data using the multicenter stroke registry database.

BACKGROUND: Identifying acute ischemic stroke (AIS) among potential stroke cases is crucial for stroke research based on claims data. However, the accuracy of using the diagnostic codes of the International Classification of Diseases 10th revision was less than expected. METHODS: From the National Health Insurance Service (NHIS) claims data, stroke cases admitted to the hospitals participating in the multicenter stroke registry (Clinical Research Collaboration for Stroke in Korea, CRCS-K) during the study period with principal or additional diagnosis codes of I60-I64 on the 10th revision of International Classification of Diseases were extracted. The datasets were randomly divided into development and validation sets with a ratio of 7:3. A stroke identification algorithm using the claims data was developed and validated through the linkage between the extracted datasets and the registry database. RESULTS: Altogether, 40,443 potential cases were extracted from the NHIS claims data, of which 31.7% were certified as AIS through linkage with the CRCS-K database. We selected 17 key identifiers from the claims data and developed 37 conditions through combinations of those key identifiers. The key identifiers comprised brain CT, MRI, use of tissue plasminogen activator, endovascular treatment, carotid endarterectomy or stenting, antithrombotics, anticoagulants, etc. The sensitivity, specificity, and diagnostic accuracy of the algorithm were 81.2%, 82.9%, and 82.4% in the development set, and 80.2%, 82.0%, and 81.4% in the validation set, respectively. CONCLUSIONS: Our stroke identification algorithm may be useful to grasp stroke burden in Korea. However, further efforts to refine the algorithm are necessary.

Three-month modified Rankin Scale as a determinant of 5-year cumulative costs after ischemic stroke: An analysis of 11,136 patients in Korea.

OBJECTIVE: Stroke is a devastating and costly disease; however, there is a paucity of information on long-term costs and on how they differ according to 3-month modified Rankin scale (mRS) score, which is a primary outcome variable in acute stroke intervention trials. METHODS: We analyzed a prospective multicenter stroke registry (Clinical Research Collaboration for Stroke in Korea) database through linkage with claims data from the National Health Insurance Service with follow-up to December 2016. Healthcare expenditures were converted into daily cost individually, and annual and cumulative costs up to 5 years were estimated and compared according to the 3-month mRS score. RESULTS: Between January 2011 and November 2013, 11,136 patients were enrolled in the study. The mean age was 68 years, and 58% were men. The median follow-up period was 3.9 years (range 0-5 years). Mean cumulative cost over 5 years was $117,576 (US dollars [USD]); the cost in the first year after stroke was the highest ($38,152 USD), which increased markedly from the cost a year before stroke ($8,718 USD). The mean 5-year cumulative costs differed significantly according to the 3-month mRS score (p < 0.001); the costs for a 3-month mRS score of 0 or 5 were $53,578 and $257,486 USD, respectively. Three-month mRS score was an independent determinant of long-term costs after stroke. CONCLUSIONS: We show that 3-month mRS score plays an important role in the prediction of long-term costs after stroke. Such estimates relating to 3-month mRS categories may be valuable when undertaking health economic evaluations related to stroke care.

Intensive Statin Treatment in Acute Ischaemic Stroke Patients with Intracranial Atherosclerosis: a High-Resolution Magnetic Resonance Imaging study (STAMINA-MRI Study).

OBJECTIVE: Intracranial atherosclerosis is a major cause of ischaemic stroke worldwide. A number of studies have shown the effects of statin treatment on coronary and carotid artery plaques, but there is little evidence on the effects of statin treatment on intracranial atherosclerotic plaques. METHODS: The Intensive Statin Treatment in Acute Ischaemic Stroke Patients with Intracranial Atherosclerosis - High-Resolution Magnetic Resonance Imaging (STAMINA-MRI) Trial is a single-arm, prospective, observational study monitoring imaging and clinical outcomes of high-dose statin treatment among statin-naive patients with acute ischaemic stroke caused by symptomatic intracranial atherosclerosis. The primary outcome was the change in vascular remodelling and plaque characteristics before and after 6 months (median: 179 days, IQR 163-189 days) of statin treatment measured by high-resolution MRI (HR-MRI). RESULTS: A total of 77 patients (mean age: 62.6±13.7 years, 61.0% women) were included in this study. Low-density lipoprotein cholesterol (LDL-C) levels (mg/dL) at initial and follow-up assessments were 125.81±35.69 and 60.95±19.28, respectively. Overall, statin treatment significantly decreased enhancement of plaque volume (mm3, 32.07±39.15 vs 17.06±34.53, p=0.013), the wall area index (7.50±4.28 vs 5.86±4.05, p=0.016) and stenosis degree (%, 76.47±20.23 vs 64.05±21.29, p<0.001), but not the remodelling index (p=0.195). However, 35% patients showed no change or increased enhancement volume and stenosis degree after statin treatment. Higher reduction of LDL-C and longer duration of statin treatment were associated with decreased enhancement volume after statin treatment. CONCLUSIONS: High-dose statin treatment effectively stabilised symptomatic intracranial atherosclerotic plaques as documented by HR-MRI. Further study is needed to determine laboratory and genetic factors associated with poor response to statins and alternative therapeutic options, such as proprotein convertase subtilisin-kexin type 9 inhibitors, for these patients. TRIAL REGISTRATION NUMBER: ClinicalTrials.gov NCT02458755.