Mechanism and use strategy of uric acid-lowering drugs on coronary heart disease.

Coronary heart disease (CHD) is a serious cardiovascular illness, for which an elevated uric acid (UA) level presents as a considerable risk factor. This can be treated with UA-lowering drugs such as allopurinol and benzbromarone, which can reduce UA levels by the inhibition of UA production or by promoting its excretion. Such drugs can also be beneficial to CHD in other ways, such as reducing the degree of coronary arteriosclerosis, improving myocardial blood supply and alleviating ventricular remodeling. Different UA-lowering drugs are used in different ways: allopurinol is preferred as a single agent in clinical application, but in absence of the desired response, a combination of drugs such as benzbromarone with ACE inhibitors may be used. Patients must be monitored regularly to adjust the medication regimen. Appropriate use of UA-lowering drugs has great significance for the prevention and treatment of CHD. However, the specific mechanisms of the drugs and individualized drug use need further research. This review article expounds the mechanisms of UA-lowering drugs on CHD and their clinical application strategy, thereby providing a reference for further optimization of treatment.

Institutional Support for the Career Advancement of Women Faculty in Science and Academic Medicine: Successes, Challenges, and Future Directions.

Institutional support is crucial for the successful career advancement of all faculty but in particular those who are women. Evolving from the past, in which gender disparities were prevalent in many institutions, recent decades have witnessed significant progress in supporting the career advancement of women faculty in science and academic medicine. However, continued advancement is necessary as previously unrecognized needs and new opportunities for improvement emerge. To identify the needs, opportunities, and potential challenges encountered by women faculty, the Women's Leadership Committee of the Arteriosclerosis, Thrombosis, and Vascular Biology Council developed an initiative termed GROWTH (Generating Resources and Opportunities for Women in Technology and Health). The committee designed a survey questionnaire and interviewed 19 leaders with roles and responsibilities in faculty development from a total of 12 institutions across various regions of the United States. The results were compiled, analyzed, and discussed. Based on our interviews and analyses, we present the current status of these representative institutions in supporting faculty development, highlighting efforts specific to women faculty. Through the experiences, insights, and vision of these leaders, we identified success stories, challenges, and future priorities. Our article provides a primer and a snapshot of institutional efforts to support the advancement of women faculty. Importantly, this article can serve as a reference and resource for academic entities seeking ideas to gauge their commitment level to women faculty and to implement new initiatives. Additionally, this article can provide guidance and strategies for women faculty as they seek support and resources from their current or prospective institutions when pursuing new career opportunities.

MiR-140-3p Normalizes Vascular Smooth Muscle Cell Behavior by Inhibiting the RhoA/ROCK Signaling Pathway in Lower-extremity Arteriosclerosis Obliterans.

BACKGROUND: Excessive vascular smooth muscle cell (VSMC) proliferation and migration are the main contributors to the symptoms of lower-extremity arteriosclerosis obliterans (ASO). Previous studies suggested that microRNAs (miRNAs) regulate VSMC activity. Nevertheless, the molecular mechanisms by which they do so are unclear. OBJECTIVE: The present study aimed to identify the biological processes accounting for the effects of miR-140-3p on VSMCs in ASO. METHODS: The expression levels of miR-140-3p in clinical samples were analyzed by real-time polymerase chain reaction. An ASO cell model was established to investigate the expression of miR-140-3p on VSMCs. The transwell® assays and MTT assays were used to assess migration and proliferation. The interaction between RhoA and miR-140-3p was verified using the Dualluciferase reporter assay. Western blot technique was used to identify RhoA, RhoA-associated protein kinase 1 (ROCK1), and ROCK2. RESULTS: We discovered that miR-140-3p inhibited the proliferation, migration, and invasion but promoted the apoptosis of VSMCs, and RhoA was its downstream target gene. RhoA, ROCK1, and ROCK2 were upregulated in vascular tissues damaged by ASO compared to normal, healthy arteries. MiR-140-3p also decreased RhoA, ROCK1, and ROCK2 mRNA and protein expression. CONCLUSION: Overall, the present work partially elucidated the mechanism by which miR-140-3p regulates VSMC function and offered novel insights into potential therapeutic approaches for patients with lower-extremity arteriosclerosis obliterans.

