Acute Vascular Events Research Articles

A study of the comparative effectiveness of dual antiplatelet therapy and a combination of acetylsalicylic acid with colchicine in patients in the acute period of “minor” ischemic atherothrombotic stroke during hospitalization. Interim analysis of data from the «COLCHIDA» study

Influence on inflammation is currently becoming a priority target for the prevention of recurrent atherothrombotic events, including stroke. In 2022, we planned the KOLCHIDA study, a two-center, prospective, randomized, open-label, controlled clinical trial with endpoint assessment (ClinicalTrials.gov identifier: NCT06102720). The purpose of this study is to conduct a comparative assessment of the clinical effectiveness of dual antiplatelet therapy with acetylsalicylic acid (ASA) and clopidogrel and the combination of ASA with colchicine in patients in the acute period of “minor” ischemic atherothrombotic stroke. The purpose of this publication is to present the basic concept of the protocol, its design and the first intermediate results. Material and methods. The intervention consisted of colchicine 0.5 mg/day in addition to ASA versus dual antiplatelet therapy (DAPT) in patients with non-severe ischemic stroke. 31 patients were included in the colchicine and ASA group, and 34 patients were included in the DAPT group. Results. In the comparison group, 7 (20.6%) recurrent non-fatal strokes were recorded, in contrast to the colchicine group, where acute vascular events were recorded in only two patients (6.5%) [RRR 2.2, NNT = 7, χ2 = 2, 9, p = 0.09]. There were no clinically significant bleeding or other adverse events in both groups. Conclusion. Interim results of the study indicate possible confirmation of the hypothesis that anti-inflammatory therapy with low doses of colchicine in combination with standard therapy is not inferior to the combination of ASA and clopidogrel, and perhaps more effectively reduces the number of early neurological deteriorations and recurrent ischemic strokes in patients in the acute period of mild atherothrombotic stroke with equal security profile.

Inflammation: Is It a Healer, Confounder, or a Promoter of Cardiometabolic Risks?

Inflammation is the body's non-specific response to injury or infection. It is a natural defense mechanism that helps to maintain homeostasis and promotes tissue repair. However, excessive inflammation can lead to cellular, tissue, or organ dysfunction, as well as contribute to the development of acute vascular events and diseases like Crohn's disease, psoriasis, obesity, diabetes, and cancer. The initial response to injury involves the activation of platelets and coagulation mechanisms to stop bleeding. This is followed by the recruitment of immune cells and the release of cytokines to promote tissue repair. Over time, the injured tissue undergoes remodeling and returns to its pre-injury state. Inflammation is characterized by the activation of inflammatory signaling pathways involving cytokines, chemokines, and growth factors. Mast cells play a role in initiating inflammatory responses. Pattern recognition receptors (PRRs) such as Toll-like receptors (TLRs) and nucleotide-binding domain (NOD)-like receptors (NLRs) are involved in the activation of these inflammatory pathways. Inflammasomes, which are cytoplasmic complexes, also contribute to inflammation by activating cytokines. Inflammation can also be triggered by factors like dietary components and the composition of the gut microbiota. Dysregulation of the gut microbiome can lead to excessive inflammation and contribute to diseases like atherosclerosis and irritable bowel syndrome (IBS). The immune system and gut-associated lymphoid tissue (GALT) play crucial roles in the inflammatory response and the development of conditions like colorectal cancer. Anti-inflammatory therapy can play a significant role in reducing or inducing the remission of inflammatory diseases such as Crohn's disease and ulcerative colitis. The fetal origin of adult diseases theory suggests that conditions during fetal development, such as low birth weight and maternal obesity, can influence the risk of cardiometabolic diseases later in life. All of the known risk factors associated with cardiometabolic diseases such as hypertension, excess weight, obesity, type-2 diabetes, and vascular diseases are accompanied by chronic low-grade inflammation. Inflammation seems to have a role in precipitating even acute vascular events such as heart attacks and stroke. Common markers of inflammation associated with cardiometabolic disease include interleukin (IL)-1β, IL-6, tumor necrosis factor (TNF-α), C-reactive protein (CRP), and soluble TNF receptors such as sTNFR1 and sTNFR2. These markers serve as indicators of systemic inflammation. However, these markers are not disease-specific but provide an insight into the overall chronic inflammatory status. In fact, inflammation has been identified as a potential target for future treatments to reduce or reverse the risk of atherosclerosis-related complications. The regulation of inflammation is complex, and further research is needed to better understand its mechanisms and develop strategies for managing inflammatory disorders. In summary, inflammation is a natural response to injury or infection, but excessive or prolonged inflammation can lead to the progression of various diseases. Understanding the underlying mechanisms of inflammation is important for developing treatments and preventive measures for inflammatory disorders.

OxLDL as a prognostic biomarker of plaque instability in patients qualified for carotid endarterectomy.

