Classical Risk Research Articles

FCA-based reasoning for privacy

Abstract Notwithstanding the potential danger to security and privacy, sharing and publishing data has become usual in Data Science. To preserve privacy, de-identification methodologies guided by risk estimation have been designed. Two issues associated with classical risk metrics are, on the one hand, the adequacy of the metric and, on the other hand, its static nature. In this paper, we present metrics for estimating risk based on the emerging semantics provided by Formal Concept Analysis. The metrics are designed to estimate the a priori risk of compromised data deletion. Furthermore, by applying specialized variable forgetting methods for association rules, it is shown how to reflect the effect of deleting attributes belonging to potentially dangerous quasi-identifier sets. Additionally, a study of the role of the risk metric in confidence-based reasoning for re-identification is presented.

Cholesterol crystal dissolution rate of serum is associated with iliofemoral calcification and predicts outcomes in patients undergoing TAVR

Abstract Background Calcific Aortic stenosis (AS) has several findings in common with atherosclerosis including inflammation and lipoprotein deposition. Histopathological examination has revealed atherosclerotic lesions, that mainly contain cholesterol crystals (CC) in resected AS cusps. Previous studies have demonstrated that CCs can activate the NLRP3 inflammasome, resulting in an IL-1 driven systemic inflammation, that leads to the development of atherosclerotic plaques. Aims Our aim was to quantify the endogenous cholesterol crystal dissolution rate (CCDR) in AS patients undergoing TAVR. We sought to examine whether CCDR may be associated with iliofemoral calcification and suitable for identifying patients at high risk for vascular complications and increased mortality. Methods The study included 348 AS patients undergoing TAVR. Pre-interventional computed tomography (CT) scans were analyzed to quantify iliofemoral calcification from the femoral artery bifurcation to the aortic bifurcation. The CCDR was measured using flow cytometry to enumerate CC, that were added to a serum solution, at baseline and after two hours of incubation. The dissolution capacity was indicated as percentage change in CC count at baseline and after incubation. The study cohort was stratified according to the median CCDC into high and low CC dissolvers. Results The study population had a mean age of 80.9±6.2 years. CT-based calcium assessment revealed significantly higher right as well as left iliofemoral calcification in low CC dissolvers as compared to high CC dissolvers (1280 vs 1083 mm3, p=0.03; 1292 vs 1043 mm3, p=0.04, respectively). Consistently, an unplanned endovascular intervention for access-related vascular injury was needed more frequently in patients with a low CCDR, as compared to patients with a high CCDR (20.5% vs 12.2%, p=0.04), Figure 1. However, the rate of major vascular complications tended to be higher in the low CCDR group (3.4%) as compared to the high CCDR group (0.6%) but was not significantly different (p=0.12). The one-year all-cause mortality was significantly higher in patients with a low CCDR (13.6%) as compared to patients with a high CCDR (7.0%, p=0.05). This difference was mainly driven by significantly increased cardiovascular death in low CC dissolvers (9.1% vs 1.7%, p=0.03), whereas non-cardiovascular mortality rates were similar between both groups (5.1% vs 5.2%, p=0.81). In multivariate analysis, only low CCDR (OR: 2.51 [95% CI: 1.02 – 6.15], p=0.05) and Albumin (OR: 0.88 [95% CI: 0.79 – 0.98], p=0.03) were independently associated with one-year mortality following TAVR. Conclusion The CCDR is a novel biomarker associated with outcomes in AS patients undergoing TAVR. We have demonstrated, that a low CCDR is associated with increased iliofemoral calcification and vascular injury as well as one-year mortality. Thus, CCDR may provide additional prognostic information to identify vulnerable patients beyond classic risk assessment.Figure 1

S-43-5: A PROSPECTIVE OBSERVATION FOR ORTHOSTATIC DYSREGULATION AND INTOLERANCE IN ADOLESCENCE: STUDY PROTOCOL OF THE SUITA OFFSPRING STUDY

