Long-term outcomes of patients with embolic stroke of undetermined source according to subtype.

The prognosis of patients with embolic stroke of undetermined source (ESUS) may vary according to the underlying cause. Therefore, we aimed to divide ESUS into subtypes and assess the long-term outcomes. Consecutive patients with acute ischemic stroke who underwent a comprehensive workup, including transesophageal echocardiography and prolonged electrocardiography monitoring, were enrolled. We classified ESUS into minor cardioembolic (CE) ESUS, arteriogenic ESUS, two or more causes ESUS, and no cause ESUS. Arteriogenic ESUS was sub-classified into complex aortic plaque (CAP) ESUS and non-stenotic (< 50%) relevant artery plaque (NAP) ESUS. A total of 775 patients were enrolled. During 1286 ± 748 days follow-up, 116 major adverse cardiovascular events (MACE) occurred (4.2 events/100 patient-years). Among the ESUS subtypes, CAP ESUS was associated with the highest MACE frequency (9.7/100 patient-years, p = 0.021). Cox regression analyses showed that CAP ESUS was associated with MACE (hazard ratio 2.466, 95% confidence interval 1.305-4.660) and any stroke recurrence (hazard ratio 2.470, 95% confidence interval, 1.108-5.508). The prognosis of ESUS varies according to the subtype, with CAP ESUS having the worst prognosis. Categorizing ESUS into subtypes could improve patient care and refine clinical trials.

Functional Outcomes Associated With Blood Pressure Decrease After Endovascular Thrombectomy.

Importance: The associations between blood pressure (BP) decreases induced by medication and functional outcomes in patients with successful endovascular thrombectomy remain uncertain. Objective: To evaluate whether BP reductions induced by intravenous BP medications are associated with poor functional outcomes at 3 months. Design, Setting, and Participants: This cohort study was a post hoc analysis of the Outcome in Patients Treated With Intra-Arterial Thrombectomy-Optimal Blood Pressure Control trial, a comparison of intensive and conventional BP management during the 24 hours after successful recanalization from June 18, 2020, to November 28, 2022. This study included 302 patients who underwent endovascular thrombectomy, achieved successful recanalization, and exhibited elevated BP within 2 hours of successful recanalization at 19 stroke centers in South Korea. Exposure: A BP decrease was defined as at least 1 event of systolic BP less than 100 mm Hg. Patients were divided into medication-induced BP decrease (MIBD), spontaneous BP decrease (SpBD), and no BP decrease (NoBD) groups. Main Outcomes and Measures: The primary outcome was a modified Rankin scale score of 0 to 2 at 3 months, indicating functional independence. Primary safety outcomes were symptomatic intracerebral hemorrhage within 36 hours and mortality due to index stroke within 3 months. Results: Of the 302 patients (median [IQR] age, 75 [66-82] years; 180 [59.6%] men), 47 (15.6%)were in the MIBD group, 39 (12.9%) were in the SpBD group, and 216 (71.5%) were in the NoBD group. After adjustment for confounders, the MIBD group exhibited a significantly smaller proportion of patients with functional independence at 3 months compared with the NoBD group (adjusted odds ratio [AOR], 0.45; 95% CI, 0.20-0.98). There was no significant difference in functional independence between the SpBD and NoBD groups (AOR, 1.41; 95% CI, 0.58-3.49). Compared with the NoBD group, the MIBD group demonstrated higher odds of mortality within 3 months (AOR, 5.15; 95% CI, 1.42-19.4). The incidence of symptomatic intracerebral hemorrhage was not significantly different among the groups (MIBD vs NoBD: AOR, 1.89; 95% CI, 0.54-5.88; SpBD vs NoBD: AOR, 2.75; 95% CI, 0.76-9.46). Conclusions and Relevance: In this cohort study of patients with successful endovascular thrombectomy after stroke, MIBD within 24 hours after successful recanalization was associated with poor outcomes at 3 months. These findings suggested lowering systolic BP to below 100 mm Hg using BP medication might be harmful.

