Assessment of New Coronary Features on Quantitative Coronary Angiographic Images With Innovative Unsupervised Artificial Adaptive Systems: A Proof-of-Concept Study.

Background and Purpose: The Active Connection Matrixes (ACMs) are unsupervised artificial adaptive systems able to extract from digital images features of interest (edges, tissue differentiation, etc.) unnoticeable with conventional systems. In this proof-of-concept study, we assessed the potentiality of ACMs to increase measurement precision of morphological structures (e.g., stenosis and lumen diameter) and to grasp morphological features (arterial walls) from quantitative coronary angiography (QCA), unnoticeable on the original images. Methods: Archive images of QCA and intravascular ultrasound (IVUS) of 10 patients (8 men, age 69.1 ± 9.7 years) who underwent both procedures for clinical reasons were retrospectively analyzed. Arterial features derived from "IVUS images," "conventional QCA images," and "ACM-reprocessed QCA images" were measured in 21 coronary segments. Portions of 1-mm length (263 for lumen and 526 for arterial walls) were head-to-head compared to assess quali-quantitative between-methods agreement. Results: When stenosis was calculated on "ACM-reprocessed QCA images," the bias vs. IVUS (gold standard) did not improve, but the correlation coefficient of the QCA-IVUS relationship increased from 0.47 to 0.83. When IVUS-derived lumen diameters were compared with diameters obtained on ACM-reprocessed QCA images, the bias (-0.25 mm) was significantly smaller (p < 0.01) than that observed with original QCA images (0.58 mm). ACMs were also able to extract arterial wall features from QCA. The bias between the measures of arterial walls obtained with IVUS and ACMs, although significant (p < 0.01), was small [0.09 mm, 95% CI (0.03, 0.14)] and the correlation was fairly good (r = 0.63; p < 0.0001). Conclusions: This study provides proof of concept that ACMs increase the measurement precision of coronary lumen diameter and allow extracting from QCA images hidden features that mirror well the arterial walls derived by IVUS.

[Barriers and facilitators for physical activity in sedentary people residing in a disadvantaged Italian neighbourhood]. / Barriere e facilitatori per l'attività fisica in soggetti sedentari residenti in un quartiere svantaggiato italiano.

OBJECTIVES: to explore which factors have a personal significance of barrier or facilitator for physical activity (PA) in sedentary subjects living in a peripheral, multiethnic, and economically disadvantaged Italian neighbourhood. DESIGN: qualitative, descriptive phenomenological study. SETTING AND PARTICIPANTS: the study was carried out in Ponte Lambro, a neighbourhood in the South-eastern outskirts of Milan (Lombardy Region, Northern Italy). Among the first 260 participants in a primary cardiovascular prevention programme (called ProSALUTE) targeted to this community, 63 subjects were categorized as sedentary. Out of these, 45 were selected through purposive sampling and 24 of them participated in this study. MAIN OUTCOME MEASURES: • qualitative content analysis of semi-structured interviews conducted through motivational interviewing; • analysis of values acquired by personal value cards. RESULTS: the factors emerged throughout the interviews were external (social support, environment, and tools) and individual (health status, self-confidence, reliance on the beneficial effects of PA, psychological issues). Barriers or facilitators were recognized in each of these factors according to the expressed significance. The most frequently chosen personal values (health, family, delight, strength and autonomy) were concordant with the contents of the interviews. CONCLUSION: distinctive barriers and facilitators to PA are identifiable among the significances expressed by residents in a disadvantaged neighbourhood. These barriers and facilitators may be the targets of socio-environmental or personal interventions aimed to promote an active life-style.

Association of lifelong occupation and educational level with subclinical atherosclerosis in different European regions. Results from the IMPROVE study.