Background: In recent years, the number of adolescents who do not attend school due to orthostatic dysregulation (OD) has increased rapidly in Japan, and countermeasures are urgently needed. In contrast, orthostatic intolerance (OI) is used as its counterpart in Western countries, and no internationally unified disease concept exists. Therefore, it is necessary to compare a population-based prospective study of OD and OI in adolescent urban communities. Objective: This study aims to show the clinical characteristics and prognosis of OD and OI in adolescent urban communities. Methods: We will launch the offspring cohort in 2022 in two school districts of Suita City, where we encourage medical examinations for all 11-, 14-, and 17-year-old adolescents. Approximately 200 adolescents of each age group will be undergoing medical examinations as research participants. We will perform a medical check-up to detect the constituents of metabolic syndrome, OD, and OI. We will implement questionnaires for the participants based on the Japanese OD Diagnostic and Treatment Guideline (OD symptoms) and diagnostic criteria in Western countries (OI symptoms). If any of the OD or OI symptoms (at least 3 points, 1 point or more) are positive, they will continue with a 10-minute standing test and their parents will fulfill the checklist for diagnosis of OD with psychosomatic disorder based on the aforementioned OD Guideline. Participants who are positive in the standing test will undergo echocardiography, Holter electrocardiography, and Parent-child home blood pressure measurements. We will refer to the Maternal and Child Health Handbook, Infant Health Examination, School Health Examination, and Lifestyle Related Disease Prevention Health Examination to explore OD and OI risk factors (for example, rapid change in growth curve and circadian rhythm formation). We will compare the prevalence of OD and OI by category using the respective diagnostic criteria in Japan and Western countries and reveal the relationship with classical risk, the diurnal variation in HBP of participants and their parents, cardiac function, and autonomic function. We will conduct follow-up studies every 3-year until 20 years old to examine morbidity and prognosis. In addition, we will perform a selected lifestyle questionnaire focusing on diet and physical activity for adolescents and then use metabolomic analysis to compare plasma metabolite profiles of with and without OD and OI participants to detect modifiable risk factors targeted in future interventions.

MO781: Patients with Scarce Options for the First Arteriovenous Access: Lessons to be Learned from Vascular Mapping

Abstract BACKGROUND AND AIMS The use of doppler ultrasound (DUS) is a non-invasive powerful tool, allowing the morphological and functional characterization of the blood vessels. Once an optimal location for vascular access (VA) creation is obtained, the risk of failure is reduced. Even the use of DUS has improved the VA creation, a significant proportion of patients remains with suboptimal VA, as the laborious umerobasilic fistulae or higher risk prosthetic fistula. Our aim was to identify patients with scarce VA options in the first VA planning, characterizing their demographical and clinical aspects, but also the ultrasound features that are described as having prognosis importance, mostly vessel diameter and calcification findings. METHOD We retrospectively analysed a cohort of consecutive chronic kidney disease (CKD) patients that underwent DUS vascular mapping at a tertiary referral hospital from 2018 to 2019. All the DUS were performed by the same operator. Patient characteristics were collected. The DUS data observed were: arterial diameter and peak systolic velocity (VPS) in both arms, presence of mono- or biphasic waveform flow and calcification (quantified according to number of the involved arteries). We defined two groups for VA comparison—patients with scarce VA options (only umerobasilic fistula or prosthetic VA) versus patients whose mapping suggested availability for a radiocephalic or umerocephalic fistulae. Appropriate tests for continuous and categorical variables were applied, recurring to SPSS v21.0. Unadjusted and adjusted multivariate logistic regression models were fitted to determine which clinical or DUS findings were predictors for scarce VA options. RESULTS A total of 153 patients were mapped by DUS, and 102 patients fulfilled the first VA creation criteria. The median age was 71 (58–79) years, 55 (54%) were male, 14 (14%) were black, 27 (28%) were already on dialysis or kidney transplantation. A total of 34 patients (33%) were identified as having scarce AV options, according to DUS. In patients with scarce VA options, there was a significant statistical difference between black race patients (0.042) and use of tobacco (0.041), within all the co-morbidities observed. Concerning arterial measurements, there was no difference in the arterial diameters. However, the radial PSV was lower in the group with fewer VA options (Table). There were more arteries with calcification in these group. In the multivariate analysis, the arterial calcification was found to be a predictor for scarce VA options [odds ratio (OR) 1.26, 95% confidence interval (95% CI) 1.01–1.58], adjusted for the radial VPS measurements and black race. CONCLUSION Starting haemodialysis with a matured and functional VA represents a successful outcome for CKD patients. Black race and arterial calcification score of the arteries were associated to suboptimal VA, which could identify these patients as having high-risk for morbidity and mortality related to VA. In our observation, the results were similar in both groups, whereas the main difference was on the radial PSV, which was consistently lower in the patients with fewer VA options. This finding showed that poorer radial haemodynamics precluded radiocephalic fistulae in these patients; otherwise, they are at higher risk for distal hypoperfusion ischaemic syndrome, which aggravates VA prognosis. The use of DUS is increasing in clinical practice due to its importance for the characterization of venous and arterial anatomy. This study, showed that high-risk patients for VA care can be identified before VA creation through a powerful tool as DUS, overcoming classical sociodemographic and clinical risk factors.