Cervicocerebral Atherosclerosis Burden Increases Long-Term Mortality in Patients With Ischemic Stroke or Transient Ischemic Attack.

BACKGROUND: The influence of burden of atherosclerosis in the brain supplying arteries on mortality in patients with acute ischemic stroke or transient ischemic attack is poorly known. We assessed whether total burden of atherosclerosis within cervicocerebral arteries is associated with long-term mortality. METHODS AND RESULTS: A total of 406 patients (median age, 71.8 years; 57.9% male) with acute ischemic stroke or transient ischemic attack were included and their cervicocerebral arteries imaged with computed tomography angiography. The presence of atherosclerotic findings was scored for 25 artery segments and points were summed as a Cervicocerebral Atherosclerosis Burden (CAB) score, analyzed as quartiles. Data on all-cause mortality came from Statistics Finland. After a median follow-up of 7.3 years, 147 (33.5%) patients had died. Compared with surviving patients, those who died had a higher median CAB score (5, interquartile range 2-10 versus 11, 7-16; P<0.001). Cumulative mortality increased from 8.9% (95% CI, 7.0-10.8) in the lowest to 61.4% (95% CI, 55.4-67.4) in the highest quartile of CAB score. Adjusted for demographics, cardiovascular risk factors, secondary preventive medication, and admission National Institute of Health Stroke Scale score, every CAB score point increased probability of death by 3%. Analyzed in quartiles, the highest CAB quartile was associated with a 2.5-fold likelihood of all-cause mortality. CONCLUSIONS: The main findings of our study were the increasing mortality with the total burden of computed tomography angiography-defined atherosclerosis in the brain supplying arteries after ischemic stroke or transient ischemic attack and that the CAB score-integrating this pathology-independently increased all-cause mortality.

Effect of alprostadil plus cilostazol on the treatment outcomes and inflammatory factors in patients with lower extremity arteriosclerosis obliterans receiving evidence-based care.

This study aims to elucidate the effect of alprostadil (ALP) plus cilostazol (CIL) on the treatment outcomes and inflammatory factors in patients with lower extremity arteriosclerosis obliterans (LEASO) receiving evidence-based care. Firstly, 130 patients with LEASO were selected from February 2020 to February 2023 and then randomly divided into two groups with 65 patients each. Excluding the dropouts, 59 patients in the control group (6 cases of dropout) received ALP and 62 patients in the research group (3 cases of dropout) received ALP plus CIL. Both groups were cared for in accordance with the evidence-based care model. Treatment outcomes, arteriosclerosis indexes (blood flow of dorsalis pedis artery [DPA], ankle-brachial index [ABI] and toe-brachial index [TBI]), hemorheological parameters (erythrocyte aggregation index [EAI], erythrocyte deformation index [EDI], high blood viscosity [HBV] and haematocrit [HCT]), inflammatory factors (interleukin [IL]-6, IL-8 and tumour necrosis factor [TNF]-α) and complications (nausea, diarrhoea, headache and transaminase elevation) were compared between the control and research groups. Results show that the overall response rate was markedly higher in the research group (90.32%) than in the control group (74.58%). Additionally, the blood flow of DPA, ABI and TBI in the research group significantly increased after the treatment and were higher than those in the control group. Meanwhile, the EAI, EDI, HBV, HCT, IL-6, IL-8 and TNF-α were significantly lower. The two groups did not differ markedly in the complication rate. The above findings suggest that ALP plus CIL is effective for patients with LEASO receiving evidence-based care. It can significantly improve arteriosclerosis indexes and hemorheological parameters while inhibiting serum inflammatory responses, with some certain safety.

Construction of prediction models for novel subtypes in patients with arteriosclerosis obliterans undergoing endovascular therapy: an unsupervised machine learning study.

