A Powerful Paradigm for Cardiovascular Risk Stratification Using Multiclass, Multi-Label, and Ensemble-Based Machine Learning Paradigms: A Narrative Review

Background and Motivation: Cardiovascular disease (CVD) causes the highest mortality globally. With escalating healthcare costs, early non-invasive CVD risk assessment is vital. Conventional methods have shown poor performance compared to more recent and fast-evolving Artificial Intelligence (AI) methods. The proposed study reviews the three most recent paradigms for CVD risk assessment, namely multiclass, multi-label, and ensemble-based methods in (i) office-based and (ii) stress-test laboratories. Methods: A total of 265 CVD-based studies were selected using the preferred reporting items for systematic reviews and meta-analyses (PRISMA) model. Due to its popularity and recent development, the study analyzed the above three paradigms using machine learning (ML) frameworks. We review comprehensively these three methods using attributes, such as architecture, applications, pro-and-cons, scientific validation, clinical evaluation, and AI risk-of-bias (RoB) in the CVD framework. These ML techniques were then extended under mobile and cloud-based infrastructure. Findings: Most popular biomarkers used were office-based, laboratory-based, image-based phenotypes, and medication usage. Surrogate carotid scanning for coronary artery risk prediction had shown promising results. Ground truth (GT) selection for AI-based training along with scientific and clinical validation is very important for CVD stratification to avoid RoB. It was observed that the most popular classification paradigm is multiclass followed by the ensemble, and multi-label. The use of deep learning techniques in CVD risk stratification is in a very early stage of development. Mobile and cloud-based AI technologies are more likely to be the future. Conclusions: AI-based methods for CVD risk assessment are most promising and successful. Choice of GT is most vital in AI-based models to prevent the RoB. The amalgamation of image-based strategies with conventional risk factors provides the highest stability when using the three CVD paradigms in non-cloud and cloud-based frameworks

A low-cost machine learning-based cardiovascular/stroke risk assessment system: integration of conventional factors with image phenotypes

Background: Most cardiovascular (CV)/stroke risk calculators using the integration of carotid ultrasound image-based phenotypes (CUSIP) with conventional risk factors (CRF) have shown improved risk stratification compared with either method. However such approaches have not yet leveraged the potential of machine learning (ML). Most intelligent ML strategies use follow-ups for the endpoints but are costly and time-intensive. We introduce an integrated ML system using stenosis as an endpoint for training and determine whether such a system can lead to superior performance compared with the conventional ML system.Methods: The ML-based algorithm consists of an offline and online system. The offline system extracts 47 features which comprised of 13 CRF and 34 CUSIP. Principal component analysis (PCA) was used to select the most significant features. These offline features were then trained using the event-equivalent gold standard (consisting of percentage stenosis) using a random forest (RF) classifier framework to generate training coefficients. The online system then transforms the PCA-based test features using offline trained coefficients to predict the risk labels on test subjects. The above ML system determines the area under the curve (AUC) using a 10-fold cross-validation paradigm. The above system so-called "AtheroRisk-Integrated" was compared against "AtheroRisk-Conventional", where only 13 CRF were considered in a feature set.Results: Left and right common carotid arteries of 202 Japanese patients (Toho University, Japan) were retrospectively examined to obtain 395 ultrasound scans. AtheroRisk-Integrated system [AUC=0.80, P<0.0001, 95% confidence interval (CI): 0.77 to 0.84] showed an improvement of similar to 18% against AtheroRisk-Conventional ML (AUC=0.68, P<0.0001, 95% CI: 0.64 to 0.72).Conclusions: ML-based integrated model with the event-equivalent gold standard as percentage stenosis is powerful and offers low cost and high performance CV/stroke risk assessment

The role of vascular biomarkers for primary and secondary prevention. A position paper from the European Society of Cardiology Working Group on peripheral circulation

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Multimodality carotid plaque tissue characterization and classification in the artificial intelligence paradigm: a narrative review for stroke application

