General European Population Research Articles

Mental Health Consequences of COVID-19 Pandemic Period in the European Population: An Institutional Challenge.

The worldwide spread of SARS-CoV-2 has been responsible for an infectious pandemic, with repercussions on socio-economic aspects and on the physical and mental health of the general population. The present systematic review aimed to evaluate the data belonging to the European framework, analyzing the population by age group. Original articles and reviews on the state of mental health of the general European population have been researched starting from 2021. Initially, a total of 1764 studies were found, among which a total of 75 were selected. Youth were the age group most affected by pandemic consequences on mental health, with emotional and behavioral alterations observed from a third to more than a half of children and adolescents examined. Among both adolescents and adults, the female gender had a higher prevalence of psychopathological symptoms. The main risk factors were poor social support, economic difficulties, and, in particular, unemployment or job changes. Additional individual risk factors were the perception of loneliness, the presence of pre-pandemic mental illness/distress, and some personality traits, such as neuroticism, impulsiveness, and the use of maladaptive coping strategies. Unexpectedly, the elderly maintained good resilience towards change, even if a stress factor was represented by the feeling of loneliness and poor social contact. As regards suicidal behaviors, among adolescents, there was an increase in attempts of 25%, with a greater risk for the female gender. This risk increased also among adults, in association with symptoms of anxiety and depression, and poor socio-environmental conditions. In conclusion, some population groups were found to be at greater risk of psychological burden during pandemic waves, thus representing priority targets for socio-health interventions.

Pilot Study: Immune Checkpoints Polymorphisms in Greek Primary Breast Cancer Patients.

Background: Breast cancer is the most prevalent and second leading cause of cancer-related death in women worldwide. Despite early detection and better treatment therapies, 30% of early-stage breast cancer patients still develop recurrent disease. Breast cancer is a heterogeneous disease comprising several molecular subtypes, commonly classified into clinical subtypes based on the hormone receptor status. These subtypes included luminal A and luminal B, which have different prognoses. Breast cancer development and progression involve many factors. Polymorphisms of PD-1, PD-L1, and PD-L2 genes have been previously associated with high risk and prognosis of cancer. However, no studies have associated PD-1, PD-L1, and PD-L2 polymorphisms with primary breast cancer subtypes. Hence, this study evaluated functional single nucleotide polymorphisms of PD-1, PD-L1, and PD-L2 with primary breast cancer subtypes, luminal A, and luminal B. In addition, we evaluated the PD-L1 protein expression in relation to primary breast cancer subtypes and stages. Results: There were no significant differences in the allele frequencies of PD-1 polymorphisms (rs2227981 G>A, rs7421861 A>G, and rs11568821 C>T) and PD-L1 polymorphisms (rs10815225 C>T and rs2282055 T>G) when compared with the general European population. However, a significant difference was detected in one of the PD-L2 polymorphisms (rs1009759 A>G), with the G allele higher in breast cancer patients than in the general European population. A higher prevalence of the T allele of PD-L1 polymorphism rs2282055 T>G was observed in luminal B breast cancer patients compared with luminal A. No significant difference was detected in other polymorphisms. We also observed that the PD-L1 rs2282055 TT genotype was more prevalent in luminal B breast cancer patients compared with luminal A. Our results found no association of the selected SNPs in the PDCD1 gene with breast cancer risk. Similarly, the protein expression data showed that PD-L1 and PD-L2 are associated with an aggressive phenotype, Luminal B, and advanced breast cancer stage. Conclusion: These findings suggest that immune checkpoint polymorphisms are associated with the risk and subtypes of breast cancer.

The burden of illness of patients with paroxysmal nocturnal haemoglobinuria receiving C5 inhibitors in France, Germany and the United Kingdom: Patient-reported insights on symptoms and quality of life.

ObjectivesTo assess the clinical, humanistic and economic burden of paroxysmal nocturnal haemoglobinuria (PNH) among C5 inhibitor (C5i)‐treated patients with PNH.MethodsThis was a web‐based, cross‐sectional survey (01FEB2021‐31MAR2021) of adults with PNH treated with eculizumab (France, Germany, United Kingdom) or ravulizumab (Germany). Self‐reported outcomes included: patient characteristics; patient‐reported symptoms; and standardised patient‐reported outcomes (e.g. Functional Assessment of Chronic Illness Therapy [FACIT]‐Fatigue, European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Core 30 [EORTC QLQ‐C30]).ResultsAmong 71 included patients, 98.6% were C5i‐treated for ≥3 months (88.7% ≥12 months); among those with self‐reported haemoglobin (Hb) levels (n = 63), most (85.7%) were anaemic (defined as ≤12.0 g/dL). Fatigue was the most common symptom at both diagnosis (73.2%) and survey time (63.4%); there were no statistically significant differences in symptom prevalence between treatment subgroups (eculizumab vs. ravulizumab). Total FACIT‐Fatigue and EORTC QLQ‐C30 scores were substantially lower than European general population references, but there were no statistically significant differences between treatment subgroups. Hb‐level subgroups (<10.5 g/dL vs. ≥10.5 d/dL) followed similar trends for all measures, with few significant subgroup differences.ConclusionsResults suggest that there remains a considerable burden and unmet need among C5i‐treated patients with PNH that requires improved therapies.

Harmonization of Human Biomonitoring Studies in Europe: Characteristics of the HBM4EU-Aligned Studies Participants.

