Acute Cerebrovascular Events Research Articles

Atrial Fibrillation in Patients with Very High Risk for Stroke and Adverse Events—Insights from the Observational ARENA Study

Background: Atrial fibrillation (AF) is a major cause of stroke. An individual risk estimation remains challenging, as AF patients with and without cerebrovascular event (CVE) may differ in yet unknown factors beyond those covered by the CHA2DS2-VASc score. We aimed to identify differences between AF patients with and without CVE with regard to AF characteristics and treatment, vascular risk factors and comorbidities, prognosis and outcome. Methods: We analyzed patients included in the Atrial Fibrillation Rhine-Neckar Region (ARENA) Project, an observational cohort study of patients with AF. Patients were recruited by their general practitioner or during a hospital stay and were divided into two groups for the present analysis: patients with acute CVE at baseline and/or history of CVE versus patients without CVE. Follow-up at 1 year was conducted via phone call. Results: Of 2061 included patients (60.6% male), 292 (14.2%) belonged to the CVE group. Patients in the CVE group were older (mean age 74.6 versus 71.7 years; p < 0.001) and had a higher CHA2DS2-VASc score at baseline (5.3 versus 3.3 points; p < 0.001) based on the preceding CVE. Moreover, patients with either acute or chronic CVE had a larger left atrium (median diameter 47/46 mm versus 44 mm; p = 0.001). Patients with acute CVE had structural heart diseases (p < 0.001) less frequently than patients with previous or without CVE. Mortality at 1 year (HR 1.95; 95%-CI 1.37–2.78) was more frequent in the CVE group (p < 0.001). During 1-year of follow-up, stroke occurred more frequently in survivors with CVE (2.9% versus 0%; p < 0.001). Conclusions: AF patients with CVE have a significantly worse prognosis than AF patients without CVE. Atrial structural remodeling, underlying cardiovascular disease, stroke-induced heart injury and further unidentified factors may account for this finding. Characterization of AF patients including echocardiography to detect atrial structural remodeling may be helpful in risk stratification beyond classical scores.

Factors associated with major adverse cardiovascular events among Arabs and Jews in Israel: a population-based cohort study

Abstract Introduction Arabs in Israel are at higher risk of cardiovascular mortality; however, there are no data on factors associated with disparities in major adverse cardiovascular events (MACE) incidence among Arabs and Jews. Purpose To study factors associated with MACE incidence among Arabs and Jews in Israel. Materials and Methods This is a cohort study carried out in urban localities of Hadera District in Israel. The study sample included 1,100 participants, stratified in equal numbers by ethnicity (Arab and Jewish), sex, and five 10-year age group (mean age: 51 years, range: 26-77). Data collected via in-person interviews conducted between 2001-2006 included socio-demographic characteristics and health-related behaviors (smoking, physical activity, and diet). Data on baseline diabetes, hypertension, dyslipidemia, and cardiovascular disease were collected from interviews and participants' health records. Information on MACE occurring during follow-up was determined based on hospital discharge diagnoses, recorded in the Israel Ministry of Health hospital admission database. MACE was defined as an acute coronary, cerebrovascular or peripheral artery event, or invasive procedure for its treatment. Factors associated with the time to first MACE were tested in Cox proportional hazards models. Sensitivity analysis included death from any cause as a competing risk, using Fine and Gray’s model. Results During a median follow-up period of 20 years, there were 221 first MACE during follow-up; 91 among Jewish participants and 130 among Arab participants, hazard ratio (HR) Arab vs. Jewish: 1.59; 95% confidence interval (CI) 1.22, 2.09, adjusted for age and sex. Arab ethnicity was no longer significantly associated with MACE, following further adjustment for years of education; HR: 1.32; 95%CI 0.95, 1.84. The HR (95%CI) associated with ethnicity after additional adjustment for health-related behaviors, body weight and baseline chronic morbidity was 1.02 (95%CI: 0.73, 1.42). A subgroup analysis among 950 participants, who did not have a baseline diagnosis of cardiovascular disease, produced similar results. These participants experience 147 first MACE during follow-up. The age and sex-adjusted HR (95%CI) associated with Arab ethnicity was 1.72 (1.23, 2.40), compared to 1.08 (0.72, 1.64) in a fully adjusted model. Competing risk analysis did not materially change these results. Conclusions Arabs in Israel are at higher risk for MACE. Lower socioeconomic position and higher prevalence of unhealthy lifestyle and cardiovascular risk factors may explain the excess risk of MACE among Arabs. Improving cardiovascular health among Arabs should consider social determinants of health and cultural aspects.

