Acute Vascular Events Research Articles

Sonodynamic therapy suppresses matrix collagen degradation in vulnerable atherosclerotic plaque by modulating caspase 3 - PEDF/HIF-1α - MMP-2/MMP-9 signaling in macrophages.

The rupture of vulnerable atherosclerotic plaque is the main cause of acute ischemic vascular events, and is characterized by pathological degradation of matrix collagen in the fibrous cap. In a previous study, we reported that 5-aminolevulinic acid-mediated sonodynamic therapy suppressed collagen degradation in rabbit plaque. However, the underlying molecular mechanism has yet to be fully elucidated. We applied sinoporphyrin sodium-mediated sonodynamic therapy (DVDMS-SDT) to balloon-denuded rabbit and apolipoprotein E-deficient (ApoE-/-) mouse models to observe collagen content in plaque. Cultured human THP-1 and mouse peritoneal macrophage-derived foam cells were used for in vitro mechanistic studies. We observed that DVDMS-SDT decreased plaque area and increased the percentages of collagen and smooth muscle cells and reduced the percentage of macrophages in rabbit and ApoE-/- mouse advanced plaques. In vitro, DVDMS-SDT modulated the caspase 3-pigment epithelium-derived factor/hypoxia-inducible factor-1α (PEDF/HIF-1α)-matrix metalloprotease-2/9 (MMP-2/MMP-9) signaling in macrophage foam cells. Our findings show that DVDMS-SDT effectively inhibits matrix collagen degradation in advanced atherosclerotic plaque by modulating caspase 3-PEDF/HIF-1α-MMP-2/MMP-9 signaling in macrophage foam cells and therefore represents a suitable and promising clinical regimen to stabilize vulnerable plaques.

Physical activity among first-onset myocardial infarction patients: Case-control MAVERIK study

Cardiovascular diseases (CVD), such as myocardial infarction (heart attacks), are the main cause of deaths globally. The Malaysian Acute Vascular Events Risk (MAVERIK) Study aimed to determine lifestyle-related cardiovascular risk factors in Malaysia. An active lifestyle has been reported to reduce the incidence of CVD.

Vulnerable Atherosclerotic Plaque: Is There a Molecular Signature?

Atherosclerosis and its clinical manifestations, coronary and cerebral artery diseases, are the most common cause of death worldwide. The main pathophysiological mechanism for these complications is the rupture of vulnerable atherosclerotic plaques and subsequent thrombosis. Pathological studies of the vulnerable lesions showed that more frequently, plaques rich in lipids and with a high level of inflammation, responsible for mild or moderate stenosis, are more prone to rupture, leading to acute events. Identifying the vulnerable plaques helps to stratify patients at risk of developing acute vascular events. Traditional imaging methods based on plaque appearance and size are not reliable in prediction the risk of rupture. Intravascular imaging is a novel technique able to identify vulnerable lesions, but it is invasive and an operator-dependent technique. This review aims to summarize the current data from literature regarding the main biomarkers involved in the attempt to diagnose vulnerable atherosclerotic lesions. These biomarkers could be the base for risk stratification and development of the new therapeutic drugs in the treatment of patients with vulnerable atherosclerotic plaques.

Rapidly progressing dyspnea and retiform purpura

Rapidly progressing dyspnea and retiform purpura

The new 2022 ESC Guidelines on Cardio-oncology and their impact on the Acute Cardiovascular Care Society.

In this perspective piece on the recently published ESC Guidelines on Cardio-oncology and the Consensus Statements from the Acute Cardiovascular Care Association, we summarize key learning points regarding the management of acute cardiovascular disease in patients with cancer. This document outlines where other pre-existing ESC Guidelines can be applied to the management of acute cardiovascular disease in patients with cancer while simultaneously highlighting important gaps in knowledge that require further research. Cancer and cardiovascular disease share common risk factors and often co-exist, especially in older patients. In addition, patients with cancer undergoing active treatment are exposed to multiple, potentially cardiotoxic drugs, which may manifest as a variety of cardiovascular events, including left-ventricular systolic dysfunction and heart failure, arrhythmias, hypertension, or acute venous and arterial vascular events. Knowledge about potential causative cancer therapeutics is necessary for rapid recognition and management to improve cardiovascular outcomes and guide ongoing cancer treatment. Specifically, the importance of rapidly interrupting culprit cancer drugs is highlighted, as well as instituting standard guideline-based therapies for conditions such as acute heart failure and acute coronary syndromes [ST-elevation myocardial infarction and high-risk non-ST-elevation acute coronary syndrome (ACS)]. Given the high prevalence of thrombocytopenia and increased bleeding risk in patients with cancer, we are provided with platelet cut-offs for the use of different antiplatelet agents and anticoagulants for patients with ACS and atrial arrhythmias. In contrast, given the hypercoagulable milieu of cancer, we are provided information regarding types of anticoagulants, drug-drug interactions, and duration of anticoagulation in patients with acute venous thromboembolism, as well as for atrial fibrillation. They also discuss the diagnostic and treatment strategies for the unique cardiotoxicities seen with novel cancer therapeutics such as immune checkpoint inhibitors and chimeric receptor antigen T-cell therapy. Last, but not least, the authors emphasize that the care of these patients requires close collaboration between cardiology and oncology to maximize both cardiovascular and cancer outcomes.