Cardiovascular disease (CVD) is one of the leading causes of morbidity and mortality in the United States of America and globally. Carotid arterial plaque, a cause and also a marker of such CVD, can be detected by various non-invasive imaging modalities such as magnetic resonance imaging (MRI), computer tomography (CT), and ultrasound (US). Characterization and classification of carotid plaque-type in these imaging modalities, especially into symptomatic and asymptomatic plaque, helps in the planning of carotid endarterectomy or stenting. It can be challenging to characterize plaque components due to (I) partial volume effect in magnetic resonance imaging (MRI) or (II) varying Hausdorff values in plaque regions in CT, and (III) attenuation of echoes reflected by the plaque during US causing acoustic shadowing. Artificial intelligence (AI) methods have become an indispensable part of healthcare and their applications to the non-invasive imaging technologies such as MRI, CT, and the US. In this narrative review, three main types of AI models (machine learning, deep learning, and transfer learning) are analyzed when applied to MRI, CT, and the US. A link between carotid plaque characteristics and the risk of coronary artery disease is presented. With regard to characterization, we review tools and techniques that use AI models to distinguish carotid plaque types based on signal processing and feature strengths. We conclude that AI-based solutions offer an accurate and robust path for tissue characterization and classification for carotid artery plaque imaging in all three imaging modalities. Due to cost, user-friendliness, and clinical effectiveness, AI in the US has dominated the most

Nutrition, atherosclerosis, arterial imaging, cardiovascular risk stratification, and manifestations in COVID-19 framework: a narrative review.

Background: Atherosclerosis is the primary cause of the cardiovascular disease (CVD). Several risk factors lead to atherosclerosis, and altered nutrition is one among those. Nutrition has been ignored quite often in the process of CVD risk assessment. Altered nutrition along with carotid ultrasound imaging-driven atherosclerotic plaque features can help in understanding and banishing the problems associated with the late diagnosis of CVD. Artificial intelligence (AI) is another promisingly adopted technology for CVD risk assessment and management. Therefore, we hypothesize that the risk of atherosclerotic CVD can be accurately monitored using carotid ultrasound imaging, predicted using AI-based algorithms, and reduced with the help of proper nutrition. Layout: The review presents a pathophysiological link between nutrition and atherosclerosis by gaining a deep insight into the processes involved at each stage of plaque development. After targeting the causes and finding out results by low-cost, user-friendly, ultrasound-based arterial imaging, it is important to (i) stratify the risks and (ii) monitor them by measuring plaque burden and computing risk score as part of the preventive framework. Artificial intelligence (AI)-based strategies are used to provide efficient CVD risk assessments. Finally, the review presents the role of AI for CVD risk assessment during COVID-19. Conclusions: By studying the mechanism of low-density lipoprotein formation, saturated and trans fat, and other dietary components that lead to plaque formation, we demonstrate the use of CVD risk assessment due to nutrition and atherosclerosis disease formation during normal and COVID times. Further, nutrition if included, as a part of the associated risk factors can benefit from atherosclerotic disease progression and its management using AI-based CVD risk assessment

Cardiovascular/Stroke Risk Stratification in Diabetic Foot Infection Patients Using Deep Learning-Based Artificial Intelligence: An Investigative Study

A diabetic foot infection (DFI) is among the most serious, incurable, and costly to treat conditions. The presence of a DFI renders machine learning (ML) systems extremely nonlinear, posing difficulties in CVD/stroke risk stratification. In addition, there is a limited number of well-explained ML paradigms due to comorbidity, sample size limits, and weak scientific and clinical validation methodologies. Deep neural networks (DNN) are potent machines for learning that generalize nonlinear situations. The objective of this article is to propose a novel investigation of deep learning (DL) solutions for predicting CVD/stroke risk in DFI patients. The Preferred Reporting Items for Systematic reviews and Meta-Analyses (PRISMA) search strategy was used for the selection of 207 studies. We hypothesize that a DFI is responsible for increased morbidity and mortality due to the worsening of atherosclerotic disease and affecting coronary artery disease (CAD). Since surrogate biomarkers for CAD, such as carotid artery disease, can be used for monitoring CVD, we can thus use a DL-based model, namely, Long Short-Term Memory (LSTM) and Recurrent Neural Networks (RNN) for CVD/stroke risk prediction in DFI patients, which combines covariates such as office and laboratory-based biomarkers, carotid ultrasound image phenotype (CUSIP) lesions, along with the DFI severity. We confirmed the viability of CVD/stroke risk stratification in the DFI patients. Strong designs were found in the research of the DL architectures for CVD/stroke risk stratification. Finally, we analyzed the AI bias and proposed strategies for the early diagnosis of CVD/stroke in DFI patients. Since DFI patients have an aggressive atherosclerotic disease, leading to prominent CVD/stroke risk, we, therefore, conclude that the DL paradigm is very effective for predicting the risk of CVD/stroke in DFI patients