Ankle brachial index,a non invasive tool predicts cardiovascular events after acute myocardial infarction:a 3 year follow -up study

Abstract Background / Introduction The ankle-brachial index (ABI) is a non-invasive tool that was initially used for the diagnosis of lower-extremity peripheral artery disease (PAD). It has been proven that ABI is a marker of atherosclerosis in other vascular sites and can therefore be used to predict cardiovascular events regardless the presence or not of PAD symptoms. Purpose This study aims to examine the prognostic value of ABI in the setting of acute myocardial infarction (MI), as up till now there is not enough relevant evidence. Method We followed up 441 patients [79% male;mean age 62 years;67% hypertnesive; 30% with diabetes mellitus (DM); 52% current smokers] who were hospitalized because of MI for a period of three years. All patients underwent baseline estimation of clinical and laboratory parameters during theri hospitalization.The ABI was measured according to established methodology using a certified automated device and abnormal ABI defined as a value ≤ 0.9. The primary endpoint was a composite of all-cause and cardiovascular death, as well as major cardiovascular events including decompensated heart failure, new acute coronary syndrome, cerebrovascular event, malignant arrhythmia, PAD event and new onset renal dysfunction. All events were assessed both in-hospital and within 3 years of follow-up. Results Our study population had a mean ABI of 1.1 (IQR: 1.00 to 1.18). With the use of reduced multivariate regression models ABI was proven to be a prognostic indicator for the in-hospital composite endpoint. Patients with an abnormal ABI had a threefold risk of in-hospital events [HR 2.93, 95% CI: 1.48-5.81, p=0.002]. After conducting multivariate analysis ABI maintained its predictive power of all-cause mortality [HR 2.88, 95% CI: 1.53 – 5.42, p=0.001], regardless of hypertension DM, LDL levels and smoking status of the study population in 3 years follow-up. Conclusion An impaired ABI is associated with greater risk of in-hospital events in patients with acute MI. Moreover, ABI emerges as an independent predictor of long-term all-cause mortality in those patients.The findings of this study suggest that subclinical and clinical PAD are associated with poor outcomes among patients with acute MI; thus, routine ABI tests enhance risk stratification and might carry important prognostic significance in these patients regardless of PAD symptoms.

Novel risk score for predicting acute cardiovascular and cerebrovascular events after chest radiotherapy in patients with breast or lung cancer.

Radiation therapy (RT) is an integral component of cancer therapy but associated with adverse events. Our goal was to establish risk prediction models for major adverse cardiovascular and cerebrovascular events (MACCE) after chest RT. A retrospective study of lung/breast cancer patients who had chest RT with planning CT at Mayo Clinic between 01/2010 and 01/2014. Predictive models were developed based on weighted independent predictors using a derivation (406 lung and 711 breast cancer) and validation cohort (179 lung and 234 breast cancer). Patient characteristics, pre-RT CT for coronary artery calcification (CAC), and post-RT MACCE data were reviewed. Post-RT MACCE occurred in 6.1 and 5.6% in the derivation and validation cohort over a mean follow-up of 42 ± 13 months. Post-therapy model (C2AD2) included CAC (two points), MACCE history (two points), age ≥74 (three points), DM (two points), and mean heart radiation dose ≥ 850 mGy (two points), and pre-therapy model (C2AD) included post-therapy model parameters minus mean heart radiation dose. Both models stratified patients into three risk groups: low (0-2), intermediate (3-5), and high (≥6). Post-RT MACCE across these groups were 2.7, 8.9, and 19.8% in the derivation, and 3.9, 6.6, and 16.4% in the validation cohort for post-therapy model (C2AD2) and 2.8, 9.2, and 20.4% in the derivation and 3.7, 9.2, and 13.2% in the validation cohort for pre-therapy model. Both models showed statistically significant graded survival outcome. Post-therapy (C2AD2) and pre-therapy (C2AD) models are simple, easy to use and effective tools to stratify breast and lung cancer patients undergoing chest radiation for post-RT MACCE.

Preventability of ischemic stroke/transient ischemic attack in a tertiary care center in Argentina

IntroductionCardiovascular disease remains a leading cause of morbidity and mortality worldwide, with many individuals presenting with acute ischemic stroke or transient ischemic attack (AIS/TIA) due to underlying vascular risk factors (VRF). While these patients typically undergo routine evaluations for acute treatment, the prevention of these conditions is often underestimated. This study reports the prevalence of non-optimized VRF and estimates their degree of avoidability in a cohort of patients treated in a tertiary care center following AIS/TIA. MethodsThis retrospective study enrolled patients older than 18 years who experienced AIS/TIA over a two-year period. Preventability was defined as the degree to which an acute cerebrovascular event could have been prevented if the VRF had been appropriately treated. Using the variables determined at the onset of AIS or TIA, we developed a 10-point scale to classify the degree of preventability (not preventable [score of 0], low preventability [score of 1–3], and high preventability [score of 4 or higher]). We further defined sub-scores based on the effectiveness of treatment of high blood pressure [HBP] (0-2 points), dyslipidemia [DLP] (0-2 points), atrial fibrillation [AF] (1 point), active smoking [AS] (1 point), obesity (1 point), previous coronary heart disease [CHD] (1 point), and previous AIS/TIA (2 points). Demographic factors, etiologies, and imaging findings were evaluated, tabulated independently, and subsequently correlated with clinical findings extracted from the available patient records. ResultsOf the 395 patients (334 with AIS and 61 with TIA), 376 (95.19 %) exhibited some degree of preventability, whereas 19 (4.81 %) presented with a nonpreventable event. In total, 296 (74.94 %) presented a low preventable event, and 80 (20.25 %) presented a high preventable event. Applying the Chi-square test of independence to stroke etiology highlighted cardio-aortic embolism and large artery atherosclerosis as groups with a significantly higher burden of risk factors necessitating intervention, while patients with stroke of other etiologies had more adequate control of VRF. In terms of stroke severity, as determined by the National Institutes of Health Stroke Scale (NIHSS), patients with NIHSS scores >5 were more likely to experience preventable events. According to the ABCD2 score, higher risk scores were significantly associated with a higher preventive factor burden; however, age, sex, vascular territory, and Canadian TIA scores were not related to the prevention of AIS/TIA. ConclusionsThe high percentage of preventable events reflects the need to study other factors that may contribute to unhealthy lifestyles in this population. Potential reasons for poor health include high levels of stress, sleep deprivation, working conditions and an unhealthy diet. Further studies are required to better understand these phenomena.