BACKGROUND: Arteriosclerosis obliterans (ASO) is a chronic arterial disease that can lead to critical limb ischemia. Endovascular therapy is increasingly used for limb salvage in ASO patients, but the outcomes vary. The development of prediction models using unsupervised machine learning may lead to the identification of novel subtypes to guide patient prognosis and treatment. METHODS: This retrospective study analyzed clinical data from 448 patients with ASOs who underwent endovascular therapy. Unsupervised machine learning algorithms were employed to identify subgroups. To validate the precision of the clustering outcomes, an analysis of the postoperative results of the clusters was conducted. A prediction model was constructed using binary logistic regression. RESULTS: Two distinct subgroups were identified by unsupervised machine learning and characterized by differing patterns of clinical features. Patients in Cluster 2 had significantly worse conditions and prognoses than those in Cluster 1. For the novel ASO subtypes, a nomogram was developed using six predictive factors, namely, platelet count, ankle brachial index, Rutherford category, operation method, hypertension, and diabetes status. The nomogram achieved excellent discrimination for predicting membership in the two identified clusters, with an area under the curve of 0.96 and 0.95 in training cohort and internal test cohort. CONCLUSION: This study demonstrated that unsupervised machine learning can reveal novel phenotypic subgroups of patients with varying prognostic risk who underwent endovascular therapy. The prediction model developed could support clinical decision-making and risk counseling for this complex patient population. Further external validation is warranted to assess the generalizability of the findings.

Atherogenic index of plasma: a new indicator for assessing the short-term mortality of patients with acute decompensated heart failure.

Objective: Arteriosclerosis is a primary causative factor in cardiovascular diseases. This study aims to explore the correlation between the atherogenic index of plasma (AIP) and the 30-day mortality rate in patients with acute decompensated heart failure (ADHF). Methods: A total of 1,248 ADHF patients recruited from the Jiangxi-Acute Decompensated Heart Failure1 (JX-ADHF1) cohort between 2019 and 2022 were selected for this study. The primary outcome was the 30-day mortality rate. Multivariable Cox regression, restricted cubic splines (RCS), and stratified analyses were utilized to assess the relationship between AIP and the 30-day mortality rate in ADHF patients. Mediation models were employed for exploratory analysis of the roles of inflammation, oxidative stress, and nutrition in the association between AIP and the 30-day mortality rate in ADHF patients. Results: During the 30-day follow-up, 42 (3.37%) of the ADHF patients died. The mortality rates corresponding to the quartiles of AIP were as follows: Q1: 1.28%, Q2: 2.88%, Q3: 2.88%, Q4: 6.41%. The multivariable Cox regression revealed a positive correlation between high AIP and the 30-day mortality rate in ADHF patients [Hazard ratio (HR) 3.94, 95% confidence interval (CI): 1.08-14.28], independent of age, gender, heart failure type, cardiac function classification, and comorbidities. It is important to note that there was a U-shaped curve association between AIP (<0.24) and the 30-day mortality rate before the fourth quartile, with the lowest 30-day mortality risk in ADHF patients around an AIP of -0.1. Furthermore, mediation analysis suggested significant mediating effects of inflammation and nutrition on the 30-day mortality rate in ADHF patients related to AIP, with inflammation accounting for approximately 24.29% and nutrition for about 8.16% of the mediation effect. Conclusion: This retrospective cohort analysis reveals for the first time the association between AIP and the 30-day mortality rate in ADHF patients. According to our findings, maintaining an AIP around -0.1 in ADHF patients could be crucial for improving poor prognoses from a medical perspective. Additionally, for ADHF patients with high AIP, it is important to assess and, if necessary, enhance nutritional support and anti-inflammatory treatment.

Hemodynamic Impairment of Blood Pressure and Stroke Mechanisms in Symptomatic Intracranial Atherosclerotic Stenosis.

