9,808 research outputs found
Angiotensin-converting enzyme inhibition by perindopril in the treatment of cardiovascular disease
No full textThe angiotensin-converting enzyme (ACE) inhibitor perindopril (Coversyl) is a long-acting lipophilic drug with a high-tissue affinity for the ACE. ACE inhibition by perindopril has two main effects: it inhibits the angiotensin II formation and potentiates bradykinin. Perindopril is one of the ACE inhibitors that has been extensively studied in randomized clinical trials within various patient populations. The clinical efficacy has been demonstrated in patients with hypertension, diabetes mellitus, cerebrovascular disease, stable coronary artery disease (CAD) and heart failure. Perindopril has a positive safety and tolerability profile. Therefore, perindopril, as an ACE inhibitor, has an established place in the major clinical treatment guidelines. This article discusses several studies that have shown that an antihypertensive treatment with perindopril reduces and prevents cardiovascular events in a large range of patients with established vascular disease. The observed cardioprotective benefits of perindopril were independent of blood pressure. The outcome of these and other trials support the concept of specific cardioprotective properties of ACE inhibition by perindopril in addition to the blood pressure-lowering effects, such as anti-atherosclerotic, anti-inflammatory and antithrombotic properties. In addition, the observed consistency of the treatment benefit across subgroups indicates that the absolute benefits conferred by treatment are mainly established by each patient's future risk of vascular complications, rather than their initial blood pressure level or other risk factors. This article describes these issues according to the main studies with perindopril or perindopril-based regimens, concluding that the blood pressure-dependent and -independent cardioprotective effects extend to all patients with vascular disease. This concept supports the provision of ACE inhibitor-based treatment, not on the basis of arbitrary cut-off points for blood pressure but rather on assessment of vascular risk, which is raised in patients with stable CAD, diabetes and stroke
Pharmacogenetics of ACE inhibition in stable coronary artery disease: steps towards tailored drugs therapy
No full textPurpose of review
Several trials demonstrated that angiotensin-converting enzyme inhibitors reduce the
incidence of cardiovascular events during long-term follow-up in high-risk and low-risk
patients. Clinical treatment guidelines propose that angiotensin-converting enzyme
inhibitors should be considered in the routine secondary prevention in the broad group
of coronary artery disease patients. This review discusses several approaches to guide
angiotensin-converting enzyme-inhibition therapy to more specific groups of patients
that are most likely to benefit.
Recent findings
The beneficial effect of angiotensin-converting enzyme inhibition has been shown to be
consistent across subgroups in stable coronary artery disease. Still, large interindividual
variability in blood pressure response is well documented. It should also be realized that
the absolute treatment effects are modest. The efficiency and cost-effectiveness of this
prolonged prophylactic treatment would be significantly enhanced if those patients can
be distinguished who benefit most. Recently, it was suggested that markers of an
activated renin–angiotensin–aldosterone system might be used to guide angiotensinconverting
enzyme-inhibition therapy.
Summary
At the start of treatment, clinical characteristics are not sufficient to distinguish between
patients who will and will not benefit from angiotensin-converting enzyme inhibitors.
Although pharmacogenetic research in coronary artery disease is still in a premature
stage, it may be expected to provide a useful tool in optimizing and individualizing the
management of angiotensin-converting enzyme-inhibitor therapy in coronary artery
disease patients
Metadata Representations for Queryable ML Model Zoos
No full textMachine learning (ML) practitioners and organizations are building model zoos of pre-trained models, containing metadata describing properties of the ML models and datasets that are useful for reporting, auditing, reproducibility, and interpretability purposes. The metatada is currently not standardised; its expressivity is limited; and there is no interoperable way to store and query it. Consequently, model search, reuse, comparison, and composition are hindered. In this paper, we advocate for standardized ML model metadata representation and management, proposing a toolkit supported to help practitioners manage and query that metadata.Web Information SystemsHuman-Centred Artificial Intelligenc
A Manifesto of Nodalism
No full textThis paper proposes the notion of Nodalism as a means describing contemporary culture and of understanding my own creative practice in electronic music composition. It draws on theories and ideas from Kirby, Bauman, Bourriaud, Deleuze, Guatarri, and Gochenour, to demonstrate how networks of ideas or connectionist neural models of cognitive behaviour can be used to contextualize, understand and become a creative tool for the creation of contemporary electronic music
ACE inhibition with perindopril and biomarkers of atherosclerosis and thrombosis: Results from the PERTINENT study