Summary of the 2023 European Society of Cardiology clinical guidelines on the management of cardiovascular disease in patients with diabetes mellitus

The prevalence of cardiovascular diseases (CVDs) is well known. According to the World Health Organization (WHO), almost 18 million people die from CVDs worldwide every year, accounting for 31% of all causes of death [1]. CVDs often develop concomitantly with diabetes mellitus (DM), with approximately 20% of cardiovascular deaths attributed to elevated blood glucose levels [2]. Notably, CVDs are the leading cause of death among patients with type 2 diabetes (T2DM). Based on data from the Federal Register of Diabetes 2022 in Russia, chronic heart failure was the direct cause of death in 24.2% of T2DM cases, followed by acute heart failure (13.1%), cerebrovascular events (10.0%), and myocardial infarction (3.7%) [3].The pathophysiological interplay between atherosclerotic cardiovascular disease and DM has led to a situation where cardiologists are increasingly involved in the treatment of patients with DM, while endocrinologists are encountering a growing number of patients with CVDs. This association has become so apparent that in a recent article published in the European Journal of Cardiology, Yu. Braunwald speculated about the emergence of a new subspecialty - diabetocardiology [4]. Unfortunately, experts predict that the global number of diabetic patients will reach 783 million [5].Recent data on the CV benefits of certain hypoglycemic drugs (primarily, certain SGLT2 inhibitors, several GLP-1 receptor agonists, and a novel non-steroidal mineralocorticoid receptor antagonist finerenone) prove the need for a unified interdisciplinary approach to managing CVDs and DM.Given the importance of integrated and coordinated efforts in managing patients with CVD and DM, the Task Force of the -European Society of Cardiology (ESC) updated, formulated, and published clinical guidelines on the treatment of CVD in diabetic patients in 2023 [6]. This article provides a concise overview of the key provisions outlined in the guidelines.

Procedural safety of rotational atherectomy and modified balloon angioplasty: insights from a German national registry.

Modified balloons (MB) and rotational atherectomy (RA) are recommended tools for treatment of coronary plaques with superficial calcium. Knowledge about in-hospital safety is limited. Patients with coronary artery disease who underwent coronary angiography with RA or MB angioplasty in Germany were identified via ICD and OPS codes from 2017 to 2020. Acute coronary syndromes were excluded. Since patients were not randomized toward MB or RA, potential confounding factors were taken into account using the propensity score methods. Thereby, inverse probability weighting was applied. Ten thousand.ninety-twopatients underwent RA with an increasing trend from 1817 in 2017 toward 3166 in 2020. MBs were used in 22,378 patients also with an increasing trend from 4771 in 2017 toward 6078 in 2020. Patients receiving RA were older (74.23 ± 8.68 vs. 71.86 ± 10.02, p < 0.001), had a higher Charlson Comorbidity Index (2.07 ± 1.75 vs. 1.99 ± 1.76, p = 0.001) and more frequently left main (17.96% vs. 12.91%, p < 0.001) or three vessel disease (66.25% vs. 58.10%, p < 0.001). Adjusted procedural risk of major adverse cardiac and cerebrovascular events (MACCE) was similar in both groups, while pericardial effusion (RR 2.69; 95% CI 1.88-3.86, p < 0.001), pericardial puncture/pericardiotomy/pericardial tamponade (RR 2.66; 95% CI 1.85-3.81, p < 0.001) and bleeding (RR 1.65; 95% CI 1.12-2.43, p < 0.011) occurred more frequently in patients receiving RA. Patients treated with RA at high volume centers were hospitalized shorter (p = 0.005) and had a lower rate of acute cerebrovascular events (p < 0.001). Rate of MACCE, bleeding and pericardial puncture were not influenced by the annual RA numbers per center. MBs had a lower risk of bleeding and pericardial puncture. Patients treated at centers with high annual RA procedure numbers had a lower risk of acute cerebrovascular events and were hospitalized shorter.