Integration of cardiovascular risk assessment with COVID-19 using artificial intelligence

Artificial Intelligence (AI), in general, refers to the machines (or computers) that mimic "cognitive" functions that we associate with our mind, such as "learning" and "solving problem". New biomarkers derived from medical imaging are being discovered and are then fused with non-imaging biomarkers (such as office, laboratory, physiological, genetic, epidemiological, and clinical-based biomarkers) in a big data framework, to develop AI systems. These systems can support risk prediction and monitoring. This perspective narrative shows the powerful methods of AI for tracking cardiovascular risks. We conclude that AI could potentially become an integral part of the COVID-19 disease management system. Countries, large and small, should join hands with the WHO in building biobanks for scientists around the world to build AI-based platforms for tracking the cardiovascular risk assessment during COVID-19 times and long-term follow-up of the survivors

The effect of antioxidant treatment with ascorbic acid on reactive hyperemia in patients with hypercholesterolemia

Background: This study was designed to study the effect of hypercholesterolemia on forearm blood flow (FBF) reactive hyperemia (RH) as well as its possible modification after administration of ascorbic acid. RH seems to be at least partly endothelium-dependent, mostly its late phase. Endothelial dysfunction has been described in subjects with hypercholesterolemia, and has been reversed with ascorbic acid administration.Method: FBF was studied with venous occlusion plethysmogaphy in 26 healthy volunteers and 46 hypercholesterolemic subjects. Hypercholesterolemic subjects were divided randomly into two groups, which were comparable for cardiovascular risk factors and use of drugs. Group A included 25 subjects, who received ascorbic acid and group B included 21 subjects, who received placebo. All subjects underwent measurement of FBF at baseline and during RH (phase A). FBF during RH was measured every 15 sec for 3 min. Subsequently subjects of group A received 2 gr of ascorbic acid orally in the form of effervent tablets, and subjects of group B received placebo orally in the same form. FBF measurements at baseline and during RH were repeated 2 hours later (phase B).Results: Maximal percent increase of RH FBF (early phase) was significantly higher in healthy subjects than in hypercholesterolemic subjects (139.1±70 % vs 78.05±78 % respectively, p<0.05). Duration of RH (late phase) was smaller in hypercholesterolemic subjects compared to normal subjects (61.15±55 sec vs 104.47±54 sec, p<0.05). Administration of ascorbic acid and not of placebo, increased the duration of RH (69.1±11 sec vs 104.1±12 sec, p<0.05) but not maximal percent increase of RH FBF.Conclusion: Hypercholsterolemia seems to impair both the early and the late phase of RH. Ascorbic acid improves only the duration of RH, that is its late phase. Knowing the ability of ascorbic acid to reverse endothelial dysfunction in subjects with hypercholesterolemia, possibly due to its antioxidant effect, it seems that the originally modified technique of venous occlusive plethysmography that was used in this population relates the late phase of RH with endothelial function better than its early phase. More studies are required in order to establish the use of duration of RH as a simple and non-invasive marker of endothelial function.