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Competing Interests: None declared.

Pulse wave velocity (PWV) is as a reliable marker of arterial stiffness and vascular aging, surpassing traditional risk factors in predicting detrimental cardiovascular events. The present meta-analysis aims to investigate PWV thresholds and assess its prognostic value in outcomes of acute ischemic stroke (AIS). A search was conducted in PubMed, Cochrane, Web of Science, and Scopus for studies published up to January 2024, focusing on patients admitted with AIS, wherein arterial stiffness was assessed through PWV measurements during hospitalization. Identified studies reported PWV values in individuals with both favorable and unfavorable outcomes at the end of follow-up. Initially, 35 eligible studies provided data for weighted mean baPWV (11,953 AIS patients) and cfPWV (2,197 AIS patients) calculations. The average age was 67 years, with approximately 60% male, 67% hypertensive, 30% diabetic and 30% smoker participants. The weighted mean systolic blood pressure was approximately 150 mmHg. In AIS patients, the mean PWV was 10 m/s for standard cfPWV and 20 m/s for baPWV. Nine cohort studies (6,006 AIS patients) were included in the quantitative analysis of clinical outcomes. Higher PWV levels were associated with poorer functional outcomes (2.3 m/s higher, 95%CI:1.2-3.4, p < 0.001; I 2  = 87.4%). AIS patients with arterial stiffness/vascular aging (higher PWV) had approximately 46.2% increased risk of poor functional outcome, 12.7% higher risk of mortality, 13.9% greater risk of major adverse cardiovascular events, and 13.9% greater risk of stroke recurrence over the long term compared to those without arterial stiffness. Advanced vascular aging, as indicated by PWV, significantly predicts adverse outcomes in AIS patients. Integrating the assessment of vascular aging into clinical practice can improve risk perception in these patients., (© 2024. The Author(s), under exclusive licence to Springer Nature Limited.)

Background: While arterial stiffening is a known risk factor for cardiovascular diseases, it remains unclear whether there is an early vascular aging (EVA) in patients who have experienced acute ischemic stroke (AIS). This systematic review and meta-analysis aims to investigate whether patients with AIS exhibit EVA through pulse wave velocity (PWV) measurements shortly after the stroke onset, shedding light on the relationship between arterial stiffness, hypertension, and stroke., Methods: Thirteen case-control studies were included, comparing PWV measurements between AIS patients and non-AIS individuals. A meta-analysis was performed to compare PWV levels, age, blood pressure, and the prevalence of different cardiovascular risk factors among 1711 AIS patients and 1551 controls., Results: Despite AIS patients showing higher PWV compared to controls (mean difference: 1.72 m/s, 95 % CI: 1.05-2.38, p < 0.001; I 2 = 88.3 %), their age did not significantly differ (95 % CI: -0.47-0.94, p = 0.519; I 2 = 0 %), suggesting EVA in AIS patients. Moreover, AIS patients exhibited elevated systolic and diastolic blood pressure and had higher odds of smoking, hypertension, diabetes, and male gender compared to controls., Conclusions: This study's findings underscore the presence of EVA in AIS patients, evident through increased PWV measurements shortly after stroke onset. Notably, smoking, hypertension, and diabetes mellitus emerge as substantial factors contributing to accelerated arterial stiffness within this population., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Competing Interests: Disclosures None.

Chronic systemic inflammation contributes to increased CVD burden in Ankylosing Spondylitis (AS). Since long-term follow-up data on subclinical atherosclerosis acceleration are lacking, we examined its progression in contemporary AS patients during 10 years. Fifty-three (89% male, aged 50.4 (36.3-55.9) years,) non-diabetic, CVD-free AS patients and 53 age-sex-matched non-diabetic, control individuals were re-evaluated after 9.2-10.2 years by ultrasonography for carotid/femoral atheromatosis, pulse wave velocity (PWV) and intima-media thickness (IMT), performed by the same operator/protocol. New atheromatic plaque formation, PWV deterioration, and IMT increase were associated only with classical CVD risk factors, as reflected by the heartSCORE (age, gender, smoking status, blood pressure and cholesterol levels) by multivariate analysis, rather than disease presence. However, among AS patients, despite remission/low disease activity at follow-up end in 79%, atheromatosis progression was associated by multivariate analysis with higher BASDAI scores (p = 0.028), independently of biologic therapies administered in 2/3 of them. Moreover, in AS patients, but not in controls, PWV values at baseline were associated with plaque progression during the 10-year follow-up after taking into account baseline heartSCORE and plaque burden status (p = 0.033). Despite comparable prevalence of both hypertension and hypercholesterolemia at baseline between patients and controls, a lower percentage of AS patients had achieved "adequate" CVD risk factor control at follow-up end (11% vs 25% respectively, p = 0.076). Classical CVD risk factors and residual disease activity account for the progression of subclinical atherosclerosis in AS, pointing to the unmet needs in the contemporary management of these patients., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Backround: Central systolic blood pressure (cSBP) provides valuable clinical and physiological information. A recent invasive study showed that cSBP can be reliably estimated from mean (MBP) and diastolic (DBP) blood pressure. In this non-invasive study, we compared cSBP calculated using a Direct Central Blood Pressure estimation (DCBP = MBP 2 /DBP) with cSBP estimated by radial tonometry., Methods: Consecutive patients referred for cardiovascular assessment and prevention were prospectively included. Using applanation tonometry with SphygmoCor device, cSBP was estimated using an inbuilt generalized transfer function derived from radial pressure waveform, which was calibrated to oscillometric brachial SBP and DBP. The time-averaged MBP was calculated from the radial pulse waveform. The minimum acceptable error (DCBP-cSBP) was set at ≤5 (mean) and ≤8 mmHg (SD)., Results: We included 160 patients (58 years, 54%men). The cSBP was 123.1 ± 18.3 mmHg (range 86-181 mmHg). The (DCBP-cSBP) error was -1.4 ± 4.9 mmHg. There was a linear relationship between cSBP and DCBP (R 2 = 0.93). Forty-seven patients (29%) had cSBP values ≥ 130 mmHg, and a DCBP value > 126 mmHg exhibited a sensitivity of 91.5% and specificity of 94.7% in discriminating this threshold (Youden index = 0.86; AUC = 0.965)., Conclusions: Using the DCBP formula, radial tonometry allows for the robust estimation of cSBP without the need for a generalized transfer function. This finding may have implications for risk stratification.