Risk Factors, Clinical Profile, and Outcomes of Coronary Artery Disease in the Elderly

Objectives This study aimed to identify risk factors in patients diagnosed with angiographically significant coronary artery disease (CAD) after 65 years of age (elderly) with a subset analysis of more than 75 years, analyze their clinical, angiographic profile and assess their major acute cardiovascular and cerebrovascular events (MACCE). Methods This was an observational retrospective and prospective study conducted from January 2022 to June 2023 among consecutive elderly who underwent CAG for suspected or diagnosed CAD between 2010 and 2018 at a tertiary center in South India. Results A total of 1,511 patients satisfied eligibility criteria with mean age of 69.38 years and male preponderance (69%). Male gender, dyslipidemia and current tobacco use contributed to angiographically significant CAD by multiple logistic regression analysis but none of the risk factors contributed in the more than 75-year age group. Female patients had higher incidence of atypical presentation, less revascularizations and higher MACCE. Fourteen percent of patients with significant CAD developed MACCE over a median 3.5-year hospital follow-up. Survival analysis of 1,027 patients with significant CAD showed one, three, 5-year mortality rate of 4.3%, 6.9% and 10.8%, respectively, with left ventricular dysfunction and triple vessel disease being associated with worse survival. MACCE and 5-year survival was significantly better among those who underwent revascularization including those with significant left main or triple vessel disease. Conclusion This study showed a high prevalence of traditional risk factors in elderly patients among which male gender, dyslipidemia, current tobacco use were found to predict angiographically significant CAD. Triple vessel disease and left ventricular dysfunction were associated with worse survival. Mortality was significantly lower among elderly who underwent revascularization compared to medical management.

Cardiac Findings Following Cerebrovascular Disease.

Accumulating evidence suggests that cardiac findings after stroke are an important, yet understudied, manifestation of brain-heart interactions. Our aim was to investigate and compare cardiac findings after different cerebrovascular events (acute ischemic stroke, transient ischemic attack, and hemorrhagic stroke). There were 7113 patients screened who were treated between December 2013 and December 2020 at the University Hospital Zurich for ischemic stroke, transient ischemic attack, and hemorrhagic stroke. Seven hundred twenty-one patients without evidence of previous cardiac disease or presumed cardioembolic origin of their cerebrovascular disease and with at least 1 cardiac checkup were included. Clinical reports from the year following disease onset were screened for new cardiac findings, which were categorized as arrhythmia/electrocardiographic changes, myocardial alterations, valvular abnormalities, and coronary perfusion insufficiency. Differences in proportions of findings among groups were analyzed using the Pearson χ2 test or Fisher exact test. ECG changes were observed in 81.7% (n=474) of patients with ischemic stroke, 71.4% (n=70) of patients with transient ischemic attack, and 55.8% (n=24) of patients with hemorrhagic stroke (P<0.001). Myocardial alterations occurred often in all 3 groups (60.9% ischemic stroke [n=353], 59.2% transient ischemic attack [n=58], 44.2% hemorrhagic stroke [n=19]; P=0.396). Cardiac findings are frequent in patients with cerebrovascular disease, even without prior cardiac problems or suspected cardiac cause. Similarities, especially between patients with ischemic stroke and transient ischemic attack, were observed. Our data suggest that all patients with acute cerebrovascular events should receive thorough workup searching for cardiac manifestations.

A novel imaging biomarker for prediction of cerebrovascular ischemic events: Pericarotid fat density

BackgroundTo investigate the relationship between pericarotid fat density measured in carotid CTA and vulnerable carotid plaque. MethodsThis retrospective study included 374 participants who underwent carotid CTA between June 1, 2021, and December 1, 2021 (234 males, median age 68 years [interquartile range: 61–75]). Two groups, symptomatic and asymptomatic, were defined based on either diffusion-weighted MRI or a clinical history of acute ischemia or TIA within 6 months before or after CTA. The relationship between pericarotid fat density and cerebrovascular ischemic events was assessed using receiver operating characteristic analysis and binary logistic regression analysis. ResultsIn the symptomatic group (n = 135), mean pericarotid fat density (−63.3 ± 21.7 vs. -81.7 ± 16.9 HU, respectively; p < 0.001) and median maximum plaque thickness (4 [interquartile range: 3–6] vs. 3.7 [interquartile range: 2.6–4.7] mm, respectively; p = 0.002) were higher, while plaque density (42.1 ± 19.6 vs. 50.6 ± 20.4 HU, respectively; p = 0.001) was lower compared to the asymptomatic group. Pericarotid fat density (OR: 1.038, 95% CI: 1.023–1.053, p < 0.001) was identified as an independent predictor for symptomatic patients. The optimal cut-off value for pericarotid fat density predicting symptomatic patients was estimated as −74 HU (area under the curve: 0.753, 95% CI:0.699–0.808, p < 0.001). Inter-reader agreement for pericarotid fat density was found to be almost perfect (intraclass correlation coefficient: 0.818, 95% CI: 0.770–0.856, p < 0.001). ConclusionPericarotid fat density may serve as an imaging biomarker in predicting acute cerebrovascular ischemic events.