BACKGROUND AND AIMS: We aimed to examine the association between socioeconomic status (SES) and subclinical atherosclerosis, as assessed by carotid intima-media-thickness (C-IMT) and to investigate whether the effect of social inequality on C-IMT is mediated by cardiovascular (CV) risk factors and whether it is dissimilar in men and women, and in different European countries. METHODS: We assessed the association of lifelong occupation and educational level with C-IMT in the IMPROVE study cohort including 3703 subjects (median age 64.4 years; 48% men) from Southern (Italy), Western (France and the Netherlands) and Northern Europe (Finland and Sweden). Three summary measures of C-IMT (IMTmean, IMTmax, IMTmean-max), obtained from four segments of both carotids, were considered. RESULTS: After adjusting for conventional CV risk factors, current employment status and diet, C-IMT was higher in manual workers than in white collars (+7.7%, +5.3%, +4.6% for IMTmax, IMTmean-max and IMTmean, respectively; all p<.0001). Similar results were obtained by stratification for educational level. The effect of occupation on C-IMT was comparable in men and women and in different age groups, and was only partially mediated by differences in CV risk factors. Of note, the association of C-IMT with occupation was significant in Western and Northern Europe but not in Italy, with a significant statistical interaction (p = .0005). CONCLUSIONS: Low SES was associated with subclinical atherosclerosis in subjects with at least three CV risk factors. Such association was stronger in Northern and Western Europe than in Italy. This difference was not completely explained by inequalities in CV risk factors and behavioural variables.

Carotid plaque-thickness and common carotid IMT show additive value in cardiovascular risk prediction and reclassification.

BACKGROUND AND AIMS: Carotid plaque size and the mean common carotid intima-media thickness measured in plaque-free areas (PF CC-IMTmean) have been identified as predictors of vascular events (VEs), but their complementarity in risk prediction and stratification is still unresolved. The aim of this study was to evaluate the independence of carotid plaque thickness and PF CC-IMTmean in cardiovascular risk prediction and risk stratification. METHODS: The IMPROVE-study is a European cohort (n = 3703), where the thickness of the largest plaque detected in the whole carotid tree was indexed as cIMTmax. PF CC-IMTmean was also assessed. Hazard Ratios (HR) comparing the top quartiles of cIMTmax and PF CC-IMTmeanversus their respective 1-3 quartiles were calculated using Cox regression. RESULTS: After a 36.2-month follow-up, there were 215 VEs (125 coronary, 73 cerebral and 17 peripheral). Both cIMTmax and PF CC-IMTmean were mutually independent predictors of combined-VEs, after adjustment for center, age, sex, risk factors and pharmacological treatment [HR (95% CI) = 1.98 (1.47, 2.67) and 1.68 (1.23, 2.29), respectively]. Both variables were independent predictors of cerebrovascular events (ischemic stroke, transient ischemic attack), while only cIMTmax was an independent predictor of coronary events (myocardial infarction, sudden cardiac death, angina pectoris, angioplasty, coronary bypass grafting). In reclassification analyses, PF CC-IMTmean significantly adds to a model including both Framingham Risk Factors and cIMTmax (Integrated Discrimination Improvement; IDI = 0.009; p = 0.0001) and vice-versa (IDI = 0.02; p < 0.0001). CONCLUSIONS: cIMTmax and PF CC-IMTmean are independent predictors of VEs, and as such, they should be used as additive rather than alternative variables in models for cardiovascular risk prediction and reclassification.

Patient-independent variables affecting the assessment of aspirin responsiveness by serum thromboxane measurement.