Effectiveness of endovascular treatment for in-hospital stroke vs. community-onset stroke: a propensity score-matched analysis.

BACKGROUND: The effectiveness of endovascular treatment for in-hospital stroke remains debatable. We aimed to compare the outcomes between patients with in-hospital stroke and community-onset stroke who received endovascular treatment. METHODS: This prospective registry-based cohort study included consecutive patients who underwent endovascular treatment from January 2013 to December 2022 and were registered in the Selection Criteria in Endovascular Thrombectomy and Thrombolytic Therapy study and Yonsei Stroke Cohort. Functional outcomes at day 90, radiological outcomes, and safety outcomes were compared between the in-hospital and community-onset groups using logistic regression and propensity score-matched analysis. RESULTS: Of 1,219 patients who underwent endovascular treatment, 117 (9.6%) had in-hospital stroke. Patients with in-hospital onset were more likely to have a pre-stroke disability and active cancer than those with community-onset. The interval from the last known well to puncture was shorter in the in-hospital group than in the community-onset group (155 vs. 355 min, p<0.001). No significant differences in successful recanalization or safety outcomes were observed between the groups; however, the in-hospital group exhibited worse functional outcomes and higher mortality at day 90 than the community-onset group (all p<0.05). After propensity score matching including baseline characteristics, functional outcomes after endovascular treatment did not differ between the groups (OR: 1.19, 95% CI 0.78-1.83, p=0.4). Safety outcomes did not significantly differ between the groups. CONCLUSION: Endovascular treatment is a safe and effective treatment for eligible patients with in-hospital stroke. Our results will help physicians in making decisions when planning treatment and counseling caregivers or patients.

Effect of Statins for Primary Prevention of Cardiovascular Disease According to the Fatty Liver Index.

INTRODUCTION: Nonalcoholic fatty liver disease (NAFLD) is associated with increased risk of cardiovascular disease (CVD). We investigated the primary preventive effect of statins on CVD according to the level of fatty liver index (FLI), which is a marker of NAFLD. METHODS: We conducted a nested case-control study on the basis of a nationwide health screening cohort in Korea. The participants were divided into tertiles (T1, T2, and T3) according to their FLI score. Cases were defined as individuals who developed CVD (composite of myocardial infarction and stroke). Three controls were matched to each case and multivariable conditional logistic regression analysis was performed. RESULTS: Within a cohort of 206,263 participants without prior CVD, 7044 individuals suffered the primary outcome. For the nested case-control study, we selected these 7044 cases along with their corresponding 20,641 matched controls. Individuals in the T3 tertiles of FLI had a higher risk of CVD than those in the T1 tertile [adjusted odds ratio (OR) 1.30; 95% confidence interval (CI) 1.20-1.40, P < 0.001]. In sub-analyses based on FLI tertiles, statin therapy was associated with a lower risk of CVD (adjusted OR 0.72; 95% CI 0.61-0.85, P < 0.001) in the T3 tertile but not in the T1 and T2 tertiles. CONCLUSIONS: Statin therapy was associated with a reduced risk of CVD in individuals with high FLI but not in those with low FLI. Further research is needed to determine the pathophysiologic mechanism between statin and NAFLD.

Risk of thromboembolism according to statin treatment in patients with cancer: A nationwide nested case-control study.

