Ischemic Stroke Mortality Research Articles

Abstract 4138332: Lipoprotein (a), Triglyceride-Glucose Index and Incident Atherosclerotic Cardiovascular Disease (ASCVD): Analysis of the UK Biobank

Background: The triglyceride-glucose index (TyG), an inexpensive novel surrogate marker for insulin resistance, and lipoprotein (a) [Lp(a)] are both risk factors for atherosclerotic cardiovascular disease (ASCVD). However, it is uncertain whether TyG modifies the relationship of Lp(a) with incident ASCVD. Objective: To investigate the relationship of Lp(a) and TyG with the risk of incident ASCVD. Methods: We included UK Biobank participants without ASCVD at enrollment. Baseline TyG was calculated as ln[fasting triglycerides (mg/dL) × fasting plasma glucose (mg/dL)/2]. We classified TyG values as high (≥75th percentile) or low (<75th percentile), and Lp(a) levels, in nmol/L, as <125 or ≥125. Participants were then stratified into four groups: Group-1: Low TyG with Lp(a), <125, Group-2: Low TyG with Lp(a) ≥125, Group-3: High TyG with Lp(a) <125, and Group-4: High TyG with Lp(a) ≥125. We used multivariable Cox regression to estimate the risk of ASCVD (a composite of peripheral arterial disease, coronary artery disease, myocardial infarction, ischemic stroke, and cardiovascular mortality) of TyG and Lp(a) adjusted for the other, and in the four combination groups. Results: Eligible participants (N=254,377) had a mean (SD) age of 56.0 (8.1) years, and 53.2% were female. The median follow-up was 14.6 years. In separate models additionally adjusted for cardiovascular risk factors (see Figure legend), the hazard ratio (HR [95% CI]) for ASCVD was 1.18(1.13–1.23) for Lp(a) ≥125 nmol/L (vs. <125 nmol/L), adjusted for TyG, and 1.09(1.05–1.13) for high TyG (vs. low), adjusted for Lp(a). A statistically significant interaction between TyG and Lp(a) was observed in the fully adjusted model (p <0.001). Compared to Group-1 (low TyG with Lp(a) <125nmol/L), the adjusted HR (95% CI) of incident ASCVD in Group-2, -3 and -4 were: 1.07(1.04–1.13), 1.15 (1.09–1.21) and 1.34(1.25–1.44), respectively (Figure). Conclusions: These findings demonstrate that TyG and Lp(a) are associated with incident ASCVD risk independently of each other. Moreover, TyG modified the effect of Lp(a) on ASCVD, suggesting that insulin resistance may amplify the atherogenic, inflammatory, and/or thrombotic effects of Lp(a), thereby further increasing ASCVD risk.

Abstract 4137424: Circulating Levels of the Pro-Fibrotic Collagen Hormone Endotrophin are Associated with the Risk of Experiencing Major Adverse Cardiovascular Events in Individuals with Type 2 Diabetes – The Thousand&2 Study

Introduction: Cardiovascular disease (CVD) complications are the leading cause of mortality in individuals with type 2 diabetes (T2D). Abnormal extracellular matrix (ECM) remodelling leads to the release of ECM protein fragments into circulation, reflecting these complications. Endotrophin, a pro-fibrotic and -inflammatory hormone, released during collagen type 6 formation, has been linked to adverse outcomes in T2D, but not previously in a long-term perspective. Aim: To assess the 12-year prognostic value of circulating endotrophin levels, measured by PRO-C6, to predict the risk of major adverse cardiovascular events (MACE) in a large cohort of individuals with T2D. Methods: Endotrophin levels were measured with the NordicPRO-C6™ ELISA in 909 serum samples from the Thousand&2 study, which was initiated in 2011 and examined individuals with T2D, with and without known CVD. Clinical data were collected at baseline. Follow-up was 100% complete and performed on the 1 st of May 2024 with the registration of data on MACE from the Danish national registers. The primary outcome was MACE, defined as incident events of hospital admission for ischemic heart disease, heart failure, stroke, or all-cause mortality. PRO-C6 was split into tertiles and examined for survival probability by Kaplan-Meier analysis. Univariate Cox proportional hazard regression analysis was conducted to examine the association between PRO-C6 and the risk of MACE. A multivariable Cox model was additionally conducted, adjusted for age at baseline, sex, systolic blood pressure, duration of diabetes, HbA1c, estimated glomerular filtration rate, use of statins, albuminuria status, and current or prior smoking. Results: The baseline mean (±SD) age of the cohort was 64 (±10) years, 66% were males, mean (±SD) PRO-C6 was 11.9 (±7.01) ng/ml, the median follow-up time was 10.6 years, and number of MACE recorded was 472. The risk of experiencing MACE was significantly higher in the third tertile compared to the first and second tertile (Log-Rank p < 0.001). In the univariate Cox model, the estimated hazard ratio (HR), corresponding to a 2-fold increase of PRO-C6, was HR [95% Confidence Interval(CI)] = 2.1 [1.8-2.4], P <0.001. In the fully adjusted Cox model, PRO-C6 remained significantly associated with the risk of MACE (HR [95% CI] = 1.5 [1.2-1.8], P <0.001). Conclusion: Elevated circulating endotrophin is associated with MACE in T2D, independent of common risk factors.