Background: The arterial pathology and mechanisms of increased cardiovascular disease (CVD) risk in HCV-infected individuals are not yet clear. The aim of this study was to identify types of arterial pathology in treatment-naive chronic HCV patients and to test their reversibility after successful treatment. Methods: Consecutive, never-treated, HCV-infected patients were compared with age and CVD-related risk factors, matched controls, healthy individuals (HI), patients with rheumatoid arthritis (RA) and people living with HIV (PLWH), in terms of arterial stiffening by pulse wave velocity, arterial atheromatosis/hypertrophy by carotid plaques/intima-media thickness and impaired pressure wave reflections by augmentation index. After three months of sustained virological response (SVR) administered using direct-acting antivirals, vascular examination was repeated in HCV-infected patients to test drug and viral-elimination effect in subclinical CVD. Results: Thirty HCV patients were examined at baseline; fourteen of them were re-examined post-SVR. Compared with HI, HCV patients had significantly more plaques, which is similar to that of RA patients and the PLWH group. No other differences were found in all other vascular biomarkers, and regression among HCV patients also revealed no differences 3 months post-SVR. Conclusions: Accelerated atheromatosis, rather than arterial stiffening, arterial remodeling and peripheral impaired hemodynamics is the underlying pathology leading to increased CVD risk in HCV patients.

Blood pressure is not a static parameter, but rather undergoes continuous fluctuations over time, as a result of the interaction between environmental and behavioural factors on one side and intrinsic cardiovascular regulatory mechanisms on the other side. Increased blood pressure variability (BPV) may indicate an impaired cardiovascular regulation and may represent a cardiovascular risk factor itself, having been associated with increased all-cause and cardiovascular mortality, stroke, coronary artery disease, heart failure, end-stage renal disease, and dementia incidence. Nonetheless, BPV was considered only a research issue in previous hypertension management guidelines, because the available evidence on its clinical relevance presents several gaps and is based on heterogeneous studies with limited standardization of methods for BPV assessment. The aim of this position paper, with contributions from members of the European Society of Hypertension Working Group on Blood Pressure Monitoring and Cardiovascular Variability and from a number of international experts, is to summarize the available evidence in the field of BPV assessment methodology and clinical applications and to provide practical indications on how to measure and interpret BPV in research and clinical settings based on currently available data. Pending issues and clinical and methodological recommendations supported by available evidence are also reported. The information provided by this paper should contribute to a better standardization of future studies on BPV, but should also provide clinicians with some indications on how BPV can be managed based on currently available data., (Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.)

Background: Pressure wave reflections (PWRs) within the circulation are assessed at various arterial sites by various noninvasive methods. We aimed at reviewing the conflicting data regarding the hypothesis that higher PWRs are associated with higher left ventricular mass and tested whether this association stands for all available indices of PWRs, all (proximal or distal to the heart) sites of assessment, and is modified by sex, age and heart rate., Methods: Based on a predefined protocol applying the Meta-Analysis of Observational Studies in Epidemiology (MOOSE) guidelines, we identified eligible for meta-analysis data regarding: augmentation index, augmentation pressure, backward pressure (Pb), reflection index, and their association with left ventricular mass index (19 studies, total population n=8686)., Results: We found statistically significant associations, independent from blood pressure level, for all indices of PWRs at all arterial sites (carotid augmentation index; odds ratio; standardized beta coefficient [β]: 0.14 [95% CI, 0.07% to 0.21%], per SD increase), radial augmentation index (β: 0.21; 0.11 to 0.31), central augmentation pressure (β: 0.15; 0.03 to 0.27), central Pb (β: 0.23; 0.05 to 0.42), and central reflection index (β: 0.14; 0.06 to 0.22), except for aortic augmentation index as estimated by generalized transfer functions. Meta-regression analysis showed that the association between carotid augmentation index and left ventricular mass was higher among populations with higher heart rate ( P =0.036, beta: 0.017 [95% CI, 0.001 to 0.033]) and tended to be higher in middle-aged ( P =0.07, beta: -0.001; -0.021 to 0.001)., Conclusions: A clinically meaningful association between PWRs and left ventricular mass, assessed at either central or peripheral arterial sites by most available methods was shown, suggesting that PWR reduction strategies might be useful. Based on the present evidence, such trials should target middle-aged populations with high normal heart rate.