Atherosclerotic plaque instability increases the risk of stroke. As such, determining the nature of an instability atherosclerotic plaque may speed up qualification for carotid endarterectomy (CEA), thus reducing the risk of acute vascular events. The aim of the study was to determine the diagnostic value of oxidized LDL cholesterol (ox-LDL), matrix metalloproteinase 9 (MMP-9) and 8-hydroxy-2'-deoxyguanosine (8-OHdG) in serum as a prognostic markers of instability atherosclerotic plaques. Serum was collected from 67 patients who underwent CEA in accordance with the qualification criteria. The levels of ox-LDL, MMP-9 and 8-OHdG were assessed by ELISA. The predictive value of the markers was determined based on an ROC curve, and the cut-off points with the highest sensitivity and specificity were determined. Patients with unstable atherosclerotic plaque had significantly higher serum ox-LDL, MMP-9 and 8-OHdG values. It was found that in patients before CEA, ox-LDL >31.4 ng/mL was associated with an 82.5% probability of unstable atherosclerotic plaque, MMP-9 >113.1 ng/mL with 78.6%, and 8-OHdG >2.15 ng/mL with 64.7%. Multivariate regression analysis found ox-LDL to be an independent factor associated with plaque instability. Patients with unstable plaques tend to have higher serum levels of ox-LDL, MMP-9 and 8-OHdG compared to those with stable plaques. The optimal cut-off point for ox-LDL (AUC 0.86, p <0.0001) was 31.14 ng/mL, with 91.18% sensitivity and 78.79% specificity. The high sensitivity and specificity of ox-LDL suggests that it can be used as an independent marker of plaque instability.

Determinants of uptake of influenza, zoster and pneumococcal vaccines in patients with cardiovascular diseases

BackgroundGlobally, cardiovascular disease (CVD) is the leading cause of death and illness. Vaccine-preventable infections may increase acute coronary vascular disease events and the risk of complications. Low vaccine coverage has been reported among adults at high risk of complications from vaccine-preventable infections. There is a gap in research evidence around determinants of uptake of vaccines among adults with CVD. This study examined the uptake of influenza, pneumococcal and zoster vaccines and the determinants of uptake of the vaccines among cardiac patients. MethodA prospective cross-sectional study was carried out among hospitalised cardiac patients through an interviewer-administered questionnaire. Descriptive statistics were used to investigate self-reported uptake of influenza, pneumococcal and zoster vaccines. Univariate and multivariate analyses of participants' social demographic and clinical characteristics were conducted to identify factors for receiving influenza vaccine. ResultsLow vaccination rates among 104 participants were found for influenza (45.2%), pneumococcal (13.5%) and zoster (5.8%) vaccines. The most common reason for not receiving influenza vaccine was concern about side effects. Lack of awareness about the pneumococcal and zoster vaccines was the main reason for the poor uptake of these vaccines. Australia–born participants were more likely to receive influenza vaccine than overseas-born participants. Working-age participants and, interestingly, people living with a current smoker were less likely to receive influenza vaccine. ConclusionInfluenza, pneumococcal and zoster vaccine uptake among cardiac patients was low. Encouraging physician recommendations for vaccination for cardiac patients under 65 years of age and addressing vaccination challenges among people from culturally and linguistically diverse backgrounds and pharmacy, workplace, and hospital vaccination may help increase vaccination uptake among cardiac patients.

Triptan use in elderly over 65 years and the risk of hospitalization for serious vascular events

BackgroundSeveral studies have focused on the use of triptan and the risk of acute vascular events but the existence of such association is still debated and has never been quantified in patients over 65 years. To assess whether triptan use among older is associated with an increased risk of hospitalization for acute vascular events.MethodsA propensity score-matched cohort study was designed using the French national health insurance database linked to hospital stays. Patients aged ≥ 65 years, newly treated by triptans between 2011 and 2014, were included… The primary event was hospitalization for an acute ischemic vascular event within de 90 days following triptan initiation. Association with triptan exposure was investigated through cox regression model, considering exposure at inclusion, and with exposure as a time-varying variable A case-crossover (CCO) and a self-controlled case series (SCCS) analyses were also conducted to address potential residual confounding.ResultsThe cohort included 24, 774 triptan users and 99 096 propensity matched controls (mean (SD) age: 71 years (5.9), 74% of women). Within 90 days after cohort entry, 163 events were observed in the triptan group, and 523 in the control group (0.66% vs. 0.53%, adjusted hazard ratio (aHR) exposed/not exposed 1.25 95%CI [1.05–1.49]; aHR time−varying 8.74 [5.21–14.66]). The association was significant (CCO) for all events (adjusted odds ratio (aOR1.63 [1.22–2.19]) with a more consistent association with cerebral events (aOR 2.14 [1.26–3.63]). The relative incidence (RI) for all events was 2.13 [1.76–2.58] in the SCCS, for cardiac (RI: 1.67 [1.23–2.27]) and for cerebral events (RI: 3.20, [2.30–4.45]).ConclusionThe incidence of acute vascular events was low among triptan users. We found that triptan use among older may be associated with a low increased risk for acute vascular events, which may be more marked for cerebral events such as stroke, than for cardiac events.