The serum TXB2 (sTXB2) assay reflects the pharmacodynamics of platelet inhibition by low-dose aspirin. However, different studies reported variable sTXB2 values. sTXB2 assay requires whole blood incubation at 37 °C as a condition for optimal thrombin generation, arachidonic acid release and its metabolism by platelet cyclooxygenase-1 to form TXA2. Access to 37 °C incubation may be variably delayed, and different methods to quantitate sTXB2 may contribute to variable results between different Centers. We investigated whether delaying 37 °C incubation and/or analytical issues affect sTXB2 concentrations, biasing the assessment of aspirin responsiveness. Sixty-eight samples from 54 volunteers, on- and off-aspirin, were incubated at 37 °C immediately after sampling (reference sample) or after 5, 10, 15, 20, 30 or 60 minutes at room temperature (RT); 8 samples remained at RT 60 minutes, without subsequent incubation; 314 sera were measured by enzyme immunoassay (EIA) and liquid chromatography-tandem mass-spectrometry (LC/MS-MS) methods. sTXB2 concentrations decreased exponentially as a function of the delay before 37 °C incubation, ranging from 94 ± 11 % at 5 minutes to 23 ± 22 % of the reference sample after 60 minutes at RT. There was high agreement between EIA and LC/MS-MS. Moreover, we simulated the influence of a 15- or 30-minute delayed incubation on 300 sTXB2 measurements from previously-studied, aspirin-treated patients. Delayed incubation reduced the percentage of aspirin 'non-responders' by 22 % to 52 %, depending on the response threshold. In conclusion, a variable delay in the 37 °C incubation of blood samples may affect the assessment of platelet cyclooxygenase-1 inhibition by aspirin and confound the characterization of the determinants of aspirin responsiveness.

Clinical assessment of endothelial function in patients with rheumatoid arthritis: A meta-analysis of literature studies.

BACKGROUND: Several studies reported an increased cardiovascular (CV) morbidity and mortality in patients with rheumatoid arthritis (RA). Flow-mediated (FMD) and nitrate-mediated dilation (NMD) are considered non-invasive methods to assess endothelial function and surrogate markers of subclinical atherosclerosis. METHODS: We performed a systematic review with meta-analysis and meta-regression of literature studies evaluating the impact of RA on FMD and NMD. Studies evaluating the relationship between RA and markers of CV risk (FMD and NMD) were systematically searched in the PubMed, Web of Science, Scopus and EMBASE databases. The random-effect method was used for analyses and results were expressed as mean difference (MD). RESULTS: A total of 20 studies (852 RA patients, 836 controls) were included in the final analysis. In detail, 20 studies with data on FMD (852 cases, 836 controls) and 5 studies with data on NMD (207 cases, 147 controls) were analyzed. Compared to controls, RA patients showed a significantly lower FMD (MD: -2.16%; 95% CI: -3.33, -0.98; P=0.0003), with no differences in NMD (MD: -0.41%; 95% CI: -2.89, 2.06; P=0.74). Interestingly, a lower FMD (MD: -2.00%; 95% CI: -3.20, -0.80; P=0.001) and no differences in NMD (P=0.49) were confirmed when excluding data on patients with early-RA. Meta-regression models showed that a more severe inflammatory status was associated with a more significant impairment in FMD. CONCLUSIONS: RA patients show impaired FMD, which is currently considered an independent predictor of CV events. The presence of endothelial dysfunction in RA should be taken into account to plan adequate prevention strategies and therapeutic approaches.

Non-invasive assessment of arterial stiffness in patients with rheumatoid arthritis: a systematic review and meta-analysis of literature studies.

INTRODUCTION: Patients with rheumatoid arthritis (RA) have an increased cardiovascular (CV) morbidity and mortality. Pulse-wave velocity (PWV) and augmentation index (AIx) are non-invasive methods to assess arterial stiffness, a marker of CV risk. We performed a meta-analysis evaluating the impact of RA on aortic-PWV, brachial-PWV, brachial-ankle (ba-) PWV, AIx, and AIx normalized to a 75 beats/minute heart rate (AIx@75). MATERIALS AND METHODS: Studies evaluating the relationship between RA and aortic-PWV, brachial-PWV, ba-PWV, AIx, and AIx@75 were systematically searched. A total of 25 studies (1,472 RA patients, 1,583 controls) were included. RESULTS: Compared to controls, RA patients showed a significantly higher aortic-PWV (mean difference 1.32 m/s; 95% CI 0.77, 1.88; P < 0.00001), ba-PWV (MD 198.42 cm/s; 95% CI 45.79, 342.76; P = 0.01), AIx (MD 11.50%; 95% CI 5.15, 17.86; P = 0.0004), and AIx@75 (MD 6.99%; 95% CI 4.92, 9.06; P < 0.00001), with a trend toward a higher brachial-PWV (MD 0.34 m/s; 95% CI -0.03, 0.70; P = 0.07). When analyzing studies on early RA, the difference in aortic-PWV among RA patients and controls was even higher (MD 2.30 m/s; 95% CI 1.15, 3.45; P < 0.0001). CONCLUSION: Meta-regression showed that a more severe inflammatory status impacted on aortic-PWV, AIx, and AIx@75. Arterial stiffness, a recognized marker of CV risk, is increased in RA patients. This alteration is associated with the severity of the inflammatory status and is present even in early-stage disease.