Background: Breakfast consumption has been associated with the improvement of many cardiovascular disease (CVD) risk factors, yet data regarding its association with subclinical vascular damage, which precedes the onset of CVD, are scarce. The aim of this study is to investigate this association in a large sample of adults with CVD risk factors., Methods: Anthropometric measurements, vascular biomarkers and dietary intake with two 24-h dietary recalls, focusing on breakfast frequency and its quantity and content, were assessed in 902 adults (45.2% males). Breakfast quality was assessed by identifying a posteriori breakfast dietary pattern (DP) by using principal component analysis (PCA)., Results: Systematic breakfast consumption (SBC) was inversely associated with central systolic blood pressure (b: -3.28, 95% C.I.: -5.7 to -0.86), diastolic blood pressure (b: -1.85, 95% C.I.: -3.34 to -0.36), augmentation index (b: -3.17, 95% C.I.:-4.98 to 1.35) and left carotid intima media thickness (b: -0.03, 95% C.I.:-0.06 to -0.01) compared to breakfast skipping independently of age, sex, hypertension, diabetes, dyslipidemia, smoking, and BMI. SBC of 10-20% of daily total energy intake (dTEI) was inversely associated with Aix (b: -2.31, 95% C.I.:-4.05 to -0.57) compared to <10% dTEI after adjustment for the aforementioned confounders. DP1 (high coffee and sugar consumption, low consumption of low- and full-fat dairy products, fruits, and fresh juices) was positively associated with Aix (b: 1.19, 95% C.I.: 0.48 to 1.90)., Conclusion: SBC comprised of medium-energy density and high-nutrient content food items may be a simple daily habit associated with better vascular health.

Objective: The purpose of this study was to investigate the association of blood pressure (BP) time-in-target range (TTR) derived from 24-h ambulatory BP monitoring (ABPM) during the acute phase of ischemic stroke (AIS), with the severity of stroke and its predictive value for the 3 months outcome., Methods: A total of 228 AIS patients (prospective multicenter follow-up study) underwent ABPM every 20 min within 48 h from stroke onset using an automated oscillometric device. Clinical and laboratory findings were recorded. Mean BP parameters, BP variability and TTR for SBP (90-140 mmHg), DBP (60-90 mmHg), and mean arterial pressure (MAP) were calculated. Endpoints were death and disability/death at 3 months., Results: A total of 14 942 BP measurements were recorded (∼66 per AIS patient) within 72 h of stroke onset. Patient's 24-h TTR was 34.7 ± 29.9, 64.3 ± 24.2, and 55.3 ± 29.4% for SBP, DBP and MAP, respectively. In patients without prior hypertension, TTR was lower as stroke severity increased for both DBP (P = 0.031) and MAP (P = 0.016). In 175 patients without prior disability, increase in TTR of DBP and MAP associated significantly with a decreased risk of disability/death (hazard ratio 0.96, 95% CI 0.95-0.99, P = 0.007 and hazard ratio 0.97, 95% CI 0.96-0.99, P = 0.007). TTR of SBP in 130-180 mmHg and 110-160 mmHg ranges seems to be related with mortality and disability outcomes, respectively., Conclusion: TTR can be included for a more detailed description of BP course, according to stroke severity, and for the evaluation of BP predictive role, in addition to mean BP values, derived from ABPM during the acute phase of AIS., Clinical Trial Registrationurl: http://www.clinicaltrials.gov. Unique identifier: NCT01915862., (Copyright © 2022 Wolters Kluwer Health, Inc. All rights reserved.)

Motivation : The price of medical treatment continues to rise due to (i) an increasing population; (ii) an aging human growth; (iii) disease prevalence; (iv) a rise in the frequency of patients that utilize health care services; and (v) increase in the price. Objective: Artificial Intelligence (AI) is already well-known for its superiority in various healthcare applications, including the segmentation of lesions in images, speech recognition, smartphone personal assistants, navigation, ride-sharing apps, and many more. Our study is based on two hypotheses: (i) AI offers more economic solutions compared to conventional methods; (ii) AI treatment offers stronger economics compared to AI diagnosis. This novel study aims to evaluate AI technology in the context of healthcare costs, namely in the areas of diagnosis and treatment, and then compare it to the traditional or non-AI-based approaches. Methodology: PRISMA was used to select the best 200 studies for AI in healthcare with a primary focus on cost reduction, especially towards diagnosis and treatment. We defined the diagnosis and treatment architectures, investigated their characteristics, and categorized the roles that AI plays in the diagnostic and therapeutic paradigms. We experimented with various combinations of different assumptions by integrating AI and then comparing it against conventional costs. Lastly, we dwell on three powerful future concepts of AI, namely, pruning, bias, explainability, and regulatory approvals of AI systems. Conclusions: The model shows tremendous cost savings using AI tools in diagnosis and treatment. The economics of AI can be improved by incorporating pruning, reduction in AI bias, explainability, and regulatory approvals.

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.

Background and Purpose: Stroke patients' management might be improved by addressing the role of aortic stiffness (carotid-femoral pulse wave velocity: cfPWV) and pressure wave reflections (PWRs, augmentation index: AIx) in their pathogenesis and outcome. We tested the hypothesis that cfPWV and AIx, separately and combined, predict long-term outcomes [all-cause mortality, incidence of cardiovascular events, stroke recurrence and disability defined by modified Ranking Scale (mRS) ≥3] in patients with acute stroke, using data from the 'Athens Stroke Registry'., Methods: Data from 552 patients (70% men, age: 66.1 ± 10.4 years, 13.4% deaths from any cause, 21.2% cardiovascular events, 14.1% stroke recurrences and 20.1% poor mRS, mean follow-up 68.4 ± 41.4 months) were analyzed., Results: The main findings were that: high aortic stiffness (cfPWV > 13 m/s) alone is an independent predictor of all-cause mortality and cardiovascular (CV) events, but not of stroke recurrence and poor functional outcome; evaluated separately from aortic stiffness, neither low nor high PWRs have any prognostic value; even after multiple adjustments, patients with both high aortic stiffness (cfPWV > 13 m/s) and low PWRs (Aix < 22%) have almost two-fold higher hazard ratio, not only for all-cause mortality and CV events but also for stroke recurrence and poor functional outcome., Conclusions: The present study provides evidence about the role of aortic stiffness, PWRs and their combined incremental value in the long-term survival, morbidity, and functional disability after acute stroke., (Copyright © 2022 Wolters Kluwer Health, Inc. All rights reserved.)