Risk of cardiovascular toxicity with combination of immune-checkpoint inhibitors and angiogenesis inhibitors: a meta-analysis.

Combinations of immune checkpoint inhibitors (ICIs) and angiogenesis inhibitors (AIs) have been investigated for the treatment of several tumor types. Both ICIs and AIs may lead to cardiovascular adverse events, and their combination may potentially increase the risk for cardiovascular toxicity. In the present meta-analysis, we aim to assess the cardiovascular toxicity of ICIs plus AIs vs. AIs alone. Secondary objectives are non-cardiovascular adverse events and efficacy. Systematic review was performed according to PRISMA statement. Phase II and III randomized clinical trials were identified by searching the MEDLINE/PubMed, Cochrane Library and ASCO Meeting abstracts, from inception to June 2022. The pooled risks for overall response rate (ORR), 1-year progression-free survival (PFS), adverse events (AEs), immune-related AEs, (irAEs), hypertension, and vascular events defined as stroke, myocardial infarction and pulmonary embolisms, were calculated. In terms of cardiovascular toxicity, we found higher risk for severe hypertension among patients treated with ICIs plus AIs as compared with those receiving AIs (OR 1.24, 95% CI: 1.01-1.53), but no significant difference was found for any-grade hypertension, and for vascular events. There was also no difference in terms of overall AEs, whereas the incidence of irAEs was increased in the ICIs plus AIs arm, as expected. In terms of efficacy, ICIs plus AIs achieved better ORR (OR 2.25, 95% CI: 1.70-2.97) and PFS (HR 0.49, 95% CI: 0.39-0.63) as compared to AIs alone. The addition of ICIs to AIs significantly increased the risk of high-grade hypertension, but not that of acute vascular events.

Infection, delirium, and risk of dementia in patients with and without white matter disease on previous brain imaging: a population-based study

The increased risk of dementia after delirium and infection might be influenced by cerebral white matter disease (WMD). In patients with transient ischaemic attack (TIA) and minor stroke, we assessed associations between hospital admissions with delirium and 5-year dementia risk and between admissions with infection and dementia risk, stratified by WMD severity (moderate or severe vs absent or mild) on baseline brain imaging. We included patients with TIA and minor stroke (National Institutes of Health Stroke Score <3) from the Oxford Vascular Study (OXVASC), a longitudinal population-based study of the incidence and outcomes of acute vascular events in a population of 94 567 individuals, with no age restrictions, attending eight general practices in Oxfordshire, UK. Hospitalisation data were obtained through linkage to the Oxford Cognitive Comorbidity, Frailty, and Ageing Research Database-Electronic Patient Records (ORCHARD-EPR). Brain imaging was done using CT and MRI, and WMD was prospectively graded according to the age-related white matter changes (ARWMC) scale and categorised into absent, mild, moderate, or severe WMD. Delirium and infection were defined by ICD-10 coding supplemented by hand-searching of hospital records. Dementia was diagnosed using clinical or cognitive assessment, medical records, and death certificates. Associations between hospitalisation with delirium and hospitalisation with infection, and post-event dementia were assessed using time-varying Cox analysis with multivariable adjustment, and all models were stratified by WMD severity. From April 1, 2002, to March 31, 2012, 1369 individuals were prospectively recruited into the study. Of 1369 patients (655 with TIA and 714 with minor stroke, mean age 72 [SD 13] years, 674 female and 695 male, and 364 with moderate or severe WMD), 209 (15%) developed dementia. Hospitalisation during follow-up occurred in 891 (65%) patients of whom 103 (12%) had at least one delirium episode and 236 (26%) had at least one infection episode. Hospitalisation without delirium or infection did not predict subsequent dementia (HR 1·01, 95% CI 0·86-1·20). In contrast, hospitalisation with delirium predicted subsequent dementia independently of infection in patients with and without WMD (2·64, 1·47-4·74; p=0·0013 vs 3·41, 1·91-6·09; p<0·0001) especially in those with unimpaired baseline cognition (cognitive test score above cutoff; 4·01, 2·23-7·19 vs 3·94, 1·95-7·93; both p≤0·0001). However, hospitalisation with infection only predicted dementia in those with moderate or severe WMD (1·75, 1·04-2·94 vs 0·68, 0·39-1·20; pdiff=0·023). The increased risk of dementia after delirium is unrelated to the presence of WMD, whereas infection increases risk only in patients with WMD, suggesting differences in underlying mechanisms and in potential preventive strategies. National Institute for Health and Care Research and Wellcome Trust.

Magnetic Resonance Angiography with Hour-Scale Duration after Single Low-Dose Administration of Biocompatible Gadolinium Oxide Nanoprobe.