Association of long-term exposure to ozone with cardiovascular mortality and its metabolic mediators: evidence from a nationwide, population-based, prospective cohort study

Previous studies about chronic effects of ozone (O3) on cardiovascular mortality are scarce and inconclusive. We aimed to investigate the association between cardiovascular mortality and a broad range of long-term O3 exposure levels. This analysis included 3,206,871 participants aged 35-75 years enrolled in the ChinaHEART study. Participants were recruited from the 31 provinces of the Chinese mainland between January 2015 and December 2020. The five-year average O3 concentrations before baseline visits were calculated to represent long-term exposure. Over a median follow-up period of 4.7 (interquartile range: 3.7-6.2) years, 35,553 (1.1%) participants died from cardiovascular diseases (CVD). Following multivariable adjustment, nonlinear relationships were identified between O3 concentrations and CVD and ischemic heart disease (IHD) mortality, with inflection points at 85.44 and 88.15μg/m3, respectively. Above these points, a 10.0μg/m3 increase in the O3 level was associated with a 13.9% (hazard ratio [HR]: 1.139, 95% confidence interval [CI]: 1.096-1.184) and 25.0% (HR: 1.250, 95% CI: 1.151-1.357) greater risk of CVD and IHD mortality, respectively. Conversely, O3 exposure exhibited a linear relationship with ischemic stroke mortality. Moreover, the metabolic factors explained more than half of the association between O3 exposure and CVD mortality. Substantial influences of long-term O3 exposure on CVD mortality were identified, with notable mediation proportions attributed to metabolic factors. These findings could facilitate the air quality standard revisions and risk reduction strategy making in the future. This study was supported by the CAMS Innovation Fund for Medical Science (2021-1-I2M-011), the CAMS Innovation Fund for Medical Science (CIFMS, 2022-I2M-C&T-A-010), the National High Level Hospital Clinical Research Funding (2022-GSP-GG-4), the Ministry of Finance of China and National Health Commission of China, the 111 Project from the Ministry of Education of China (B16005).

Incidence and outcomes of transient new-onset atrial fibrillation complicating acute coronary syndromes: results from a systematic review and meta-analysis

Abstract Background The overall risk of long-term adverse events of a transient episode of new-onset atrial fibrillation (AF) in patients with acute coronary syndrome (ACS) remains uncertain. This meta-analysis aimed to assess the prognostic impact of transient new-onset AF complicating ACS. Methods and results Cohort studies examining the risk of adverse events in patients with transient new-onset AF compared to those in sinus rhythm after ACS were identified through a comprehensive search of MEDLINE, Scopus, Cochrane, and Google Scholar Library. Studies reporting the incidence of ischaemic stroke events, recurrent AF, or all-cause mortality at the longest follow-up were included. Adjusted hazard ratios (aHRs) with 95% confidence intervals (CI) were synthesized using inverse variance-weighted random-effects meta-analysis. In the seven observational studies included, comprising 151 735 patients, 6 597 (4.3%) experienced transient new-onset AF, which was associated with an increased risk of ischaemic stroke, recurrent AF, or all-cause mortality (HR: 2.24, 95% CI: 1.75–2.85; P < 0.0001; I2 = 30.76%; seven studies). The results remained consistent across each individual endpoint, including ischaemic stroke (HR 2.38, 95% CI: 1.64–3.44; P < 0.01; I2 = 50.2%; five studies), recurrent AF (HR 4.68, 95% CI: 2.07–10.59; P = 0.0002; I2 = 50.2%; four studies), and all-cause mortality (HR 1.36, 95% CI: 1.08–1.71; P = 0.0089; I2 = 53.25%; four studies). Meta-regression analyses revealed a significant increase in these adverse events associated with ST-elevation myocardial infarction (P = 0.001), while there was a tendency for their decrease associated with oral anticoagulant prescription at discharge (P = 0.07). Conclusions The occurrence of transient new-onset AF is associated with an elevated long-term risk of stroke, recurrent AF, and all-cause mortality in patients with ACS. Consequently, these data urge randomized clinical trials to assess the best antithrombotic regimen while potentially helping the current treatment decision-making process for these patients.

Comparing ischemic cardiovascular effectiveness and safety between individual SGLT-2 inhibitors and DPP-4 inhibitors in patients with type 2 diabetes: a nationwide population-based cohort study.

