Procalcitonin kinetics following abdominal aortic surgery and its value for postoperative intestinal ischaemia detection.

OBJECTIVE: The purpose of our study was to describe perioperative kinetics of procalcitonin (PCT) in patients undergoing aortic surgery, to compare the kinetics in the open abdominal aortic aneurysm (AAA) repair and aortobifemoral bypass for aortoiliac occlusive disease (AIOD), and to evaluate the ability of PCT to detect intestinal ischaemia. METHODS: A prospective non-randomized observational cohort study in 80 patients (62 men and 18 women) undergoing elective aortic surgery was performed. Serum PCT was measured at baseline and defined intraoperative and postoperative timepoints up to postoperative day 7. MRI contrast-enhanced imaging was used to detect intestinal ischaemia. RESULTS: The comparison of the AAA and AIOD cohort did not show any significant difference in PCT levels. Patients with intestinal ischaemia had higher serum PCT at multiple timepoints postoperatively. The most accurate timepoints for early diagnosis were postoperative day 3, followed by 24 h after declamping of the vascular reconstruction, and postoperative day 7. The sensitivity and negative predictive values were 100% in all mentioned timepoints. However, event at the best timepoint the specificity was 89% and the positive predictive value 43%. CONCLUSIONS: Procalcitonin levels in the postoperative period at proper timepoints might help to detect postoperative intestinal ischaemia. The limitation of this marker is its low specificity for intestinal ischaemia and low positive predictive value. The highest value of this marker is that it can rule out this complication because normal PCT levels mean that intestinal ischaemia is very unlikely.

Theories and Molecular Basis of Vascular Aging: A Review of the Literature from VascAgeNet Group on Pathophysiological Mechanisms of Vascular Aging.

Vascular aging, characterized by structural and functional alterations of the vascular wall, is a hallmark of aging and is tightly related to the development of cardiovascular mortality and age-associated vascular pathologies. Over the last years, extensive and ongoing research has highlighted several sophisticated molecular mechanisms that are involved in the pathophysiology of vascular aging. A more thorough understanding of these mechanisms could help to provide a new insight into the complex biology of this non-reversible vascular process and direct future interventions to improve longevity. In this review, we discuss the role of the most important molecular pathways involved in vascular ageing including oxidative stress, vascular inflammation, extracellular matrix metalloproteinases activity, epigenetic regulation, telomere shortening, senescence and autophagy.

Genetic Counseling and Management: The First Study to Report NIPT Findings in a Romanian Population.

Background and Objectives: Non-invasive prenatal testing (NIPT) has been confirmed as the most accurate screening test for trisomies 21, 18, 13, sex chromosomes aneuploidies and several microdeletions. This study aimed to assess the accuracy of cell free DNA testing based on low-level whole-genome sequencing to screen for these chromosomal abnormalities and to evaluate the clinical performance of NIPT. Materials and Methods: 380 consecutive cases from a single genetic center, from Western Romania were included in this retrospective study. Cell-free nucleic acid extraction from maternal blood, DNA sequencing and analysis of sequenced regions were performed by BGI Hong Kong and Invitae USA to determine the risk of specific fetal chromosomal abnormalities. In high-risk cases the results were checked by direct analysis of fetal cells obtained by invasive methods: 6 chorionic villus sampling and 10 amniocenteses followed by combinations of QF-PCR, karyotyping and aCGH. Results: NIPT results indicated low risk in 95.76% of cases and high risk in 4.23%. Seven aneuploidies and one microdeletion were confirmed, the other results were found to be a false-positive. A gestational age of up to 22 weeks had no influence on fetal fraction. There were no significant differences in fetal fraction across the high and low risk groups. Conclusions: This is the first study in Romania to report the NIPT results. The confirmation rate was higher for autosomal aneuploidies compared to sex chromosome aneuploidies and microdeletions. All cases at risk for trisomy 21 were confirmed. Only one large fetal microdeletion detected by NIPT has been confirmed. False positive NIPT results, not confirmed by invasive methods, led to the decision to continue the pregnancy. The main limitation of the study is the small number of patients included. NIPT can be used as a screening method for all pregnancies, but in high-risk cases, an invasive confirmation test was performed.

Kinetics of platelet adhesion to a fibrinogen-coated surface in whole blood under flow conditions.