BACKGROUND: Thromboembolic events exhibit increased prevalence in patients with cancer and can negatively affect prognoses. We investigated whether statin treatment would reduce thromboembolic risk in patients with cancer. METHODS: We conducted a nested case-control study using a Korean nationwide health claims database. The study included patients newly diagnosed with cancer without a prior history of cardiovascular disease between 2014 and 2016. Cases who developed arterial thromboembolism (ATE) or venous thromboembolism (VTE) after cancer diagnosis and three individually matched controls were selected. Conditional logistic regression was used to assess the association between thromboembolic risk and statin therapy after cancer diagnosis. RESULTS: Among 455,805 newly diagnosed patients with cancer followed for a mean of 4.3 ± 2.0 years, 22,249 patients developed thromboembolic events (ATE: 6341, VTE: 15,908), resulting in an incidence rate of 1133 per 100,000 person-years. The nested case-control study included 21,289 cases with thromboembolic events and 63,867 controls. Statin use was less frequent in the case group (18.0 % vs. 23.7 %). Statin treatment was associated with a lower risk of thromboembolic events (adjusted odds ratio [OR] 0.70; 95 % confidence interval [CI] 0.67-0.73). This association was observed for both ATE (adjusted OR 0.68; 95 % CI 0.63-0.74) and VTE (adjusted OR 0.71; 95 % CI 0.67-0.75). Longer statin use and better adherence were also associated with lower risk for thromboembolic events. Statin treatment was significantly associated with fewer thromboembolic events in most cancer types. CONCLUSIONS: Statin use was associated with lower risk for thromboembolic events in patients newly diagnosed with cancer.

Discontinuation of antiplatelet therapy after stent-assisted coil embolisation of cerebral aneurysm: a nationwide cohort study.

INTRODUCTION: Stent-assisted coil embolisation (SACE) for the treatment of unruptured cerebral aneurysms has been increasingly used. Long-term advantages of antiplatelet therapy (APT) post-SACE treatment are still not well understood. We investigated the long-term effects of APT on clinical prognosis after SACE. PATIENTS AND METHODS: We conducted a retrospective study using nationwide health insurance claims data from South Korea, including patients with cerebral aneurysm treated with SACE from January 2009 to December 2020. The study outcomes consisted of the occurrence of cerebral infarction and major haemorrhage. To evaluate the impact of APT, we employed a multivariable time-dependent Cox proportional hazards regression model for each of the three distinct periods: 1-12 months, 12-24 months and >24 months after SACE. RESULTS: This study included 17 692 unruptured cerebral aneurysm patients treated with SACE. During the mean follow-up of 4.2 years, there were 379 (2.1%) patients with cerebral infarction and 190 (1.1%) patients with major haemorrhage. The percentage of patients receiving APT was 79.5% at 1 year, which gradually decreased to 58.3% at 2 years after SACE. APT was beneficial in preventing cerebral infarction within 12 months after SACE (adjusted HR (aHR) 0.56; 95% CI, 0.35 to 0.89; p=0.014). After 12 months, this association was not evident. APT increased the risk of haemorrhage after 24 months (aHR 1.76; 95% CI 1.11 to 2.87; p=0.016). DISCUSSION AND CONCLUSION: Our findings suggest that in patients with unruptured cerebral aneurysm treated with SACE, the reasonable duration of APT for preventing cerebral infarction might be 1 year after SACE.

Duration of dual-antiplatelet therapy after stent-assisted coil for unruptured intracranial aneurysm: A nationwide cohort study.

BACKGROUND: Stent-assisted coil (SAC) is increasingly used to treat unruptured intracranial aneurysm (UIA). However, the optimal duration of dual-antiplatelet therapy (DAPT) after SAC insertion remains unknown. AIM: To assess the time-dependent effect of DAPT on the risk of ischemic and hemorrhagic complications after SAC. METHODS: This is a retrospective cohort study among patients with UIA treated with SAC using the nationwide health claims database in South Korea between 2009 and 2020. Multivariate Cox regression analysis was used, which included the use of DAPT as a time-dependent variable. The effect of DAPT was investigated for each period of "within 90 days," "91 to 180 days," "181 to 365 days," and "366 to 730 days" after SAC. The primary outcome was a composite of ischemic stroke and major bleeding in each period within two years after SAC. RESULTS: Of the 15,918 patients, mean age at SAC was 57.6 ± 10.8 years, and 3815 (24.0%) were men. The proportion of patients on DAPT was 79.4% at 90 days, 58.3% at 180 days, and 28.9% at 1 year after SAC. During the 2 years after SAC, the primary composite outcome occurred in 356 patients (2.2%). DAPT significantly reduced the primary composite outcome within 90 days after SAC (adjusted hazard ratio (aHR), 0.44; 95% confidence interval (CI), 0.28-0.69; p < 0.001); however, this was not the case after 90 days (all p > 0.05). DAPT reduced ischemic stroke risk within 90 days (aHR, 0.31; 95% CI 0.18-0.54; p < 0.001), and 91 to 180 days after SAC (aHR 0.40; 95% CI 0.18-0.88; p = 0.022); however, after 180 days, DAPT was no longer beneficial. CONCLUSIONS: In patients with UIA treated with SAC, 3 months of DAPT was associated with a decreased risk of the composite of ischemic and hemorrhagic complications.