Age-associated gadolinium leakage into ocular structures in patients with acute traumatic brain injury

BackgroundGadolinium Leakage into Ocular Structures (GLOS) is common following acute cerebrovascular events. The objective of this study was to investigate the occurrence of GLOS in an acute traumatic brain injury (TBI) cohort without acute cerebrovascular injury and to explore associated factors. MethodsEnrolled acute TBI patients had a baseline MRI ≤48 h of injury (TP1) and follow-up MRI ≤72 h after baseline (TP2). Vitreous chamber enhancement and signal intensity ratios (SIRs) were calculated using pre- and post-contrast Fluid Attenuated Inversion Recovery (FLAIR). White matter hyperintensities (WMHs) were assessed using the Fazekas scale. ResultsOf the 128 TBI patients included, median age was 47 years, 70% male, and 66% presented with Glasgow Coma Scale of 15. No GLOS was detected at TP1 but was present in 23% of patients at TP2. GLOS+ patients were older (68 years [56–76] vs 39 years [27–53], p < 0.001), more likely to report falls as injury mechanism (62% vs 36%, p = 0.006), report history of hypertension (41% vs 19%, p = 0.025), and had a higher burden of WMHs (59% vs 14% with a total Fazekas ≥2, p < 0.001). Quantitative SIRs confirmed qualitative assessments: GLOS+ patients had higher SIRs at TP2 (0.43 vs 0.22, p < 0.001). Age (OR 3.28, 95%CI [1.88–5.71], p < 0.001) and prior TBI history (OR 4.99, 95%CI [1.46–17.06], p = 0.010) were independent predictors of GLOS. When age was removed, total Fazekas score (OR 2.53, 95%CI [1.60–4.00], p < 0.001) was an independent predictor of GLOS. ConclusionsGLOS is primarily associated with age and may serve as another imaging marker of chronic vascular disease.

Protein glycation products associate with progression of kidney disease and incident cardiovascular events in individuals with type 1 diabetes

BackgroundDespite improved glycemic treatment, the impact of glycation on pathological consequences may persist and contribute to adverse clinical outcomes in diabetes. In the present study we investigated the association between serum protein glycation products and progression of kidney disease as well as incident major adverse cardiovascular events (MACE) in type 1 diabetes.MethodsFructosamine, advanced glycation end products (AGEs), and methylglyoxal-modified hydro-imidazolone (MG-H1) were measured from baseline serum samples in the FinnDiane study (n = 575). Kidney disease progression was defined as steep eGFR decline (> 3 mL/min/1.73 m2/year) or progression of albuminuria (from lower to higher stage of albuminuria). MACE was defined as acute myocardial infarction, coronary revascularization, cerebrovascular event (stroke), and cardiovascular death.ResultsFructosamine was independently associated with steep eGFR decline (OR 2.15 [95% CI 1.16–4.01], p = 0.016) in the fully adjusted model (age, sex, baseline eGFR). AGEs were associated with steep eGFR decline (OR 1.58 per 1 unit of SD [95% CI 1.07–2.32], p = 0.02), progression to end-stage kidney disease (ESKD) (HR 2.09 per 1 unit of SD [95% CI 1.43–3.05], p < 0.001), and pooled progression (to any stage of albuminuria) (HR 2.72 per 1 unit of SD [95% CI 2.04–3.62], p < 0.001). AGEs (HR 1.57 per 1 unit of SD [95% CI 1.23–2.00], p < 0.001) and MG-H1 (HR 4.99 [95% CI 0.98–25.55], p = 0.054) were associated with incident MACE. MG-H1 was also associated with pooled progression (HR 4.19 [95% CI 1.11–15.89], p = 0.035). Most AGEs and MG-H1 associations were no more significant after adjusting for baseline eGFR.ConclusionsOverall, these findings suggest that protein glycation products are an important risk factor for target organ damage in type 1 diabetes. The data provide further support to investigate a potential causal role of serum protein glycation in the progression of diabetes complications.

Lipoproteins and Their Receptors Association in Cerebrovascular Disease Pathogenesis: A Comprehensive Analysis

Atherosclerosis, a leading cause of cardiovascular and cerebrovascular diseases, is driven by dyslipidemia and inflammatory processes. This study aimed to assess the relationship between lipoproteins and their receptors in patients with acute cerebrovascular accidents, using Receiver Operating Characteristic (ROC) analysis to evaluate their predictive value for stroke risk. A total of 165 patients with acute cerebrovascular events were included, and comprehensive assessments, including enzyme immunoassays for lipoprotein A (Lp(a)) and lipoprotein-associated phospholipase A2 (Lp-PLA2), were conducted. Results revealed significant associations between lipoprotein levels and neurological deficits, with a 2.3-fold increase in Lp(a) and a 2.2-fold decrease in low-density lipoprotein receptors (LDLR) in severe cases. Elevated lectin-like oxidized LDL receptor (LOX-1) and Lp-PLA2 levels were also noted, highlighting their roles in plaque destabilization and inflammation. The findings underscore the complex interplay of lipid metabolism, thrombus formation, and endothelial dysfunction in cerebrovascular events. This study emphasizes the importance of early detection and targeted interventions to modulate lipoprotein levels and reduce inflammation, offering potential strategies to mitigate stroke risk in atherosclerosis patients.