AIM: To test a novel method of assessment of platelet adhesion to a fibrinogen-coated surface in whole blood under flow conditions. METHODS: We developed a fluidic device that mimics blood flow in vessels. The method of detection of platelet adhesion is based on recording of a scattered laser light signal from a fibrinogen-covered surface. Testing was performed in platelet-rich plasma (PRP) and whole blood of healthy volunteers. Control measurements were performed, followed by tests with inhibition of platelet GPIIa/IIIb and GPIb receptors. Then, the same testing sequence was performed in whole blood of persons with autoimmune thrombocytopenia and type 3 von Willebrand disease. RESULTS: The change in intensity of scattered light was 2.7 (2.4; 4.1) times higher in whole blood (0.2 ± 0.08V, n = 7) than in PRP (0.05 ± 0.02 V, n = 7), p < 0.01. The blocking of GP IIb/IIIa receptors decreased the intensity of scattered light to 8.5 (6.5;12)%; the blocking of GPIb receptors decreased it to 34 (23;58)%, p < 0.01. In the whole blood of a person with autoimmune thrombocytopenia, the inhibition of GPIb receptors decreased platelet adhesion, but no effect was observed in type 3 von Willebrand disease. Inhibition of platelet GPIIb/IIIa receptors alone or combined inhibition of GPIb and GPIIb/IIIa receptors resulted in almost total suppression of adhesion in both cases. CONCLUSION: Our system effectively registers platelet adhesion to a fibrinogen-coated surface under controlled-flow conditions and may successfully be applied to the investigation of platelet adhesion kinetics.

Regulatory Requirements For Medical Devices And Vascular Ageing: An Overview.

The development and use of medical devices are subject to regulations and approval activities to enter the market. These are mandatory for manufacturers and have important implications for all involved professionals. In fact, the innovation process, starting from a clinical need, includes the identification of a solution and its implementation, and requires taking into account crucial aspects according to regulatory requirements in each phase. These include exemplary validation or risk management. The aim of this work is to provide an overview of some key aspects of regulation and their implementation in medical devices for vascular ageing assessment. In particular, regulatory scenarios in Europe, Australia and the United States of America are described and examples of marketed medical devices for vascular ageing assessment are provided. Strong and active links among industry, research, clinical experts and governments adds value for the community, requiring the ability to communicate between different skills and backgrounds: this multidisciplinary and multi-partner collaboration can speed up the innovation process and can increase the system's efficiency related to both social and ethical impact.

The Relationship Between Dietary Choices and Health and Premature Vascular Ageing.

The paper aims to review the available data about the main mechanisms enabling improvement or accelerating vascular ageing due to food choices, considering recent experimental and clinical data, and emphasising potential implications for clinical practice and therapy. The main food choices which will be discussed are diets rich in fruits and vegetables, the Mediterranean diet, polyunsaturated fatty acids, cocoa, caffeine, tea, meat, dairy products, sodium, and potassium intake.

Sex and Gender Aspects in Vascular Ageing - Focus on Epidemiology, Pathophysiology, and Outcomes.

Sex and gender are important modifiers of cardiovascular system physiology, pathophysiology, and disease development. The atherosclerosis process, together with the progressive loss of arterial elasticity with age, is a major factor influencing the development of overt cardiovascular, renal, and cerebrovascular disease. While differences between women and men in epidemiology and pathophysiology of vascular ageing are increasingly reported, sex-disaggregated data are still scarcely available for prospective studies. A better knowledge of sex differences in physiological ageing as well as in disease-related changes in vascular ageing trajectories is crucial to avoid misdiagnosis and mistreatment. This review presents key concepts and knowledge gaps identified in vascular ageing due to gonadal function, vascular physiology, pathophysiology, psychosocial factors, pregnancy, and prognostic relevance. Gender roles determine the effectiveness of any cardiovascular preventive strategy and acceptance for non-invasive or invasive diagnostics and therapeutics. Gender differences in health behaviour, also due to sociocultural norms conditioned by society, contribute to behaviours that may lead to premature arterial vascular ageing. These include differences in risk behaviours like smoking, diet, exercise, and in stress, but also conditions such as housing, noise pollution, poverty, disability, and any kind of stigmatisation. The VascAgeNet Gender Expert Group aims to advance the use of non-invasive vascular ageing measures in routine clinical settings by providing facts to fill in the gaps concerning sex and gender differences at each step of this process, and to search for solutions.