Impact of statin treatment on cardiovascular risk in patients with type 1 diabetes: a population-based cohort study.

BACKGROUND: Cardiovascular disease (CVD) is a major complication in type 1 diabetes mellitus (T1D) patients. Previous studies have suggested that statins may be helpful for prevention of CVD in T1D, but there are limited data on the role of statins in T1D. We investigated the relationship between statin treatment and cardiovascular risk in T1D patients using a population-based cohort. METHODS: We conducted a retrospective cohort study using the Korean nationwide health insurance database from January 2007 to December 2017. This study included 11,009 T1D patients aged ≥ 20 years without a prior history of CVD. The primary outcome was a composite development of stroke or myocardial infarction. Statin use during follow-up was treated as a time-varying variable. We performed a multivariable time-dependent Cox regression analysis adjusting for sex, age, type of insurance, hypertension, renal disease, and use of antiplatelets and renin-angiotensin-aldosterone system inhibitors. RESULTS: During the mean follow-up of 9.9 ± 3.7 years of follow-up, 931 T1D patients (8.5%) suffered primary outcome. Statin treatment was associated with a reduced risk of the primary outcome (adjusted hazard ratio, 0.76; 95% confidence interval 0.66-0.88; p < 0.001). Statin use led to decreased risks of ischemic stroke and myocardial infarction, but was not related to hemorrhagic stroke. We also found that the risk of cardiovascular events decreased as the cumulative exposure duration of statins increased. CONCLUSIONS: Statin use was associated with a lower risk of cardiovascular events in T1D patients. Further prospective studies are needed to confirm the potential role of statins in prevention of CVD in patients with T1D.

Effect of Smoking Cessation on the Risk of Subarachnoid Hemorrhage: A Nested Case-Control Study in Korean Men.

BACKGROUND: Smoking is a well-established risk factor for subarachnoid hemorrhage (SAH), and current smokers have an increased risk of SAH. However, there are insufficient data on whether smoking cessation in current smokers reduces the risk of SAH. METHODS: A nested case-control study was conducted based on the National Health Insurance Service-National Health Screening Cohort, which comprises nationwide health claims data and a national health screening program in Korea (2002-2019). We constructed a cohort of current male smokers without a history of stroke at the baseline health screening (2002-2003). From this cohort, cases were defined as individuals who experienced a nontraumatic SAH during the follow-up period up to 2019. Five controls were matched to each case using incidence density sampling. Smoking status (continuation or cessation) before the occurrence of SAH was evaluated using the repeated national health screening program. We conducted a multivariable conditional logistic regression analysis, adjusting for alcohol consumption, physical activity, body mass index, systolic blood pressure, and fasting blood glucose levels, to evaluate the association between SAH risk and smoking cessation. RESULTS: At baseline, there were 112 142 current male smokers. After excluding individuals with prior stroke or insufficient data, the cohort consisted of 105 223 eligible participants (mean age, 50.3±8.5 years). Among them, we identified 318 cases of SAH and 1590 matched controls. Those who quit smoking had a significantly lower risk of SAH compared with current smokers (adjusted odds ratio, 0.55 [95% CI, 0.41-0.73]). The risk of SAH decreased with a longer period of smoking cessation. The risk reduction with smoking cessation was consistent even among prior heavy smokers. CONCLUSIONS: Smoking cessation in current male smokers reduced the risk of SAH, and the risk reduction was greater as the cessation period increased. These findings warrant intensive efforts to encourage smokers, even heavy smokers, to quit.