Study Objective: The present systematic review investigates the hypothesis that specific components of the intestinal microbiome and/or their metabolites are associated with early stages of subclinical arterial damage (SAD)., Design: Based on the MOOSE criteria, we conducted a systematic review of the literature (Scopus, Medline) investigating the potential association between gut microbiota and the most widely applied arterial biomarkers of SAD., Participants: All studies included individuals without established cardiovascular disease, either with or without SAD., Intervention: No interventions were made., Main Outcome Measures: Association between exposure (components/metabolites of microbiota) and outcome (presence of SAD)., Results: Fourteen articles met the predefined criteria. Due to the large heterogeneity, their meta-analysis was not possible. Our review revealed (a) two studies on endothelial dysfunction, out of which one found an inverse relation between plasma trimethylamine N-oxide levels and FMD and the other did not substantiate a statistically significant correlation with RHI. (b) Twelve studies on atheromatosis, assessed as intimal-medial thickness (IMT), coronary artery calcium (CAC) and arterial plaque, of which, seven studies showed statistically significant associations (negative or positive depending on the microorganism or microbiota metabolite) with IMT, one study revealed significant associations with coronary artery calcium, while one showed absence of correlation and four studies reported statistically significant correlations with arterial plaque. (c) Three studies on arterial stiffness (pulse wave velocity - PWV) with two of them concluding in statistically significant association while the third study did not. Some articles investigated multiple of the correlations described and therefore, belonged to more than one section., Conclusion: Evidence of both positive and inverse associations of gut microbiota composition and their metabolites with different types of SVD has been found. However the small number and heterogeneity of available studies cannot allow to confirm or disprove the hypothesis., Competing Interests: All authors of the present scientific article “Association of gut microbiota composition and their metabolites with subclinical atheromatosis: A systematic review” declare that they have no conflicts of interest. All authors disclose any financial and personal relationships with other people or organizations that could inappropriately influence (bias) their work. All authors agree on the submission and publication of the article titled “Association of gut microbiota composition and their metabolites with subclinical atheromatosis: a systematic review”., (© 2022 Published by Elsevier Inc.)

The SARS-CoV-2 virus has caused a pandemic, infecting nearly 80 million people worldwide, with mortality exceeding six million. The average survival span is just 14 days from the time the symptoms become aggressive. The present study delineates the deep-driven vascular damage in the pulmonary, renal, coronary, and carotid vessels due to SARS-CoV-2. This special report addresses an important gap in the literature in understanding (i) the pathophysiology of vascular damage and the role of medical imaging in the visualization of the damage caused by SARS-CoV-2, and (ii) further understanding the severity of COVID-19 using artificial intelligence (AI)-based tissue characterization (TC). PRISMA was used to select 296 studies for AI-based TC. Radiological imaging techniques such as magnetic resonance imaging (MRI), computed tomography (CT), and ultrasound were selected for imaging of the vasculature infected by COVID-19. Four kinds of hypotheses are presented for showing the vascular damage in radiological images due to COVID-19. Three kinds of AI models, namely, machine learning, deep learning, and transfer learning, are used for TC. Further, the study presents recommendations for improving AI-based architectures for vascular studies. We conclude that the process of vascular damage due to COVID-19 has similarities across vessel types, even though it results in multi-organ dysfunction. Although the mortality rate is ~2% of those infected, the long-term effect of COVID-19 needs monitoring to avoid deaths. AI seems to be penetrating the health care industry at warp speed, and we expect to see an emerging role in patient care, reduce the mortality and morbidity rate.

Background and Motivation : Parkinson's disease (PD) is one of the most serious, non-curable, and expensive to treat. Recently, machine learning (ML) has shown to be able to predict cardiovascular/stroke risk in PD patients. The presence of COVID-19 causes the ML systems to become severely non-linear and poses challenges in cardiovascular/stroke risk stratification. Further, due to comorbidity, sample size constraints, and poor scientific and clinical validation techniques, there have been no well-explained ML paradigms. Deep neural networks are powerful learning machines that generalize non-linear conditions. This study presents a novel investigation of deep learning (DL) solutions for CVD/stroke risk prediction in PD patients affected by the COVID-19 framework. Method : The PRISMA search strategy was used for the selection of 292 studies closely associated with the effect of PD on CVD risk in the COVID-19 framework. We study the hypothesis that PD in the presence of COVID-19 can cause more harm to the heart and brain than in non-COVID-19 conditions. COVID-19 lung damage severity can be used as a covariate during DL training model designs. We, therefore, propose a DL model for the estimation of, (i) COVID-19 lesions in computed tomography (CT) scans and (ii) combining the covariates of PD, COVID-19 lesions, office and laboratory arterial atherosclerotic image-based biomarkers, and medicine usage for the PD patients for the design of DL point-based models for CVD/stroke risk stratification. Results : We validated the feasibility of CVD/stroke risk stratification in PD patients in the presence of a COVID-19 environment and this was also verified. DL architectures like long short-term memory (LSTM), and recurrent neural network (RNN) were studied for CVD/stroke risk stratification showing powerful designs. Lastly, we examined the artificial intelligence bias and provided recommendations for early detection of CVD/stroke in PD patients in the presence of COVID-19. Conclusion : The DL is a very powerful tool for predicting CVD/stroke risk in PD patients affected by COVID-19.