This study compared the ischemic cardiovascular events (iCVEs) effectiveness and safety of initiating empagliflozin or dapagliflozin with those of dipeptidyl peptidase-4 inhibitors (DPP-4is), as well as the comparative effects between empagliflozin and dapagliflozin. Using data from the National Health Insurance Service in Korea, patients with type 2 diabetes mellitus (T2DM) who were newly prescribed empagliflozin, dapagliflozin, or DPP-4is from 2016 to 2019 and who did not have a recent CVE history were included. A Cox proportional hazards regression model was used to estimate the adjusted hazard ratio (aHR) with 95% confidence intervals (CIs) for iCVEs and safety events. Empagliflozin and dapagliflozin significantly reduced the risks of ischemic stroke (aHR 0.568, 95% CI 0.408-0.791; aHR 0.612, 95% CI 0.476-0.786, respectively) and all-cause mortality (aHR 0.590, 95% CI 0.442-0.788; aHR 0.730, 95% CI 0.603-0.884, respectively) compared with DPP-4is. Initiating dapagliflozin or empagliflozin was associated with significantly lower incidence of severe hypoglycemia, bone fracture, urinary tract infection, and acute kidney injury than that of DPP-4is. No significant differences were observed between empagliflozin and dapagliflozin in iCVEs and most safety outcomes. Empagliflozin and dapagliflozin showed significant preventive effects on ischemic stroke and all-cause mortality compared with DPP-4is in patients with T2DM, and their protective effects were similar. Both empagliflozin and dapagliflozin were not related to the harmful effects on most safety events. These results suggest that it may be beneficial to initiate empagliflozin or dapagliflozin for ischemic stroke prevention in patients with T2DM. However, further validation studies, such as randomized controlled trials, are needed to generalize these results.

High ABCD2-score after transient ischemic attack is associated with a two-fold higher stroke-rate during long-term follow-up

Abstract Background The ABCD2-score is a validated risk score used to estimate the short-term risk of stroke after transient ischemic attack (TIA). However, "real-world" contemporary data on the long-term risk of stroke after TIA according to ABCD2-score are needed in order to guide preventive strategies. Purpose To determine the long-term risk of stroke after TIA according to modified ABCD2-score (high-risk (≥4 points) versus low-risk (<4 points)). Methods Patients aged ≥18 years with first-time TIA were included from the Danish Stroke Registry (2014-2020). The study population was stratified in high-risk (≥4 points) and low-risk (<4 points) ABCD2-score group. We utilized a modified ABCD2-score consisting of the following parameters: age ≥60 years, hypertension, clinical features, and diabetes. The 3-year risk of ischemic stroke and all-cause mortality was compared between the high-risk and low-risk group using the Aalen-Johansen and Kaplan-Meier estimator. A cox regression model was also conducted. Results In total, 21,433 patients with first-time TIA were included; 1,281 (6.0%) in the high-risk and 20,152 (94.0%) in the low-risk group. Patients in the high-risk group were older (77.5 years [interquartile range [IQR] 70.8-84.1] versus 70.3 years [IQR 60.1-78.2]), more often females (52.2% versus 46.6%) (p <0.001), more comorbid and received more medication compared with the low-risk group at baseline. The 3-year cumulative incidence of stroke was 6.0% [95% CI: 4.6-7.5] in the high-risk group and 4.2% [95% CI: 3.9-4.5] in the low-risk group, and the unadjusted hazard ratio (HR) was 1.6 (95% CI 1.2 – 2.0) (Figure 1). The cumulative incidence of all-cause mortality within three-years after TIA was 28.9% [95% CI: 26.1-31.7] in the high-risk group and 10.3% [95% CI: 9.9-10.8] in the low-risk group. The unadjusted HR was 3.2 (95% CI 2.8 – 3.6). Conclusions Patients with high-risk ABCD2-scores had an almost two-fold higher associated long-term stroke-rate compared to those with low-risk scores. Trials focusing on preventive measures, including evidence-based antithrombotic strategies, especially for the high-risk group are warranted.

Resumption of anticoagulation therapy among Non-Valvular Atrial Fibrillation (NVAF) patients with prior intracranial haemorrhage

Abstract Purpose Resumption of anticoagulation therapy (OAC) in patients with non-valvular atrial fibrillation (NVAF) suffering from intracranial haemorrhage (ICH) is challenging in clinical practice. The aim of this study was to evaluate impact of resumption of OAC on clinical outcomes in NVAF patients with history of ICH. Methods Consecutive patients with NVAF with or without OAC who survived from an index ICH between January 2018 and July 2022 in 16 public hospitals in Hong Kong were identified and analyzed retrospectively. Resumption of OAC was substantiated by new prescription obtained from electronic medical records. Patients were divided into 5 groups: (i) OAC naïve (as reference group); (ii) resume direct oral anticoagulant (DOAC); (iii) resume Vitamin K antagonist (VKA); (iv) discontinue DOAC; (v) discontinue VKA. Risks of ischemic stroke, recurrent ICH and all-cause mortality were estimated for all groups and compared with individuals without OAC, using adjusted sub-distribution hazard ratios (aSHR) derived from Fine and Gray regression models, accounting for death as competing risk, adjusting for components of CHA2DS2VASC and HASBLED scores. Sub-analysis was conducted to compare outcomes between different DOAC agents (i.e, apixaban, dabigatran, edoxaban, rivaroxaban), using VKA as reference among patients who resumed DOAC or VKA. Results Of 982 patients who met inclusion criteria (mean age 77.7±10.9, female 40.9%), 39.1% (n=384) were OAC naive, 32.2% (n=316) resumed DOAC, 12.6% (n=124) resumed VKA, 9.0% (n=88) discontinued DOAC and 7.1% (n=70) discontinued VKA. During a median follow-up period of 2.0 (IQR: 0.7-3.5) years, no statistically significant difference in risk of ischemic stroke was observed among 5 groups. Discontinuation of DOAC was associated with markedly higher risk of ischemic stroke (aSHR=8.32 (1.8-39.3)) only among AF patients with CHA2DS2VASC score ≥ 4, Risk of recurrent ICH was higher in patients who resumed VKA (aSHR=1.6(1.0-2.5)). Sub-analysis demonstrated resumption of apixaban was associated with lowest risk of recurrent ICH (aSHR=0.6(0.4-0.9)). Compared to OAC naïve patients, those who resumed DOAC (aSHR=0.5(0.4-0.7)) had lowest risk of all-cause mortality, whereas discontinuation DOAC (aSHR=1.9(0.4-2.5) and VKA (aSHR=1.6(0.2-2.2)) were both associated with increased mortality. Conclusion Our real-world data revealed among NVAF patients with prior ICH long term discontinuation of OAC was associated with increased risk of ischemic stroke. Recurrent ICH was highest among patients who resumed VKA and lowest with apixaban.