No full textThe PERTINENT study measured biomarkers of atherosclerosis and thrombosis in a stable coronary artery disease population from EUROPA receiving ACE inhibition with perindopril 8 mg/day or placebo. Biomarkers of inflammation, C-reactive protein (CRP), fibrinogen, and tumor necrosis factor-alpha (TNF-alpha), and a biomarker of thrombosis, D-dimer, were measured at baseline and 1 year. CRP was recorded in 1157 patients; fibrinogen, TNF-alpha, and D-dimer in 291 patients. There was no significant effect of treatment on CRP or fibrinogen. In contrast, there were significant reductions in TNF-alpha (27.60-25.20 pg/mL; P<0.05) and D-dimer (0.24-0.18 microg/mL; P<0.05) with perindopril over 1 year. Survival analysis of the prognostic significance of baseline CRP failed to detect a significant role for the prediction of cardiovascular events over 4 years (lower versus higher tertile: 1.54; 95% confidence interval 0.88-2.68; P=0.16). In conclusion, in the PERTINENT trial, we observed significant effects of ACE inhibition on biomarkers of the atherothrombotic complications (D-dimer) and the proinflammatory cytokine TNF-alpha, but not on biomarkers of inflammation associated with atherosclerosis (CRP and fibrinogen)
ACE inhibition with perindopril and endothelial function. Results of a substudy of the EUROPA study: PERTINENT
No full textACE inhibition with perindopril and endothelial function. Results of a substudy of the EUROPA study: PERTINEN
Optimizing ML Inference Queries Under Constraints
No full textThe proliferation of pre-trained ML models in public Web-based model zoos facilitates the engineering of ML pipelines to address complex inference queries over datasets and streams of unstructured content. Constructing optimal plan for a query is hard, especially when constraints (e.g. accuracy or execution time) must be taken into consideration, and the complexity of the inference query increases. To address this issue, we propose a method for optimizing ML inference queries that selects the most suitable ML models to use, as well as the order in which those models are executed. We formally define the constraint-based ML inference query optimization problem, formulate it as a Mixed Integer Programming (MIP) problem, and develop an optimizer that maximizes accuracy given constraints. This optimizer is capable of navigating a large search space to identify optimal query plans on various model zoos.Green Open Access added to TU Delft Institutional Repository ‘You share, we take care!’ – Taverne project https://www.openaccess.nl/en/you-share-we-take-care Otherwise as indicated in the copyright section: the publisher is the copyright holder of this work and the author uses the Dutch legislation to make this work public.Web Information SystemsHuman-Centred Artificial Intelligenc
Risk stratification of patients with classic angina pectoris and no history of coronary artery disease by dobutamine stress echocardiography
No full textnot availabl
Right ventricular volumes and function in thalassemia major patients in the absence of myocardial iron overload
No full textAim: We aimed to define reference ranges for right ventricular (RV) volumes, ejection fraction (EF) in thalassemia major patients (TM) without myocardial iron overload.Methods and results: RV volumes, EF and mass were measured in 80 TM patients who had no myocardial iron overload (myocardial T2* > 20 ms by cardiovascular magnetic resonance). All patients were receiving deferoxamine chelation and none had evidence of pulmonary hypertension or other cardiovascular comorbidity. Forty age and sex matched healthy non-anemic volunteers acted as controls. The mean RV EF was higher in TM patients than controls (males 66.2 +/- 4.1% vs 61.6 +/- 6%, p = 0.0009; females 66.3 +/- 5.1% vs 62.6 +/- 6.4%, p = 0.017), which yielded a raised lower threshold of normality for RV EF in TM patients (males 58.0% vs 50.0% and females 56.4% vs 50.1%). RV end-diastolic volume index was higher in male TM patients (mean 98.1 +/- 17.3 mL vs 88.4 +/- 11.2 mL/m(2), p = 0.027), with a higher upper limit (132 vs 110 mL/m(2)) but this difference was of borderline significance for females (mean 86.5 +/- 13.6 mL vs 80.3 +/- 12.8 mL/m(2), p = 0.09, with upper limit of 113 vs 105 mL/m(2)). The cardiac index was raised in TM patients (males 4.8 +/- 1.0 L/min vs 3.4 +/- 0.7 L/min, p < 0.0001; females 4.5 +/- 0.8 L/min vs 3.2 +/- 0.8 L/min, p < 0.0001). No differences in RV mass index were identified.Conclusion: The normal ranges for functional RV parameters in TM patients with no evidence of myocardial iron overload differ from healthy non-anemic controls. The new reference RV ranges are important for determining the functional effects of myocardial iron overload in TM patients
Prognostic significance of left anterior hemiblock in patients with suspected coronary artery disease.
No full textThis study was designed to assess the functional and prognostic significance of left anterior hemiblock (LAHB) in patients with no history of myocardial infarction referred for dobutamine stress echocardiography (DSE). BACKGROUND: The significance of isolated LAHB in patients with suspected coronary artery disease (CAD) is unclear. METHODS: We studied 1,187 patients with suspected CAD and no history of myocardial infarction who underwent DSE and were followed for occurrence of cardiac death. RESULTS: Left anterior hemiblock was detected on baseline electrocardiogram in 159 patients (13%). Ischemia occurred more frequently in patients with LAHB (43% vs. 33%, p = 0.02). During a mean follow-up of 5.0 +/- 2.5 years, 125 patients (11%) died of cardiac causes. The annual cardiac death rate was 4.9% in patients with LAHB and 1.9% for patients without (p < 0.0001). Patients with both LAHB and an abnormal DSE had the highest annual cardiac death rate (6.3%). In a Cox multivariable analysis, independent predictors of cardiac death were age, smoking, history of heart failure, diabetes, and ischemia. Left anterior hemiblock was independently associated with increased risk of cardiac death among patients with normal DSE (hazard ratio 1.8, 95% confidence interval 1.1 to 3.8) and in patients with abnormal DSE (hazard ratio 1.7, 95% confidence interval 1.1 to 2.7). CONCLUSIONS: In patients with suspected CAD referred for stress testing, LAHB is associated with increased risk of cardiac death. This risk is persistent after adjustment for major clinical data and abnormalities on the stress echocardiogram. Therefore, isolated LAHB should not be considered a benign electrocardiographic abnormality in these patients
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