High-Density Lipoprotein Function and Dysfunction in Health and Disease

High-density lipoprotein cholesterol (HDL-c) has long been referred to as ‘good cholesterol’ due to its apparent inverse relationship with future CVD risk. More recent research has questioned a causal role for HDL-c in this relationship, however, as both genetic studies and numerous large-scale randomised controlled trials have found no evidence of a cardiovascular protective effect when HDL-c levels are raised. Instead, focus has switched to the functional properties of the HDL particle. Evidence suggests that both the composition and function of HDL may be significantly altered in the context of an inflammatory milieu, transforming the particle from a vasoprotective anti-atherogenic particle to a noxious pro-atherogenic equivalent. This review will summarise evidence relating HDL to CVD risk, explore recent evidence characterising changes in the composition and function of HDL that may occur in chronic inflammatory diseases, and discuss the potential for future HDL-modifying therapeutic interventions

Twenty-year trajectories of alcohol consumption during midlife and atherosclerotic thickening in early old age: findings from two British population cohort studies.

BACKGROUND: Epidemiological evidence indicates a protective effect of light-moderate drinking on cardiovascular disease and an increased risk for heavier drinking. Nevertheless, the effect of alcohol on atherosclerotic changes in vessel walls is disputed. Most previous studies have only looked at the cross-sectional relationship between alcohol and carotid intima media thickness (cIMT) - a surrogate marker of atherosclerosis. Single measurements of alcohol assume that alcohol exposure is stable and ignore the possible cumulative effects of harm, leading to possibly incorrect inferences. METHODS: Data were retrieved from two UK population based cohort studies: the Whitehall II cohort of civil servants and the MRC National Survey of Health and Development (combined sample size of 5403 men and women). Twenty year-drinking trajectories during midlife were linked to measures of cIMT when participants were in early old age, and adjusted for age, sex, socioeconomic position, ethnicity and smoking. RESULTS: Those who consistently drank heavily had an increased cIMT compared to stable moderate drinkers (pooled difference in cIMT 0.021 mm; 95 % CI 0.002 to 0.039), after adjustment for covariates. This was not detected in cross-sectional analyses. Former drinkers also had an increased cIMT compared to moderate drinkers (pooled difference in cIMT 0.021; 95 % CI 0.005 to 0.037). There were no appreciable differences in cIMT between non-drinkers and consistent moderate drinkers. CONCLUSION: The drinking habits among adults during midlife affect the atherosclerotic process and sustained heavy drinking is associated with an increased cIMT compared to stable moderate drinkers. This finding was not seen when only using cross-sectional analyses, thus highlighting the importance of taking a life course approach. There was no evidence of a favourable atherosclerotic profile from stable moderate drinking compared to stable non-drinking.Both SB and AB are supported by a grant from the European Research Council (ERC-StG-2012-309337_AlcoholLifecourse, PI: Britton, http://www.ucl.ac.uk/ alcohol-lifecourse) and UK Medical Research Council/Alcohol Research UK (MR/ M006638/1). NSHD, RH and DK are supported by the UK Medical Research Council (MC_UU_12018/1 and MC_UU_12019/2). JD is supported by the British Heart Foundation. The Whitehall II study is supported by grants from the Medical Research Council (K013351), British Heart Foundation (RG/07/008/ 23674), Stroke Association, National Heart Lung and Blood Institute (HL036310) and National Institute on Aging (AG13196 and AG034454).This is the final version of the article. It first appeared from BioMed Central via http://dx.doi.org/10.1186/s12916-016-0656-

Impact of prospective measurement of outflow tracts in the prediction of coarctation of the aorta

Background: Prenatal diagnosis of coarctation of the aorta (COA) is associated with reduced mortality and morbidity, however, accurate prenatal prediction remains challenging. To date, studies have measured the outflow tracts retrospectively to gauge the potential to predict COA. Our primary objective was to evaluate prospectively acquired measurements of the outflow tracts in prenatally suspected COA. A secondary aim was to report the postnatal prevalence of bicuspid aortic valve in this cohort. Methods: Measurement of the aortic valve, pulmonary valve, distal transverse aortic arch (DTAA) and arterial duct (AD) diameters were undertaken routinely in fetuses with suspected COA between 2002–2017. Using published reference ranges based on >7000 fetuses from our own unit, z scores were computed. Results: COA was confirmed after birth in 77/149 (52%) cases. DTAA z score and the z score of DTAA:AD were smaller in cases with confirmed COA compared to false positive (FP) (-2.8 vs -1.9, p=0.039; -3.13 vs -2.61, p=0.005, respectively). Multiple regression analysis demonstrated that z scores of DTAA and AD were the only significant predictors (p=0.001). Bicuspid aortic valve was identified in 30% of the FP group. Conclusion: Measurement of the DTAA and AD z scores can be used to attribute risk for postnatal COA in a selected cohort. The significance of the high incidence of bicuspid aortic valve in FP cases merits further study both with respect to aetiology and longer- term significance