Long-term contrast-enhanced angiography offers significant advantages in theranostics for diverse vascular diseases, particularly in terms of real-time dynamic monitoring during acute vascular events; However, achieving vascular imaging with a duration of hours through a single administration of low-dose contrast agent remains challenging. Herein, a hyaluronic acid-templated gadolinium oxide (HA@Gd2O3) nanoprobe-enhanced magnetic resonance angiography (MRA) is proposed to address this bottleneck issue for the first time. The HA@Gd2O3 nanoprobe synthesized from a facile one-pot biomineralization method owns ultrasmall size, good biocompatibility, optimal circulation half-life (≈149 min), and a relatively high T1 relaxivity (r1) under both clinical 3 T (8.215 mM-1s-1) and preclinical 9.4 T (4.023 mM-1s-1) equipment. The HA@Gd2O3 nanoprobe-enhanced MRA highlights major vessels readily with significantly improved contrast, extended imaging duration for at least 2 h, and ultrahigh resolution of 0.15mm under 9.4 T, while only requiring half clinical dosage of Gd. This technique can enable rapid diagnosis and real-time dynamic monitoring of vascular changes in a model of acute superior mesenteric vein thrombosis with only a single injection of nanoprobe. The HA@Gd2O3 nanoprobe-enhanced MRA provides a sophisticated approach for long-term (hour scale) vascular imaging with ultrahigh resolution and high contrast through single administration of low-dose contrast agent.

Abstract 16988: Conventional and Regionally Distinctive Risk Factors for First-Onset Myocardial Infarction in Bangladesh. The Bangladesh Risk of Acute Vascular Events (BRAVE) Study

Background: South Asians may be particularly susceptible to premature myocardial infarction (MI) owing both to classic cardiovascular risk factors and distinctive practices more common in South Asian populations. Hypothesis: Identifying modifiable risk factors for MI in South Asian populations should inform prevention strategies. Goal: To study conventional risk factors and several distinctive South Asian characteristics and practices in relation to the likelihood of first-ever MI in Bangladesh. Methods: In a case-control study involving 8,133 first MI cases and 8,122 controls, we calculated odds ratios (ORs) for MI (adjusted, when appropriate, for age, sex, smoking status, history of diabetes, history of hypertension, family history of MI, and LDL-cholesterol) and assessed their potential public health impact using population attributable fractions (PAFs). Results: The mean (SD) age of first MI was 53 (11) years. Adjusted ORs (95% CIs) were 2.75 (2.53-2.99) for cigarette smoking, 2.33 (2.08-2.60) for parental history of MI, 2.26 (2.07-2.48) for history of hypertension, 1.79 (1.61-1.98) for history of diabetes, and 1.61 (1.55-1.67) per 1-SD higher LDL-cholesterol. The highest PAFs (95% CIs) were for current cigarette smoking (48.9% [46.1%-51.6%]), higher LDL-cholesterol (32.4% [30.2%-34.4%]) and history of hypertension (14.7% [13.2%-16.1%]). As for regionally distinctive practices, ORs were 4.05 (3.15-5.21) with biri smoking, 2.04 (1.48-2.81) with chewing tobacco, and 1.26 (1.05-1.51) with parental history of first cousin marriage. Conclusion: In a large case-control study, we confirmed the relevance of several conventional risk factors to risk of first-onset MI in the Bangladesh population. We also identified significant associations with MI of practices distinctive to South Asian populations, including indigenous modes of tobacco consumption and parental first-cousin marriage, apparently independent of conventional risk factors. These findings should help identify opportunities for cardiovascular disease prevention in South Asia that embrace both conventional and regionally distinctive risk factors.

Acute Cerebral Vascular Events after Carotid Endarterectomy

Introduction. Acute cerebrovascular accident is recognized as the leading pathology in the structure of cerebrovascular diseases (CVD). Annually 6 million cases of CVD are registered in the world. Fatal outcomes from this pathology in Russia occur 1.5–2 times more often than in developed countries. According to the All-Russian Center for Preventive Medicine, 25% of males and 39% of females die from CVD. The incidence of CVD in Russia ranges from 460 to 560 cases per 100 thousand people. This pathology may be caused by carotid artery stenosis resulting from atherosclerotic vascular lesions and plaque formation which lead to embolism and stroke.Materials and methods. The study analyzed 341 medical histories of patients hospitalized at the Bashkir State Medical University Clinic (BSMU Clinic) in 2022, who underwent carotid endarterectomy (CEE) (288 of them had a history of chronic cerebrovascular accident) and 278 medical histories of patients with acute cerebrovascular accident, hospitalized at the Neurologic Clinic of the Avicenna Tajik State Medical University in 2022.Results and discussion. Perioperative complications that occurred during CEE at BSMU Clinic in 2022 included 12 cases of acute cerebrovascular accident of ischemic type (3.52%) and 2 cases of transient ischemic attack (0.6%), which is lower than the same rates in previously published observations at the same clinic.Conclusion. The number of complications resulting from the CEE does not exceed the global rates. Quantitative and qualitative indicators of carotid reconstructions demonstrate positive trends. Acute cerebrovascular accident requires clarifying the cause of its occurrence and taking measures to prevent ischemic strokes, including angiosurgical interventions.