Factors impacting D-dimer levels in patients with acute ischemic cerebrovascular events

Background and objectivesA better understanding of the factors influencing D-dimer levels in code stroke patients is needed to guide further investigations of concomitant thrombotic conditions. This study aimed to investigate the impact of time from symptom onset and other factors on D-dimer levels in patients with acute ischemic stroke (AIS) or transient ischemic attack (TIA). MethodsData on consecutive AIS and TIA patients treated at our tertiary-care stroke center between January 2015 and December 2020 were retrospectively assessed. Patients with available D-dimer levels were evaluated for eligibility. Multivariable non-linear regression analyses were performed. ResultsIn total, 2467 AIS patients and 708 TIA patients were included. The median D-dimer levels differed between the AIS and TIA groups (746 µg/L [interquartile range 381–1468] versus 442 µg/L [interquartile range 244–800], p<0.001). In AIS patients, an early increase in D-dimer levels was demonstrated within the first 6 h (standardized beta coefficient [β] 0.728; 95% confidence interval [CI] 0.324–1.121). This was followed by an immediate decrease (β −13.022; 95% CI −20.401 to −5.643) and then by a second, late increase after 35 h (β 11.750; 95% CI 4.71–18.791). No time-dependent fluctuation in D-dimer levels was observed in TIA patients. ConclusionThe time from symptom onset may affect D-dimer levels in patients with AIS but not those with TIA. Further studies confirming these findings and validating time-specific variations are needed to enable D-dimer levels to be used efficiently as an acute stroke and thrombotic risk biomarker.

Cardiovascular Events and Androgen Receptor Signaling Inhibitors in Advanced Prostate Cancer

Cardiovascular (CV) events remain a substantial cause of mortality among men with advanced and metastatic prostate cancer (PCa). The introduction of novel androgen receptor signaling inhibitors (ARSI) has transformed the treatment landscape of PCa in recent years; however, their associated CV toxic effects remains unclear. To assess the incidence of CV events with addition of ARSI to standard of care (SOC) in locally advanced (M0) and metastatic (M1) PCa. Systematic searches of PubMed, Scopus, Web of Science, EMBASE, and ClinicalTrials.gov were performed from inception up to May 2023. Randomized clinical trials of ARSI agents (abiraterone, apalutamide, darolutamide, enzalutamide) that reported CV events among individuals with M0 and M1, hormone-sensitive prostate cancer (HSPC) and castration-resistant prostate cancer (CRPC). A systematic review was performed in accordance with PRISMA guidance. Two authors screened and independently evaluated studies eligible for inclusion. Data extraction and bias assessment was subsequently performed. A random-effects meta-analysis was performed to estimate risk ratios for the incidence of all grade and grade 3 or higher CV events (primary outcomes), in addition to hypertension, acute coronary syndrome (ACS), cardiac dysrhythmia, CV death, cerebrovascular event, and venous thromboembolism (secondary outcomes). Sources of heterogeneity were explored using meta-regression. There were 24 studies (n = 22 166 patients; median age range, 63-77 years; median follow-up time range, 3.9-96 months) eligible for inclusion. ARSI therapy was associated with increased risk of all grade CV event (risk ratio [RR], 1.75; 95% CI, 1.50-2.04; P < .001) and grade 3 or higher CV events (RR, 2.10; 95%, 1.72-2.55; P < .001). ARSI therapy also was associated with increased risk for grade 3 or higher events for hypertension (RR, 2.25; 95% CI, 1.74-2.90; P < .001), ACS (RR, 1.93; 95% CI, 1.43-1.60; P < .01), cardiac dysrhythmia (RR, 1.64; 95% CI, 1.23-2.17; P < .001), cerebrovascular events (RR, 1.86; 95% CI, 1.34-2.59; P < .001) and for CV-related death (RR, 2.02; 95% CI, 1.32-3.10; P = .001). Subgroup analysis demonstrated increased risk of all CV events across the disease spectrum (M0 HSPC: RR, 2.26; 95% CI, 1.36-3.75; P = .002; M1 HSPC: RR, 1.85; 95% CI, 1.47-2.31; P < .001; M0 CRPC: RR, 1.79; 95% CI, 1.13-2.81; P = .01; M1 CRPC: RR, 1.46; 95% CI, 1.16-1.83; P = .001). This systematic review and meta-analysis found that the addition of ARSIs to traditional ADT was associated with increased risk of CV events across the prostate cancer disease spectrum. These results suggest that patients with prostate cancer should be advised about and monitored for the potential of increased risk of CV events with initiation of ARSI therapy alongside conventional hormonal therapy.