Analysis of factors associated with arterial stiffness in the general working-age population

Aim. To examine associations of cardio-ankle vascular index (CAVI) with classical, behavioral and social risk factors (RFs) of cardiovascular disease (CVD) in adult population.Material and methods. The study included 1365 people (women, 59%) from a representative sample aged 25-64 years (ESSE-RF), who underwent standard cardiology screening and volume sphygmography (VaSera-1500). All respondents signed an informed consent to participate in the study. The analysis included blocks of classical, social and behavioral risk factors for CVD. A linear model was used to identify associations. An error rate of <5% was considered significant.Results. Age, sex, systolic blood pressure (SBP), triglycerides were associated with higher CAVI values, and body mass index (BMI) was associated with lower values, respectively. After 45 years, a direct association with heart rate (HR) became increasingly important, while after 50 years — with diabetes and the intake of beta-blockers, while the association between diabetes and CAVI was observed only among individuals not taking angiotensin-converting enzyme (ACE) inhibitors. A direct association was found with high-sensitivity C-reactive protein (hsCRP) in men, and an inverse association with diuretics in women, respectively. A sedentary work in combination with a history of bronchitis or with positive family history for CVD showed a direct relationship, while a sufficient physical activity (PA) showed an inverse relationship with the studied indicator, but only among people with belowaverage income.Conclusion. According to the data obtained, in addition to age and sex, the following risk factors made a significant contribution to CAVI parameters in the examined population: BMI, SBP, triglycerides, diabetes, HR, intake of betablockers, diuretics, ACE inhibitors; hsCRP, PA. The unfavorable role of betablockers, high HR, diabetes, sedentary work, chronic lung pathology, hereditary burden, as well as the protective role of ACE inhibitors, diuretics and intense PA in relation to arterial stiffness in the working-age population has been shown. Additional studies are needed to determine the nature of a number of associations. The results obtained may contribute to the study of CAVI role in risk stratification and further development of methodological approaches to CVD prevention.

Development and validation of polygenic risk scores for prediction of breast cancer and breast cancer subtypes in Chinese women

BackgroundStudies investigating breast cancer polygenic risk score (PRS) in Chinese women are scarce. The objectives of this study were to develop and validate PRSs that could be used to stratify risk for overall and subtype-specific breast cancer in Chinese women, and to evaluate the performance of a newly proposed Artificial Neural Network (ANN) based approach for PRS construction.MethodsThe PRSs were constructed using the dataset from a genome-wide association study (GWAS) and validated in an independent case-control study. Three approaches, including repeated logistic regression (RLR), logistic ridge regression (LRR) and ANN based approach, were used to build the PRSs for overall and subtype-specific breast cancer based on 24 selected single nucleotide polymorphisms (SNPs). Predictive performance and calibration of the PRSs were evaluated unadjusted and adjusted for Gail-2 model 5-year risk or classical breast cancer risk factors.ResultsThe primary PRSANN and PRSLRR both showed modest predictive ability for overall breast cancer (odds ratio per interquartile range increase of the PRS in controls [IQ-OR] 1.76 vs 1.58; area under the receiver operator characteristic curve [AUC] 0.601 vs 0.598) and remained to be predictive after adjustment. Although estrogen receptor negative (ER−) breast cancer was poorly predicted by the primary PRSs, the ER− PRSs trained solely on ER− breast cancer cases saw a substantial improvement in predictions of ER− breast cancer.ConclusionsThe 24 SNPs based PRSs can provide additional risk information to help breast cancer risk stratification in the general population of China. The newly proposed ANN approach for PRS construction has potential to replace the traditional approaches, but more studies are needed to validate and investigate its performance.

Latest Advances in Transcatheter Aortic Valve Implantation (2022)

Since the last decade, transcatheter aortic valve implantation (TAVI) has become the treatment of choice in patients with symptomatic severe aortic stenosis (AS) who are ineligible or at higher risk for surgery. Due to the high safety profile of current device generation, TAVI has emerged as a qualified alternative to surgical aortic valve replacement (SAVR) in patients with classic aortic stenosis and intermediate surgical risk, severe bicuspid aortic valve stenosis, and isolated pure aortic regurgitation. Moderate aortic stenosis, with and without concomitant heart failure with reduced ejection fraction, are under investigation in randomized controlled clinical trials from which we will gain exciting insights on the best timing of TAVI to protect the left ventricle from further functional deterioration due to increasing AS. In these cases, a meticulous diagnostic approach including advanced imaging is becoming more and more important. Current evidence on antithrombotic strategies after TAVI is weak, contributing to poor levels of standardization and high variability in daily clinical practice. This review will provide a short overview of recent clinical trials including best timing for TAVI with moderate AS and antithrombotic strategies after TAVI with current and future TAVI generations.

Why Do These Microbes Like Me and How Could There Be a Link with Cardiovascular Risk Factors?

Cardiovascular diseases are the most common causes of hospitalization, death, and disability in Europe. Due to high prevalence and ensuing clinical complications, they lead to very high social and economic costs. Despite the knowledge of classical cardiovascular risk factors, there is an urgent need for discovering new factors that may play a role in the development of cardiovascular diseases or potentially influence prognosis. Recently, particular attention has been drawn to the endogenous microflora of the human body, mostly those inhabiting the digestive system. It has been shown that bacteria, along with their host cells, create an interactive ecosystem of interdependencies and relationships. This interplay could influence both the metabolic homeostasis and the immune processes of the host, hence leading to cardiovascular disease development. In this review, we attempt to describe, in the context of cardiovascular risk factors, why particular microbes occur in individuals and how they might influence the host’s cardiovascular system in health and disease.