Outcomes and Readmission in Patients With Retinal Artery Occlusion (from the Nationwide Readmission Database)

Retinal artery occlusion (RAO) is an ophthalmologic emergency, leading to sudden vision loss. Understanding its risk factors and garnering information on the incidence of adverse events can provide helpful information on the cost-effective evaluation of patients and secondary prevention. In this retrospective cohort study, we used the Nationwide Readmission Database from 2016 to 2018 and queried the database to identify patients with RAO. The clinical outcomes were cumulative incidence of myocardial infarction (MI), stroke, death (in-hospital and 6 months after discharge), resource utilization, all-cause readmission at 6 months, and reasons for all-cause readmission. We identified a total of 14,527 patients with RAO. The mean age of patients with RAO was 69 ± 13 years. Hypertension (11,839, 82%), hyperlipidemia (8,868, 61%), ischemic cardiomyopathy (4,826, 33%), smoking (4,772, 33%), and diabetes (4,588, 32%) were common co-morbidities in patients with RAO. Of 14,527 patients with RAO, 308 patients (2.1%) died, 1,577 (10.9%) developed stroke, and 615 (4.2%) developed MI within 6 months. A total of 2,841 patients (24.9%) were readmitted within 6 months of discharge. Carotid artery stenosis (386, 10.8%) was the most common cause of readmission. History of stroke or transient ischemic attack and Elixhauser co-morbidity index ≥3 were predictors of stroke. Female gender, ischemic cardiomyopathy, carotid artery disease, heart failure, chronic kidney disease, and cancer were predictors of MI. Cancer, chronic kidney disease, Elixhauser co-morbidity index ≥3, Medicare/Medicaid payer status, nonelective index admission, atrial fibrillation, and carotid artery disease were predictors of 6-month all-cause readmission. In conclusion, patients with RAO have a significant burden of co-morbidities, death, stroke, MI, and readmission. RAO may be used as a clinical marker of future stroke and MI, and should trigger screening for acute vascular ischemic events.

Acute neurological disease as a trigger or co-occurrence of transient global amnesia: a case series and systematic review.

Transient global amnesia (TGA) represents a benign neurological syndrome of unknown pathophysiology, often accompanied by vanishing hippocampal punctate lesions on diffusion-weighted imaging (hippocampal punctate diffusion lesion, HPDL). The recent literature suggests that TGA may be triggered by acute neurological conditions. To study patients with TGA triggered by an acute neurological disease. We retrospectively reviewed patients from two neurology centres with TGA (with or without HPDL) in whom an acute neurological condition could be identified as trigger. We also performed a systematic review of the literature of this situation using predefined search terms. We identified 38 patients (median age 62years, 55.3% female): 6 from our centres and 32 from the literature. Acute neurovascular diseases that preceded or were associated with TGA included ischemic and haemorrhagic strokes, convexity subarachnoid haemorrhage, and reversible cerebral vasoconstriction syndrome. As non-vascular acute neurological diseases, we identified migraine and peripheral-origin vertigo. The clinical manifestation of the neurological trigger showed a variable temporal relation with TGA onset; in some cases preceding and in others co-occurring with TGA manifestation. In some cases, presumed neurological triggers were asymptomatic and diagnosed from the neuroimaging done for the TGA. Acute vascular and non-vascular neurological events may trigger TGAs or may occur simultaneously. In the first case, such an acute neurological disease may activate direct pathways within the nervous systems leading to TGA, or alternatively elicit a bodily sympathetic overactivity cascade. In the second case, both neurological events may be the result of a common external stressor.