Assessment of atherosclerosis: the role of flow-mediated dilatation

Evidence suggests that endothelial dysfunction is on the causal pathway for both atherogenesis and destabilization of established plaques. In this review, the role of flow-mediated dilatation (FMD) as a non-invasive method to assess endothelial function is discussed. Technical modifications and development of analysis software have significantly improved the variability of the method. Following a strict standardized protocol enables reproducible measurements to be achieved and export of the technique from specialized laboratories to population studies and multicentre settings. Endothelial function assessed by FMD has been shown to be affected by cardiovascular risk factors, to be related to structural arterial disease and to cardiovascular outcome, validating its use for studying the pathophysiology of arterial disease. Numerous studies have also demonstrated that it is responsive to physiological and pharmacological interventions. Flow-mediated dilatation provides unique opportunities in drug development programmes to assess an early rapidly responsive signal of risk or benefit, complementing endpoints of structural arterial disease and cardiovascular outcomes that take much longer and are more expensiv

Statins in Peripheral Arterial Disease

Peripheral arterial disease (PAD) is a common atherosclertico condition affecting the lower extremities. PAD patients share similar cardiovascular risk factors to coronary artery disease patients and suffer from increased cardiovascular morbidity and mortality. Statins have been widely used in coronary artery disease patients but have been underused in patients with PAD. In the current review, we present data which support the beneficial role of statins in both reducing cardiovascular events and improving symptom-related outcomes in PAD patients. Alongside their lipid lowering effects, their pleiotropic actions are also discussed. Recent guidelines, which strongly recommend the administration of statins in PAD patients, are also presented

Carotid intima media thickness in older childrenand adolescents with HIV taking antiretroviraltherapy

Increased carotid intima-media thickness (cIMT) is reported in both adults and children with human immunodeficiency virus (HIV) in high income settings and is associated with an increased risk of cardiovascular disease, but data from sub-Saharan Africa is lacking. We assessed cIMT using ultrasound in perinatally HIV-infected children aged 6 to 16 years taking antiretroviral therapy (ART) for ≥6 months compared with HIV-uninfected controls in Harare, Zimbabwe. Groups were compared using unpaired t test and potential predictors of cIMT were assessed using multiple linear regression. A total of 117 participants with HIV, of whom 55 (45%) were female and 75 healthy uninfected controls were included. Participants with HIV were younger than uninfected controls, 10.7 (2.4) years versus 11.9 (2.6) years (P = .001). Mean cIMT was 0.40 (0.05) mm in those with HIV versus 0.40 (0.04) mm in healthy controls (P = .377). There was no association between cluster of differentiation 4 count, HIV viral load, and duration on ART and cIMT. Children with HIV taking ART have similar cIMT to uninfected children. Increasing numbers of children with HIV are reaching adulthood and longitudinal studies to assess the effect of long-term HIV and ART on vascular changes are required

Το φαινόμενο brain drain - Διερέυνηση των απόψεων ελλήνων νέων για τις δημόσιες πολιτικές αντιμετώπισης του φαινομένου

Η διαρροή εγκεφάλων είναι ένα κοινό φαινόμενο στις αναπτυσσόμενες χώρες, αλλά προκαλεί ανησυχία και στις ανεπτυγμένες χώρες. Σκοπός της έρευνας ήταν είναι να διερευνήσει τις απόψεις Ελλήνων νέων σχετικά με το φαινόμενο brain drain και να μελετήσει εάν οι Έλληνες νέοι είναι ικανοποιημένοι από τις δημόσιες πολιτικές για την αντιμετώπιση του φαινομένου. Πραγματοποιήθηκε ποσοτική έρευνα με τη χρήση ερωτηματολογίου. Το δείγμα ήταν 300 Έλληνες νέοι. Διαπιστώθηκε ότι οι σημαντικότεροι λόγοι οι οποίοι ωθούν τους νέους να μεταναστεύσουν είναι ο καλύτερος μισθός και η ανεργία. Ακόμη, βρέθηκε ότι υπάρχει μέτρια πρόθεση των Ελλήνων νέων να μεταναστεύσουν. Επιπλέον, η πλειοψηφία των νέων δεν είναι ικανοποιημένοι με τις δημόσιες πολιτικές αντιμετώπισης του brain drain και δεν θεωρούν ότι το κράτος έχει λάβει αρκετές και αποτελεσματικές στρατηγικές για να αντιμετωπίσει το brain drain. Ακόμη, οι περισσότεροι νέοι επισήμαναν ότι δημόσιες πολιτικές που έχουν ληφθεί χαρακτηρίζονται από γραφειοκρατία, καθυστερήσεις πληρωμών και λίγες αιτήσεις γίνονται δεκτές. Ακόμη, η έρευνα αυτή διαπίστωσε ότι το φύλο, η ηλικία και η επαγγελματική κατάσταση σχετίζονται με την πρόθεση μετανάστευσης και το μορφωτικό επίπεδο σχετίζεται με τους λόγους μετανάστευσης. Το ελληνικό κράτος σε συνεργασία με την Ευρωπαϊκή Ένωση και τις περιφερειακές αρχές θα πρέπει να αναπτύξει αποτελεσματικότερες στρατηγικές για την καταπολέμηση του φαινομένου brain drain.Brain drain is a common phenomenon in developing countries, but it is also a concern in developed countries. The purpose of the research was to investigate the views of Greek youth on the brain drain phenomenon and to study whether Greek youth are satisfied with public policies to address the phenomenon. A quantitative survey was conducted using a questionnaire. The sample was 300 young Greeks. It was found that the most important reasons that push young people to emigrate are the best wages and unemployment. It was also found that there is a moderate intention of Greek youth to emigrate. In addition, the majority of young people are dissatisfied with public policies to address brain drain and do not consider that the state has taken sufficient and effective strategies to address brain drain. Moreover, most young people pointed out that the public policies that have been taken are characterized by bureaucracy, late payments and few applications are accepted. Furthermore, this research found that gender, age and professional status are related to the intention to immigrate and educational level is related to the reasons for immigration. The Greek state in cooperation with the European Union and the regional authorities should develop more effective strategies to combat the brain drain phenomenon