Lipoedema: detailed left atrial volumetric and strain analysis by three-dimensional speckle-tracking echocardiography from the MAGYAR-Path Study.

IntroductionLipoedema is a chronic feminine disease with disproportional painful fat deposition of the lower body half and occassional arm affection.AimThe objective of the present study was to assess LA volumetric and functional properties by three-dimensional speckle-tracking echocardiography (3DSTE) in patients with lipoedema and to compare their results to age- and gender-matched healthy controls. It was also aimed to examine whether one-hour use of medical compression stockings (MCS) has any effect on LA volumes and functional properties.Material and methodsThe study comprised 25 female patients with stage 2 lipoedema (mean age: 42.5 ±12.2 years). Their results were compared to those of the control group consisting of 54 age- and gender-matched healthy female subjects (mean age: 42.7 ±10.6 years) without classic risk factors.ResultsIncreased LA volumes could be measured in lipoedema patients as compared to controls regardless of the phase of the cardiac cycle it was measured in, and the LA volumes showed further increase after 1-hour use of MCS. Similarly, LA total and active stroke volumes and LA passive emptying fraction were increased in lipoedema patients, and these parameters were further increased in systole and early-diastole. Peak global radial and 3D strains were increased in lipoedema patients. Peak global longitudinal strain increased in lipoedema patients after one-hour use of MCS compared to data measured at rest.ConclusionsLipoedema is associated with increased LA volumes and changes in LA functional properties. The use of MCS further increases some of the LA volumetric parameters.

A Vicious Circle of Clonal Haematopoiesis of Indeterminate Potential and Cardiovascular Disease.

Clonal haematopoiesis of indeterminate potential (CHIP) represents a recently identified overlap between cancer and cardiovascular disease (CVD). CHIP develops as a result of certain acquired somatic mutations that predispose to leukaemia, but clinically even more prevalent, associate with increased risk for CVD and CVD-related death. Experimental studies suggest a causal role for CHIP aggravating inflammatory processes in CVD, and recent epidemiologic and genetic studies indicate that classical CVD risk factors may increase the risk of acquiring CHIP driver mutations, thus fuelling a vicious circle. The potential mechanism underlying the associative link between CHIP and CVD and mortality has been the focus of a few recent excellent experimental and observational studies which are summarized and discussed in this concise non-systematic review article. These data support a pathomechanistic view of a spiralling vicious circle in which CHIP aggravates the inflammatory immune response in CVD, and CVD-driven elevated haematopoietic activity promotes CHIP development.

Obesity and Clinical Activity in Psoriatic Arthritis Patients Treated with Synthetic Disease-Modifying Antirheumatic Drugs

Introduction: Comorbidities are prevalent in psoriatic arthritis (PsA) and which may affect disease activity and response to therapy. Aims: To evaluate comorbidities among patients with PsA naïve to biologics, and their association with basal inflammatory activity status, before starting them. Methods: We performed a retrospective cross-sectional a study of cohort of patients with PsA (CASPAR criteria), treated with synthetic disease-modifying antirheumatic drugs. Patients were managed according to EULAR/GRAPPA recommendations, and the collected variables included demographics, clinical, serological, classical CV risk factors, and treatment. Disease activity was assessed using the Disease Activity Score for Psoriatic Arthritis and clinical DAPSA scores. The tests were two-tailed, with a significance level of <0.05. Results: A total of 416 patients were included in the study: 222 maintained remission or low disease activity being treated without biologics, and 194 who needed to be treated with bDMARD because they did not response well to csDMARD. From patients who were waiting to start biologics, 38.1% had obesity and had increased risk of MetS for age > 50 years old (OR 3.287 [95%CI: 1.258-8.591], p 0.015) and CRP > 0.5 mgr/dL (OR 2.684 [95%CI: 1.141-6.313], p 0.024) but not for cDAPSA>13 (OR 1.539 [95%CI: 0.695-3.409], p 0.288). DAPSA score was higher in patients with obesity, 20.3 (14.4) vs 13.8 (8.5), p0.010 and these patients had an OR for cDAPSA>13 of 3.15 [95%CI: 1.07-9.25], p 0.037). Patients with obesity had a higher frequency of DAPSA and cDAPSA MoDA-HDA (p = 0.022; p = 0.032). In the linear logistic regression analysis, a high-moderate DAPSA score was associated with obesity (p = 0.017), CRP (p <0.0001), and cDAPSA score with obesity (0.029) but not with CRP (p = 0.748). Obesity and corticosteroid treatment were independent factors for cDAPSA>13 and the presence of enthesitis for cDAPSA≤13. Conclusion: PsA patients who did not respond well to csDMARD had a higher prevalence of MetS, associated with age > 50 years and CRP higher than normal values. The DAPSA score was higher in patients with obesity and corticosteroid treatment. Enthesitis was more frequent in patients with low disease activity by DAPSA score.