BACKGROUND: Hemodynamic impairment of blood pressure may play a crucial role in determining the mechanisms of stroke in symptomatic intracranial atherosclerotic stenosis). We aimed to elucidate this issue and assess the impacts of modifications to blood pressure on hemodynamic impairment. METHODS: From the Third China National Stroke Registry III, computed fluid dynamics modeling was performed using the Newton-Krylov-Schwarz method in 339 patients with symptomatic intracranial atherosclerotic stenosis during 2015 to 2018. The major exposures were translesional systolic blood pressure (SBP) drop and poststenotic mean arterial pressure (MAP), and the major study outcomes were cortex-involved infarcts and borderzone-involved infarcts, respectively. Multivariate logistic regression models and the bootstrap resampling method were utilized, adjusting for demographics and medical histories. RESULTS: In all, 184 (54.3%) cortex-involved infarcts and 70 (20.6%) borderzone-involved infarcts were identified. In multivariate logistic model, the upper quartile of SBP drop correlated with increased cortex-involved infarcts (odds ratio, 1.92 [95% CI, 1.03-3.57]; bootstrap analysis odds ratio, 2.07 [95% CI, 1.09-3.93]), and the lower quartile of poststenotic MAP may correlate with increased borderzone-involved infarcts (odds ratio, 2.07 [95% CI, 0.95-4.51]; bootstrap analysis odds ratio, 2.38 [95% CI, 1.04-5.45]). Restricted cubic spline analysis revealed a consistent upward trajectory of the relationship between translesional SBP drop and cortex-involved infarcts, while a downward trajectory between poststenotic MAP and borderzone-involved infarcts. SBP drop correlated with poststenotic MAP negatively (rs=-0.765; P<0.001). In generating hemodynamic impairment, simulating blood pressure modifications suggested that ensuring adequate blood pressure to maintain sufficient poststenotic MAP appears preferable to the reverse approach, due to the prolonged plateau period in the association between the translesional SBP drop and cortex-involved infarcts and the relatively short plateau period characterizing the correlation between poststenotic MAP and borderzone-involved infarcts. CONCLUSIONS: This research elucidates the role of hemodynamic impairment of blood pressure in symptomatic intracranial atherosclerotic stenosis-related stroke mechanisms, underscoring the necessity to conduct hemodynamic assessments when managing blood pressure in symptomatic intracranial atherosclerotic stenosis.

Linking peripheral atherosclerosis to blood-brain barrier disruption: elucidating its role as a manifestation of cerebral small vessel disease in vascular cognitive impairment.

Aging plays a pivotal role in the pathogenesis of cerebral small vessel disease (CSVD), contributing to the onset and progression of vascular cognitive impairment and dementia (VCID). In older adults, CSVD often leads to significant pathological outcomes, including blood-brain barrier (BBB) disruption, which in turn triggers neuroinflammation and white matter damage. This damage is frequently observed as white matter hyperintensities (WMHs) in neuroimaging studies. There is mounting evidence that older adults with atherosclerotic vascular diseases, such as peripheral artery disease, ischemic heart disease, and carotid artery stenosis, face a heightened risk of developing CSVD and VCID. This review explores the complex relationship between peripheral atherosclerosis, the pathogenesis of CSVD, and BBB disruption. It explores the continuum of vascular aging, emphasizing the shared pathomechanisms that underlie atherosclerosis in large arteries and BBB disruption in the cerebral microcirculation, exacerbating both CSVD and VCID. By reviewing current evidence, this paper discusses the impact of endothelial dysfunction, cellular senescence, inflammation, and oxidative stress on vascular and neurovascular health. This review aims to enhance understanding of these complex interactions and advocate for integrated approaches to manage vascular health, thereby mitigating the risk and progression of CSVD and VCID.

Impact of Early Rehabilitation after Endovascular Treatment for Peripheral Arterial Disease.

Objectives: The prevalence of peripheral arterial disease (PAD) is on the rise, with endovascular treatment being a widely accepted surgical intervention. Patients with PAD often experience reduced activities of daily living (ADL). Therefore, we conducted a retrospective cohort study to investigate the impact of early rehabilitation after endovascular treatment in patients with PAD. Methods: Using data from the JMDC hospital database, the study included 529 patients who were hospitalized for PAD and underwent endovascular treatment. Patients were classified into two independent variables: early rehabilitation group (rehabilitation started within 2 days postoperatively) and control group (rehabilitation started within 3-7 days postoperatively). The outcome measures were the occurrence of hospital-associated disability (HAD) and duration of hospitalization. Results: Unadjusted data showed that the early rehabilitation group (n=469) had fewer HAD events (8.5% vs. 23.3%, P <0.001) and a shorter mean hospitalization duration (4.4 vs. 18.9 days, P <0.001) than the control group (n=60). The difference remained significant after adjustment by propensity score analysis. Conclusions: In patients with PAD, early rehabilitation after endovascular treatment may be beneficial in preventing the development of HAD and reducing the duration of hospitalization.

Developing technologies to assess vascular ageing: a roadmap from VascAgeNet.

Vascular ageing is the deterioration of arterial structure and function which occurs naturally with age, and which can be accelerated with disease. Measurements of vascular ageing are emerging as markers of cardiovascular risk, with potential applications in disease diagnosis and prognosis, and for guiding treatments. However, vascular ageing is not yet routinely assessed in clinical practice. A key step towards this is the development of technologies to assess vascular ageing. In this Roadmap, experts discuss several aspects of this process, including: measurement technologies; the development pipeline; clinical applications; and future research directions. The Roadmap summarises the state of the art, outlines the major challenges to overcome, and identifies potential future research directions to address these challenges.