The Influence of Non-High-Density Lipoprotein Cholesterol on the Efficacy of Genotype-Guided Dual Antiplatelet Therapy in Preventing Stroke Recurrence.

Non-high-density lipoprotein cholesterol (non-HDL-C), which represents the total cholesterol content of all pro-atherogenic lipoproteins, has recently been included as a new target for lipid-lowering therapy in high-risk atherosclerotic patients in multiple guidelines. Herein, we aimed to explore the relationship between non-HDL-C level and the efficacy and safety of ticagrelor-aspirin versus clopidogrel-aspirin in preventing stroke recurrence. This study comprised a post hoc analysis of the CHANCE-2 (Ticagrelor or Clopidogrel in High-Risk Patients with Acute Nondisabling Cerebrovascular Events II) trial, from which 5,901 patients with complete data on non-HDL-C were included and categorized by median non-HDL-C levels, using a cutoff of 3.5 mmol/L. The primary efficacy and safety outcomes were recurrent stroke and severe or moderate bleeding within 90 days. Ticagrelor-aspirin significantly reduced the risk of recurrent stroke in patients with low non-HDL-C (71 [4.8%] vs. 119 [7.7%]; adjusted hazard ratio [HR] 0.54; 95% confidence interval [CI], 0.40-0.74), but not in those with high non-HDL-C (107 [7.3%] vs. 108 [7.6%]; adjusted HR, 0.88; 95% CI, 0.67-1.16), compared with clopidogrel-aspirin (P for interaction=0.010). When analyzed as a continuous variable, the benefit of ticagrelor-aspirin for recurrent stroke decreased as non-HDL-C levels increased. No significant differences in the treatment assignments across the non-HDL-C groups were observed in terms of the rate of severe or moderate bleeding (5 [0.3%] vs. 8 [0.5%] in the low non-HDL-C group; 4 [0.3%] vs. 2 [0.1%] in the high non-HDL-C group; P for interaction=0.425). CHANCE-2 participants with low non-HDL-C levels received more clinical benefit from ticagrelor-aspirin versus clopidogrel-aspirin compared to those with high non-HDL-C, following minor ischemic stroke or transient ischemic attack.

Photon-Counting Computed Tomography in Atherosclerotic Plaque Characterization.

Atherosclerotic plaque buildup in the coronary and carotid arteries is pivotal in the onset of acute myocardial infarctions or cerebrovascular events, leading to heightened levels of illness and death. Atherosclerosis is a complex and multistep disease, beginning with the deposition of low-density lipoproteins in the arterial intima and culminating in plaque rupture. Modern technology favors non-invasive imaging techniques to assess atherosclerotic plaque and offer insights beyond mere artery stenosis. Among these, computed tomography stands out for its widespread clinical adoption and is prized for its speed and accessibility. Nonetheless, some limitations persist. The introduction of photon-counting computed tomography (PCCT), with its multi-energy capabilities, enhanced spatial resolution, and superior soft tissue contrast with minimal electronic noise, brings significant advantages to carotid and coronary artery imaging, enabling a more comprehensive examination of atherosclerotic plaque composition. This narrative review aims to provide a comprehensive overview of the main concepts related to PCCT. Additionally, we aim to explore the existing literature on the clinical application of PCCT in assessing atherosclerotic plaque. Finally, we will examine the advantages and limitations of this recently introduced technology.

TAKOTSUBO SYNDROME PRECEDING THE INDEX EVENT: A DANGEROUS CLINICAL SETTING

Abstract We describe the case of a 68–year–old patient who presented to the Emergency Department following an unwitnessed syncopal episode with slow recovery of consciousness. On admission, the patient had dyspnoea together with physical signs of pulmonary congestion. Cardiac ultrasound showed severe left ventricular dysfunction with an ejection fraction of 30%, and apical and paraapical akinesis. The admission electrocardiogram showed sinus tachycardia and diffuse repolarization abnormalities, hs TnI was elevated and BNP vl blood gas analysis were unremarkable. During observation in the Emergency Department, the patient experienced epileptic seizure, promptly resolved by intravenous Midazolam. Contrast–enhanced chest CT ruled out aortic dissection disclosing a clinically irrelevant subsegmental pulmonary embolism. A non–contrast CT scan of the brain yielded negative results. In consideration of the atypical clinical presentation and scattered evidence of an acute coronary syndrome, the patient was admitted to our Cardiac Intensive Care Unit (CICU) for additional diagnostic workup delaying coronary angiography in the presence of stable TnI elevation. Three hours after admission the patient continued showing altered consciousness and a subsequent brain CT was performed, demonstrating an intraparenchymal hemorrhagic spreading. Repeat ECGs showed precordial T wave inversion and prolongation of the QT interval. These data, together with LV apical dysfunction, raised the suspicion of Takotsubo syndrome secondary to an acute cerebrovascular event. During the hospital stay, recovery of consciousness, spontaneous absorption of the cerebral hemorrhagic spread and complete recovery of left ventricular function at repeat cardiac ultrasound examinations were observed, confirming the almost unequivocal diagnosis of Takotsubo syndrome. The patient was discharged uneventfully and was scheduled for an outpatient coronary CT scan. This case underscores the crucial importance of a thorough clinical assessment in the management of complex patients in the presence of nonunivocal clinical signs and misleading blood test and imaging data. Moreover, Takotsubo syndrome is a protean clinical entity that can precede the index event as in our patient, i.e. cerebral hemorrhage. Misclassification of these patients as having an acute coronary syndrome could have led to the initiation of antithrombotic therapy, with potential fatal outcomes for the patient.