Abstract 10369: Artificial Intelligence-Assisted Prediction of Blood Cells Regenerative Capacity in Patients with Diabetes Mellitus

Introduction: Peripheral blood mononuclear cell (PBMC) regenerative capacity is impaired in pre/diabetes mellitus patients (DMPs). In vitro evaluation of PBMCs pre/post vasculogenic conditioning (VC) and integrative assessment of classical clinical risk factors using complex machine learning-based (ML) methods may help to distinguish patients' immune cell regenerative potential. Methods: Eighteen DMPs diagnosed with myocardial infarction and sixteen controls were enrolled. Isolated PBMC regenerative capability was evaluated pre/post-VC using endothelial progenitor cell colony formation assay/unit (EPC-CFA/U) and flow cytometry analysis. The following classification ML algorithms were used for data analysis: support vector machine (SVM), logistic regression (LR), random forest (RF), decision tree (DT), and adaptive boosting (AB). Results: An in vitro EPC-CFA assay revealed that DMPs showed decreased fresh PBMC-derived definitive EPCs (DEPCs) compared with controls. Decreased colony formation was observed in patients with a reduced number of circulating EPCs and they did not appropriately respond to VC according to ML findings. Furthermore, proinflammatory M1 macrophages significantly increased (P = 0.03) in the majority of DMPs (non-responders) compared to that in controls, whereas VC shifted the phenotype toward M2 along with CD4 + T and Treg cell expansion. Clinical, pre/post culture cell phenotype, and EPC-CFU data integration and comprehensive ML analyses distinguished “non-responder”-associated distinct biomarkers, clinical parameters, such as elevated proinflammatory cells and systemic inflammation, and elderly patients from those of responders. Notably, SVM prediction accuracy was 100%; both LR and RF were 86%; and those of AB and DT were 71% and 43%, respectively. Conclusions: Applying comprehensive ML methods, as well as integrative analysis of the findings of in vitro assays, such as EPC-CFA; such as EPCs, M1/M2 macrophages, and T cells pre/post-VC; and clinical-laboratory parameters, enabling us to precisely evaluate regeneration capacity of impaired PBMNC functions. Moreover, this cell culture methodology can be used before cell therapy to define optimal dose and cell ratio for transplantation.

Association of glycated hemoglobin A1c levels with cardiovascular outcomes in the general population: results from the BiomarCaRE (Biomarker for Cardiovascular Risk Assessment in Europe) consortium

BackgroundBiomarkers may contribute to improved cardiovascular risk estimation. Glycated hemoglobin A1c (HbA1c) is used to monitor the quality of diabetes treatment. Its strength of association with cardiovascular outcomes in the general population remains uncertain. This study aims to assess the association of HbA1c with cardiovascular outcomes in the general population.MethodsData from six prospective population-based cohort studies across Europe comprising 36,180 participants were analyzed. HbA1c was evaluated in conjunction with classical cardiovascular risk factors (CVRFs) for association with cardiovascular mortality, cardiovascular disease (CVD) incidence, and overall mortality in subjects without diabetes (N = 32,496) and with diabetes (N = 3684).ResultsKaplan–Meier curves showed higher event rates with increasing HbA1c levels (log-rank-test: p < 0.001). Cox regression analysis revealed significant associations between HbA1c (in mmol/mol) in the total study population and the examined outcomes. Thus, a hazard ratio (HR) of 1.16 (95% confidence interval (CI) 1.02–1.31, p = 0.02) for cardiovascular mortality, 1.13 (95% CI 1.03–1.24, p = 0.01) for CVD incidence, and 1.09 (95% CI 1.02–1.17, p = 0.01) for overall mortality was observed per 10 mmol/mol increase in HbA1c. The association with CVD incidence and overall mortality was also observed in study participants without diabetes with increased HbA1c levels (HR 1.12; 95% CI 1.01–1.25, p = 0.04) and HR 1.10; 95% CI 1.01–1.20, p = 0.02) respectively. HbA1c cut-off values of 39.9 mmol/mol (5.8%), 36.6 mmol/mol (5.5%), and 38.8 mmol/mol (5.7%) for cardiovascular mortality, CVD incidence, and overall mortality, showed also an increased risk.ConclusionsHbA1c is independently associated with cardiovascular mortality, overall mortality and cardiovascular disease in the general European population. A mostly monotonically increasing relationship was observed between HbA1c levels and outcomes. Elevated HbA1c levels were associated with cardiovascular disease incidence and overall mortality in participants without diabetes underlining the importance of HbA1c levels in the overall population.