The association between pulse wave velocity and pregnancy-associated diseases: A systematic review and meta-analysis.

Background: Maintaining healthy vascular structure and function is important for a healthy pregnancy. Obesity is a well-known predictor for poor postoperative outcomes of vascular surgery. However, the association between pulse wave velocity (PWV), a well-recognized parameter for arterial stiffness assessment, and pregnancy-associated diseases is still unclear. Therefore, we conducted this systematic review, and a meta-analysis was performed to assess the relevant associations. Methods: We systematically searched the Web of Science and PubMed databases to obtain articles on PWV and pregnancy-associated diseases published before April 2023. The mean with standard deviation was used to assess the differences in PWV in pregnant women with or without relevant diseases. Subgroup analysis was conducted according to specific types of PWV. The Newcastle‒Ottawa Scale was used to evaluate the quality of the enrolled studies. Results: A total of 6488 individuals from 21 studies were included. All enrolled studies were high-quality. Overall, the PWV was elevated in pregnant women who suffered from preeclampsia (mean difference (MD) = 0.67, 95 % confidence interval (CI): 0.51,0.83, P < 0.00001), hypertension (MD = 1.04, 95 % CI: 1.00,1.08, P < 0.00001), gestational diabetes mellitus (MD = 0.34, 95%CI: 0.19,0.48, P < 0.00001), and diabetes (MD = 0.49, 95%CI: 0.27,0.70, P < 0.00001). Subgroup analysis based on specific types of PWV showed similar results. Conclusion: In our study, PWV is elevated in pregnancy-associated diseases, including preeclampsia, hypertension, and diabetes. The PWV assessment should be regarded as a clinical routine for pregnant women to prevent and manage cardiovascular diseases during pregnancy.

Arterial Adventitial Vasa Vasorum Hyperplasia involved in Atherosclerotic Plaque Formation in a Rabbit Model.

OBJECTIVE: It was previously believed that atherosclerotic (AS) plaque starts to develop from the intima and that intraplaque vasa vasorum (VV) hyperplasia promotes adventitial VV (AVV) hyperplasia. However, recent studies have shown that arterial AVV hyperplasia precedes early intimal thickening, suggesting its possible role as an initiating factor of AS. To provide further insight into this process, in this study, we examine the evolution of AAV and VV development in a preclinical model of early AS with longitudinal ultrasound imaging. METHODS: Models of early AS were established. Duplex ultrasound scanning and contrast-enhanced ultrasound were performed for diagnosis. Pearson correlation tests were used to analyze the relationships between AVV hyperplasia and VV hyperplasia, or between AVV hyperplasia and intima-media thickness (IMT). RESULTS: During 0-12 wk of high-fat feeding, AVV gradually increased and intima-media thickened gradually in the observation area; in the 2nd wk of high-fat feeding, the observation area showed obvious AVV proliferation; at the 4th wk, the intima-media membrane became thicker; at the 12th wk, early plaque formation and intraplaque VV proliferation were observed. There was a strong positive correlation between AVV proliferation and IMT thickening and a strong negative correlation between AVV proliferation and the change rate of vessel diameter. CONCLUSION: This study demonstrated that AVV proliferation in the arteries occurred earlier than IMT thickening and was positively correlated with IMT. At present, the indicators of ultrasonic diagnosis of AS, such as IMT, Intraplaque VV, Echo property, all appear in the advanced stage of AS. The AVV may be an innovative diagnostic target for the early stage of AS plaque.

The role of periodontitis in the development of atherosclerotic cardiovascular disease in participants with the components of metabolic syndrome: a systematic review and meta-analysis.