Heterogeneity of obesity and the main pathogenetic factors of its development (a review of resources)

Introduction. Among medical and social problems, obesity (Ob) occupies one of the leading places. This is related to the established pathogenetic connection of Ob with type 2 diabetes mellitus, arterial hypertension, acute vascular events, dementia, osteoarthritis, obstructive sleep apnea and some forms of cancer. Ob is also associated with social problems and reduced work capacity. Despite numerous studies on the study of Ob, a number of unresolved issues and controversial points of view remain. The aim – is to analyze the currently existing data on the heterogeneity of Ob and the main pathogenetic factors of its development based on the study of literary sources, mainly for a period of 10 years. Materials and methods – an electronic search was carried out in MEDLINE/PubMed, Google Scholar and Web of Science databases using the keywords "obesity", "obesity heterogeneity", "obesity etiopathogenesis" with subsequent analysis of literature sources published mainly in the last 10 years. The results. To date, there is no single universally accepted classification of Ob, and those currently used in clinical practice and during scientific research are based on one or another criterion. Such criteria include etiopathogenetic factors, type of adipose tissue deposition, degree of weight gain, etc. The use of bioimpedancemetry became the basis for the assertion about the heterogeneity of Ob with the selection of its separate forms, namely: metabolically healthy Ob; metabolic Ob with normal body weight, sarcopenic and metabolically unhealthy Ob. Despite the lack of clear diagnostic criteria for each of these forms, their differences in clinical course, pathogenetic factors of development and degree of cardiovascular risk have been established. Considering the indicated heterogeneity, the selection of the leading etiological factor of Ob remains a rather controversial and difficult issue. The exceptions, obviously, should include cases of the secondary form of this pathology, when Ob is one of the symptoms and is pathogenetically related to the underlying disease. In general, it is believed that, being hereditary, Ob is the result of the interaction between genetic, hormonal-metabolic, behavioral and environmental factors. Conclusions. Ob is a chronic multifactorial and heterogeneous disease, the individual clinical forms of which differ in the course and level of metabolic disorders. Etiopathogenetic factors of the development and progression of Ob are multifactorial and include genetic predisposition, factors of the external and internal environment, eating behavior and hormonal and metabolic shifts. According to the data obtained today regarding the heterogeneity of Ob and the pathogenetic mechanisms of its development, a new generally accepted characteristic and classification of this pathology should be accepted.

Early atherosclerosis and acute vascular events in ulcerative colitis patients-a case series

Introduction: In inflammatory bowel disease uncontrolled inflammation may play a role in the early progression of systemic atheromatosis with increased cardiovascular risk. Endothelial dysfunction is mediated by pro-inflammatory cytokines but also by an increased level of CRP which is involved in the expression of adhesion molecules and atheroma plaque rupture. Tailored treatment with better control of the ulcerative colitis and endoscopic healing might result in decrease risk of atherothrombotic events. Aim: We decided to use a well-established method (vascular Doppler ultrasound with media-intimate index measurement) to detect an increased incidence of endothelial lesions as predictors of early atheromatosis in patients with ulcerative colitis treated with biological or conventional therapy. Material and methods: We prospectively analyzed 25 patients with RCUH with a mean age of 40 years, 16 with biological treatment. The Student t test, the Mann Whitney U test and the ANOVA test were used to compare continuous variables. Results: A discriminant analysis was performed with the presence of atheroma plaque as a dependent variable and several predictor variables, such as age, triglycerides, cholesterol of patients with ulcerative colitis. Univariate ANOVA analyzes revealed that the presence or absence of atheroma plaque differs in the variables predicting the age, INR and ecoIMT of patients with ulcerative colitis (in the age of patients (F = 8.511, degrees of freedom = 11, p = 0.014) Patients ‚INR (F = 50,437, degrees of freedom = 11, p = 0.001) and Patients’ ecoIMT (F = 7,398, degrees of freedom = 11, p = 0.020) In another analysis of discriminatory function s -introduced the predictor variables specific to measuring the evolution of ulcerative colitis, respectively Mayo and Mayo E (age (F = 0.8511, degrees of freedom = 11, p = 0.014), INR (F = 50.437, degrees of freedom = 11, p = 0.001), ecoIMT (F = 7.398, df = 11, p = 0.020) and Mayo (F = 14.885, degrees of freedom = 11, p = 0.003). Conclusions: Age, endoscopic activity, and INR were correlated with predictive ultrasound changes for atheromatosis. Strengths are the prospective nature of the study and weaknesses are the limited number of patients and the fact that most patients were in remission and treated with biologicals, which could create bias in the sense of reducing the atherosclerotic risk directly correlated with active inflammation.

