Ischemic Stroke.

This concise review of the epidemiology, pathophysiology, evaluation, acute management, and prevention of ischemic stroke targets internists, family practitioners, and emergency physicians who manage patient with stroke.

Trends, Predictors and Outcomes of Ischemic Stroke Among Patients Hospitalized with Takotsubo Cardiomyopathy.

OBJECTIVES: This study assessed the temporal trends in the incidence of ischemic stroke among patients hospitalized with takotsubo cardiomyopathy (TCM) stratified by the subtypes of ischemic stroke (cardioembolic versus thrombotic). Predictors of each stroke subtype, the association with atrial fibrillation (AF), the occurrence of ventricular fibrillation/ventricular tachycardia (VF/VT), cardiogenic shock (CS), in-hospital mortality, length of stay (LOS), and total healthcare cost were also assessed. BACKGROUND: Ischemic stroke in TCM is thought to be primarily cardioembolic from left ventricular mural thromboembolism. Limited data are available on the incidence of thrombotic ischemic stroke in TCM. MATERIALS AND METHODS: We identified 27,970 patients hospitalized with the primary diagnosis of TCM from the 2008 to 2017 National Inpatient Sample, of which 751 (3%) developed ischemic stroke. Of those with ischemic stroke, 571 (76%) had thrombotic stroke while 180 (24%) had cardioembolic stroke. Cochrane armitage test was used to assess the incidence of thrombotic and cardioembolic strokes and multivariate regression was used to identify risk factors associated with each stroke subtype. We compared the incidence of AF, VF/VT, CS, LOS, in-hospital mortality and total cost between hospitalized patients with TCM alone to those with cardioembolic and thrombotic strokes. RESULTS: From 2008 - 2017, the incidence of thrombotic stroke (4.7%-9.5% (p< 0.0001) increased while it was unchanged for cardioembolic stroke (0.5%-0.7% P=0.5). In the multivariate regression, peripheral artery disease, prior history of stroke, and hyperlipidemia were significantly associated with thrombotic stroke, while CS, AF, and Asian race (compared to White race) were associated with cardioembolic stroke. Both cardioembolic and thrombotic strokes were associated with higher odds of IHM, AF, CS, longer LOS and increased cost. Trends in in-hospital mortality and the utilization of thrombolysis, cerebral angiography, and mechanical thrombectomy among patients with TCM and ischemic stroke were unchanged from 2008 to 2017. CONCLUSION: Among patients with TCM and ischemic stroke, thrombotic stroke was more common compared to cardioembolic stroke. Ischemic stroke was associated with poorer outcomes, including higher in-hospital mortality and increased healthcare resource utilization in TCM.

Association of alcohol consumption with prognosis of ischemic stroke by subtype in different follow-up periods: a hospital-based study in China.

OBJECTIVES: Alcohol consumption is a risk factor for stroke. However, there are no available data on the effect of alcohol consumption on the long-term outcome of ischemic stroke in China. Therefore, this study aimed to explore the association of alcohol consumption with the prognosis of ischemic stroke by subtype in different follow-up periods after stroke. METHODS: This 12-month follow-up study recruited 3830 acute ischemic stroke patients from Tianjin, China, between 2016 and 2018. Patients were categorized into two groups according to their consumption of alcohol. Differences in mortality, recurrence, and dependency rates at 3 and 12 months after stroke were compared between both groups. RESULTS: The mortality, recurrence, and dependency rates at 12 months after stroke were significantly higher in patients who previously consumed alcohol than in those without previous alcohol consumption (all P < 0.005). A similar trend was observed for mortality rate at 3 months after stroke (P < 0.001). The risk of death at 3 months after an atherothrombotic stroke decreased by 63.4% (relative risk [RR], 0.366; 95% confidence interval [CI], 0.144-0.935) among patients who previously consumed alcohol compared with those who never consumed alcohol. Moreover, for patients with small artery disease classified according to the Trial of ORG 10,172 in Acute Stroke Treatment (TOAST), the recurrence and dependency rates at 12 months after stroke decreased by 49.2% (RR, 0.508; 95% CI, 0.259-0.996) and 49.5% (RR, 0.505; 95% CI, 0.258-0.990), respectively, among patients who consumed alcohol. CONCLUSIONS: Previous alcohol consumption decreased the risk of death at 3 months after stroke among patients with atherothrombotic stroke according to the TOAST classification. Furthermore, for patients with small artery disease (according to TOAST classification), alcohol consumption significantly decreased the risk of recurrence and dependency at 12 months after stroke. This study highlights an urgent need to quantify the association of alcohol consumption with outcomes after stroke in China to improve stroke prognosis.