Background: The previous COVID-19 lung diagnosis system lacks both scientific validation and the role of explainable artificial intelligence (AI) for understanding lesion localization. This study presents a cloud-based explainable AI, the “COVLIAS 2.0-cXAI” system using four kinds of class activation maps (CAM) models. Methodology: Our cohort consisted of ~6000 CT slices from two sources (Croatia, 80 COVID-19 patients and Italy, 15 control patients). COVLIAS 2.0-cXAI design consisted of three stages: (i) automated lung segmentation using hybrid deep learning ResNet-UNet model by automatic adjustment of Hounsfield units, hyperparameter optimization, and parallel and distributed training, (ii) classification using three kinds of DenseNet (DN) models (DN-121, DN-169, DN-201), and (iii) validation using four kinds of CAM visualization techniques: gradient-weighted class activation mapping (Grad-CAM), Grad-CAM++, score-weighted CAM (Score-CAM), and FasterScore-CAM. The COVLIAS 2.0-cXAI was validated by three trained senior radiologists for its stability and reliability. The Friedman test was also performed on the scores of the three radiologists. Results: The ResNet-UNet segmentation model resulted in dice similarity of 0.96, Jaccard index of 0.93, a correlation coefficient of 0.99, with a figure-of-merit of 95.99%, while the classifier accuracies for the three DN nets (DN-121, DN-169, and DN-201) were 98%, 98%, and 99% with a loss of ~0.003, ~0.0025, and ~0.002 using 50 epochs, respectively. The mean AUC for all three DN models was 0.99 (p < 0.0001). The COVLIAS 2.0-cXAI showed 80% scans for mean alignment index (MAI) between heatmaps and gold standard, a score of four out of five, establishing the system for clinical settings. Conclusions: The COVLIAS 2.0-cXAI successfully showed a cloud-based explainable AI system for lesion localization in lung CT scans.

Tuberculosis is an infectious disease that mainly affects the lungs (known as pulmonary tuberculosis). Mycobacterium tuberculosis is a species of pathogenic bacteria in the family of Mycobacteriaceae and the causative agent of tuberculosis; it was discovered by Robert Koch in 1882. From about 1918 to 1939, tuberculosis in Greece was characterized as a social disease because it seemed to spread among the lower social classes, including displaced people living in refugee camps. The battle against tuberculosis involved private initiatives aimed at educating people on hygiene and establishing anti-tuberculosis institutions, such as sanatoria and preventoria., Competing Interests: The authors have declared that no competing interests exist., (Copyright © 2022, Michaleas et al.)

Background: COVID-19 is a disease with multiple variants, and is quickly spreading throughout the world. It is crucial to identify patients who are suspected of having COVID-19 early, because the vaccine is not readily available in certain parts of the world. Methodology: Lung computed tomography (CT) imaging can be used to diagnose COVID-19 as an alternative to the RT-PCR test in some cases. The occurrence of ground-glass opacities in the lung region is a characteristic of COVID-19 in chest CT scans, and these are daunting to locate and segment manually. The proposed study consists of a combination of solo deep learning (DL) and hybrid DL (HDL) models to tackle the lesion location and segmentation more quickly. One DL and four HDL models—namely, PSPNet, VGG-SegNet, ResNet-SegNet, VGG-UNet, and ResNet-UNet—were trained by an expert radiologist. The training scheme adopted a fivefold cross-validation strategy on a cohort of 3000 images selected from a set of 40 COVID-19-positive individuals. Results: The proposed variability study uses tracings from two trained radiologists as part of the validation. Five artificial intelligence (AI) models were benchmarked against MedSeg. The best AI model, ResNet-UNet, was superior to MedSeg by 9% and 15% for Dice and Jaccard, respectively, when compared against MD 1, and by 4% and 8%, respectively, when compared against MD 2. Statistical tests—namely, the Mann−Whitney test, paired t-test, and Wilcoxon test—demonstrated its stability and reliability, with p < 0.0001. The online system for each slice was <1 s. Conclusions: The AI models reliably located and segmented COVID-19 lesions in CT scans. The COVLIAS 1.0Lesion lesion locator passed the intervariability test.

Objective: Accurate and easy to use methods for dietary Na intake estimation in population level are lacking. We aimed at (i) estimating the mean Na intake in the group level using a variety of dietary methods (DM) and urinary methods (UM) and correlating them with 24-h urine collection (24UCol) and (ii) improving the accuracy of the existing DM., Design: The most common DM (three 24-h dietary recalls (24DR) and FFQ) and UM (24UCol and spot urine collection using common equations) were applied. To improve the existing: (i) 24DR, discretionary Na was quantified using salt-related questions or adding extra 15 % in total Na intake and (ii) FFQ, food items rich in Na and salt-related questions were added in the standard questionnaire (NaFFQ)., Setting: National and Kapodistrian University of Athens, Greece., Participants: Totally, 122 high cardiovascular risk subjects (56·0 ± 12·6 years; 55·7 % males)., Results: Mean 24 h Na excretion (24UNa) was 2810 ± 1304 mg/d. Spot urine methods overestimated the 24UNa (bias range: -1781 to -492 mg) and were moderately correlated to 24UCol (r = 0·469-0·596, P ≤ 0·01). DM underestimated the 24UNa (bias range: 877 to 1212 mg) and were weakly correlated with 24UCol. The improved DM underestimated the 24UNa (bias range: 877 to 923 mg). The NaFFQ presented the smallest bias (-290 ± 1336 mg) and the strongest correlation with 24UCol (r = 0·497, P ≤ 0·01), but wide limits of agreement in Bland-Altman plots (-2909 mg; 2329 mg), like all the other methods did., Conclusions: The existing methods exhibit poor accuracy. Further improvement of the newly developed NaFFQ could be promising for more accurate estimation of mean dietary Na intake in epidemiological studies. Additional validation studies are needed.