Intensive vs Conventional Blood Pressure Lowering After Endovascular Thrombectomy in Acute Ischemic Stroke: The OPTIMAL-BP Randomized Clinical Trial.

Importance: Optimal blood pressure (BP) control after successful reperfusion with endovascular thrombectomy (EVT) for patients with acute ischemic stroke is unclear. Objective: To determine whether intensive BP management during the first 24 hours after successful reperfusion leads to better clinical outcomes than conventional BP management in patients who underwent EVT. Design, Setting, and Participants: Multicenter, randomized, open-label trial with a blinded end-point evaluation, conducted across 19 stroke centers in South Korea from June 2020 to November 2022 (final follow-up, March 8, 2023). It included 306 patients with large vessel occlusion acute ischemic stroke treated with EVT and with a modified Thrombolysis in Cerebral Infarction score of 2b or greater (partial or complete reperfusion). Interventions: Participants were randomly assigned to receive intensive BP management (systolic BP target <140 mm Hg; n = 155) or conventional management (systolic BP target 140-180 mm Hg; n = 150) for 24 hours after enrollment. Main Outcomes and Measures: The primary outcome was functional independence at 3 months (modified Rankin Scale score of 0-2). The primary safety outcomes were symptomatic intracerebral hemorrhage within 36 hours and death related to the index stroke within 3 months. Results: The trial was terminated early based on the recommendation of the data and safety monitoring board, which noted safety concerns. Among 306 randomized patients, 305 were confirmed eligible and 302 (99.0%) completed the trial (mean age, 73.0 years; 122 women [40.4%]). The intensive management group had a lower proportion achieving functional independence (39.4%) than the conventional management group (54.4%), with a significant risk difference (-15.1% [95% CI, -26.2% to -3.9%]) and adjusted odds ratio (0.56 [95% CI, 0.33-0.96]; P = .03). Rates of symptomatic intracerebral hemorrhage were 9.0% in the intensive group and 8.1% in the conventional group (risk difference, 1.0% [95% CI, -5.3% to 7.3%]; adjusted odds ratio, 1.10 [95% CI, 0.48-2.53]; P = .82). Death related to the index stroke within 3 months occurred in 7.7% of the intensive group and 5.4% of the conventional group (risk difference, 2.3% [95% CI, -3.3% to 7.9%]; adjusted odds ratio, 1.73 [95% CI, 0.61-4.92]; P = .31). Conclusions and Relevance: Among patients who achieved successful reperfusion with EVT for acute ischemic stroke with large vessel occlusion, intensive BP management for 24 hours led to a lower likelihood of functional independence at 3 months compared with conventional BP management. These results suggest that intensive BP management should be avoided after successful EVT in acute ischemic stroke. Trial Registration: ClinicalTrials.gov Identifier: NCT04205305.

Growth and Electronic Structure of Copper Oxide Monolayer Epitaxial Films.

Copper-based high-temperature superconductors share a common feature in their crystal structure, which is the presence of a CuO2 plane, where superconductivity takes place. Therefore, important questions arise as to whether superconductivity can exist in a single layer of the CuO2 plane and, if so, how such superconductivity in a single CuO2 plane differs from that in a bulk cuprate system. To answer these questions, studies of the superconductivity in cuprate monolayers are necessary. In this study, we constructed a heterostructure system with a La2-xSrxCuO4 (LSCO) monolayer containing a single CuO2 plane and measured the resulting electronic structures. Monolayer LSCO has metallic and bulk-like electronic structures. The hole doping ratio of the monolayer LSCO is found to depend on the underlying buffer layer due to the interface effect. Our work will provide a platform for research into ideal two-dimensional cuprate systems.

Statin Treatment on Cardiovascular Risk After Retinal Artery Occlusion: A Historical Cohort Study.