Temporal trends of prescription rates, dosing of non-vitamin K antagonist oral anticoagulants and clinical outcomes in patients with atrial fibrillation

Abstract Background The launch of non-vitamin K antagonist oral anticoagulant (NOAC) has revolutionized the landscape of stroke prevention in atrial fibrillation (AF). We aimed to analyze the temporal trends of prescription rates of oral anticoagulants (OACs), NOAC dosing, clinical outcomes and in patients with AF. Methods This was a retrospective study using the Taiwan National Health Insurance Research Database. During 2011 to 2020, A total of 249,107 patients aged ≥30 years with newly diagnosed AF were identified. We analyzed the 1-year risks of ischemic stroke, intracranial hemorrhage (ICH), and all-cause mortality for overall population and specifically for NOAC users. Results The prescription rate of OAC increased from 22.1% in year 2011 to 57.7% in 2020 (P<0.001) with NOAC accounting for 91.0% of overall OAC prescriptions. Compared to patients with incident AF diagnosed in 2011, there were increasing trends for a greater decrease in the risks of ischemic stroke (adjusted hazard ratios [aHRs] 0.914 in 2012, 0.879 in 2013, 0.925 in 2014, 0.822 in 2015, 0.754 in 2016, 0.763 in 2017, 0.769 in 2018, 0.713 in 2019 and 0.707 in 2020; all P<0.05) and mortality (aHRs 0.903 in 2014, 0.899 in 2015, 0.830 in 2016, 0.808 in 2017, 0.788 in 2018, 0.810 in 2019, 0.788 in 2020; all P<0.05), while the risk of ICH did not change significantly (Figure 1). For NOAC users, the percentages of high-dose NOACs increased from 11.04% in year 2012 to 44.29% in year 2019 to 2020. The increasing trend in the use of high-dose NOACs was temporally associated with a lower risk of ischemic stroke observed for patients receiving NOACs in year 2015 to 2017 (aHR 0.794) and year 2018 to 2020 (aHR 0.688) compared to those in year 2012 to 2014 (Figure 2). Conclusion In this nationwide cohort study, there was an increasing trend of OAC prescription, temporally associated with a decline of the risk of ischemic stroke and mortality. Even among NOACs users, the risk of ischemic stroke declined gradually, partly explained by the increasing prescriptions of high-dose NOACs.

The role of anticoagulation in atrial high-rate episodes: a meta-analysis

Abstract Background The role of anticoagulation in patients with atrial high-rate episodes (AHRE), who have no prior history of atrial fibrillation or atrial flutter, is being extensively studied. Purpose Given the increased thrombo-embolic risk in patients who have atrial high-rate episodes, our aim was to evaluate whether anticoagulation leads to enhanced clinical outcomes compared to no anticoagulation (1). Methods We searched PubMed, EMBASE, and the Cochrane Library, through February 2024, for studies evaluating outcomes in patients with atrial high-rate episodes managed with oral anticoagulation (OAC) compared to those not managed with oral anticoagulation. Outcomes assessed were ischemic stroke, thromboembolic events, major bleeding, and all-cause mortality. A fixed-effects model was used to calculate pooled risk risk ratios (RR) and their 95% confidence intervals (CI). Results A total of 4 studies comprising 6788 patients were included. Anticoagulation was associated with a significant reduction in the risks of ischemic stroke (RR 0.66; 95% CI 0.49 - 0.90; P = 0.0084) and thromboembolic events (RR 0.70; 95% CI 0.55 - 0.89; P = 0.0037). Compared to atrial high-rate episodes not managed with anticoagulation, there was a significantly increased risk of major bleeding with anticoagulation (RR 1.57; 95% CI 1.23 - 2.00; P = 0.0002), while the risk of all-cause mortality was similar (RR 1.07; 95% CI 0.95 - 1.21; P = 0.2437). Conclusion Our study suggests that anticoagulation in patients with atrial high-rate episodes decreases the risks of ischemic stroke and thromboembolic events, while increasing the risk of major bleeding, compared patients not managed with anticoagulation. Our study does not show a mortality benefit with the use of anticoagulation in patients with atrial high-rate episodes. Further studies are needed to confirm the safety and efficacy of anticoagulation in atrial high-rate episodes.Forest Plots of Outcomes Assessed

Impact of protruding and ulcerated aortic atheroma on periprocedural ischemic stroke in patients undergoing transcatheter aortic valve replacement: a comprehensive analysis