Transdermal oestradiol for androgen suppression in prostate cancer: long-term cardiovascular outcomes from the randomised Prostate Adenocarcinoma Transcutaneous Hormone (PATCH) trial programme.

BACKGROUND: Androgen suppression is a central component of prostate cancer management but causes substantial long-term toxicity. Transdermal administration of oestradiol (tE2) circumvents first-pass hepatic metabolism and, therefore, should avoid the cardiovascular toxicity seen with oral oestrogen and the oestrogen-depletion effects seen with luteinising hormone releasing hormone agonists (LHRHa). We present long-term cardiovascular follow-up data from the Prostate Adenocarcinoma Transcutaneous Hormone (PATCH) trial programme. METHODS: PATCH is a seamless phase 2/3, randomised, multicentre trial programme at 52 study sites in the UK. Men with locally advanced or metastatic prostate cancer were randomly allocated (1:2 from August, 2007 then 1:1 from February, 2011) to either LHRHa according to local practice or tE2 patches (four 100 µg patches per 24 h, changed twice weekly, reducing to three patches twice weekly if castrate at 4 weeks [defined as testosterone ≤1·7 nmol/L]). Randomisation was done using a computer-based minimisation algorithm and was stratified by several factors, including disease stage, age, smoking status, and family history of cardiac disease. The primary outcome of this analysis was cardiovascular morbidity and mortality. Cardiovascular events, including heart failure, acute coronary syndrome, thromboembolic stroke, and other thromboembolic events, were confirmed using predefined criteria and source data. Sudden or unexpected deaths were attributed to a cardiovascular category if a confirmatory post-mortem report was available and as other relevant events if no post-mortem report was available. PATCH is registered with the ISRCTN registry, ISRCTN70406718; the study is ongoing and adaptive. FINDINGS: Between Aug 14, 2007, and July 30, 2019, 1694 men were randomly allocated either LHRHa (n=790) or tE2 patches (n=904). Overall, median follow-up was 3·9 (IQR 2·4-7·0) years. Respective castration rates at 1 month and 3 months were 65% and 93% among patients assigned LHRHa and 83% and 93% among those allocated tE2. 157 events from 145 men met predefined cardiovascular criteria, with a further ten sudden deaths with no post-mortem report (total 167 events in 153 men). 26 (2%) of 1694 patients had fatal cardiovascular events, 15 (2%) of 790 assigned LHRHa and 11 (1%) of 904 allocated tE2. The time to first cardiovascular event did not differ between treatments (hazard ratio 1·11, 95% CI 0·80-1·53; p=0·54 [including sudden deaths without post-mortem report]; 1·20, 0·86-1·68; p=0·29 [confirmed group only]). 30 (34%) of 89 cardiovascular events in patients assigned tE2 occurred more than 3 months after tE2 was stopped or changed to LHRHa. The most frequent adverse events were gynaecomastia (all grades), with 279 (38%) events in 730 patients who received LHRHa versus 690 (86%) in 807 patients who received tE2 (p<0·0001) and hot flushes (all grades) in 628 (86%) of those who received LHRHa versus 280 (35%) who received tE2 (p<0·0001). INTERPRETATION: Long-term data comparing tE2 patches with LHRHa show no evidence of a difference between treatments in cardiovascular mortality or morbidity. Oestrogens administered transdermally should be reconsidered for androgen suppression in the management of prostate cancer. FUNDING: Cancer Research UK, and Medical Research Council Clinical Trials Unit at University College London.