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.

Background: Evidence suggests marginal superiority of static aortic systolic blood pressure (aSBP) compared with brachial SBP (bSBP) regarding the association with organ damage and prognosis of cardiovascular disease (CVD). The noninvasive 24-hour aSBP assessment is feasible and associates better with presence of left ventricular hypertrophy compared with 24-hour bSBP. We aimed at comparing the association of 24-hour aSBP and 24-hour bSBP with indices of arterial damage and examining the role of 24-hour SBP amplification variability (within-subjects' SD) in this association., Methods: Consecutive subjects referred for CVD risk assessment underwent 24-hour aortic and brachial ambulatory BP monitoring using a validated oscillometric device (Mobil-O-Graph). Arterial damage was assessed by carotid intima-media thickness (IMT) and detection of carotid and femoral atheromatosis (plaque presence)., Results: Cross-sectionally 501 individuals (aged 54±13 years, 57% men, 80% hypertensives) were examined. Multivariable analysis revealed superiority of 24-hour aSBP regarding the association with IMT, carotid hypertrophy and carotid-but not femoral-atheromatosis. In receiver operator characteristics analysis, 24-hour aSBP displayed a higher discriminatory ability-compared to 24-hour bSBP-for the detection of both carotid hypertrophy (area under the curve, 0.662 versus 0.624, P <0.05) and carotid atheromatosis (area under the curve, 0.573 versus 0.547, P <0.05). This effect was more prominent in individuals with above-median 24-hour SD of SBP amplification., Conclusions: Our results suggest that 24-hour aSBP assessment may be of significant value in clinical practice to detect site-specific arterial damage on the basis of pressure amplification variability and should be prospectively examined in clinical trials.

Late-night overeating (LNO) is associated with several cardiovascular disease (CVD) risk factors. Limited data exist regarding the association between late-night (LN) systematic food consumption, LNO, and LN poor food quality with subclinical vascular damage (SVD) which precedes the onset of CVD. This study aimed to investigate the above associations with SVD in a large sample of adults, free of established CVD, with one or more CVD risk factors. In total, 901 adults (45.2% males) underwent anthropometric, dietary (through two 24 h dietary recalls) and vascular assessment. LN systematic eating was defined as consumption of food after 19:00 h in both dietary recalls and LNO was defined as systematic consumption of >40% of daily total energy intake (dTEI) after 19:00 h. Systematic LN food consumption was inversely associated with diastolic blood pressure (DBP) (−1.44 95% C.I. (−2.76, −0.12)) after adjusting for age, sex, hypertension, diabetes, dyslipidemia, smoking, BMI and dTEI. LNO was positively associated with existence of carotid plaques (1.70 95% C.I. (1.07, 2.68)), while LN increased consumption of red meat, refined grains and wine and low consumption of whole wheat grains was positively associated with Aix (Augmentation Index) (0.84 95% C.I. (0.09, 1.59)), after adjusting for all the mentioned confounders. Systematic LN eating is associated with lower DBP while systematic LNO and consumption of poor-quality food late at night, is associated with SVD. Further research is needed to define more accurately the impact of LN eating habits on vascular health.

Central (aortic) systolic blood pressure (cSBP) is the pressure seen by the heart, the brain, and the kidneys. If properly measured, cSBP is closer associated with hypertension-mediated organ damage and prognosis, as compared with brachial SBP (bSBP). We investigated 24-hour profiles of bSBP and cSBP, measured simultaneously using Mobilograph devices, in 2423 untreated adults (1275 women; age, 18-94 years), free from overt cardiovascular disease, aiming to develop reference values and to analyze daytime-nighttime variability. Central SBP was assessed, using brachial waveforms, calibrated with mean arterial pressure (MAP)/diastolic BP (cSBP MAP/DBPcal ), or bSBP/diastolic blood pressure (cSBP SBP/DBPcal ), and a validated transfer function, resulting in 144 509 valid brachial and 130 804 valid central measurements. Averaged 24-hour, daytime, and nighttime brachial BP across all individuals was 124/79, 126/81, and 116/72 mm Hg, respectively. Averaged 24-hour, daytime, and nighttime values for cSBP MAP/DBPcal were 128, 128, and 125 mm Hg and 115, 117, and 107 mm Hg for cSBP SBP/DBPcal , respectively. We pragmatically propose as upper normal limit for 24-hour cSBP MAP/DBPcal 135 mm Hg and for 24-hour cSBP SBP/DBPcal 120 mm Hg. bSBP dipping (nighttime-daytime/daytime SBP) was -10.6 % in young participants and decreased with increasing age. Central SBP SBP/DBPcal dipping was less pronounced (-8.7% in young participants). In contrast, cSBP MAP/DBPcal dipping was completely absent in the youngest age group and less pronounced in all other participants. These data may serve for comparison in various diseases and have potential implications for refining hypertension diagnosis and management. The different dipping behavior of bSBP versus cSBP requires further investigation.