OBJECTIVES: Prevention of atherosclerotic cardiovascular disease (ASCVD) is important in individuals with metabolic syndrome components (MetS), and periodontitis may play an important role in this process. This study aims to evaluate the association between periodontitis and ASCVD in participants with the components of MetS, including obesity, dysglycemia, hypertension, and dyslipidemia. MATERIALS AND METHODS: This study conducted followed the MOOSE reporting guidelines and the PRISMA 2020 guidelines. EMBASE, MEDLINE, Web of Science, Cochrane Library, PubMed and OpenGrey were searched for observational studies about the linkage of periodontitis to ASCVD in people with MetS components up to April 9, 2023. Cohort, case-control and cross-sectional studies were included after study selection. Quality evaluation was carried out using the original and modified Newcastle-Ottawa Scale as appropriate. Random-effects model was employed for meta-analysis. RESULTS: Nineteen studies were finally included in the quality analysis, and all of them were assessed as moderate to high quality. Meta-analyses among fifteen studies revealed that the participants with periodontitis were more likely to develop ASCVD in those who have dysglycemia (RR = 1.25, 95% CI = 1.13-1.37; p < 0.05), obesity (RR = 1.13, 95% CI = 1.02-1.24; p < 0.05), dyslipidemia (RR = 1.36, 95% CI = 1.13-1.65; p < 0.05), or hypertension (1.20, 95% CI = 1.05-1.36; p < 0.05). CONCLUSIONS: Periodontitis promotes the development of ASCVD in participants with one MetS component (obesity, dysglycemia, hypertension or dyslipidemia). CLINICAL RELEVANCE: In people with MetS components, periodontitis may contribute to the ASCVD incidence.

Recent Translational Research Models of Intracranial Atherosclerotic Disease.

Intracranial atherosclerotic disease (ICAD) is a leading cause of ischemic stroke worldwide. However, research on the pathophysiology of ICAD is scarce due to the relative inaccessibility of histology samples and the lack of comprehensive experimental models. As a result, much of the current understanding of ICAD relies on research on extracranial atherosclerosis. This approach is problematic as intracranial and extracranial arteries are anatomically, structurally, physiologically, and metabolically distinct, indicating that intracranial and extracranial atherosclerosis likely develop through different biologic pathways. The current standard of care for ICAD treatment relies predominantly on therapeutics developed to treat extracranial atherosclerosis and is insufficient given the alarmingly high risk of stroke. To provide a definitive treatment for the disease, a deeper understanding of the pathophysiology underlying ICAD is specifically required. True mechanistic understanding of disease pathogenesis is only possible using robust experimental models. In this review, we aim to identify the advantages and limitations of the existing in vivo and in vitro models of ICAD and basic atherosclerotic processes, which may be used to inform better models of ICAD in the future and drive new therapeutic strategies to reduce stroke risk.

Extracellular vesicles in atherosclerosis: Current and forthcoming impact?

Atherosclerosis is the main pathogenic substrate for cardiovascular diseases (CVDs). Initially categorized as a passive cholesterol storage disease, nowadays, it is considered an active process, identifying inflammation among the key players for its initiation and progression. Despite these advances, patients with CVDs are still at high risk of thrombotic events and death, urging to deepen into the molecular mechanisms underlying atherogenesis, and to identify novel diagnosis and prognosis biomarkers for their stratification. In this context, extracellular vesicles (EVs) have been postulated as an alternative in search of novel biomarkers in atherosclerotic diseases, as well as to investigate the crosstalk between the cells participating in the processes leading to arterial remodelling. EVs are nanosized lipidic particles released by most cell types in physiological and pathological conditions, that enclose lipids, proteins, and nucleic acids from parental cells reflecting their activation status. First considered cellular waste disposal systems, at present, EVs have been recognized as active effectors in a myriad of cellular processes, and as potential diagnosis and prognosis biomarkers also in CVDs. This review summarizes the role of EVs as potential biomarkers of CVDs, and their involvement into the processes leading to atherosclerosis.

Revised contraindications for the use of non-medical WB-electromyostimulation. Evidence-based German consensus recommendations.