The prognostic role of RBP-4 and adiponectin in patients with peripheral arterial disease undergoing lower limb endovascular revascularization

BackgroundRBP4 is an adipokine with an established role in atherosclerosis, while adiponectin has unique anti-inflammatory properties. We investigated the association of RBP4 and adiponectin with the presence of symptomatic peripheral artery disease (PAD) and their possible prognostic role in major adverse cardiovascular events (MACE).MethodsWe enrolled 168 consecutive patients with symptomatic, established PAD, requiring revascularization by endovascular means of any or both of their lower limbs. 88 age- and sex-matched subjects with less than 2 classical cardiovascular risk factors served as controls. Clinical parameters, glycemic and lipid profile, RBP4 and adiponectin levels were assayed. The occurrence of MACE was recorded during the 6-month follow-up and patients were assigned to MACE and non-MACE subgroups.ResultsThe presence of symptomatic PAD was significantly correlated with age, diabetes, hsCRP, RBP4 and low adiponectin levels (p < 0.05). After adjustment for age, RBP4 (β = 0.498, p < 0.001), and adiponectin (β = –0.288, p < 0.001) levels remained as independent predictors of PAD presence in the whole study cohort. At baseline, MACE subgroup appeared with higher RBP-4 and hsCRP serum levels than non-MACE subgroup (p < 0.001), but no differences were detected for adiponectin (p = 0.758). Serum RBP4 levels remained independent predictor of MACE (β = 0.455, p < 0.001) after adjustment for traditional cardiovascular risk factors.ConclusionsHigh RBP4 and low adiponectin serum levels are independently associated with PAD presence. In addition, RBP4 is an independent predictor of MACE incidence in symptomatic PAD patients.

Risk factors for childhood illness and death in rural Uttar Pradesh, India: perspectives from the community, community health workers and facility staff

BackgroundUttar Pradesh (UP), India continues to have a high burden of mortality among young children despite recent improvement. Therefore, it is vital to understand the risk factors associated with under-five (U5) deaths and episodes of severe illness in order to deliver programs targeted at decreasing mortality among U5 children in UP. However, in rural UP, almost every child has one or more commonly described risk factors, such as low socioeconomic status or undernutrition. Determining how risk factors for childhood illness and death are understood by community members, community health workers and facility staff in rural UP is important so that programs can identify the most vulnerable children.MethodsThis qualitative study was completed in three districts of UP that were part of a larger child health program. Twelve semi-structured interviews and 21 focus group discussions with 182 participants were conducted with community members (mothers and heads of households with U5 children), community health workers (CHWs; Accredited Social Health Activists and Auxiliary Nurse Midwives) and facility staff (medical officers and staff nurses). All interactions were recorded, transcribed and translated into English, coded and clustered by theme for analysis. The data presented are thematic areas that emerged around perceived risk factors for childhood illness and death.ResultsThere were key differences among the three groups regarding the explanatory perspectives for identified risk factors. Some perspectives were completely divergent, such as why the location of the housing was a risk factor, whereas others were convergent, including the impact of seasonality and certain occupational factors. The classic explanatory risk factors for childhood illness and death identified in household surveys were often perceived as key risk factors by facility staff but not community members. However, overlapping views were frequently expressed by two of the groups with the CHWs bridging the perspectives of the community members and facility staff.ConclusionThe bridging views of the CHWs can be leveraged to identify and focus their activities on the most vulnerable children in the communities they serve, link them to facilities when they become ill and drive innovations in program delivery throughout the community-facility continuum.

How genetics and epigenetics can improve cardiovascular risk prediction: examples from the Moli-sani and Moli-family studies

Abstract One of the goals of personalized medicine (PM) is to use the ever-growing understanding of biology to provide a higher level of precision in disease prevention and patient care. The simultaneous study of the risk markers and epigenetic factors may have the desired discriminatory accuracy to distinguish between high-risk and low-risk subjects. The presentation will illustrate how genetics and epigenetics can improve cardiovascular risk (CVD) prediction in Italian adults from the general population. A subcohort of 1160 subjects (55.3±11.7 years; men 47.7%) was randomly selected from the Moli-sani cohort study (N = 24,325, yrs:2005-2010) and compared in a nested case-cohort design with incident CVD events (N = 592 validated myocardial infarctions or strokes), identified in a median follow-up of 9.2 years. DNA samples were used to genotype 14 tag SNPs in the genes NMU (encoding for Neuromedin U, a hypothalamic peptide), NMUR1 and NMUR2 (receptors) and NMS (Neuromedin S) and to quantify methylation levels at 17 CpG sites of two NMU regions through pyrosequencing. ELISA tests on circulating NMU levels are on-going. The associations between variants and incident CVD events using classical CVD risk factors as covariates and prediction metrics using standard risk alogrithms as reference were calculated. Four SNPs in NMU and NMUR1 genes and 6 NMU CpG sites showed a statistically significant association with events (p from 0.037 to &amp;lt; 0.0001), independently from classical CVD risk factors. Combined epigenetic and genetic variants in genes from the NMU pathway are associated with increased CVD risk and could have a potential clinical utility when added to current CVD risk algorithms for CVD prediction.