Abstract Backgrounds Aortic atherosclerosis has the potential to impact both the strategy and outcomes of transcatheter aortic valve replacement (TAVR). Past research has established a correlation between the thickness and volume of aortic atheroma with periprocedural ischemic stroke and long-term mortality. However, there is limited investigation into the relationship between the morphology of aortic atheroma and outcomes following TAVR. Purpose The study aimed to assess the influence of protruding and ulcerated aortic atheroma on the occurrence of periprocedural ischemic stroke following TAVR. Methods A total of 979 patients who underwent TAVR between February 2012 and May 2019, and had retrospectively available data from contrast-enhanced computed tomography, were included in this analysis. The presence of protruding or ulcerated atheroma was evaluated across four aortic segments: ascending aorta, aortic arch, descending aorta, and abdominal aorta. Protruding aortic atheroma was defined as atheroma with a thickness exceeding 3 mm and protruding components. Ulcerated aortic atheroma was defined as atheroma presenting with ulcer-like disruption of the intima. The primary endpoint assessed was periprocedural ischemic stroke occurring within 48 hours following TAVR. Results The frequencies of protruding and ulcerated aortic atheroma were as follows: 0.2% in the ascending aorta, 6.5% in the aortic arch, 11.1% in the descending aorta, 15.7% in the abdominal aorta, and 24.2% in the entire aorta (Figure 1). Among the 979 patients analyzed, 25 (2.6%) experienced periprocedural ischemic stroke. Patients with protruding or ulcerated aortic atheroma exhibited a significantly higher incidence of periprocedural ischemic stroke compared to those without (5.5% vs. 1.6%, p=0.0010). Multivariate logistic analysis revealed that protruding or ulcerated aortic atheroma, particularly in the aortic arch, independently increased the risk of periprocedural ischemic stroke. (Table 1). Among the subset of patients (309, 34%) undergoing transfemoral TAVR (TF-TAVR) with a self-expandable valve, those with protruding or ulcerated aortic atheroma had a notably higher incidence of periprocedural ischemic stroke compared to those without (9.6% vs. 1.6%, p=0.0083). Conversely, among patients (587, 66%) undergoing TF-TAVR with a balloon-expandable valve, there was no statistically significant difference in the incidence of periprocedural ischemic stroke between those with and without protruding or ulcerated aortic atheroma (4.2% vs. 1.8%, p=0.102). Conclusions Protruding and ulcerated aortic atheroma, particularly in the aortic arch, were linked to a higher risk of periprocedural ischemic stroke post-TAVR. Consequently, careful selection of TAVR strategy, including valve type and procedural approach, is essential for patients with such aortic lesions.Figure 1Table 1

The effect of Glucagon-like peptide-1 receptor agonists on cardiovascular outcomes in type 2 diabetes mellitus patients with coronary artery disease

Abstract Background Cardiovascular disease is the primary cause of mortality in patients with type 2 diabetes mellitus (T2DM). Randomized controlled trials (RCT) have shown that Glucagon-like peptide-1 receptor agonists (GLP-1RA) improve cardiovascular outcomes in T2DM patients, with greater therapeutic benefits observed in patients with established atherosclerotic cardiovascular disease. However, the effect of GLP1-RA therapy on cardiovascular outcomes has been inconsistent and the RCT have not been sufficiently powered to examine the effect of GLP1-RA on mortality or their therapeutic effect in different subgroups of T2DM patients. Purpose This study aimed to examine the effect of GLP1-RA therapy on cardiovascular outcomes and mortality in a real-world cohort of T2DM patients with coronary artery disease (CAD). Methods This study included T2DM patients with CAD who were treated with metformin at a daily dose of ≥ 1g for a period of ≥ 180 days. CAD was defined as ≥ 50% luminal stenosis in any coronary artery segment according to a nationwide angiography and angioplasty registry. We performed sequential emulated target trials at monthly intervals between January 1, 2013 and December 31, 2020 to examine the effect of GLP1-RA therapy on major adverse cardiovascular outcomes (MACE), a composite of myocardial infarction, ischemic stroke and all-cause mortality. Secondary outcomes included the individual components of MACE. Marginal structural models were used to compute pooled effect estimates. This was an intention-to-treat analysis with 5 years of follow-up for each emulated target trial. Inverse probability of treatment weighting was used to adjust for confounding due to differences in patient demographics at baseline. Results This study consisted of 26,746 individuals who were treated with GLP1-RA and 74,638 controls. The 5-year cumulative risk of MACE was 27.7 % in the GLP1-RA group and 32.7 % in the control group (risk ratio 0.85 [95% confidence interval 0.82 – 0.88]). GLP1-RA therapy was associated with a lower risk of all-cause mortality (risk ratio 0.76 [95% confidence interval 0.72 – 0.79]) and myocardial infarction (risk ratio 0.95 [95% confidence interval 0.89 – 1.00]). We found little or no effect of GLP1-RA therapy on the risk of ischemic stroke (risk ratio 1.13 [95% confidence interval 0.97 – 1.27]). Conclusions In this large real-world cohort of T2DM patients with established CAD, we observed that GLP1-RA therapy was associated with a lower risk of MACE, myocardial infarction and all-cause mortality.