Роль геомагнитных возмущений в развитии окклюзионных поражений ретинальных вен (обзор литературы)

The review presents modern information on pathogenesis of retinal vein occlusions and risk factors for their formation. An in-depth analysis of role of external factors, among which influence of geomagnetic field and geomagnetic disturbances, has been carried out. The definition is given to such notions as magnetosensitivity, its pathogenetic mechanisms, and their role in formation of acute vascular events. Information about influence of geomagnetic disturbances on the formation of retinal vein occlusion is presented. Key words: geomagnetic disturbancies; magnetosensitivity; retinal vein occlusion.

Acute Vascular Events: Cellular and Molecular Mechanisms

Cardiovascular diseases (CVDs) are the leading cause of death worldwide. An estimated 17.9 million individuals died from CVDs in 2019, representing 32% of all global deaths. Of these deaths, 85% were due to heart attack and stroke. Cardiometabolic risks, such as hypertension, excess weight, obesity, type 2 diabetes, and vascular diseases, contribute significantly to the progression of coronary artery disease. Known sequelae of events that lead to these cardiometabolic diseases include oxidative stress, inflammation, development of dysfunction of vascular adipose tissue, altered blood pressure and blood lipids, altered glucose metabolism, hardening of the arteries, endothelial dysfunction, development of atherosclerotic plaques, and activation of platelet and coagulation pathways. The Framingham Heart Study Group has developed a Risk Score that estimates the risk of developing heart disease in a 10-year period. This group of experts has developed mathematical functions for predicting clinical coronary disease events. These prediction capabilities are derived by assigning weights to major CVD risk factors such as sex, age, blood pressure, total cholesterol, low-density lipoprotein, high-density lipoprotein cholesterol, smoking behavior, and diabetes status. Currently, there is a growing interest in the use of artificial intelligence and machine learning applications. AI-based mimetic pattern-based algorithms seem to be better than the conventional Framingham Risk Score, in predicting clinical events related to CVDs. However, there are limitations to these applications as they do not have access to data on the specific factors that trigger acute vascular events, such as heart attack and stroke. This overview briefly discusses some salient cellular and molecular mechanisms involved in precipitating thrombotic conditions. Further improvements in emerging technologies will provide greater opportunities for patient selection and treatment options. Several clinical studies have demonstrated that most CVDs can be prevented by addressing behavioral risk factors such as tobacco use, unhealthy diet and obesity, physical activity, and harmful use of alcohol. Early detection and better management of the modifiable risks seem to be the only way to reduce, reverse, or prevent these diseases.

Association between acute liver injury & severity and mortality of COVID-19 patients: A systematic review and meta-analysis

BackgroundAcute liver injury (ALI), a complication often seen in COVID-19 patients, can lead to severe liver damage, multi-organ failure, acute vascular events, and can potentially escalate to patient mortality. Given this, we initiated a meta-analysis to investigate the correlation between ALI and adverse outcomes in COVID-19 patients. MethodsWe conducted an exhaustive search of databases, including Medline, Embase, PubMed Central, ScienceDirect, Google Scholar, and the Cochrane Library, from the November 2019 until January 2022. The quality of the included studies was evaluated using the Newcastle Ottawa (NO) scale. Our meta-analysis was carried out using a random-effects model and results were presented as pooled odds ratios (ORs) with their corresponding 95% confidence intervals (CIs). ResultsOur analysis incorporated 20 studies involving a total of 13,850 participants, predominantly from China and the United States. According to the NO scale, the majority of these studies were categorized as low-quality. Patients with ALI faced approximately 7 times higher odds of severe COVID-19 symptoms (pooled OR = 7.09; 95%CI: 4.97 to 10.12) and over 5 times higher odds of mortality (pooled OR = 5.50; 95%CI: 3.37 to 8.99) when compared to those without ALI. ConclusionOur findings affirm that ALI is a potent predictor of adverse outcomes, including severity and mortality, among COVID-19 patients. Recognizing and promptly addressing ALI in COVID-19 patients could be pivotal in improving prognosis and tailoring individualized patient management strategies. This underscores the need for clinicians to be vigilant about liver complications in the COVID-19 patients and integrate appropriate interventions in the treatment paradigm.

