Public attitudes towards automated external defibrillators: results of a survey in the Australian general population

BackgroundSwift defibrillation by lay responders using automated external defibrillators (AEDs) increases survival in out-of-hospital cardiac arrest (OHCA). This study evaluated newly designed yellow–red vs. commonly used green–white signage for AEDs and cabinets and assessed public attitudes to using AEDs during OHCA.MethodsNew yellow–red signage was designed to enable easy identification of AEDs and cabinets. A prospective, cross-sectional study of the Australian public was conducted using an electronic, anonymised questionnaire between November 2021 and June 2022. The validated net promoter score investigated public engagement with the signage. Likert scales and binary comparisons evaluated preference, comfort and likelihood of using AEDs for OHCA.ResultsThe yellow–red signage for AED and cabinet was preferred by 73.0% and 88%, respectively, over the green–white counterparts. Only 32% were uncomfortable with using AEDs, and only 19% indicated a low likelihood of using AEDs in OHCA.ConclusionThe majority of the Australian public surveyed preferred yellow–red over green–white signage for AED and cabinet and indicated comfort and likelihood of using AEDs in OHCA. Steps are necessary to standardise yellow–red signage of AED and cabinet and enable widespread availability of AEDs for public access defibrillation

Buddhist meditation for vascular function : a narrative review

Background: High blood pressure represents an important risk factor for diseases related to cardiovascular system and is directly associated with high oxidative stress, inflammation and vascular endothelial dysfunction. Recently, there is promising data available to suggest that meditation-based low-cost and low-risk lifestyle modification strategies may provide beneficial effects on chronic inflammation, oxidative stress and maintenance of blood pressure, both in young and older adults. This review aims to summarize the evidence regarding the effectiveness of Buddhist meditation for vascular endothelial function and blood pressure. Method: A search was conducted using Ovid MEDLINE, Scopus, CINAHL and PsycINFO for articles published from 1990 to 2018. Results: Relevant articles (n = 407) were reviewed and 5 met selection criteria. Several lines of studies have provided compelling data showing that Buddhist meditation approach was effective in improving inflammation and vascular function (endothelial vasodilation and arterial stiffness) in both young and elderly cohorts. Particularly, Buddhist meditation approach has shown to be effective in reducing plasma inflammatory markers, increasing nitric oxide concentration and improving vascular endothelial function and glycemic control, which in turn can be favorable factors for demonstrated positive effects of Buddhist meditation on blood pressure and vascular function. Conclusion: This paper presents brief overview of clinical outcomes of complementary therapeutic approach of Buddhist meditation in vascular function. In future, well-structured systematic reviews are essential to report specificity of Buddhist mindfulness-based approach on vascular function, blood pressure and other cardiovascular risk factors

Elevated parathyroid hormone predicts high asymmetric dimethylarginine (ADMA) concentrations in obese diabetic patients

Impaired vascular endothelial function has been suggested as a possible mechanism to explain the nexus between vitamin D deficiency and increased adverse cardiovascular outcomes. In addition, elevated PTH is also found associated with increased arterial stiffness and impaired endothelial function, improved after lowering of PTH with parathyroidectomy. Previously, we have shown that in an ageing population, low vitamin D levels are associated with elevated plasma concentrations of asymmetric dimethylarginine (ADMA). Asymmetric dimethylarginine (ADMA) is an endogenous inhibitor of endothelial nitric oxide synthase (eNOS), has been shown to be a critical circulating biomarker of endothelial function, and adverse cardiovascular outcomes. However, we did not assess the relationship between ADMA and PTH. Given, the high prevalence of low vitamin D and high parathyroid hormone (PTH) levels in obese diabetic patients, we sought to examine in this study, whether the relationship between ADMA and vitamin D is independent of PTH levels in obese diabetic

Does vascular endothelial dysfunction play a role in physical frailty and sarcopenia? : a systematic review