Background and Aims: The association between dietary sugars and vascular damage has been scarcely examined out of the context of established cardiovascular disease. We aimed to investigate the association between different types of sugars with subclinical atheromatosis and arteriosclerosis, in individuals free of cardiovascular disease being, however, at moderate-to-high cardiovascular risk., Methods and Results: Two 24-h dietary recalls were conducted to estimate sugars intake. Subclinical atheromatosis was assessed by B-mode ultrasonography and arteriosclerosis (arterial stiffness) via tonometry (carotid-to-femoral pulse wave velocity). Multiple logistic regression analysis was performed to determine the relationship of quartiles of total sugars, monosaccharides and disaccharides with atheromatosis and arteriosclerosis, adjusting for potential confounders [Odds Ratio (95%Confidence Interval)]. In 901 participants (52.4 ± 13.8 years, 45.2% males), total sugars intake was not associated with any type of subclinical vascular damage. Subjects at 4th quartile of lactose intake (15.3 ± 5.5 g/day) had lower probability to present atheromatosis compared to those at 1st quartile (0.00 ± 0.01 g/day) even in the fully adjusted model [0.586 (0.353-0.974)]. Subjects at 3rd quartile of total disaccharides intake and particularly sucrose (15.1 ± 2.2 g/day) had higher probability to present arteriosclerosis compared to those at 1st quartile (3.0 ± 1.9 g/day) even after adjustment for all potential confounders [2.213 (1.110-4.409)]., Conclusions: Overall, the present data suggest a distinct role of each type of sugars on vascular damage. These observations highlight the need for further studies investigating not only foods rich in sugars, but sugars as separate components of food as they probably contribute via different ways on the development of arterial pathologies., Competing Interests: Declaration of competing interest None., (Copyright © 2021. Published by Elsevier B.V.)

Objective: Unhealthy diet is a modifiable risk factor leading to subclinical arterial damage (SAD), high BP and CVD. It was aimed to investigate the possible associations of dietary patterns (DPs) with SAD in adults having multiple CVD risk factors., Design: Dietary intake was evaluated through two 24-h dietary recalls and principal component analysis was used to identify DPs. Oscillometry, applanation tonometry with pulse wave analysis and carotid ultrasound were used to assess peripheral and aortic BP, arterial stiffness and pressure wave reflections., Setting: Laiko University Hospital, Athens, Greece., Participants: A total of 470 individuals (53·1 ± 14·2 years) with CVD risk factors were enrolled., Results: A pattern characterised by increased consumption of whole-grain cereals, white meat and reduced consumption of sugar was positively associated with common carotid compliance (β = 0·01, 95 % CI 0·00, 0·01), whereas a pattern high in refined cereals, red and processed meat was positively associated with brachial but not aortic systolic pressure (β = 1·76, 95 % CI 0·11, 3·42) and mean arterial pressure (MAP) (β = 1·18, 95 % CI 0·02, -2·38). Low consumption of low-fat dairy products, high consumption of full-fat cheese and butter was positively associated with MAP (β = 0·97, 95 % CI 0·01, 1·95). Increased consumption of vegetables, fruits, fresh juices, fish and seafood was inversely associated with augmentation index (AIx) (β = -1·01, 95 % CI -1·93, -0·09)., Conclusion: Consumption of whole grains, white meat, fruits/vegetables, fish/seafood and avoidance of sugar was associated with improved SAD. Preference in refined grains, red/processed meat, high-fat cheese/butter and low intake of low-fat dairy products were associated with BP elevation. Future studies are needed to confirm the present findings.

The last decade, a growing number of evidence support J-shape or inverse - instead of positive linear -- associations between dietary sodium intake and cardiovascular morbidity/mortality. A careful evaluation of these studies leads to the following observations: less accurate methods for dietary sodium assessment are usually used; most studies included high-risk participants, enhancing the possibility of a 'reverse causality' phenomenon. However, these limitations do not explain all the findings. Few carefully designed randomized clinical trials comparing different levels of sodium intake that address the issue of the optimal and safe range exist; therefore, current guidelines recommend a higher cut-off instead of a safe range of intake. Given the demonstrated harmful effects of very low sodium diets leading to subclinical vascular damage in animal studies, the 'J-shape hypothesis' cannot yet be either neglected or verified. There is a great need of well-designed general population-based prospective randomized clinical trials to address the issue., (Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved.)

Background: With the number of people living with human immunodeficiency virus (HIV) steadily increasing, cardiovascular disease has emerged as a leading cause of non-HIV related mortality. People living with HIV (PLWH) appear to be at increased risk of coronary artery disease and heart failure (HF), while the underlying mechanism appears to be multifactorial. In the general population, ectopic cardiac adiposity has been highlighted as an important modulator of accelerated coronary artery atherosclerosis, arrhythmogenesis and HF with preserved ejection fraction (HFpEF). Cardiac adiposity is also strongly linked with obesity, especially with visceral adipose tissue accumulation., Aims: This review aims to summarize the possible role of cardiac fat depositions, assessed by imaging modalities,as potential contributors to the increased cardiac morbidity and mortality seen in PLWH, as well as therapeutic targets in the current ART era., Materials & Methods: Review of contemporary literature on this topic., Discussion: Despite antiretroviral therapy (ART), PLWH have evidence of persistent, HIV-related systemic inflammation and body fat alterations. Cardiac adiposity can play an additional role in the pathogenesis of cardiovascular disease in the HIV setting. Imaging modalities such as echocardiography, cardiac multidetector computed tomography and cardiac magnetic resonance have demonstrated increased adipose tissue. Studies show that high cardiac fat depots play an additive role in promoting coronary artery atherosclerosis and HFpEF in PLWH. Systemic inflammation due to HIV infection, metabolic adverse effects of ART, adipose alterations in the ageing HIV population, inflammation and immune activation are likely important mechanisms for adipose dysfunction and disproportionately occurrence of ectopic fat depots in the heart among PLWH., Conclusions: High cardiac adiposity seems to plays an additive role in promoting coronary artery atherosclerosis and HFpEF in PLWH. The underlying mechanisms are multiple and warrant further investigation. Improved understanding of the regulating mechanisms that increase cardiovascular risk in HIV infection may give rise to more tailored therapeutic strategies targeting cardiac fat depots., (© 2021 British HIV Association.)