Galectin-3 modulates microglial activation and neuroinflammation in early brain injury after subarachnoid hemorrhage

BackgroundAneurysmal subarachnoid hemorrhage (SAH) is a devastating acute cerebrovascular event with high mortality and permanent disability rates. Higher galectin-3 levels on days 1–3 have been shown to predict the development of delayed cerebral infarction or adverse outcomes after SAH. Recent single-cell analysis of microglial transcriptomic diversity in SAH revealed that galectin could influence the development and course of neuroinflammation after SAH. MethodsThis study aimed to investigate the role and mechanism of galectin-3 in SAH and to determine whether galectin-3 inhibition prevents early brain injury by reducing microglia polarization using a mouse model of SAH and oxyhemoglobin-treated activation of mouse BV2 cells in vitro. ResultsWe found that the expression of galectin-3 began to increase 12 h after SAH and continued to increase up to 72 h. Importantly, TD139-inhibited galectin-3 expression reduced the release of inflammatory factors in microglial cells. In the experimental SAH model, TD139 treatment alleviated neuroinflammatory damage after SAH and improved defects in neurological functions. Furthermore, we demonstrated that galectin-3 inhibition affected the activation and M1 polarization of microglial cells after SAH. TD139 treatment inhibited the expression of TLR4, p-NF-κB p65, and NF-κB p65 in microglia activated by oxyhemoglobin as well as eliminated the increased expression and phosphorylation of JAK2 and STAT3. ConclusionThese findings suggest that regulating microglia polarization by galectin-3 after SAH to improve neuroinflammation may be a potential therapeutic target.

LDL-C Levels and Bleeding Risk in Patients Taking DAPT After Minor Ischemic Stroke or TIA

Evidence on the bleeding risk associated with low-density lipoprotein cholesterol (LDL-C) levels in patients receiving dual antiplatelet therapy (DAPT) remains sparse. To investigate the association of LDL-C levels with bleeding risk in patients with minor ischemic stroke (MIS) or high-risk transient ischemic attack (HRTIA) receiving DAPT. This cohort study was an analysis of pooled data from 2 randomized, double-blind, placebo-controlled clinical trials in China of patients with MIS or HRTIA who were receiving DAPT: the CHANCE (Clopidogrel in High-Risk Patients With Acute Nondisabling Cerebrovascular Events) trial enrolled patients at 114 sites from October 2009 to July 2012, and the CHANCE-2 enrolled patients at 202 centers from September 2019 to March 2021. Both sets of patients were followed up for 90 days. Data analysis was performed from August 2022 to May 2023. Baseline LDL-C levels and receipt of ticagrelor-aspirin and clopidogrel-aspirin DAPT. The primary outcome was any bleeding, and the secondary outcome was severe or moderate bleeding within 3 months after randomization. The association of LDL-C levels and all outcomes was assessed by using the Cox proportional hazard model. Hazard ratios (HRs) with 95% CIs were calculated on univariable (unadjusted) Cox regression models. Adjusted HRs (aHRs) and their 95% CIs were calculated on multivariable Cox regression models. In total, 8996 patients with acute MIS or HRTIA who were receiving DAPT were included in the 2 trials, of whom 1066 without serum specimens and 490 patients with missing baseline LDL-C value were excluded. Finally, 7440 patients with DAPT (4486 in the clopidogrel-aspirin group and 2954 in the ticagrelor-aspirin group) were included in this study. The median (IQR) age was 64.32 (56.56-71.30) years, and 2479 patients (33.32%) were women. A total of 270 (3.63%) bleeding events were reported at 3 months, and LDL-C less than 70 mg/dL was associated with an increased risk of both any bleeding (aHR, 1.48; 95% CI, 1.03-2.12), and severe or moderate bleeding (aHR, 2.78; 95% CI, 1.18-6.53). The risk of any bleeding was increased at lower LDL-C levels in the ticagrelor-aspirin group (aHR, 1.71; 95% CI, 1.08-2.72). However, an increased risk of any bleeding was not observed in the clopidogrel-aspirin group (aHR, 1.30; 95% CI, 0.73-2.30). There was no significant association between LDL-C levels and the risk of severe or moderate bleeding in either the ticagrelor-aspirin or clopidogrel-aspirin group. These findings suggest that low LDL-C levels are associated with an increased bleeding risk within 3 months among patients with MIS or HRTIA receiving DAPT, especially those taking ticagrelor-aspirin. Weighing the risks and benefits is crucial when simultaneously considering the selection of LDL-C target strategies and DAPT regimens among these patients.