The Prognostic Value of a Naples Score in Determining in-Hospital Mortality in Patients with Acute Ischemic Stroke Undergoing Endovascular Treatment.

Background/Objectives: The Naples prognostic score (NPS), reflecting inflammation and nutritional status, has prognostic value, especially in cancer. This study evaluated its ability to predict in-hospital mortality in acute ischemic stroke (AIS) patients undergoing endovascular treatment (EVT). Methods: We retrospectively studied 244 patients with AIS who were admitted between April 2020 and December 2023. Patients were included if they presented within 6 h of symptom onset with evidence of intracranial proximal arterial occlusion. The EVT was performed using aspiration catheters, stent retrievers, or both. The NPS was calculated based on the neutrophil-lymphocyte ratio, lymphocyte-monocyte ratio, and albumin and total cholesterol levels. Results: We found a significant association between higher NPS scores and in-hospital mortality. Patients with a high NPS (3 or 4) had a mortality rate of 41.6% compared to 21.0% in the low-NPS group (0, 1, or 2). The full model incorporating NPS showed superior predictive ability for in-hospital mortality compared with the baseline model (areas under the curve 0.881 vs. 0.808). A receiver-operating characteristic analysis at a cutoff of >2.5 for the NPS showed a sensitivity of 86.6% and specificity of 41.9%. This study demonstrated that incorporating the NPS into the predictive model improved the accuracy and calibration for predicting in-hospital mortality. A decision curve analysis showed the net benefit of using the full model incorporating NPS over the baseline model, emphasizing its potential clinical application in prognostication. Conclusions: NPS is a reliable predictor of in-hospital mortality in AIS patients undergoing EVT. Incorporating NPS into clinical practice could help to identify high-risk patients and improve outcomes through tailored interventions.

Short-term ozone exposure on stroke mortality and mitigation by greenness in rural and urban areas of Shandong Province, China

BackgroundShort-term exposure to ozone (O3) has been associated with higher stroke mortality, but it is unclear whether this association differs between urban and rural areas. The study aimed to compare the association between short-term exposure to O3 and ischaemic and haemorrhagic stroke mortality across rural and urban areas and further investigate the potential impacts of modifiers, such as greenness, on this association.MethodsA multi-county time-series analysis was carried out in 19 counties of Shandong Province from 2013 to 2019. First, we employed generalized additive models (GAMs) to assess the effects of O3 on stroke mortality in each county. We performed random-effects meta-analyses to pool estimates to counties and compare differences in rural and urban areas. Furthermore, a meta-regression model was utilized to assess the moderating effects of county-level features.ResultsShort-term O3 exposure was found to be associated with increased mortality for both stroke subtypes. For each 10-µg/m3 (lag0-3) rise in O3, ischaemic stroke mortality rose by 1.472% in rural areas and 1.279% in urban areas. For each 0.1-unit increase in the Enhanced Vegetation Index (EVI) per county, the ischaemic stroke mortality caused by a 10-µg/m3 rise in O3 decreased by 0.60% overall and 1.50% in urban areas.ConclusionsOur findings add to the evidence that short-term O3 exposure increases ischaemic and haemorrhagic stroke mortality and has adverse effects in urban and rural areas. However, improving greenness levels may contribute to mitigating the detrimental effects of O3 on ischaemic stroke mortality.

The Significance of an Initial Controlling Nutritional Status Score in Predicting the Functional Outcome, Complications, and Mortality in a First-Ever Ischemic Stroke

Background and Purpose: Nutritional status can influence the outcomes and mortality of various diseases. The association between initial nutritional status and ischemic stroke outcomes, however, remains poorly understood. This study investigated whether the Controlling Nutritional Status (CONUT) score at admission could predict functional recovery, complications, and survival following an ischemic stroke. Methods: We enrolled a total of 938 patients experiencing their first acute ischemic stroke and categorized them into three groups based on their CONUT score at admission: CONUT 0–1, CONUT 2–4, and CONUT 5–12. The CONUT score was assessed using the serum albumin, total cholesterol, and lymphocyte count. We evaluated the incidence of complications during their hospital stay. Outcomes, including the Modified Rankin Scale (mRS), Functional Independence Measurement (FIM), Functional Ambulatory Classification (FAC), and mortality, were assessed at baseline, as well as at three and six months post-stroke. Results: CONUT scores were significantly associated with functional outcomes (mRS, FIM, and FAC) and mortality during the six-month follow-up period post-stroke (all p < 0.05). The CONUT 5–12 group exhibited significantly poorer improvements in mRS, FIM, and FAC scores (all p < 0.05) and a lower survival rate (p < 0.01) during the six-month follow-up compared to the CONUT 0–1 and CONUT 2–4 groups. Additionally, the incidence of pneumonia, urinary tract infections, pressure sores, falling injuries, and fractures was significantly higher in the CONUT 5–12 group than in the other groups (all p < 0.01). Conclusions: CONUT scores at admission are associated with functional recovery, mortality, and the incidence of complications following a first-ever ischemic stroke. Consequently, the early identification of patients at risk of malnutrition via CONUT scores can be crucial in enhancing patient assessment after an acute stroke.