Negative correlation between early recovery and lipoprotein-associated phospholipase A2 levels after intravenous thrombolysis.

ObjectiveLipoprotein-associated phospholipase A2 (Lp-PLA2) is considered a biomarker for systemic inflammation and the risk of myocardial infarction and stroke. However, little is known about the effect of acute vascular events on marker levels. The purpose of this study was to assess the potential association of early recovery with Lp-PLA2 levels in patients with acute ischemic stroke (AIS) after intravenous thrombolysis (IVT).MethodsForty-three consecutive AIS patients who had their first stroke and were hospitalized within 5 hours of the onset of stroke were enrolled. All patients were treated with IVT using alteplase or urokinase. Plasma Lp-PLA2 levels were measured within 24 hours after IVT. Variables that showed a significant association with Lp-PLA2 in univariate analysis were included in the multivariate ordered logistic regression model.ResultsEarly recovery was associated with Lp-PLA2 levels after IVT, and Lp-PLA2 levels tended to decrease with increased probability of early recovery. This study is the first to report a negative correlation between early recovery and Lp-PLA2 levels after IVT.ConclusionEarly recovery after IVT was negatively correlated with Lp-PLA2 A2 levels.

Invasive dental treatment and acute vascular events: A systematic review and meta‐analysis

BackgroundAcute infection/inflammation increases the risk of acute vascular events (AVEs). Invasive dental treatments (IDTs) trigger short‐term acute inflammation.PurposeThe aim of this work is to critically appraise the evidence linking IDTs and AVEs.Data SourcesSix bibliographical databases were searched up to 31 August 2021. A systematic review following PRISMA guidelines was performed.Study SelectionIntervention and observational studies reporting any AVEs following IDT were included.Data ExtractionTwo reviewers independently extracted data and rated the quality of studies. Data were pooled using fixed‐effect, inverse variance weights analysis.Risk of BiasRisk of bias was assessed by the Newcastle–Ottawa Quality Assessment Scale for observational studies and the Cochrane Handbook–Rob 2.0 for randomized controlled trials.Data SynthesisIn 3 out of 16 clinical studies, a total of 533,175 participants, 124,344 myocardial infarctions, and 327,804 ischaemic strokes were reported. Meta‐analysis confirmed that IDT did not increase incidence ratios (IR) for combined vascular events either at 1‐4 weeks (IR of 1.02, 95% CIs: 0.92 to 1.13) and at 5‐8 weeks (IR of 1.04, 95% CIs: 0.97 to1.10) after treatment.LimitationsA high level of heterogeneity (study designs and time point assessments) was found.ConclusionPatients who received IDT exhibited no substantial increase in vascular risk over 8 weeks post treatment.

Arterial and Venous Thromboembolism in Critically Ill, COVID-19 Positive Patients Admitted to Intensive Care Unit

Arterial and Venous Thromboembolism in Critically Ill, COVID-19 Positive Patients Admitted to Intensive Care Unit

An Updated Review of Cardiovascular Events in Giant Cell Arteritis.

Giant cell arteritis (GCA) is a systemic vasculitis with a direct and indirect increased risk of acute and chronic vascular events, affecting large and medium vessels, and responsible for most of the morbidity and mortality of this disease. We aimed in this review to provide an updated synthesis of knowledge regarding cardiovascular events observed in GCA. By definition, GCA patients are over 50 and often over 70 years old, and subsequently also present age-related cardiovascular risk factors. In addition, the systemic and vascular inflammation as well as glucocorticoids (GC) probably contribute to an accelerated atherosclerosis and to vascular changes leading to arterial stenoses and aortic dilations and/or dissections. GCA-related ischemic complications, especially ophthalmologic events, stroke or myocardial infarcts are mostly observed within the first months after the diagnosis, being mainly linked to the vasculitic process. Conversely, aortic complications, including dilations or dissections, generally occur several months or years after the diagnosis, mainly in patients with large-vessel vasculitis. In these patients, other factors such as atherosclerosis, GC-related endothelial damage and vascular wall remodeling/healing probably contribute to the vascular events. GCA management includes the detection and treatment of these previous and newly induced cardiovascular risk factors. Hence, the use of cardiovascular treatments (e.g., aspirin, anticoagulation, statins, anti-hypertensive treatments) should be evaluated individually. Aortic structural changes require regular morphologic evaluations, especially in patients with previous aortitis. The initial or secondary addition of immunosuppressants, especially tocilizumab, an anti-IL-6 receptor antibody, is discussed in patients with GCA-related cardiovascular complications and, more consensually, to limit GC-mediated comorbidities.