Effects of uremic toxins on hippocampal synaptic transmission: implication for neurodegeneration in chronic kidney disease

Patients affected by chronic kidney disease (CKD) have an increased risk of developing cognitive impairment. The cause of mental health disorders in CKD and in chronic hemodialysis patients is multifactorial, due to the interaction of classical cardiovascular disease risk factors, kidney- and dialysis-related risk factors with depression, and multiple drugs overuse. A large number of compounds, defined as uremic toxins that normally are excreted by healthy kidneys, accumulate in the circulations, in the tissues, and in the organs of CKD patients. Among the candidate uremic toxins are several guanidino compounds, such as Guanidine. Uremic toxins may also accumulate in the brain and may have detrimental effects on cerebral resident cells (neurons, astrocytes, microglia) and microcirculation. The present study aims to analyze the effect of Guanidine on hippocampal excitatory postsynaptic field potentials (fEPSPs) and in CA1 pyramidal neurons recorded intracellularly. Moreover, we compared these effects with the alterations induced in vitro by CKD patients derived serum samples. Our results show an increased, dose-dependent, synaptic activity in the CA1 area in response to both synthetic Guanidine and patient’s serum, through a mechanism involving glutamatergic transmission. In particular, the concomitant increase of both NMDA and AMPA component of the excitatory postsynaptic currents (EPSCs) suggests a presynaptic mechanism. Interestingly, in presence of the lower dose of guanidine, we measure a significant reduction of EPSCs, in fact the compound does not inhibit GABA receptors allowing their inhibitory effect of glutamate release. These findings suggest that cognitive symptoms induced by the increase of uremic compounds in the serum of CKD patients are caused, at least in part, by an increased glutamatergic transmission in the hippocampus.

Immunological monitoring in cardiac allograft vasculopathy

Abstract Background The interaction of immunological determinants and classic cardiovascular risk factors can accelerate the development of cardiac allograft vasculopathy (CAV) with deleterious consequences for the graft function in heart transplantation (HTx). When it comes to immunological risk assessment, inverse CD4/CD8 ratio can be a poor prognostic marker in coronary artery disease, but its influence is unclear in CAV. Aim To evaluate the role of the T-lymphocyte count in peripheral blood as well as CD4/CD8 ratio as a predictive marker for CAV severity in a very long-term follow-up after HTx. Methods We performed a retrospective analysis of patient data collected during routine clinical follow-up visits. These data included innate and adaptive immune cell count in peripheral blood (lymphocyte count, CD3+, CD4+, CD8+ and CD19+ T cells and NK cells). Results The study population consisted of 174 patients with a mean follow-up of 13.1±6.5 years and a mean age at the time of HTx of 45.2±15.0 years. CAV was diagnosed in 71 patients (40.8%), more than half of which underwent interventional procedure or surgical therapy (n=40, 56.3%). A comparison of the cytoimmunological profile of patients with no CAV or mild disease (group 1, n=134) vs. with CAV requiring treatment (group 2, n=40), revealed significantly reduced percentage of CD4+ T cells (46.4±11.4% vs. 41.2±9.6%, p=0.01) and elevated percentage of CD8+ T lymphocytes in group 2 (28.3±14.1% vs. 35.8±13.7%, p=0.003). Thus, the CD4/CD8 ratio was altered in therapy requiring CAV (2.3±2.0 vs. 1.5±1.0, respectively, p&amp;lt;0.001). However, we observed no differences in the absolute count of T-helper cells (CD4+ T cells: 692.2±329.2 vs. 653.8±390.5 cells/μL, p=0.54) and cytotoxic T lymphocytes (CD8+ T cells: 474.7±450.2 vs. 600.0±469.0 cells/μL, p=0.13). Further analysis showed no differences regarding lymphocyte count and absolute count or percentage of CD3+ and CD19+ T cells as well as NK cells. Inverse CD4/CD8 ratio (&amp;lt;1) was associated with greater risk for therapy requiring CAV (OR 2.8, 95% CI 1.3 – 5.9, p=0.009) in a univariate logistic regression analysis. Conclusions Decreased CD4+ T cell count along with increased cytotoxic T lymphocyte count resulting in inverse CD4/CD8 ratio is associated with increased CAV severity in HTx. Given the possible interactions with the immunosuppressive agents and prednisolone, monitoring of the cytomimmunological profile can help identify patients at risk and be useful in establishing therapeutic strategies. Funding Acknowledgement Type of funding sources: None.