Global, regional, and national temporal trends in metabolism-related ischemic stroke mortality and disability from 1990 to 2021

BackgroundStroke ranks as the second leading cause of mortality and the third leading cause of disability worldwide. Nonetheless, the evolving burden of ischemic stroke attributable to various metabolic risk factors remains inadequately elucidated. A thorough grasp of these trends is crucial for a nuanced comprehension of stroke epidemiology and the formulation of effective preventive and interventional measures. MethodBased on the Global Burden of Disease, Injury, and Risk Factors Study 2021 (GBD), we analyzed national temporal trends in the burden of metabolism-associated ischemic stroke in 204 countries and territories globally from 1990-2021, as measured by the average annual percentage change (AAPC), using join-point regression models. The burden of disease was assessed using age-standardized (ASR) mortality rates and disability-adjusted life years (DALY) per 100 000 population. Cross-country inequalities in ischemic stroke burden were quantified using standard health equity methods and changes in ischemic stroke burden were projected to 2045. ResultsGlobally, the ASR for ischemic stroke mortality linked to overall dietary metabolic risk declined by an average of 1.6% annually, while the ASR for disability-adjusted life years saw an average annual decrease of 1.3%. High systolic blood pressure remained a primary contributor to metabolism-related ischemic stroke, accounting for 57.9% of deaths and 58.0% of disability in 2021. Disparities associated with the sociodemographic index (SDI) diminished, with the gap in DALYs between countries with the highest and lowest SDIs narrowing from 592.2 (95% CI: 440.2-744.4) to 480.4 (95% CI: 309.7-651.2) in 2021. Projections indicate a continued decline in overall metabolism-related ischemic stroke deaths, mortality rates, and ASRs through 2045, although an increase in DALYs and ASRs is anticipated within the male population. ConclusionThe global burden of metabolic risk-associated ischemic stroke has generally been decreasing from 2019 to 2021. This study highlights significant challenges in controlling and managing metabolic risk-associated ischemic stroke, including an increase in the number of cases in certain countries and regions, as well as an uneven distribution worldwide. These findings may provide valuable insights for the development of improved public health policies and the rational allocation of healthcare resources.

Endovascular intervention for carotid blowout syndrome and predictors of recurrence: A retrospective and multicenter cohort study

IntroductionCarotid blowout syndrome (CBS) is a potentially life-threatening complication of head and neck cancer and associated treatment. In this study, we assess the safety and efficacy of deconstructive and reconstructive procedures with a focus on CBS recurrence. MethodsWe conducted a multicenter retrospective analysis of a prospectively maintained database and identified 80 consecutive neurointerventions for CBS from 2016 to 2020. Patients were divided into 2 groups: deconstructive embolization (68 patients) and reconstructive stenting (12 patients). A comparative analysis was performed between the two groups. ResultsThe CBS recurrence rate was 23.8 % with 84.2 % of recurrences occurring within 90 days of the primary event. The median time to rebleeding was 8.0 days (IQR: 2.0 – 28.5) with a mortality rate of 26.3 %. There was no significant difference in rates of peri-operative ischemic stroke (1.5 % vs. 0 %, p=0.672) or peri-operative mortality (1.5 % vs. 0 %, p=0.670). CBS recurrence was significantly higher in the reconstructive group (58.3 % vs. 17.6 %, p=0.002). On multivariate analysis, reconstructive stenting independently predicted rebleeding (adjusted hazard ratio 8.31, 95 % CI: 2.34–29.59, p=0.001). There was no significant association between CBS recurrence and pre-operative (p=0.600) or post-operative (p=0.275) anticoagulant/antiplatelet use. ConclusionCBS remains a challenging and potentially catastrophic complication of head and neck cancers. Reconstructive procedures, including stenting, predicted CBS recurrence independent of bleeding site or tumor invasion. Postoperative surveillance based on time intervals to CBS recurrence and engineering advancements including improved vessel reconstruction devices have the potential to reduce rehemorrhage rates and improve patient outcomes. Further clinical investigations amongst larger cohorts are needed.

Value of plasma alpha- and beta-synuclein levels in the diagnosis, severity, and functional outcome of acute ischemic stroke

Abstract OBJECTIVE: We aimed to determine the role of plasma alpha- and beta-synuclein levels and other routine inflammatory parameters in the diagnosis, outcome, and mortality of acute ischemic stroke (AIS). METHODS: In our study, serum alpha- and beta-synuclein levels and clinical data were prospectively evaluated in 93 subjects (43 controls and 50 AIS patients) admitted to the emergency department. The outcome status and prognostic classification were performed according to the modified Rankin Scale (mRS) scores on the 30th day from hospital admission. RESULTS: The mean age of the subjects was 70.6 ± 11 years. Thirty-eight percentage were female. Plasma α-synuclein levels in the AIS group (33.6 ± 8.5 ng/mL) were significantly higher than those in the control group (4.22 ± 2.1 ng/mL) (P < 0.001). Plasma β-synuclein levels in the AIS group (13.07 ± 2.7 ng/mL) were significantly higher than those in the control group (2.17 ± 1.4 ng/mL) (P < 0.001). There was no significant difference in alpha- and beta-synuclein levels between the subgroups formed according to the 30th-day results of the patients using the mRS scores (P = 0.813 and 0.812, respectively). CONCLUSION: The serum alpha- and beta-synuclein concentrations of patients with AIS at admission were significantly higher than the healthy control group. At admission, serum alpha- and beta-synuclein levels do not have definitive clinically predictive value in predicting stroke progression and outcome in patients with AIS.