Initial Experience of Superb Microvascular Imaging for Key Cardiac Views in Foetal Assessment before 15 Weeks Gestation

Background: In the first trimester, ultrasound confirmation of normal or abnormal cardiac anatomy is difficult. B-mode and colour flow Doppler (CFD) are used to assess the foetal heart. Superb microvascular imaging (SMI) can visualise blood flow within the heart and vessels in early gestation. Objective: We report an initial experience of SMI for visualisation of normal and abnormal cardiac anatomy in the first trimester. Methods: Transabdominal foetal echocardiography was performed between 11 + 6 and 14 + 3 weeks (Aplio 500 US system, Toshiba Medical Systems, Tokyo, Japan) from January 2017 to December 2017. All scans were performed at a tertiary foetal cardiology unit. To assess the potential utility of the technique for early gestation screening, normal scans were reviewed by foetal medicine trainees with respect to the B-mode, CFD and SMI. Three key views were selected to compare modalities: the 4-chamber view, outflow tracts and the 3-vessel and trachea view (VTV). Visualisation rates of key echocardiographic features of significant cardiac abnormalities by SMI were reviewed. Results: Fifty-five normal echocardiograms and 34 cardiac abnormalities were included. In the normal heart, when B-mode, CFD and SMI were assessed separately, SMI had the highest rate of visualisation of 4-chamber, outflow tracts and 3-VTV (93, 85 and 83%, respectively). Intra-observer reliability was moderate for SMI of the 3 standard views (kappa 1, 0.64 and 0.64); inter-observer for 4-chamber and outflow tract views was moderate (kappa 0.64 and 0.77). In 29/34 abnormal cases, SMI showed key features, enhancing greyscale visualisation. Conclusion: SMI has potential to become a useful, complementary modality for early foetal echocardiography. Further prospective studies are warranted to establish the place of the technique in assessment of the first trimester foetal heart.info:eu-repo/semantics/publishedVersio

Reference ranges for the size of the fetal cardiac outflow tracts from 13 to 36 weeks gestation: a single-center study of over 7000 cases

BACKGROUND: Assessment of the outflow tract views is an integral part of routine fetal cardiac scanning. For some congenital heart defects, notably coarctation of the aorta, pulmonary valve stenosis, and aortic valve stenosis, the size of vessels is important both for diagnosis and prognosis. Existing reference ranges of fetal outflow tracts are derived from a small number of cases. METHODS AND RESULTS: The study population comprised 7945 fetuses at 13 to 36 weeks’ gestation with no detectable abnormalities from pregnancies resulting in normal live births. Prospective measurements were taken of (1) the aortic and pulmonary valves in diastole at the largest diameter with the valve closed, (2) the distal transverse aortic arch on the 3 vessel and trachea view beyond the trachea at the distal point at its widest systolic diameter, and (3) the arterial duct on the 3 vessel and trachea view at its widest systolic diameter. Regression analysis, with polynomial terms to assess for linear and nonlinear contributors, was used to establish the relationship between each measurement and gestational age. The measurement for each cardiac diameter was expressed as a z score (difference between observed and expected value divided by the fitted SD corrected for gestational age) and percentile. Analysis included calculation of gestation-specific SDs. Regression equations are provided for the cardiac outflow tracts and for the distal transverse aortic arch:arterial duct ratio. CONCLUSIONS: The study established reference ranges for fetal outflow tract measurements at 13 to 36 weeks’ gestation that are useful in clinical practice