Immune checkpoint inhibitors (ICIs) with or without anti-angiogenic agents (AAAs) and cardiovascular toxicity: A meta-analysis.

e24084 Background: ICIs have extended survival across many tumor types at the cost of immune-related adverse events (irAEs) that can involve any organ or system, including cardiovascular system. Emerging evidence suggest that ICIs may have a role in promoting the atherosclerotic plaque progression, thus leading to acute vascular events (AVEs) This may represent a concern when combining ICIs with other anti-cancer agents burdened by cardiovascular toxicity, such as anti-angiogenic agents (AAAs), that are associated with increased risk of hypertension (HTN) and AVEs. In the present meta-analysis, we aimed to evaluate the odds of adverse events (AEs), irAEs, HTN and AVEs with ICI+AAAs, as compared with AAAs alone. Methods: Phase III randomized controlled trials were identified by searching the MEDLINE/PubMed, Cochrane Library and ASCO Meeting abstracts, from inception until June 2022. Systematic review and metanalysis were conducted according to PRISMA guidelines. AEs, irAEs, HTN and AVEs were collected (main outcomes of this metanalysis), objective response rate (ORR) and progression free survival (PFS) were also collected (secondary outcomes). AVEs were defined as stroke, myocardial infarction, thrombotic events, pulmonary embolism. Severe AEs, irAE, HTNs and AVEs were defined as grade ≥3 according to the National Cancer Institute Common Terminology for Adverse Events (CTCAE) version 4.0 or 4.03, as reported in each trial. Results: Twelve trials with a total of 8124 patients (4159 in the experimental arms and 3965 in the control arms) were included in the meta-analysis. The addition of ICIs to AAAs did not increase the rate of AEs (any grade, OR 1.15, 95%CI 0.71-1.85; severe, OR 1.18, 95% CI 0.96-1.44). In contrast, the incidence of irAE was significantly higher in the ICIs+AAA- group versus AAAs (any grade: OR 1.97, 95%CI 1.21-3.21, p = 0.007; severe: OR 3.20, 95%CI1.41-7.29, p = 0.006), as expected. There was no difference in terms of any grade HTN between the 2 groups (OR 1.17, 95%CI 0.91-1.50, p &gt; 0.05), but severe HTN was higher among patients treated with ICIs+AAAs as compared with those receiving AAAs alone (OR 1.24, 95%CI 1.01-1.53, p = 0.04). AVEs rates were low in both groups (2.2% and 1.9% for ICI+AAA and AAA alone, respectively). A subset analysis of trials specifically reporting AVEs did not show any increase in ICIs+AAAs versus AAAs alone (any grade: OR 1.21, 95%CI 0.68-2.16, p &gt; 0.05; severe: OR 1.14, 95%CI 0.61-2.15, p &gt; 0.05). Overall, the ORR and PFS were higher in the ICIs+AAAs group as compared to AAAs alone (OR 2.25, 95%CI 1.70-2.97, p &lt; 0.001; OR 4.37, 95%CI 2.91-5.83, p &lt; 0.001, respectively). Conclusions: The addition of ICIs to AAAs significantly increased the risk for irAEs and severe HTN, but not the risk for AVEs.

MTHFR C677T polymorphism, homocysteine, burden, and location of AMI and ACI.

We aimed to investigate the relationship between homocysteine levels and MTHFR C677T polymorphisms and acute ischemic vascular events and focused on the differential effects of the MTHFR C677T polymorphisms on the burden and location of AMI and ACI. 102 acute cerebral infarction (ACI) and acute myocardial infarction (AMI) patients who were admitted to the First Hospital of Jilin University in northeast China as the patient group, 83 healthy people who were hospitalized during the same period served as a control group. MTHFR C677T genotypes were identified via Polymerase Chain Reaction (PCR)-Fluorescent Probe Method. Patient group had higher serum homocysteine levels (p=0.013), lower serum folic acid (p<0.001), and Vit B12 levels (p=0.004) compared to the control group. Homocysteine levels in the patient group with the TT genotypes of the MTHFR C677T polymorphisms were higher than those with the CC and CT genotypes (p<0.05). Folic acid levels in the patients with TT genotypes were lower than those with the CC genotypes (p<0.05), but not in the control group (p>0.05). There were negative and significant associations between serum homocysteine levels and serum vitamin B12 levels in the control group (r=-0.234, p=0.033), but not between serum homocysteine levels and serum folic acid levels (r=-0.103, p=0.355). Conversely, there was a negative and significant association between serum homocysteine levels and serum folic acid levels in the patients' group (r=-0.257, p=0.01), but not between serum homocysteine levels and serum vitamin B12 levels (r=-0.185, p=0.64). No statistically significant differences in MTHFR C677T genotype and C/T alleles distribution were investigated between the patient and control group (p>0.05). The MTHFR C677T polymorphism did not differentially affect the burden and location of AMI and ACI. Homocysteine played a common role in atherosclerosis-related acute ischemic vascular events. These correlations were modified by MTHFR C677T polymorphisms and influenced by folic acid levels. The MTHFR C677T polymorphisms were not directly related to acute ischemic vascular events, nor did they differentially affect the burden and location of AMI and ACI.