Polyploidy in First and Second Trimester Pregnancies in Romania - a Retrospective Study.

BACKGROUND: Polyploidy is a rare lethal cytogenetic anomaly in pregnancies, generally leading to pregnancy termination. This study aims to compare first and second trimester polyploidy in pregnancies and describe the underlying mechanisms. METHODS: A retrospective study was conducted in three medical genetics laboratories, collecting cases from Eastern, Southern, and Western Romania. The period of interest was January 2008 to December 2018. Prenatal samples (chorionic villi and amniotic fluid) and miscarriage samples were tested by standard karyotyping, as well as QF-PCR or FISH as complementary or alternative techniques. RESULTS: In first trimester pregnancies, we report cytogenetic results of chorionic villi samples from miscarriages: 25 triploid cases and 13 tetraploid cases. In second trimester samples obtained by amniocentesis, cytogenetic findings were positive for 17 triploid cases. Maternal age, age of the pregnancy, and fetal gender identified by ultrasound were recorded in all cases and, additionally, data on biochemical risk and ultrasonographic findings for second trimester pregnancies. CONCLUSIONS: Cytogenetic investigations of spontaneous abortions provide valuable information on the cause of abortion. This information is crucial for genetic counseling and may also contribute to prenatal diagnosis in subsequent pregnancies.

The therapeutic effect of B-type natriuretic peptides in acute decompensated heart failure.

B-type natriuretic peptide (BNP) exhibits roles in natriuresis and diuresis, making it an ideal drug that may aid in diuresing a fluid-overloaded patient with poor or worsening renal function. Several randomized clinical trials have tested the hypothesis that infusions of pharmacological doses of BNP to acute heart failure (HF) patients may enhance decongestion and preserve renal function in this clinical setting. Unfortunately, none of these have demonstrated beneficial outcomes. The current challenge for BNP research in acute HF lies in addressing a failure of concept and a reluctance to abandon an ineffective research model. Future success will necessitate a detailed understanding of the mechanism of action of BNP, as well as better integration of basic and clinical science.

Markers of Atherosclerosis: Part 2 - Genetic and Imaging Markers.

This is Part 2 of a two-part review summarising current knowledge on biomarkers of atherosclerosis. Part 1 addressed serological biomarkers. Here, in part 2 we address genetic and imaging markers, and other developments in predicting risk. Further improvements in risk stratification are expected with the addition of genetic risk scores. In addition to single nucleotide polymorphisms (SNPs), recent advances in epigenetics offer DNA methylation profiles, histone chemical modifications, and micro-RNAs as other promising indicators of atherosclerosis. Imaging biomarkers are better studied and already have a higher degree of clinical applicability in cardiovascular (CV) event prediction and detection of preclinical atherosclerosis. With new methodologies, such as proteomics and metabolomics, discoveries of new clinically applicable biomarkers are expected.

Markers of Atherosclerosis: Part 1 - Serological Markers.

Atherosclerosis is a major contributor to morbidity and mortality worldwide. With therapeutic consequences in mind, several risk scores are being used to differentiate individuals with low, intermediate or high cardiovascular (CV) event risk. The most appropriate management of intermediate risk individuals is still not known, therefore, novel biomarkers are being sought to help re-stratify them as low or high risk. This narrative review is presented in two parts. Here, in Part 1, we summarise current knowledge on serum (serological) biomarkers of atherosclerosis. Among novel biomarkers, high sensitivity C-reactive protein (hsCRP) has emerged as the most promising in chronic situations, others need further clinical studies. However, it seems that a combination of serum biomarkers offers more to risk stratification than either biomarker alone. In Part 2, we address genetic and imaging markers of atherosclerosis, as well as other developments relevant to risk prediction.

Matrix metalloproteinase-3 gene polymorphism (rs3025058) affects markers atherosclerosis in type 2 diabetes mellitus.