Investigating Genetic and Other Determinants of First-Onset Myocardial Infarction in Malaysia: Protocol for the Malaysian Acute Vascular Events Risk Study.

BackgroundAlthough the burden of premature myocardial infarction (MI) is high in Malaysia, direct evidence on the determinants of MI in this multi-ethnic population remains sparse.ObjectiveThe Malaysian Acute Vascular Events Risk (MAVERIK) study is a retrospective case-control study established to investigate the genomic, lipid-related, and other determinants of acute MI in Malaysia. In this paper, we report the study protocol and early results.MethodsBy June 2019, we had enrolled approximately 2500 patients with their first MI and 2500 controls without cardiovascular disease, who were frequency-matched by age, sex, and ethnicity, from 17 hospitals in Malaysia. For each participant, serum and whole blood have been collected and stored. Clinical, demographic, and behavioral information has been obtained using a 200-item questionnaire.ResultsTobacco consumption, a history of diabetes, hypertension, markers of visceral adiposity, indicators of lower socioeconomic status, and a family history of coronary disease were more prevalent in cases than in controls. Adjusted (age and sex) logistic regression models for traditional risk factors indicated that current smoking (odds ratio [OR] 4.11, 95% CI 3.56-4.75; P<.001), previous smoking (OR 1.34, 95% CI 1.12-1.60; P=.001), a history of high blood pressure (OR 2.13, 95% CI 1.86-2.44; P<.001), a history of diabetes mellitus (OR 2.72, 95% CI 2.34-3.17; P<.001), a family history of coronary heart disease (OR 1.28, 95% CI 1.07-1.55; P=.009), and obesity (BMI >30 kg/m2; OR 1.19, 95% CI 1.05-1.34; P=.009) were associated with MI in age- and sex-adjusted models.ConclusionsThe MAVERIK study can serve as a useful platform to investigate genetic and other risk factors for MI in an understudied Southeast Asian population. It should help to hasten the discovery of disease-causing pathways and inform regionally appropriate strategies that optimize public health action.International Registered Report Identifier (IRRID)RR1-10.2196/31885

Acute arterial events across all vascular territories in the FOURIER trial

Abstract Background In the FOURIER (Further Cardiovascular Outcomes Research With PCSK9 Inhibition in Patients With Elevated Risk) trial, adding the PCSK9 inhibitor evolocumab to statin therapy reduced low-density lipoprotein cholesterol (LDL-C) and cardiovascular risk. Although atherosclerotic coronary, cerebrovascular, and peripheral vascular events share a related pathobiology, the effect of aggressive LDL-C lowering with PCSK9 inhibition on the risk of acute arterial events across all three vascular beds is not well-described. Purpose To assess the efficacy of evolocumab on acute arterial events in all vascular territories including coronary, cerebral, and peripheral vascular beds. Methods In the FOURIER trial, patients (n=27,564) with stable atherosclerotic cardiovascular disease and LDL-C ≥70 mg/dL on a statin were randomly assigned to evolocumab versus placebo and followed for a median of 2.2 years (1.8–2.5). Acute arterial events were defined as a composite of coronary (coronary heart disease [CHD] death, myocardial infarction [MI], or urgent coronary revascularization), cerebrovascular (ischemic stroke, transient ischemic attack [TIA], or urgent cerebral revascularization), or peripheral vascular (acute limb ischemia, major amputation, or urgent peripheral revascularization) events. Cox proportional-hazard models were used to assess the efficacy of evolocumab on these outcomes. Landmark and total event analyses were also done. Results Of the 2,210 first acute arterial events occurring during follow-up, 74% were coronary, 22% were cerebrovascular, and 4% were peripheral vascular. Evolocumab reduced the risk of a first acute arterial event by 19% (HR 0.81, 95% CI 0.74–0.88; P&amp;lt;0.001), with significant individual reductions in acute coronary (HR 0.83; 95% CI 0.75–0.91; P&amp;lt;0.001), acute cerebrovascular (HR 0.77; 95% CI 0.65–0.92; P=0.004), and acute peripheral vascular (HR 0.58; 95% CI 0.38–0.88; P=0.01) events (Figure, top). The magnitude of the risk reduction with evolocumab tended to increase over time, with a 16% reduction (HR 0.84; 95% CI 0.75–0.96) in the first year followed by a 24% reduction (HR 0.76; 95% CI 0.67–0.85) thereafter (Figure, bottom). There were 3,780 total acute arterial events (first plus recurrent), with a 22% reduction with evolocumab (incidence rate ratio [RR] 0.78; 95% CI 0.70–0.87). Evolocumab prevented 496 total acute arterial events as compared to 222 first events. Conclusions The addition of the PCSK9 inhibitor evolocumab to statin therapy reduced the risk of acute arterial events across all vascular territories with a robust effect over time. These findings indicate a pan-vascular impact of aggressive lipid-lowering therapy on these acute and clinically meaningful events. Funding Acknowledgement Type of funding sources: Private company. Main funding source(s): The FOURIER trial was supported by Amgen.