Background: Frailty is strongly associated with adverse cardiovascular outcomes; however, the underlying pathophysiological processes are largely unknown. Vascular endothelial dysfunction (VED) is the earliest stage of cardiovascular disease (CVD) progression and predicts long-term CVD outcomes. Both these conditions share an elevated inflammatory state as a common pathological factor. Objective: Systematic literature review was conducted to examine the evidence supporting an association between VED and physical frailty and/or sarcopenia, in electronic databases including Scopus, Ovid Medline, CINAHL, ScienceDirect, ProQuest Health & Medicine and Embase from January 1980 to August 2019. Results: A total of 18 studies met the inclusion criteria. VED is independently associated with increased frailty phenotypes and measures of sarcopenia. Several markers of VED, including higher levels of asymmetric dimethylarginine, abnormal ankle brachial index, pulse wave velocity, pulse pressure and lower levels of flow-mediated dilatation, peripheral blood flow and endothelial progenitor cell counts, have been associated with frailty/sarcopenia measurements. Some studies demonstrated the effect of inflammation on the association. Conclusions: Recent studies, although limited, showed that VED could be one of the underlying mechanisms of frailty. It is entirely possible that inflammation-related pathological changes in the vascular endothelium are involved in the early causative mechanisms in physical frailty. The exact mechanism(s) underlying this association are still unclear and will need to be evaluated. The outcomes of these future research studies could potentially inform early preventative strategies for physical frailty and sarcopenia

Vascular endothelial dysfunction may be an early predictor of physical frailty and sarcopenia : a meta-analysis of available data from observational studies

Background: Physical frailty and sarcopenia (PF & S) are major public health problems in the older population and promising predictors of adverse cardiovascular outcomes. However, the underlying mechanisms linking physical frailty, sarcopenia and adverse cardiovascular outcomes are not well defined. We recently published a systematic review which highlighted early-stage vascular endothelial dysfunction (VED) as one of the potential underlying mechanisms of physical frailty and the role of inflammation in modulating this association. Objective and method: A meta-analysis was performed to estimate the pooled effect size of studies examining the relationship between VED and PF & S. Results: Out of 18 cross-sectional studies selected for the original review, 13 studies were excluded due to lack of available data for pooled analysis. The five remaining studies had a total of 6616 participants, of which the pooled sample size of the frail or sarcopenic cohort was 607 and robust or pre-frail or non-sarcopenic cohort was 6009. Mean age of the participants ranging from 64 to 80 years or over. In this analysis, high heterogeneity was observed among studies (99.35% of the variation between studies was due to heterogeneity). Parameters used to assess both PF & S and VED were very different across the studies. Conclusion: The absence of a standardized and valid operational definition of the frailty and sarcopenia is a principal limiting factors for frailty research and this is clearly reflected in our study findings. This limits the ability to interpret and define the effects of vascular endothelial dysfunction on these different parameters of frailty and sarcopenia. Similarly, assessment of vascular endothelial dysfunction was very heterogeneous with different parameters utilized across these studies

Incidence of immune checkpoint inhibitor mediated cardiovascular toxicity : a systematic review and meta-analysis

Background: Immune checkpoint inhibitors (ICI) are a novel class of anti-cancer therapy becoming increasingly associated with fatal cardiovascular toxicities (CVTs). The aim is to determine the incidence of CVTs in cohorts treated with ICIs as sole anti-cancer therapy. Methods: A systematic literature search of scientific and medical databases was performed using PRISMA principles to identify relevant cohorts (PROSPERO registration CRD42021272470). Data for specific CVTs (pericardial disease, myocarditis, heart failure, arrhythmia, myocardial infarction/ischaemia and angina), CVT-related death and CV risk factors were extracted. Presence of CVTs in ICI-monotherapy versus combination-ICI therapy, and programmed death 1/programmed death ligand 1- (PD1/PDL1-) versus cytotoxic T-lymphocyte-associated protein 4- (CTLA4-) inhibitor groups were dichotomised and meta-analysed using random-effect models. Results: Forty-eight studies (11,207 patients) were identified, from which 146 CVTs were observed (incidence 1.30%). ICI-monotherapy led to more CVTs than combination therapy (119/9009; 1.32% vs. 18/2086; 0.86%). Across monotherapies, PD1/PDL1-inhibitors had lower incidence of CVTs compared to CTLA4-inhibitors (62/6950; 0.89% vs. 57/2059; 2.77%). Based on eight studies that were meta-analysed, no significant difference was observed comparing monotherapy versus combination-ICI therapy (RR-0.69, 95% CI −1.47 to 0.09) for all CVTs, or PD1/PDL1- to CTLA4-inhibitors (RR-0.27, 95% CI −2.06 to 1.53), for all CVTs including CVT-death. CV risk factors could not be attributed to an ICI group as data was population based rather than individual based. Conclusion: ICI-mediated CVTs are rare and potentially fatal. The role of CV risk factors in their development remains unclear. © 2022 Stichting European Society for Clinical Investigation Journal Foundation. Published by John Wiley & Sons Ltd