INTRODUCTION: Retinal artery occlusion (RAO) is a major cause of acute visual loss and patients with RAO have an increased risk for subsequent cardiovascular events. However, there is little evidence of whether the use of statins is associated with the prevention of cardiovascular events in patients with RAO. We investigated whether statin treatment in patients with RAO is associated with a lower risk of cardiovascular events. METHODS: This study was a historical cohort study with nested case-control analysis. Using the nationwide health insurance claims database in Korea, we retrospectively established a cohort of newly diagnosed RAO patients without prior cardiovascular events between January 2008 and March 2020. We defined the case group as those who had cardiovascular events (stroke or myocardial infarction) and the control group as RAO patients without primary outcome matched by sex, age, comorbidities, and duration of follow-up (1:2 incidence density sampling). Conditional logistic regression was performed. RESULTS: Among 13,843 patients newly diagnosed with RAO, 1030 patients had cardiovascular events (mean follow-up period of 6.4 ± 3.7 years). A total of 957 cases were matched to 1914 controls. Throughout the study period, the proportion of patients taking statin was less than half. Statin treatment after RAO was associated with a low risk of cardiovascular events (adjusted OR, 0.637; 95% CI 0.520-0.780; P < 0.001). A longer duration of statin exposure was associated with a lower cardiovascular risk. CONCLUSIONS: In patients with newly diagnosed RAO, treatment with statins, particularly long-term use, was associated with a low risk of future cardiovascular events.

Cancer Prediction With Machine Learning of Thrombi From Thrombectomy in Stroke: Multicenter Development and Validation.

BACKGROUND: We aimed to develop and validate machine learning models to diagnose patients with ischemic stroke with cancer through the analysis of histopathologic images of thrombi obtained during endovascular thrombectomy. METHODS: This was a retrospective study using a prospective multicenter registry which enrolled consecutive patients with acute ischemic stroke from South Korea who underwent endovascular thrombectomy. This study included patients admitted between July 1, 2017 and December 31, 2021 from 6 academic university hospitals. Whole-slide scanning was performed for immunohistochemically stained thrombi. Machine learning models were developed using transfer learning with image slices as input to classify patients into 2 groups: cancer group or other determined cause group. The models were developed and internally validated using thrombi from patients of the primary center, and external validation was conducted in 5 centers. The model was also applied to patients with hidden cancer who were diagnosed with cancer within 1 month of their index stroke. RESULTS: The study included 70 561 images from 182 patients in both internal and external datasets (119 patients in internal and 63 in external). Machine learning models were developed for each immunohistochemical staining using antibodies against platelets, fibrin, and erythrocytes. The platelet model demonstrated consistently high accuracy in classifying patients with cancer, with area under the receiver operating characteristic curve of 0.986 (95% CI, 0.983-0.989) during training, 0.954 (95% CI, 0.937-0.972) during internal validation, and 0.949 (95% CI, 0.891-1.000) during external validation. When applied to patients with occult cancer, the model accurately predicted the presence of cancer with high probabilities ranging from 88.5% to 99.2%. CONCLUSIONS: Machine learning models may be used for prediction of cancer as the underlying cause or detection of occult cancer, using platelet-stained immunohistochemical slide images of thrombi obtained during endovascular thrombectomy.

Association of triglyceride/high-density lipoprotein cholesterol ratio with severe complications of COVID-19.