Bowel ischemia as onset of COVID‐19 in otherwise asymptomatic patients with persistently negative swab

BackgroundAsymptomatic patients with Severe Acute Respiratory Syndrome Coronavirus 2 (SARS‐CoV‐2) can develop hypercoagulable conditions and acute vascular events. The objective of this study is to determine whether SARS‐CoV‐2 was present in resected specimens from patients with acute bowel ischemia, but asymptomatic for Coronavirus Disease 2019 (COVID‐19) and with persistently real‐time polymerase chain reaction negative pharyngeal swab.MethodsThree consecutive patients presented severe abdominal symptoms due to extensive ischemia and necrosis of the bowel, with co‐existent thrombosis of abdominal blood vessels. None had the usual manifestations of COVID‐19, and repeated pharyngeal swabs tested negative. They underwent emergency surgery with intestinal resection. Immunohistochemical testing for SARS‐CoV‐2 on resected tissue was performed.ResultsAll tested samples were strongly positive for SARS‐CoV‐2.ConclusionsThis is the first case report in which patients with severe intestinal symptoms presented a marked SARS‐CoV‐2 positivity in the resected tissues, without any usual clinical manifestations of COVID‐19. These results suggest that the patients might be infected with SARS‐CoV‐2 presenting acute abdominal distress but without respiratory or constitutional symptoms.

Acute Graft-Versus-Host Disease, Infections, Vascular Events and Drug Toxicities Affecting the Central Nervous System.

Allogeneic hematopoietic cell transplantation (allo-HCT) is a curative therapy for patients with hematological malignancies. Acute Graft versus host diseases (GVHD) is a major immune mediated side effect of allo-HCT that can affect the central nervous system (CNS) in addition to post-allo-HCT vascular events, drug toxicity or infections. Here we summarize and discuss recent preclinical data on the CNS as a target of acute GVHD and the known mechanisms contributing to neurotoxicity with a focus on microglia and T cells. We also discuss open questions in the field and place the findings made in mouse models in a clinical context. While in mice the neurological deficits can be assessed in a controlled fashion, in patients the etiology of the CNS damage is difficult to attribute to acute GVHD versus infections, vascular events, and drug-induced toxicity. Ultimately, we discuss novel therapies for GVHD of the CNS. Our understanding of the biological mechanisms that lead to neurotoxicity after allo-HCT increased over the last decade. This review provides insights into CNS manifestations of GVHD versus other etiologies of CNS damage in mice and patients.

Effect of evolocumab on acute arterial events across all vascular territories : results from the FOURIER trial