BACKGROUND: The study was designed to test the possible association between either polymorphisms of the matrix metalloproteinase-9 (MMP-9) gene (rs17576, rs3918242) or the MMP-3 5A/6A gene polymorphism (rs3025058) with markers of carotid atherosclerosis in patients with type 2 diabetes mellitus (T2DM). The second aim of the study was to demonstrate an association between either the rs17576, rs3918242 or rs3025058 and subclinical markers of coronary artery disease in the same subset of patients with T2DM. PATIENTS AND METHODS: A total of 595 subjects with T2DM and 200 subjects without T2DM (control group) were enrolled in the prospective study. Subclinical markers of carotid atherosclerosis were assessed ultrasonographically. Additionally, in a subset of subjects with T2DM a coronary computed tomography angiography (CCTA) was performed for diagnostic purposes. Genotyping of all three polymorphisms (rs17576, rs3918242, rs3025058) was performed with real-time PCR systems. RESULTS: The comparison of atherosclerosis parameters was performed with regard to different genotypes of MMP-9 rs17576, rs3918242, and MMP-3 rs3025058 polymorphisms upon enrolment and during follow-up. In our study, we found an association between the MMP-3 rs3025058 and CIMT at the time of recruitment. Multiple linear regression analysis revealed the association of either the A- allele or the A- genotypes of the rs3025058 (MMP-3) with carotid intima media thickness (CIMT) progression in a 3.8-year follow-up. We demonstrated the effect of the rs3025058 on subclinical markers of coronary atherosclerosis (coronary calcium score, number of coronary arteries with more than 50 % stenosis, and presence of at least one vessel with more than 50 % stenosis). CONCLUSIONS: We found an association between the MMP-3 rs3025058 and subclinical markers of carotid (CIMT) and coronary atherosclerosis at the time of recruitment. Moreover, we demonstrated the effect of the MMP-3 rs3025058 on CIMT progression in the 3.8-year follow-up in patients with T2DM.

Glycemic Variability and Vascular Complications in Patients with Type 2 Diabetes Mellitus.

BACKGROUND: Presence of macro- and microvascular complications in patients with diabetes mellitus (DM) is not only related to chronic hyperglycemia represented by glycated hemoglobin (HbA1c) but also to acute glycemic fluctuations (glycemic variability, GV). The association between GV and DM complications is not completely clear. Aim of our study was to evaluate GV by MAGE index in patients with type 2 DM and to verify association of MAGE index with presence of macro- and microvascular DM complications. METHODS: 99 patients with type 2 DM were included in the study. Every patient had done big glycemic profile, from which MAGE index was calculated. Anthropometric measurements, evaluation of HbA1c and fasting plasma glucose (FPG) and assessment for macrovascular (coronary artery disease - CAD; peripheral artery disease - PAD; cerebral stroke - CS) and microvascular (diabetic retinopathy - DR; nephropathy - DN; peripheral neuropathy - DPPN) DM complications were done. RESULTS: Average MAGE index value was 5.15 ± 2.88 mmol/l. We found no significant differences in MAGE index values in subgroups according to presence of neither CAD, CS, PAD nor DR, DN, DPPN. MAGE index value significantly positively correlated with FPG (p < 0.01) and HbA1c (p < 0.001) and negatively with weight (p < 0.05). CONCLUSION: In our study we failed to show association of MAGE index with presence of macrovascular and microvascular complications in patients with type 2 DM. However, this negative result does not necessarily disprove importance of glycemic variability in pathogenesis of diabetic complications.

Global Longitudinal Strain and Strain Rate in Type Two Diabetes Patients with Chronic Heart Failure: Relevance to Osteoprotegerin.

BACKGROUND: Biomechanical stress and inflammatory biomarkers relate to global contractility dysfunction; however, adding these biomarkers into a risk model constructed on clinical data does not improve its prediction value in chronic heart failure (CHF). AIM: The aim of this study was to evaluate whether biomarkers predict declining of left ventricular global contractility function in diabetic patients with ischemia-induced CHF. PATIENTS AND METHODS: The study retrospectively evolved 54 diabetic patients who had systolic or diastolic ischemia-induced CHF that was defined as left-ventricular ejection fraction (LVEF) ≤45% or 46-55% respectively assessed by quantitative echocardiography and other conventional criteria according to current clinical guidelines. Two-dimensional transthoracic echocardiography and tissue Doppler imaging were performed according to a conventional method. Radial, longitudinal, and circumferential strain and strain rate values were obtained by speckle-tracking Imaging analysis of both LV short axis and long axis views. Serum adiponectin, NT-pro brain natriuretic peptide (BNP), osteoprotegerin, and hs- C-reactive protein (CRP) were determined at baseline by ELISA. RESULTS: We found lower global longitudinal strain and strain rate in diabetic patients with LVEF <45% than these in diabetic patients that did not have LVEF (Р=0.001 for all cases). Multivariate logistic regression analysis showed that NT-proBNP (r=0.432; P=0.001 and r=0.402; P=0.001, respectively), osteoprotegerin (r=0.422; P=0.001 and r=0.401; P=0.001, respectively), hs-CRP (r=0.408; P=0.001 and r=0.404; P=0.001, respectively) were independently inversely associated with global longitudinal strain and strain rate in CHF patients. CONCLUSION: We suggest that osteoprotegerin may be useful in improving the NT-proBNP based model as predictor of decreased global contractility function in diabetic patients with CHF.