Background: The coronavirus disease 2019 (COVID-19) caused by the SARS-CoV-2 virus can lead to serious complications such as respiratory failure, requiring mechanical ventilation or ICU care, and can even result in death, especially in older patients with comorbidities. The ratio of triglyceride to high-density lipoprotein cholesterol (TG/HDL), a biomarker of atherosclerotic dyslipidemia and insulin resistance, is related to cardiovascular mortality and morbidity. We aimed to evaluate the link between serious complications of COVID-19 and TG/HDL in the general population. Methods: We conducted a comprehensive analysis of 3,933 COVID-19 patients from a nationwide cohort in Korea spanning from January 1 to June 4, 2020. TG/HDL ratio was calculated from the national health screening examination data underwent before the COVID-19 infection. Serious complications of COVID-19 were defined as a composite of high-flow oxygen therapy, mechanical ventilation, admission to the intensive care unit (ICU), and mortality. We employed logistic regression analysis to investigate the relationship between the TG/HDL ratio and the likelihood of developing severe complications within 2 months of the diagnosis. To visualize this association, we used a smoothing spline plot based on the generalized additive regression model. Multivariate analysis was performed with adjustment for age, gender, body mass index, lifestyle measures, and comorbidities. Results: Among the 3,933 COVID-19 patients, the proportion of serious complications was 7.53%. Regarding individual outcomes, the number of patients who received high-flow oxygen therapy, mechanical ventilation, ICU care, and died was 84 (2.14%), 122 (3.10%), 173 (4.40%), and 118 (3.00%), respectively. In the multivariable logistic regression, a positive association was found between TG/HDL ratio and serious complications of COVID-19 (adjusted OR, 1.09; 95% CI [1.03-1.15], p = 0.004). Conclusion: Our study revealed a significant positive association between TG/HDL ratio and the risk of developing severe complications in COVID-19-infected patients. While this finding provides valuable insight into the potential prognostic role of TG/HDL ratio in COVID-19, further studies are needed to fully elucidate the underlying mechanisms behind this relationship.

Lobeglitazone, a novel thiazolidinedione, for secondary prevention in patients with ischemic stroke: a nationwide nested case-control study.

INTRODUCTION: Ischemic stroke patients with diabetes are at high risk for recurrent stroke and cardiovascular complications. Pioglitazone, a type of thiazolidinedione, has been shown to reduce cardiovascular complications in patients with ischemic stroke and type 2 diabetes (T2D) or insulin resistance. Lobeglitazone is a novel thiazolidinedione agent that improves insulin resistance and has similar glycemic efficacy to pioglitazone. Using population-based health claims data, we evaluated whether lobeglitazone has secondary cardiovascular preventive effects in patients with ischemic stroke and T2D. METHODS: This study has a nested case-control design. From nationwide health claims data in Korea, we identified patients with T2D admitted for acute ischemic stroke in 2014-2018. Cases were defined who suffered the primary outcome (a composite of recurrent stroke, myocardial infarction, and all-cause death) before December 2020. Three controls were selected by incidence density sampling for each case from those who were at risk at the time of their case occurrence with exact matching on sex, age, the presence of comorbidities, and medications. As a safety outcome, we also evaluated the risk of heart failure (HF) according to the use of lobeglitazone. RESULTS: From the cohort of 70,897 T2D patients with acute ischemic stroke, 20,869 cases and 62,607 controls were selected. In the multivariable conditional logistic regression, treatment with lobeglitazone (adjusted OR 0.74; 95% CI 0.61-0.90; p = 0.002) and pioglitazone (adjusted OR 0.71; 95% CI 0.64-0.78; p < 0.001) were significantly associated with a lower risk for the primary outcome. In a safety outcome analysis for HF, treatment with lobeglitazone did not increase the risk of HF (adjusted OR 0.90; 95% CI 0.66-1.22; p = 0.492). CONCLUSIONS: In T2D patients with ischemic stroke, lobeglitazone reduced the risk of cardiovascular complications similar to that of pioglitazone without an increased risk of HF. There is a need for further studies on the cardioprotective role of lobeglitazone, a novel thiazolidinedione.

Impact of statin treatment on cardiovascular events in patients with retinal vein occlusion: a nested case-control study in Korea.

OBJECTIVES: Retinal vein occlusion (RVO) is associated with an increased risk of future cardiovascular events. Statin therapy is a key cornerstone in prevention for patients at high cardiovascular risk. However, little is known about the role of statin therapy for patients with RVO. This study evaluated whether statin treatment in patients with RVO was associated with a lower risk of cardiovascular events. METHODS: A population-based, nested case-control study was conducted with a cohort of newly diagnosed RVO patients without prior cardiovascular disease between 2008 and 2020 using a nationwide health claims database in Korea. From this cohort of RVO patients, we identified cases of cardiovascular events (stroke or myocardial infarction) after RVO and matched controls based on sex, age, insurance type, antiplatelet use, and underlying comorbidities using 1:2 incidence density sampling. RESULTS: Using a cohort of 142,759 patients with newly diagnosed RVO, we selected 6,810 cases and 13,620 matched controls. A significantly lower risk of cardiovascular events (adjusted odds ratio, 0.604; 95% confidence interval, 0.557 to 0.655) was observed in RVO patients with statin treatment than in those without statin treatment. Statin treatment was associated with a reduced risk for both stroke and myocardial infarction after RVO. Longer statin treatment after RVO was associated with a lower risk for cardiovascular events. CONCLUSIONS: Statin treatment was associated with a lower risk for future cardiovascular events in patients with newly diagnosed RVO. Further studies are warranted to clarify the potential cardiovascular preventive role of statins in patients with RVO.