Abstract 148: Genetically-Determined LDL Negatively Impacts Clinical Evolution Of Ischemic Stroke Survivors

Introduction: Ischemic Stroke survivors are at high risk of stroke recurrence. Understanding the genetic risk factors for stroke recurrence will help guide future prevention strategies. Hypothesis: Genetically-elevated LDL-cholesterol (LDL-c) negatively impact clinical trajectories after stroke, leading to higher risk of post-stroke acute vascular events. Methods: We analyzed clinical and genetic data from the Vitamin Intervention Stroke Prevention (VISP) clinical trial, which examined high-dose vitamins in stroke survivors. Genetic susceptibility to increased LDL-c was modeled through a polygenic risk score built with genetic data on 38 known genetic risk variants for LDL-cholesterol (variants influencing other lipid traits were excluded). We divided the LDL-related polygenic risk score into 0-20, 20-80, and 80-100 percentile categories labeled as low, intermediate and high genetic predisposition to high LDL. We fitted multivariable (adjusting for age, sex, vascular risk factors, and statin treatment) Cox proportional hazards and logistic regression models to test whether higher polygenic risk for elevated LDL-c was associated with observed LDL-c, ischemic stroke recurrence, and composite risk of ischemic stroke and myocardial infarction. Results: Of the 2,164 stroke survivors enrolled in VISP, 1,567 (72%) had available LDL-c and genetic data. The mean LDL in the low, intermediate and high polygenic risk categories was 114.5 (SD 2.21), 123.2 (SD 1.23), and 128.8 (SD 2.35), respectively (unadjusted p&lt;0.001). Compared to stroke survivors with low polygenic risk, those with intermediate (HR 1.52, 95% CI 0.91-2.54) and high (HR 2.03, 95% CI 1.14-3.61) polygenic risk had significantly higher risk of stroke recurrence (p test-for-trend 0.01). We observed similar associations when evaluating the composite risk of stroke and myocardial infarction (all p&lt;0.05) and when conducting these analyses using logistic regression (all p&lt;0.05). Conclusions: A higher polygenic risk for increased LDL-c is associated with worse clinical trajectories after stroke. Further research is needed to determine whether stroke survivors with an elevated genetic risk benefit from unique care pathways with additional monitoring and treatment.

Abstract WMP102: Diabetes-Related Polygenic Risk Is Associated With Poor Glycemic Control And Higher Risk Of Acute Cardiovascular Events In Stroke Survivors

Introduction: Though uncontrolled diabetes leads to recurrent cardiovascular events in stroke survivors, many don’t achieve appropriate glycemic control. We hypothesize an adverse polygenic risk profile leads to worse glycemic control and higher risk of recurrent cardiovascular events in stroke survivors. Methods: We conducted a population genetic study using data of stroke survivors enrolled in the UK Biobank and the Vitamin Intervention for Stroke Prevention (VISP) trial. In both studies, we modeled polygenic risk to diabetes through a polygenic risk score that included 462 single nucleotide polymorphisms known to associate with type 2 diabetes mellitus. Participants were stratified as low, intermediate, or high polygenic risk according to percentile values of this score (&lt;20 th , 20-80 th and &gt;80 th percentile). We used multivariable linear, logistic, and Cox regression models to test for association between polygenic risk to diabetes and 1) hemoglobin A1c (HbA1c), 2) risk of treatment-resistant diabetes (HbA1c ≥7 despite pharmacological therapy), and 3) composite risk of recurrent stroke or coronary artery disease (CAD). Results: In 5,670 stroke survivors enrolled in the UK Biobank (mean age 61, 41% females), a higher polygenic risk to diabetes was associated with higher HbA1c in both participants with and without diabetes, and with higher risk of treatment-resistant diabetes (all p&lt;0.05, see Table). In 1,750 stroke survivors (mean age 68, 35% female 34) enrolled in VISP, a higher polygenic risk to diabetes was associated with higher composite risk of recurrent stroke or CAD (p&lt;0.05, see Table). Conclusions: Among stroke survivors, a higher polygenic risk to diabetes is associated with worse glycemic control and higher risk of recurrent acute vascular events. Further research is needed to evaluate the portability of these results to non-white individuals and identify specific medications that may be more effective in patients with adverse genomic profiles.

Effectiveness and safety of Inclisiran in hyperlipidemia treatment: An overview of systematic reviews.

This paper aimed to comprehensively evaluate the effectiveness and safety of Inclisiran in treating hyperlipidemia through an overview of systematic reviews (SRs). The Cochrane Library, EMBASE, PubMed, CNKI, WANGFANG database, VIP database, ClinicalTrials.gov, and ICRT were searched electronically to collect SRs and meta-analysis of Inclisiran in hyperlipidemia treatment from the establishment of the database till May 2022. Two researchers independently screened the relevant literature, then the assessment of multiple systematic reviews tool was made into assess the methodological quality of the included studies. Data extracted were used to perform the study through RevMan5.3 software. The grading of recommendations assessment, development, and evaluation tool was used to grade the quality of the evidence of the outcomes included in the SRs. Prospero ID: CRD 42022326845. A total of 10 relevant SRs were included, involving 7 randomized controlled trials. The assessment results of the assessment of multiple systematic reviews tool suggested that the quality of the SRs included needed to be improved. The reduced level of low-density lipoprotein cholesterol of the experimental group was lower than the control group, and the difference in the amount of effectiveness was statistically significant (MD = -50.13, 95%CI: -56.2 to -44.06, P < .00001). The grading of recommendations assessment, development, and evaluation results showed that out of 27 outcomes, 8 were high-quality, 3 were of medium quality, 6 were of low quality, and 10 were of the most inferior quality. 300mg Inclisiran with 2 injections a year has the best therapeutic effect, which can significantly reduce low-density lipoprotein cholesterol and total cholesterol, and increase high-density lipoprotein cholesterol levels in patients with hyperlipidemia. Inclisiran has a favorable safety profile, with no significant difference in the incidence of adverse reactions compared to a placebo. Most of the adverse effects were associated with the reaction on the injection site.