Εισαγωγή: Η παρούσα μελέτη σχεδιάσθηκε για να εκτιμηθεί η επίδραση της υπερχοληστερολαιμίας στην αντιδραστική υπεραιμία (ΑΥ) του αντιβραχίου του ανθρώπου καθώς και η πιθανή τροποποίηση της μετά από οξεία χορήγησης ρ.ο. ασκορβικού οξέος. Η ΑΥ είναι ένα φαινόμενο εν μέρει ενδοθηλιο-εξαρτώμενο, κυρίως η όψιμη φάση της, χωρίς εντούτοις να έχει μελετηθεί διεξοδικά η σχέση ενδοθηλιακής λειτουργίας και των διαφόρων παραμέτρων της ΑΥ. Οξεία αναστροφή της ενδοθηλιακής δυσλειτουργίας, η οποία παρατηρείται σε άτομα με υπερχοληστερολαιμία, έχει επιτευχθεί μετά από την χορήγηση ασκορβικού οξέος. Δεύτερος στόχος της μελέτης ήταν η συσχέτιση των φάσεων της ΑΥ με την ενδοθηλιακή λειτουργία.Μεθοδολογία: Η αιματική ροή του αντιβραχίου μελετήθηκε με μία τροποποιημένη και διεθνώς πρωτότυπη μέθοδο της φλεβοαποφρακτικής πληθυσμογραφίας σε 26 υγιή άτομα και 46 άτομα με υπερχοληστερολαιμία. Τα υπερχοληστερολαιμικά άτομα χωρίσθηκαν τυχαία σε δύο ομάδες οι οποίες δεν διέφεραν μεταξύ τους ως προς την παρουσία άλλων γνωστών παραγόντων (φάρμακα ή παράγοντες κινδύνου για ανάπτυξη αθηροματικής νόσου) που να επηρεάζουν την ενδοθηλιακή λειτουργία και την αντιδραστική υπεραιμία. Η ομάδα A (25 άτομα) έλαβε ασκορβικό οξύ, και η ομάδα Β (21 άτομα) έλαβε εικονικό φάρμακο. Όλα τα άτομα υποβλήθηκαν σε μέτρηση της αιματικής ροής στο αντιβράχιο σε συνθήκες ηρεμίας και κατά τη διάρκεια της A Y (φάση A). Κατά την A Y η ροή μετρήθηκε κάθε 15 δευτερόλεπτα για 3 λεπτά. Στη συνέχεια τα άτομα της ομάδας A έλαβαν 2 gr ασκορβικό οξύ και τη ομάδας Β εικονικό φάρμακο. Οι μετρήσεις της αιματικής ροής επαναλήφθηκαν 2 ώρες αργότερα (φάση Β).Αποτελέσματα: Η μέγιστη της επί τοις εκατό μεταβολής της υπεραιμικής ροής (πρώιμη φάση) βρέθηκε σημαντικά μεγαλύτερη στα υγιή σε σχέση με τα υπερχοληστερολαιμικά άτομα (139,1±70 % έναντι 78,05±78 %, αντίστοιχα ρ<0,05). Η διάρκεια της ΑΥ (όψιμη φάση) βρέθηκε μικρότερη στα άτομα με υπερχοληστερολαιμία σε σχέση με τα υγιή άτομα(6,15±55 sec έναντι 104,4±54 sec, αντίστοιχα ρ<0.05). Η χορήγηση του ασκορβικού οξέος και όχι του εικονικού φαρμάκου βελτίωσε την διάρκεια της AY (69,1±11 sec έναντι 104,1±12 sec, αντίστοιχα, ρ<0.05), αλλά όχι και τη μέγιστη επί τοις εκατό μεταβολή της υπεραιμικής ροής.Συμπέρασμα: Η υπερχοληστερολαιμία επηρεάζει τόσο την πρώιμη όσο και την όψιμη φάση της ΑΥ. Το ασκορβικό οξύ βελτιώνει μόνο τη διάρκεια της ΑΥ, δηλαδή την όψιμη φάση της. Συνυπολογίζοντας 1) τη γνωστή ιδιότητα του ασκορβικού οξέος να αναστρέφει την ενδοθηλιακή δυσλειτουργία σε άτομα με υπερχοληστερολαιμία, πιθανότατα μέσω της αντιοξειδωτικής του δράσης στο αγγειακό ενδοθήλιο, και 2) το παρόν εύρημα διαπιστώνεται ότι η διάρκεια της ΑΥ (όψιμη φάση) όπως αυτή εκτιμήθηκε από τη συγκεκριμένη πρωτότυπη τεχνική της φλεβοαποφρακτικής πληθυσμογραφίας εκφράζει καλύτερα το φαινόμενο της αναστροφής της ενδοθηλιακής λειτουργίας από ότι η όψιμη φάση της ΑΥ, γεγονός που υποστηρίζεται από μεγάλο τμήμα της διεθνούς βιβλιογραφίας. Περαιτέρω έρευνες είναι απαραίτητες προκειμένου η διάρκεια της αντιδραστικής υπεραιμίας να μπορεί να χρησιμοποιηθεί στο μέλλον για την αναίμακτη και απλή μελέτη του αγγειακού ενδοθηλίου στη περιφερική μικροκυκλοφορία του ανθρώπου