Oral Health and Risk of Retinal Vascular Occlusions: A Nationwide Cohort Study.

Retinal vascular occlusions are a common cause of visual loss. The association between oral health and the risk of retinal vascular occlusions remains unknown. We investigated whether oral health was associated with the risk of retinal vascular occlusions. We conducted a retrospective cohort study including 138,484 participants who completed a national health screening program with an oral health examination from the National Health Insurance Service-National Health Screening Cohort (NHIS-HEALS) 2002-2015. Oral health markers, such as the presence of periodontitis, tooth loss, and dental caries, and the frequency of daily tooth brushing, were evaluated. The primary outcome was the occurrence of retinal vascular occlusions up to December 2015. In total, 2533 participants developed retinal vascular occlusions (215 with retinal artery occlusion, 1686 with retinal vein occlusion, 632 with unspecified retinal vascular occlusion). In the multivariable Cox regression analysis, periodontitis was an independent risk factor for retinal vascular occlusions (adjusted hazard ratio: 1.18; 95% confidence interval: 1.02-1.36; p = 0.024). Frequent tooth brushing was negatively associated with the risk of retinal vascular occlusions (adjusted hazard ratio: 0.89; 95% confidence interval: 0.80-0.98; p = 0.022). Improving oral hygiene may contribute to the attenuation of the risk of retinal vascular occlusions.

Association between statin therapy and the risk of stroke in patients with moyamoya disease: a nationwide cohort study.

BACKGROUND AND OBJECTIVE: Knowledge regarding the pharmacological treatment for moyamoya disease (MMD), a chronic and progressive cerebrovascular disease conferring greater stroke risk, is limited. In the present study, whether statin therapy is associated with a reduced risk of stroke in patients with MMD was investigated. METHODS: This was a retrospective cohort study in which the occurrence of stroke in patients with newly diagnosed MMD was investigated using the nationwide health insurance database in Korea from January 2007 to March 2021. A multivariable Cox proportional hazards regression model was constructed for stroke, in which statin therapy after MMD diagnosis was treated as a time-dependent variable. Adjustment was done for sex, age, presence of comorbidities, concurrent stroke, revascularisation surgery and treatment with antiplatelets. RESULTS: The present study included 13 373 newly diagnosed patients with MMD; 40.8% had a concurrent stroke at the time of MMD diagnosis. During the mean follow-up of 5.1±3.3 years, 631 patients (4.7%) suffered a stroke event (haemorrhagic stroke: 458 patients, ischaemic stroke: 173 patients). Statin therapy after MMD diagnosis was significantly associated with a reduced risk of stroke (adjusted HR 0.74; 95% CI 0.60 to 0.91, p=0.004). In the secondary outcome analysis, the risk of haemorrhagic stroke (adjusted HR 0.74; 95% CI 0.58 to 0.95, p=0.018) and ischaemic stroke (adjusted HR 0.75; 95% CI 0.52 to 1.08, p=0.124) were reduced with the statin treatment. Taking statins was also associated with a lower risk of all-cause mortality (adjusted HR 0.47; 95% CI 0.33 to 0.67, p<0.001). CONCLUSION: In patients with MMD, statin therapy was associated with a reduced risk of subsequent stroke. The findings indicate statin treatment may be beneficial for patients with MMD, however the results should be confirmed in randomised controlled trials.

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.