Risk factors for early concentric left ventricular remodelling in women and men at risk for heart failure

Abstract Background/Purpose Heart failure with preserved ejection fraction (HFpEF) is currently hard to treat, and more prevalent in women as compared to men. Therefore, focus on prevention is key. Concentric remodelling is considered a pre-stage of HFpEF, yet knowledge on distributions and risk factor relations are scarce. Therefore, we identified the prevalence of early remodelling in women and men, and studied risk factors for early remodelling in women and men at risk for heart failure. Methods Clinical and echocardiographic data from 880 individuals, included in the HELPFul cohort were analysed (mean age 62.9 ±SD 9.3 years, 68.6% women). Relative wall thickness was calculated with the formula (2*LVPWD)/LVEDD and expressed as percentage. Concentric remodelling was defined as a relative wall thickness &amp;gt;42%. The relationship of classical cardiovascular risk factors, anthropometric -, lifestyle -, and pregnancy factors with relative wall thickness was tested using uni- and multivariable analyses for women and men separately. The association of continuous variables with relative wall thickness was analysed per standard deviation (SD) increase. Results Relative wall thickness was similar for both men (mean 43.2 ±SD 9.5) and women (mean 42.6 ±SD 8.1). Concentric remodelling (RWT &amp;gt;42%) was present in 49.1% of the population. Multivariable analyses showed that age, heart rate, systolic blood pressure, hypertension, and the usage of antihypertensive medication were independently associated with relative wall thickness in women. In men, heart rate and hypertension were independently associated with relative wall thickness. No associations were found for lifestyle factors such as smoking and alcohol intake. In women, there was no significant association of hypertensive pregnancy disorders and gestational diabetes with relative wall thickness. When relative wall thickness was dichotomized with &amp;gt;42% as cut-off for concentric remodelling the same risk factors remained independently associated in women. Per SD increase age, systolic blood pressure, heart rate, a diagnosis of hypertension and usage of antihypertensive medication were associated with an increased risk of concentric remodelling (OR=1.39 (95% CI: 1.18–1.64), 1.27 (95% CI: 1.05–1.53), 1.32 (95% CI: 1.10–1.58), 1.61 (95% CI: 1.09–2.36) and 1.67 (95% CI: 1.16–2.43), respectively) (Figure 1). In men, only a diagnosis of hypertension was a risk factor for concentric remodelling (OR=1.80 (95% CI: 1.05–3.06)). Conclusion Left ventricular concentric remodelling was as common in women as in men visiting outpatient cardiology clinics and found in half of the population. No sex-specific -, or lifestyle related risk factors could be identified. A relation with hypertension was evident in both sexes, but surprisingly no association of hypertensive pregnancy disorders was found. Concentric remodelling in women and men remains a common, but poorly understood, phenomenon that warrants further attention. Funding Acknowledgement Type of funding sources: None.

Myocardial infarction with non obstructive coronary arteries (MINOCA) according to definitions of 2020 ESC Guidelines: clinical profile and prognosis

Abstract Background MINOCA's physiopathology, treatment and prognosis are yet to be completely understood. The aim of this study is to compare baseline characteristics and prognosis of MINOCA patients and those of patients with myocardial infarction (MI) and obstructive coronary arteries. Methods We analysed all consecutive patients with MI who underwent coronary angiography admitted in a University Hospital covering a population of 220.000 people during a period of 60 months. The database and the all the patient's angiographies were revised by a group of experts in order to adequate MINOCA to 2020 ESC Guidelines definition and the American Heart Association position paper. Results 680 patients, 68 of whom were MINOCA (10%) with a median of follow up of 31±16 months were analysed (see table 1). We found no differences in both groups' age. Female gender was more prevalent among MINOCA patients. The underlying mechanism in MINOCA was coronary spasm (17.6%), plaque rupture (13.2%), coronary embolism (7.4%), coronary dissection (2.9%), type II infarction (19.1%) or unknown (39.7%). Coronary arteries in MINOCA patients had no obstructions at all in 57.4%, and 30–50% obstruction in 42.6% of the cases. MINOCA patients didn't have higher prevalence of cancer, autoimmune or psychiatric diseases, dyslipidaemia, hypertension or inflammatory analytical parameters. However, we found significant differences in atrial fibrillation, migraine, connective tissue diseases, tobacco use and diabetes. We found no effect of stress in the development of MINOCA (measured with validated STAI and DS-14 scales). Symptoms at admission didn't differ between the two groups, but those with MINOCA had normal ECG more frequently. Prognosis showed relevant differences, as MINOCA patients had less major cardiovascular complications, such as inotropic requirements (0% Vs 4.8%, p=0.04), shock (0% vs 6.6%, p=0.013) and left ventricular dysfunction (11.8 vs 30.2, p=0.015). Furthermore, myocardial injury biomarkers' levels were, significantly lower in MINOCA patients. Death rates tend to be lower both in hospital (0% vs 3.1%, p=0.131) and during follow up (9.1% vs 11.5%, p=0.369). Conclusion Analysing MINOCA patients' clinical profile might help us understanding the underlying physiopathology, prognosis and treatment targets. In these patients, classic cardiovascular risk factors don't appear to be as important as in obstructive patients. At admission, we found no clinical differences that could help making an early diagnosis, even if those with normal ECG and lower levels of myocardial injury biomarkers are more likely to have non-obstructive coronary arteries. These patients seem to have better prognosis and lower myocardial injury than those with obstructive coronary arteries. Further research is needed to provide more evidence on the accurate treatment of these patients. Funding Acknowledgement Type of funding sources: None.