Whole-body electromyostimulation has proven to be a highly effective alternative to conventional resistance-type exercise training. However, due to adverse effects in the past, very extensive contraindications have been put in place for the commercial, non-medical WB-EMS market. Considering recent positive innovations e.g., federal regulation, mandatory trainer education, revised guidelines, and new scientific studies on WB-EMS application, we believe that a careful revision of the very restrictive contraindications on WB-EMS is needed. This applies all the more because many cohorts with limited options for conventional exercise have so far been excluded. During a first meeting of an evidence-based consensus process, stakeholders from various backgrounds (e.g., research, education, application) set the priorities for revising the contraindications. We decided to focus on four categories of absolute contraindications: "Arteriosclerosis, arterial circulation disorders", "Diabetes mellitus" (DM), "Tumor and cancer" (TC), "Neurologic diseases, neuronal disorders, epilepsy". Based on scientific studies, quality criteria, safety aspects and benefit/risk assessment of the category, DM and TC were moved to the relative contraindication catalogue, while arteriosclerosis/arterial circulation disorders and neurologic diseases/neuronal disorders/epilepsy were still considered as absolute contraindications. While missing evidence suggests maintaining the status of neurologic diseases/neuronal disorders as an absolute contraindication, the risk/benefit-ratio does not support the application of WB-EMS in people with arteriosclerosis/arterial circulation diseases. Despite these very cautious modifications, countries with less restrictive structures for non-medical WB-EMS should consider our approach critically before implementing the present revisions. Considering further the largely increased amount of WB-EMS trials we advice regular updates of the present contraindication list.

Clinical characterization and detection of subclinical atherosclerosis in subjects with extreme hyperalphalipoproteinemia. / Caracterización clínica y detección de arteriosclerosis subclínica en sujetos con hiperalfalipoproteinemia extrema.

INTRODUCTION AND OBJECTIVES: The association between HDL cholesterol (HDL-C) levels and death from cardiovascular disease follows a U-shaped pattern, increasing at the extremes. The objective of the study was to characterize a sample of subjects with extreme hyperalphalipoproteinemia (HAE). MATERIAL AND METHODS: 53 cases with HAE were recruited, 24 women (HDL-C>135mg/ dL) and 29 men (HDL-C>116mg/ dL). A detailed medical history was taken and questionnaires on adherence to the Mediterranean diet and physical activity were collected. Carotid ultrasounds were performed to detect the presence of suclinical atherosclerosis. RESULTS: The most prevalent cardiovascular risk factor (CVRF) was dyslipidemia (64%) with no significant differences between men and women, unlike hypertension (21% in women, versus 55% in men, p=0.01) and others CVRF, for example, diabetes. 7% of the series had previous cardiovascular disease, women had higher LDL cholesterol (p=0.002) and HDL-C than men (without significant differences). Plaque was detected in 53% of cases, being more prevalent in men. Patients with plaque were older, drank more alcohol and smoked more (p<0.05). CONCLUSIONS: Men had a higher prevalence of CVRF than women, except for dyslipidemia. Subclinical atherosclerosis occurred in more than half of the series. Age, alcohol consumption and smoking were independently associated with the presence of plaque, however, our data do not show a significant influence of HDL-C levels.

Cincinnati Prehospital Stroke Scale (CPSS) as a Screening Tool for Early Identification of Cerebral Large Vessel Occlusions; a Systematic Review and Meta-analysis.

Introduction: Large vessel occlusion (LVO) strokes are associated with worse functional outcomes and higher mortality rates. In the present systematic review and meta-analysis, we evaluated the diagnostic yield of the Cincinnati Prehospital Stroke Scale (CPSS) in detecting LVO. Methods: We performed an extensive systematic search among online databases including Medline, Embase, Web of Science, and Scopus, until July 31st, 2023. We also conducted a manual search on Google and Google scholar, along with citation tracking to supplement the systematic search in retrieving all studies that evaluated the diagnostic accuracy of the CPSS in detecting LVO among patients suspected to stroke. Results: Fourteen studies were included in the present meta-analysis. CPSS showed the sensitivity of 97% (95% CI: 87%-99%) and the specificity of 17% (95% CI: 4%-54%) at the cut-off point of ≥1. The optimal threshold was determined to be ≥2, with a sensitivity of 82% (95% CI: 74%-88%) and specificity of 62% (95% CI: 48%-74%) in detecting LVO. At the highest cut-off point of ≥3, the CPSS had the lowest sensitivity of 60% (95% CI: 51%-69%) and the highest specificity of 81% (95% CI: 71%-88%). Sensitivity analyses showed the robustness of the results regardless of study population, inclusion of hemorrhagic stroke patients, pre-hospital or in-hospital settings, and the definition of LVO. Conclusion: A very low level of evidence demonstrated that CPSS, with a threshold set at ≥2, is a useful tool for identifying LVO stroke and directing patients to CSCs, both in prehospital and in-hospital settings.