The link between ventricular repolarization variables and arterial function.

AIM: To assess the relationship between repolarization variables and arterial function. METHODS: A total of 54 participants, aged 33±10years, underwent arteriography and standard 12-lead electrocardiography (ECG). Arteriography was performed using a noninvasive automated oscillometric method, assessing: brachial (Aix Brach) and aortic augmentation index (Aix Ao), pulse wave velocity (PWV), arterial age (AA), diastolic reflection area (DRA) and diastolic area index (DAI). Standard 12-lead ECG enabled measurement of QT and Tpeak-Tend (TpTe) intervals and TpTe/QT ratios. RESULTS: QT interval was prolonged in patients with elevated blood pressure or body mass index. Significant associations were found between electrocardiographic repolarization parameters, such as QT intervals, TpTe and TpTe/QT and arteriography variables, such as Aix Brach, Aix Ao, PWV and AA. CONCLUSION: Prolonged QTc and Tpe are associated with endothelial dysfunction, arterial stiffness, impaired coronary perfusion and accelerated arterial aging.

Atrial Fibrillation and Early Vascular Aging: Clinical Implications, Methodology Issues and Open Questions-A Review from the VascAgeNet COST Action.

Atrial fibrillation (AF), the most common cardiac arrhythmia, is associated with adverse CV outcomes. Vascular aging (VA), which is defined as the progressive deterioration of arterial function and structure over a lifetime, is an independent predictor of both AF development and CV events. A timing identification and treatment of early VA has therefore the potential to reduce the risk of AF incidence and related CV events. A network of scientists and clinicians from the COST Action VascAgeNet identified five clinically and methodologically relevant questions regarding the relationship between AF and VA and conducted a narrative review of the literature to find potential answers. These are: (1) Are VA biomarkers associated with AF? (2) Does early VA predict AF occurrence better than chronological aging? (3) Is early VA a risk enhancer for the occurrence of CV events in AF patients? (4) Are devices measuring VA suitable to perform subclinical AF detection? (5) Does atrial-fibrillation-related rhythm irregularity have a negative impact on the measurement of vascular age? Results showed that VA is a powerful and independent predictor of AF incidence, however, its role as risk modifier for the occurrence of CV events in patients with AF is debatable. Limited and inconclusive data exist regarding the reliability of VA measurement in the presence of rhythm irregularities associated with AF. To date, no device is equipped with tools capable of detecting AF during VA measurements. This represents a missed opportunity to effectively perform CV prevention in people at high risk. Further advances are needed to fill knowledge gaps in this field.

QT and Tpeak-Tend intervals in shift workers.

PURPOSE: The present study investigated the relationship between working time and QT and Tpeak-Tend (Tpe) intervals in three shift workers and identified factors associated with the prolongation of these intervals. METHODS: A total of 60 shift workers underwent a standard 12-lead ECG during the morning, afternoon and night shifts. QT intervals and T wave variables were manually measured. RESULTS: The maximum increase in the QT and Tpe interval durations between shifts was significantly associated with hypertension, age, smoking status, body mass index, and the number of months performing shift work. Cox regression analysis identified independent predictors of prolonged QT and Tpe intervals. CONCLUSION: QT and Tpe intervals are prolonged during the night and morning shifts with the afternoon shift as the reference group. QT and Tpe interval prolongation is highest in hypertensive, overweight and obese participants, smokers, and those with prolonged exposure to shift work. Participant age, hypertension and body mass index are independent predictors of QT interval prolongation, while age and smoking status predict Tpe prolongation.