We assessed the impact of the proprotein convertase subtilisin-kexin type 9 (PCSK9) inhibitor evolocumab on acute arterial events across all vascular territories, including coronary, cerebrovascular, and peripheral vascular beds, in patients with established atherosclerotic cardiovascular disease (ASCVD). In the FOURIER trial, 27 564 patients with stable ASCVD on statin therapy were randomly assigned to evolocumab or placebo. Acute arterial events were a composite of acute coronary (coronary heart disease death, myocardial infarction, or urgent coronary revascularization), cerebrovascular (ischaemic stroke, transient ischaemic attack, or urgent cerebral revascularization), or peripheral vascular (acute limb ischaemia, major amputation, or urgent peripheral revascularization) events. Of the 2210 first acute arterial events, 74% were coronary, 22% were cerebrovascular, and 4% were peripheral vascular. Evolocumab reduced first acute arterial events by 19% (hazard ratio [HR] 0.81 [95% confidence interval 0.74-0.88]; P < 0.001), with significant individual reductions in acute coronary (HR 0.83 [0.75-0.91]), cerebrovascular (HR 0.77 [0.65-0.92]), and peripheral vascular (HR 0.58 [0.38-0.88]) events. There were 3437 total events (first plus recurrent), with evolocumab reducing total events by 24% (incidence rate ratio 0.76 [0.69-0.85]). The magnitude of reduction in acute arterial events with evolocumab numerically increased over time, with a 16% reduction (HR 0.84 [0.75-0.95]) in the first year followed by a 24% reduction (HR 0.76 [0.67-0.85]) thereafter. The addition of the PCSK9 inhibitor evolocumab to statin therapy reduced acute arterial events across all vascular territories with a robust effect over time, indicating a pan-vascular impact of aggressive lipid-lowering therapy on these acute and clinically meaningful events. URL: https://www.clinicaltrials.gov. Unique identifier: NCT01764633.

Anticoagulation in intensive care medicine

Kritisch kranke Patienten sind in hohem Maße durch Störungen der Hämostase gefährdet, diese können sowohl mit einer verstärkten Blutungsneigung als auch mit einem erhöhten Risiko für thromboembolische Ereignisse einhergehen. Bei akuten vaskulären Ereignissen ist die spezifische Therapie mit medikamentöser Antikoagulation bzw. Plättchenaggregationshemmung essenziell, bei Patienten mit Vorerkrankungen ist die angepasste Fortführung einer vorbestehenden Antikoagulation während intensivmedizinischer Behandlung von Bedeutung, des Weiteren sind sowohl medikamentöse Thromboseprophylaxe als auch die Frage nach potenziell therapeutischen Optionen, wie Antikoagulanzien bei Sepsis und infektionsgetriggerten Störungen der Blutgerinnung, im klinischen Alltag wichtig. Spezifische Fragestellungen ergeben sich bei der Anwendung extrakorporaler Maßnahmen wie Nierenersatzverfahren sowie Kreislaufunterstützungs- und Ersatzverfahren. In den letzten Jahren sind eine Reihe neuer Präparate zur Antikoagulation und Plättchenhemmung verfügbar geworden. Die Therapiekontrolle über labordiagnostische Verfahren stellt einen zentralen Punkt dar. In dieser Übersichtsarbeit werden aktuelle Aspekte zu diesen Themen praxisnah aufgeführt.

Residential exposure to traffic-borne pollution as a risk factor for acute cardiocerebrovascular events: a population-based retrospective cohort study in a highly urbanized area.

BackgroundLong-term exposure to traffic-borne noise and air pollution has been variably associated with incidence of acute vascular events, namely acute myocardial infarction, ischaemic stroke and haemorrhagic stroke. This study aims at exploring this association within a highly urbanized city.MethodsThis is a population-based retrospective dynamic cohort study including all residents aged ≥ 35 years in the municipality of Milan over the years 2011–18 (1 087 110 inhabitants). Residential exposure to road traffic noise (day-evening-night levels) and nitrogen dioxide was estimated using a noise predictive model and a land use regression model, respectively. Cox proportional hazards regression analyses were performed to assess the incidence of acute vascular events and specific outcomes in single-exposure and two-exposure models including adjustment for sociodemographic confounders, fine particulate matter and surrounding greenness.ResultsA total of 27 282 subjects (2.5%) had an acute vascular event. Models using nitrogen dioxide produced inconsistent results. The strongest effect was observed for noise, with an optimal cut-off for dichotomization set at 70 dBA (hazard ratio 1.025, 95% confidence interval 1.000–1.050). This association was observed specifically for ischaemic and haemorrhagic stroke. When stratifying by age group and sex, a remarkable effect was found for haemorrhagic stroke in men aged <60 years (hazard ratio 1.439, 95% confidence interval 1.156–1.792).ConclusionsLiving by roads with a day-evening-night noise level above 70 dBA exerts a small but tangible independent effect on the risks of both ischaemic and haemorrhagic stroke. It is urgent to propose mitigation measures against pollution and noise originating from vehicular traffic in order to reduce their impact, especially in the population younger than 60 years.