COMORBID PATHOLOGY IN FATAL CASES DUE TO CORONAVIRUS DISEASE (COVID-19) IN VICTIMS OF THE CHORNOBYL NPP ACCIDENT.

The victims of the Chornobyl accident, as well as whole population of Ukraine, have become the object of the COVID-19 pandemic in today's conditions. As of 01.01.2020, 108,898 victims had documented permanent disability (persons with disabilities) and, as a rule, suffered from 4-6 types of non-tumor chronic diseases of internal organs, primarily the circulatory system, as well as oncological and endocrine pathology, that significantly affect the course of COVID-19 in a severe scenario and contribute to death. This determines the relevance of the issue of the impact of comorbid pathology in fatal cases due to coronavirus disease (COVID-19) in victims of the Chornobyl accident.The Objective of the study was to study the nature and significance of comorbid pathology in the victims of the Chernobyl accident who died from COVID-19.Design, object and methods of the study - a retrospective non-randomized, comparative comprehensive analysis of the materials of 134 medical expert cases of male clean-up workers of the Chornobyl accident who died from COVID-19 in 2020-2022 during the pandemic was carried out. The analysis of the materials of expert cases included the study of clinically significant and morphologically confirmed pathological processes. The source of the data was the materials of the Central Interdepartmental Expert Commission of the Ministry of Health of Ukraine on the establishment of causal relationship of diseases, disability and death with the action of ionizing radiation and other harmful factors as a result of the Chernobyl accident. In the structure of comorbid pathology in the clean-up workers of the Chornobyl accident who died due to COVID-19 during 2020-2022, diseases of the circulatory system dominate, which occurred in 86.57% of cases of consideration of medical expert cases. AH complicated the course and contributed to the development of fatal consequences in 52.24% of cases, ChIHD - in 34.32% of cases. The consequences of acute vascular events in the form of post-infarction cardiosclerosis in patients with ChIHD contributed to death in COVID-19 in 29 (21.64%) cases.Cerebrovascular pathology represented by cerebral atherosclerosis was detected in 76 (56.72%) cases of death from COVID-19. Acute vascular cerebral events in the cerebral basin (ischemic and hemorrhagic strokes) contributed to fatal outcomes in 19 (14.18%) cases. The presence and course of diabetes mellitus also had a significant impact on the course and fatal mortality of COVID-19 - 24.63% (33 cases). Chronic respiratory diseases (COPD) influenced the course of COVID-19 and contributed to death in 6.72% (9) of cases, nephrological pathology (ChTIN) - in 2.98% (4) of cases, peptic ulcer disease of the duedenum - in 2.24% (3) of cases. More than half of the clean-up workers of the Chornobyl NPP accident who died due to COVID-19 had more than two severe chronic diseases of the comorbid component and their complications. Сlean-up workers of the Chornobyl accident who died from COVID-19 had another severe comorbid chronic disease, or several diseases that influenced the course of coronavirus disease and each other and contributed to the development of fatal consequences. Death from COVID-19 is much more common in clean-up workers of the Chornobyl accident suffering from severe disabling non-oncological diseases of the cardiovascular system (arterial hypertension, coronary heart disease), cerebrovascular diseases with consequences of acute vascular events, as well as diabetes mellitus. Victims of the Chornobyl catastrophe, especially clean-up workers of the Chornobyl NPP accident, are at special risk for severe coronavirus disease and death from COVID-19.

Euglycemic diabetic ketoacidosis associated with sodium–glucose cotransporter-2 inhibitors after surgery: A case report and review of literature

Abstract Euglycemic diabetic ketoacidosis is a rare, acute, and life-threatening complication of diabetes mellitus associated with several risk factors such as infection, surgery, pregnancy, fasting, alcohol intake, acute vascular events (acute coronary syndrome or stroke), and the use of sodium–glucose cotransporter 2 (SGLT2) inhibitors. It is characterized by euglycemia, high-anion-gap metabolic acidosis, and ketoacidosis. Herein, we report two patients who used SGLT2 inhibitors before surgery and presented with severe metabolic acidosis after surgery. Subsequently, one patient required intubation, and both patients received two cycles of hemodialysis despite normal renal parameters. This was done to correct the metabolic acidosis, which led to early recovery.