Elevated parathyroid hormone predicts high asymmetric dimethylarginine (ADMA) concentrations; independent of vitamin D status

Vitamin D deficiency and secondary hyperparathyroidism, either in combination or independently, have been associated with increased cardiovascular (CV) events. We have demonstrated that low 25-hydroxyvitamin D3 (25(OH)D3) concentrations are associated with increased concentrations of asymmetric dimethylarginine (ADMA), an eNOS inhibitor and biomarker of increased CV morbidity and mortality. It remains unclear if this relationship is independent of parathyroid hormone (PTH). Obese diabetic subjects frequently have low vitamin D and high parathyroid hormone (PTH) concentrations. We have currently sought to evaluate the PTH:ADMA relationship in normal subjects and compare this relationship with obese diabetics (a group characterized by vitamin D deficiency and high PTH levels)

Incidence and treatment of arrhythmias secondary to coronavirus infection in humans : a systematic review

Background: The Coronavirus disease 2019 (COVID‐19) pandemic has affected millions of people worldwide resulting in significant morbidity and mortality. Arrhythmias are prevalent and reportedly, the second most common complication. Several mechanistic pathways are proposed to explain the pro‐arrhythmic effects of severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) infection. A number of treatment approaches have been trialled, each with its inherent unique challenges. This rapid systematic review aimed to examine the current incidence and available treatment of arrhythmias in COVID‐19, as well as barriers to implementation. Methods: Our search of scientific databases identified relevant published studies from 1st January 2000 until 1st June 2020. We also searched Google Scholar for grey literature. We identified 1729 publications of which 1704 were excluded. Results: The incidence and nature of arrhythmias in the setting of COVID‐19 was poorly documented across studies. The cumulative incidence of arrhythmia across studies of hospitalised patients was 6.9%. Drug‐induced long QT syndrome secondary to antimalarial and antimicrobial therapy was a significant contributor to arrhythmia formation, with an incidence of 14.15%. Torsades de pointes (TdP) and sudden cardiac death (SCD) was reported. Treatment strategies aim to minimise this through risk stratification and regular monitoring of corrected QT interval (QTc). Conclusion: Patients with SARS‐CoV‐2 are at an increased risk of arrhythmias. Drug therapy is pro‐arrhythmogenic and may result in TdP and SCD in these patients. Risk assessment and regular QTc monitoring are imperative for safety during the treatment course. Further studies are needed to guide future decision making

Twin D-frail study protocol : does vitamin D link vascular endothelial dysfunction to sarcopenic frailty