Background: Recent epidemiological evidence suggests a J-shaped, rather than the classical linear, association between dietary sodium (Na) intake and cardiovascular (CV) disease. Numerous animal studies have shown the acceleration of atheromatosis in a low-salt diet but data in humans are scarce. Our aim was to test the hypothesis that in a cohort of patients who are CV-free, yet at increased CV risk, moderate Na intake is associated with lower prevalence of atheromatosis and arterial stiffening than those at very low Na intake., Methods: Two 24-h dietary recalls were conducted to estimate Na intake. Atheromatosis (carotid and femoral plaques) was assessed by B-mode ultrasonography and arterial stiffness through tonometry (carotid-to-femoral pulse wave velocity, cf-PWV)., Results: In 901 individuals (age: 52.4 ± 13.8 years, 45.2% males), only females at 3rd and 4th quartile of total Na intake (derived from food and discretionary salt) had significantly lower probability to present femoral plaques than those at 1st quartile (751.0 ± 215.5 mg/day), even in the full-adjusted model [0.462(0.229-0.935) and p = 0.032 3rd quartile; 0.274(0.118-0.638) and p = 0.003 4th quartile]. On the contrary, male and female individuals at 3rd quartile had significantly higher probability to present arterial stiffness (PWV >10 m/s) than those at 1st quartile [1.991(1.047-3.785) and p = 0.036]., Conclusions: Overall, the present data suggest that very low Na intake is associated with: a) accelerated atheromatosis, verifying findings from animal models, and providing a possible explanation of the modern epidemiology and b) lower arterial stiffness, which is in line with previous human findings, therefore suggesting a diverging effect of Na in the two major arterial pathologies., Competing Interests: Declarations of interest None., (Copyright © 2021 Hellenic Society of Cardiology. Published by Elsevier B.V. All rights reserved.)

Objective: Epidemiological data suggest that moderate habitual coffee consumption associates with lower cardiovascular disease (CVD) risk; however scarce data exist regarding the association of coffee with subclinical vascular disease (SVD). We aimed at investigating the above association with habitual instant coffee consumption - a widely consumed coffee in Greece-in high CVD risk but free of established CVD adults., Research Methods & Procedures: In a cross-sectional design study we measured: (i) two 24 h dietary recalls to assess coffee consumption, (ii) arterial stiffness, by carotid to femoral pulse wave velocity - (PWV) and carotid compliance, arterial remodeling by carotid intima-media thickness (IMT), pressure wave reflection by augmentation index (AIx) and atheromatosis by carotid plaques., Results: In 1041 participants (55.6% females, 53.6 ± 14.0 years), 30% habitually consumed instant coffee (0.53 ± 1.15 cups/day). Consumption of instant coffee was inversely associated with systolic blood pressure (β = -1.19, p = 0.007), AIx (β = -0.71, p = 0.043), PWV (β = -0.22, p = 0.000) and IMT (β = -0.01, p = 0.025), but these associations lost their significance after multiple adjustments for confounders. Instant coffee consumption was positively associated with carotid compliance independent from all possible confounders (β = 0.005, p = 0.003)., Conclusion: Habitual moderate instant coffee consumption is inversely associated with arterial stiffening and potential with arterial remodeling. These favorable vascular associations offer a potential pathophysiological link between habitual coffee consumption and lower incidence of CVD. Future studies are needed to examine the long-term effects of habitual instant coffee consumption on vascular structure and function., (Copyright © 2021 European Society for Clinical Nutrition and Metabolism. Published by Elsevier Ltd. All rights reserved.)

Experimental studies suggest that sodium induced inflammation might be another missing link leading to atherosclerosis. To test the hypothesis that high daily sodium intake induces systemic inflammatory response in humans, we performed a systematic review according to PRISMA guidelines of randomized controlled trials (RCTs) that examined the effect of high versus low sodium dose (HSD vs. LSD), as defined per study, on plasma circulating inflammatory biomarkers. Eight RCTs that examined CRP, TNF-a and IL-6 were found. Meta-analysis testing the change of each biomarker in HSD versus LSD was possible for CRP ( n = 5 studies), TNF-a ( n = 4 studies) and IL-6 ( n = 4 studies). The pooled difference (95% confidence intervals) per biomarker was for: CRP values of 0.1(-0.3, 0.4) mg/L; TNF-a -0.7(-5.0, 3.6) pg/mL; IL-6 -1.1(-3.3 to 1.1) pg/mL. Importantly, there was inconsistency between RCTs regarding major population characteristics and the applied methodology, including a very wide range of LSD (460 to 6740 mg/day) and HSD (2800 to 7452 mg/day). Although our results suggest that the different levels of daily sodium intake are not associated with significant changes in the level of systemic inflammation in humans, this outcome may result from methodological issues. Based on these identified methodological issues we propose that future RCTs should focus on young healthy participants to avoid confounding effects of comorbidities, should have three instead of two arms (very low, "normal" and high) of daily sodium intake with more than 100 participants per arm, whereas an intervention duration of 14 days is adequate.