Assessment and relevance of carotid intima-media thickness (C-IMT) in primary and secondary cardiovascular prevention.

Interventions aimed to prevent cardiovascular diseases (CVD) are more effective if administered to subjects carefully selected according to their CVD risk. Usually, this risk is evaluated on the basis of the presence and severity of conventional vascular risk factors (VRFs); however, atherosclerosis, the main pathologic substrate of CVD, is not directly revealed by VRFs. The measurement of the arterial wall, using imaging techniques, has increased the early identification of individuals prone to develop atherosclerosis and to quantify its changes over time. B-mode ultrasound is a technique which allows a non-invasive assessment of the arterial wall of peripheral arteries (e.g. extracranial carotid arteries), and provides measures of the intima-media thickness complex (C-IMT) and additional data on the occurrence, localization and morphology of plaques. Being an independent predictor of vascular events, C-IMT has been considered as a tool to optimize the estimation of CVD risk but this application is still a matter of debate. Though the technique is innocuous, relatively inexpensive and repeatable, its use in the clinical practice is limited by the lack of standardized protocols and clear guidelines. This review outlines the rationale for the potential use of C-IMT in the stratification of cardio- and cerebro-vascular risk and discusses several topics related to the measurement of this variable, which are still controversial among experts of the field.

Assessment of oxidative stress in coronary artery bypass surgery: comparison between the global index OXY-SCORE and individual biomarkers.

The performances of the OXY-SCORE, a summary index of oxidative stress, and of its individual components (plasma malondialdehyde (MDA), oxidized and reduced glutathione, individual antioxidant capacity, alpha- and gamma-tocopherol and urinary isoprostanes) were assessed in 47 patients undergoing coronary surgery, randomly assigned to cardiopulmonary bypass (CPB) or off-pump procedure (OPCAB) associated with less oxidative stress. The ability of the OXY-SCORE to classify correctly the patients was high (area under the ROC curve 0.90). Only free MDA showed a similar performance, but it was insensitive to the minor variations of the oxidative balance in the OPCAB group.

Nonrheumatic calcific aortic stenosis: an overview from basic science to pharmacological prevention.

Calcific aortic stenosis is a frequent degenerative disease, which represents the most common indication for adult heart valve surgery, and carries substantial morbidity and mortality. Due to ageing populations in western countries, its prevalence is expected to increase in the coming years. Basic science studies suggest that the progression of aortic valve stenosis involves an active biological process, and that the molecular mechanisms promoting this development resemble those of atherosclerosis, as stenotic aortic valves are characterized by complex histological lesions, consisting of activated inflammatory cells, lipid deposits, extracellular matrix remodeling, calcific nodules, and bone tissue. This has led to the hypothesis that drugs effective in delaying atherosclerosis progression (e.g. statins) might also be able to prevent the progression of calcific aortic valve stenosis. The potential benefit of statin therapy, however, is controversial and widely debated, as recent randomized studies done in patients with moderate to severe degrees of aortic stenosis failed to consistently show substantial benefits of this class of drugs. This review focuses on various aspects of molecular mechanisms underlying calcific aortic valve stenosis and discusses recent experimental and clinical studies that address the potential benefit of targeted drug therapies. Taken together, current evidence suggests that the progression of calcific aortic stenosis is a multi-factorial process; the multitude of the mechanisms potentially involved in aortic valve stenosis indicates that drug therapy aimed at reducing its progression is necessarily multi-factorial and should address the earliest stages of the disease, as it is now evident that pharmacological treatment administered in more advanced stages of the disease may be ineffective or, at best, much less effective.