The Impact of the Blood Lipids Levels on Arterial Stiffness.

Arterial stiffness is a recognized predictor of cardiovascular morbidity and death. It is an early indicator of arteriosclerosis and is influenced by numerous risk factors and biological processes. The lipid metabolism is crucial and standard blood lipids, non-conventional lipid markers and lipid ratios are associated with arterial stiffness. The objective of this review was to determine which lipid metabolism marker has a greater correlation with vascular aging and arterial stiffness. Triglycerides (TG) are the standard blood lipids that have the strongest associations with arterial stiffness, and are often linked to the early stages of cardiovascular diseases, particularly in patients with low LDL-C levels. Studies often show that lipid ratios perform better overall than any of the individual variables used alone. The relation between arterial stiffness and TG/HDL-C has the strongest evidence. It is the lipid profile of atherogenic dyslipidemia that is found in several chronic cardio-metabolic disorders, and is considered one of the main causes of lipid-dependent residual risk, regardless of LDL-C concentration. Recently, the use of alternative lipid parameters has also been increasing. Both non-HDL and ApoB are very well correlated with arterial stiffness. Remnant cholesterol is also a promising alternative lipid parameter. The findings of this review suggest that the main focus should be on blood lipids and arterial stiffness, especially in individuals with cardio-metabolic disorders and residual cardiovascular risk.

Evaluating the Arterial Stiffness as a Useful Tool in the Management of Obese Children.

Childhood obesity speeds up the development of arterial stiffness and progressively increases the values of arterial pressure. The purpose of this study is to investigate the value of using pulse wave analysis (PWA) to measure arterial stiffness as a sign of vascular wall impairment in obese children. The research was focused on 60 subjects: 33 obese and 27 normal-weight. Ages ranged from 6 to 18 years old. PWA includes parameters such as pulse wave velocity (PWV), augmentation index (AIx), peripheral and central blood pressure (SBP, DBP, cSBP, cDBP), heart rate, and central pulse pressure (cPP). The device used was a Mobil-O-Graph. Blood parameters were taken from the subject's medical history, not older than 6 months. A high BMI and a large waist circumference are linked to a high PWV. The levels of LDL-c, triglycerides (TG), non-HDL-c, TG/HDL-c ratio, and total cholesterol-HDL-c ratio significantly correlate to PWV, SBP, and cSBP. Alanine aminotransferase is a reliable predictor of PWV, AIx, SBP, DBP, and cDBP, while aspartate aminotransferase is a significant predictor of AIx, mean arterial pressure (MAP), cSBP, and cPP. 25-OH-Vitamin D negatively correlates with PWV, SBP, and MAP and significantly predicts the MAP. Cortisol and TSH levels are not significant to arterial stiffness in obese children without specific comorbidities and neither is fasting glucose in obese children without impaired glucose tolerance. We conclude that PWA contributes valuable data regarding patients' vascular health and should be considered a reliable tool in the management of obese children.

Developing a Questionnaire on Knowledge, Perceptions and Application of Vascular-Aging Measurements.

BACKGROUND: Vascular age (VA) is independent and chronological age for assessing cardiovascular disease (CVD) risk. However, tools for the implementation of VA are currently lacking. We aimed to develop a questionnaire to assess the current knowledge gaps related to VA and barriers to its implementation in routine practice. METHODS: Using a stepwise mixed-method approach, a quantitative questionnaire was constructed in four phases: (1) basic item generation and the development of a semi-qualitative questionnaire (SQQ); (2) dissemination to the VascAgeNet extended network and an analysis of the semi-qualitative questionnaire responses; (3) the development of a quantitative questionnaire (QQ); and (4) an assessment of the content and face validity and internal reliability in an additional sample. RESULTS: Based on six main topics initially identified through an expert panel, a SQQ was developed and disseminated. Finally, a 22-item QQ was developed, with questions grouped around three main themes: knowledge of VA and its risk factors; perceptions and beliefs regarding the importance and contribution of VA to risk classification; and the application of VA measurements in clinical and research practice and its potential limitations (Cronbach's alpha between 0.920 and 0.982 for all three categories). CONCLUSION: We report the development of a QQ on VA addressed to both clinicians and non-clinicians aiming to assess their knowledge, perceptions and application of VA measurements.