Background: A low vitamin D state and vitamin D deficiency is common in the elderly and has been correlated with various cardiovascular risk factors and events. Vitamin D deficiency has been demonstrated to play a major role in the pathogenesis of physical frailty and hypothesized to contribute to physical frailty through sarcopenia (the loss of skeletal muscle mass and function with aging). Sarcopenia has been shown to be a major contributor to morbidity in older adults. One possible mechanism for this association could be the effect of vitamin D on subclinical vascular function (vascular endothelial dysfunction; VED). Recent data highlight the role of increased inflammation and oxidative stress coexist in VED and sarcopenic modulated frailty which implicates chronic inflammation as a major component in the pathogenesis of frailty. Vitamin D supplementation has been shown to down-regulate mediators of Vascular Endothelial Dysfunction (VED) and correct the associated inflammatory status hence may be a simple strategy for the treatment and prevention of frailty. Study objectives: The proposed research study is designed to investigate anti-inflammatory effects of vitamin D on physical frailty, sarcopenia and VED. The 2 main aims of the study are: 1) To establish a relationship between VED and sarcopenia-related physical frailty in a cohort of patient with cardiovascular conditions and 2) To investigate the effects of vitamin D supplementation in improving vascular endothelial function by correcting inflammatory and oxidative stress profiles and thus improve muscle tone in healthy working adults. Method/design: The proposed study protocol will comprise of two inter-related study arms. The first arm of the study is aimed at addressing the first aim using a single-centred, prospective cross-sectional analytical design. This arm will also investigate the independent effects of vitamin D in the relationship of physical frailty and sarcopenia with VED. The second arm of the study will address the second aim. The second arm will adopt a pilot approach focusing on delineating the effects of down-regulation of inflammation-mediated pathways affecting muscle strength and function. In particular, the impact of vitamin D supplementation on Thrombospondin-1 (TSP-1; mediator of VED) and Tumor Growth Factor β1 (TGF-β1: modulator of inflammation) will be measured in healthy working adults. Discussion: The hypothesis that vitamin D deficiency causes frailty via its inflammation related VED, which in turn leads to sarcopenia and physical frailty, will be explored. Novel frailty management strategies are essential to improve the quality of life of frail people and reduce the healthcare cost associated with frailty outcomes. The proposed research study will introduce a frailty management strategy via prevention/improvement of inflammatory status and early-stage subclinical CVD (VED) by simple and safe treatment strategy, vitamin D supplementation in older frail adults. The outcomes of the clinical intervention could be translated to better health outcomes by implementing frailty prevention/controlling strategy at early stages, before other CV complications occur by reducing the negative impact on patient’s quality of life and the healthcare systems, which will assist to reduce socioeconomic burden and improve quality of life of older people. This study will further investigate underlining mechanisms of association between vascular endothelial dysfunction and sarcopenia-related physical frailty. Positive outcome of the mechanistic study would provide baseline biomedical mechanistic insight for further studies to introduce new pharmacological interventions in frailty

Vitamin D supplementation in healthy adults lowers plasma thrombospondin-1 levels : a novel vitamin D target?

Introduction: Vitamin D deficiency is increasingly prevalent in the general population and is associated with cardiometabolic dysfunction. Thrombospondin-1 (TSP-1) is a potent inhibitor of the nitric oxide/cyclic GMP (NO/cGMP) signaling pathway in vascular cells, and contributes to vascular endothelial dysfunction. Several in vitro studies have shown that vitamin D analogs markedly down-regulate TSP-1 mRNA and protein expressions in human aortic smooth muscle cells. Hypothesis: In this clinical intervention study, we hypothesized that in vitamin D insufficient healthy subjects: 1) low 25-hydroxyvitamin D3 (25-OHD3) is associated with elevated plasma concentrations of TSP-1, and 2) vitamin D supplementation significantly reduces TSP-1 concentrations. Methods and Results: Healthy adults (n=31) (age 45±10 years) (BMI 28.2±5.9 Kg/m2) (mean±SD) without any pre-existing CV disease or diabetes, with vitamin D insufficiency (25-hydroxyvitamin D3 levels (25(OH)D3) ≤ 30 ng/mL) were recruited. Vitamin D administration (2000 IU/day for 12 weeks) significantly increased 25(OH)D3 level from 19±1.2 ng/ml to 39±1.6 ng/ml (mean ± SEM), p≤0.001. Plasma TSP-1 concentrations, measured by solid-phase ELISA, inversely correlated with 25(OH)D3 levels at baseline (r 2 = -0.530, p = 0.015). TSP-1 concentrations were markedly reduced following vitamin D supplementation (baseline 454.2±74.6 ng/ml Vs after 12 weeks 241.4±51.3 ng/ml (mean±SEM), p≤0.001). With vitamin D supplementation, there were no changes in either inhibition of ADP-induced platelet aggregation by sodium nitroprusside, or plasma asymmetric dimethylarginine (ADMA). Vitamin D supplementation significantly lowered systolic blood pressure (p=0.007), and diastolic blood pressure (p=0.008) levels. Conclusions: Our findings provide conclusive clinical evidence that vitamin D deficiency is associated with increased TSP-1 levels, and the reversal of the vitamin D deficient state markedly reduces TSP-1 concentrations. These findings support the evolving concept that vitamin D deficiency may be linked to impaired vascular NO signaling, and that early targeted vitamin D supplementation in deficient but otherwise healthy adults could prevent development of cardiometabolic diseases