Left Atrial Appendage Exclusion During Open Cardiac Surgery in Patients without Atrial Fibrillation Reduces 4-Year Ischemic Stroke and Mortality

ObjectiveThis study assessed the impact of surgical left atrial appendage exclusion (LAAE) during cardiac surgery in patients with no preoperative history of atrial fibrillation (NoAF). MethodsReal World Data Insights, an all-payers’ claims database, with approximately 90% Medicare patients was utilized. NoAF patients (>65 years) undergoing open coronary artery bypass (CAB) or valve procedures with/without concomitant surgical LAAE with an epicardial clip between 2015-2020 and a minimum of 2-year follow-up were included. Inverse probability treatment weighting (IPTW) and logistic regression were used. ResultsCAB represented 48.8% (n=29,954) and valve 51.2% (n=31,466) of procedures after adjustment. 30-day postoperative AF (POAF) was present in 12.2% patients (n=175) for LAAE and 5.8% (n=3,485) for no-LAAE (P<0.01). By day 90 after surgery rates of new AF were similar between groups through 4-year follow-up. During 4 years of follow-up more patients received oral anticoagulation (OAC) with LAAE (P<0.01). LAAE had 28% lower adjusted ischemic stroke odds (OR 0.72, CI 0.53 – 0.98, p=0.02) and 34% lower adjusted all-cause mortality (OR 0.66, CI 0.52-0.85, p<0.01). In patients who developed POAF, LAAE+OAC showed 74% lower odds of adjusted ischemic stroke (OR 0.26, CI 0.10 – 0.70, P=0.01) and 58% lower odds of adjusted all-cause mortality (OR 0.42, CI 0.18 – 1.01, P=0.05) than no-LAAE+OAC therapy alone. ConclusionLAAE during open cardiac surgery in patients with NoAF was safe, associated with higher POAF, and lower ischemic stroke and all-cause mortality. Randomized controlled studies are ongoing in a similar population.

Revisiting Left Atrial Appendage Closure Versus Oral Anticoagulants in Recurrent Atrial Fibrillation Management: An Updated Systematic Review and Meta-Analysis.

Atrial fibrillation (AF) is a significant public health problem due to its association with coronary heart disease, stroke, and mortality, especially in the elderly. Therefore, traditional warfarin therapy, direct oral anticoagulants (DOACs), and the recent left atrial appendage closure (LAAC) have been compared as treatment approaches. In this regard, we aimed to synthesize the current evidence regarding the comparison these mentioned modalities in patients with AF. A comprehensive database search for records comparing LAAC and DOACs in patients with AF was conducted until December 15, 2023. An updated meta-analysis was conducted using fixed and random effect models to calculate odds ratios (OR) or mean differences (MD) with 95% confidence intervals (CIs) for dichotomous and continuous outcomes, respectively. Eleven studies were eligible that included a total of 68171 patients. Compared to DOACs, the LAAC group had a lower rate of hospital stay duration (MD -1.23; 95% CI -1.51 to -0.95;p< 0.001). There was no statistically significant difference between LAAC and DOACs in terms of the composite outcome of stroke, systemic embolism, cardiovascular death, all-cause mortality, ischemic stroke and thromboembolic events ischemic, major bleeding and cardiovascular mortality (OR 0.83, 95% CI 0.27-2.48,P= 0.73).Our meta-analysis showed a lower rate of hospital stay duration that favors LAAC. However, the risk of composite outcomes of stroke, systemic embolism, cardiovascular death, all-cause mortality, ischemic stroke, thromboembolic events, ischemic stroke, major bleeding, and cardiovascular mortality was similar between the two treatment groups.

Systemic immune-inflammation index predicts short-term mortality in acute ischemic stroke with severe stenosis of internal carotid artery associated pneumonia.

We aimed to investigate the relationship between systemic immune-inflammation index (SII) and short-term mortality in acute ischemic stroke (AIS) with internal carotid artery (ICA) severe stenosis and stroke associated pneumonia (SAP) patients. Information on general demographic, laboratory data, CT angiography, magnetic resonance angiography, or digital subtraction angiography were obtained. The predictive power was evaluated by assessing the area under the receiver operating characteristic (ROC) curve. The logistic regression was performed to assess the association of SII and short-term mortality in severe stenosis ICA-AIS and SAP patients. Among 342 patients with severe stenosis ICA-AIS and SAP, death occurred in 66 patients during 120 days follow-up. Multivariate regression analyses indicated that increased SII predicts higher mortality in 120 days follow-up, and the risk of short-term mortality in SII>666.31 × 109/L group is increased 4.671-fold. Patients with SII>666.31 × 109/L had higher proportion of male, hypertension, smoking, higher admission NIHSS score, higher systolic blood pressure, and higher proportion of 120 days mortality. Higher SII predicted a worse 120 days mortality was worked out by Kaplan-Meier methods. An elevated SII was remarkably associated with 120 days mortality in severe stenosis ICA-AIS and SAP patients.