Bioinformatics Gene Analysis of Potential Biomarkers and Therapeutic Targets for Unstable Atherosclerotic Plaque-Related Stroke.

Atherosclerotic plaque instability is a major cause of ischemic stroke. Researchers must develop novel strategies for the detection and treatment of unstable atherosclerotic plaque (UAP)-related stroke. We aimed to identify potential biomarkers and therapeutic targets of UAP-related stroke. Differentially expressed genes (DEGs) of UAP, ischemic stroke and smoking were identified by microarray analyses from the Gene Expression Omnibus. Gene Ontology (GO) and pathway functional enrichment analyses of DEGs were performed to analyze plaque destabilization and ischemic stroke physiopathology. An integrative analysis of UAP, ischemic stroke and smoking DEGs and functional annotations was performed to identify the underlying physiopathology and hub genes in UAP-related stroke and the relationship with smoking. Online search databases were applied to confirm hub gene biofunctions and their relationships with atherosclerosis and cerebrovascular diseases. Following integrative analysis, 18 co-DEGs of UAP and ischemic stroke, including 17 upregulated and one downregulated, were identified. Inflammation, immunity, extracellular matrix degradation, blood coagulation, apoptosis and nerve degeneration were the primary physiopathological processes in UAP-related stroke. Hub genes included MMP9, ITGAM, CCR1, NCF2 and CD163, among which MMP9 and ITGAM were top 10 genes for both UAP and stroke. Smoking may upregulate MMP9, NCF2, C5AR1 and ANPEP to accelerate plaque destabilization and UAP-related stroke. MMP9, ITGAM, CCR1, NCF2, CD163, hsa-miR-3123 and hsa-miR-144-3p are potential diagnostic and prognostic biomarkers of UAP-related stroke. MMP9 and ITGAM are potential therapeutic targets of UAP-related stroke, which will contribute to the development of novel management strategies.

Long-term prognostic utility of low-density lipoprotein (LDL) triglyceride in real-world patients with coronary artery disease and diabetes or prediabetes.

BACKGROUND: Recent guidelines highlighted the association between atherosclerosis and triglyceride-enriched lipoproteins in patients with impaired glucose metabolism. However, evidence from prospective studies for long-term prognostic utility of low-density lipoprotein triglyceride (LDL-TG) in real-world patients with prediabetes (Pre-DM) or diabetes mellitus (DM) and coronary artery disease (CAD) is currently not available. The aim of the present study was to evaluate the impact of LDL-TG on major adverse cardiovascular events (MACEs) in patients with stable CAD under different glucose metabolism status. METHODS: A total of 4381 patients with CAD were consecutively enrolled and plasma LDL-TG level was measured by an automated homogeneous assay. They were categorized according to both status of glucose metabolism [DM, Pre-DM, normal glycaemia regulation (NGR)] and tertiles of LDL-TG. All subjects were followed up for the occurrence of MACEs. RESULTS: During a median of 5.1 (interquartile range 3.9 to 5.9) years' follow-up, 507 (11.6%) MACEs occurred. Cubic spline models showed a significant association between LDL-TG and MACEs in DM and Pre-DM but not in NGR. When the combined effect of elevated LDL-TG and glucose disorders was considered for risk stratification, the medium tertile of LDL-TG plus DM, and the highest tertile of LDL-TG plus Pre-DM or plus DM subgroups were associated with significantly higher risk of MACEs after adjustment of confounders including triglyceride [hazard ratios (95% confidence intervals): 1.843 (1.149-2.955), 1.828 (1.165-2.867), 2.212 (1.396-3.507), all p < 0.05]. Moreover, adding LDL-TG into the original model increased the C-statistic from 0.687 to 0.704 (∆C-statistic = 0.016, p = 0.028) and from 0.734 to 0.749 (∆C-statistic = 0.014, p = 0.002) in Pre-DM and DM, respectively. CONCLUSIONS: In this longitudinal cohort study on real-world practice, higher LDL-TG was associated with worse outcomes among Pre-DM and DM patients with stable CAD.