Human biomonitoring has become a pivotal tool for supporting chemicals’ policies. It provides information on real-life human exposures and is increasingly used to prioritize chemicals of health concern and to evaluate the success of chemical policies. Europe has launched the ambitious REACH program in 2007 to improve the protection of human health and the environment. In October 2020 the EU commission published its new chemicals strategy for sustainability towards a toxic-free environment. The European Parliament called upon the commission to collect human biomonitoring data to support chemical’s risk assessment and risk management. This manuscript describes the organization of the first HBM4EU-aligned studies that obtain comparable human biomonitoring (HBM) data of European citizens to monitor their internal exposure to environmental chemicals. The HBM4EU-aligned studies build on existing HBM capacity in Europe by aligning national or regional HBM studies. The HBM4EU-aligned studies focus on three age groups: children, teenagers, and adults. The participants are recruited between 2014 and 2021 in 11 to 12 primary sampling units that are geographically distributed across Europe. Urine samples are collected in all age groups, and blood samples are collected in children and teenagers. Auxiliary information on socio-demographics, lifestyle, health status, environment, and diet is collected using questionnaires. In total, biological samples from 3137 children aged 6–12 years are collected for the analysis of biomarkers for phthalates, HEXAMOLL® DINCH, and flame retardants. Samples from 2950 teenagers aged 12–18 years are collected for the analysis of biomarkers for phthalates, Hexamoll® DINCH, and per- and polyfluoroalkyl substances (PFASs), and samples from 3522 adults aged 20–39 years are collected for the analysis of cadmium, bisphenols, and metabolites of polyaromatic hydrocarbons (PAHs). The children’s group consists of 50.4% boys and 49.5% girls, of which 44.1% live in cities, 29.0% live in towns/suburbs, and 26.8% live in rural areas. The teenagers’ group includes 50.6% girls and 49.4% boys, with 37.7% of residents in cities, 31.2% in towns/suburbs, and 30.2% in rural areas. The adult group consists of 52.6% women and 47.4% men, 71.9% live in cities, 14.2% in towns/suburbs, and only 13.4% live in rural areas. The study population approaches the characteristics of the general European population based on age-matched EUROSTAT EU-28, 2017 data; however, individuals who obtained no to lower educational level (ISCED 0–2) are underrepresented. The data on internal human exposure to priority chemicals from this unique cohort will provide a baseline for Europe’s strategy towards a non-toxic environment and challenges and recommendations to improve the sampling frame for future EU-wide HBM surveys are discussed.

Association Between Lipids and Arterial Stiffness for Primary Cardiovascular Prevention in a General Middle-Aged European Population.

BackgroundDyslipidemia contributes to the progression of arterial stiffness (AS). The purpose of this study was to investigate the association of the different lipid parameters with arterial stiffness index (ASI) in a middle-aged population free of cardiovascular (CV) disease.MethodsAmong 71,326 volunteers from the UK Biobank population, total cholesterol (TC), triglycerides (TG), low-density lipoprotein cholesterol (LDL), high-density lipoprotein cholesterol (HDL), lipoprotein (a) [Lp(a)], apolipoproteins A and B (Apo A and Apo B), and ASI were measured. Values for non-HDL, TC/HDL, TG/HDL, and LDL/HDL were calculated. AS was defined as an ASI > 10 m/s. Associations between lipid parameters and ASI were performed using multiple linear logistic regressions. The results reported from univariate models were the squared partial correlation coefficient, r2, and from multivariate models, the adjusted coefficient of determination, R2, to describe the contribution of ASI variability for each lipid parameter.ResultsWe found that TG/HDL was mainly associated with ASI [β = 0.53 (0.01), r2 = 3.66%, p < 0.001 and adjusted β = 0.21 (0.01), R2 = 13.58%, p < 0.001] and AS [odds ratio (OR) = 1.86 (1.80–1.92), r2 = 1.65%, p < 0.001 and adjusted OR = 1.15 (1.13–1.17), R2 = 8.54%, p < 0.001] rather than the others. TG/HDL remained the only lipid parameter that showed added value in linear multivariate models. TG/HDL remained less associated with AS than age (r2 = 5.55%, p < 0.001), mean blood pressure (BP; r2 = 5.31%, p < 0.001), and gender (r2 = 4.44%, p < 0.001), but more highly associated than body mass index (BMI; r2 = 1.95%, p < 0.001), heart rate (HR; r2 = 0.81%, p < 0.001), fasting glucose (r2 = 0.18%, p < 0.001), tobacco (r2 = 0.05%, p < 0.001), and glomerular filtration rate (GFR; r2 = 0.01%, p < 0.001).ConclusionsIn primary CV prevention, lipids, especially through the TG/HDL ratio, could be more instructive in preventing the increase in AS than other modifiable factors.

The genetic architecture of Alzheimer disease risk in the Ohio and Indiana Amish.

SummaryAlzheimer disease (AD) is the most common type of dementia and is currently estimated to affect 6.2 million Americans. It ranks as the sixth leading cause of death in the United States, and the proportion of deaths due to AD has been increasing since 2000, while the proportion of many other leading causes of deaths have decreased or remained constant. The risk for AD is multifactorial, including genetic and environmental risk factors. Although APOE ε4 remains the largest genetic risk factor for AD, more than 26 other loci have been associated with AD risk. Here, we recruited Amish adults from Ohio and Indiana to investigate AD risk and protective genetic effects. As a founder population that typically practices endogamy, variants that are rare in the general population may be of a higher frequency in the Amish population. Since the Amish have a slightly lower incidence and later age of onset of disease, they represent an excellent and unique population for research on protective genetic variants. We compared AD risk in the Amish and to a non-Amish population through APOE genotype, a non-APOE genetic risk score of genome-wide significant variants, and a non-APOE polygenic risk score considering all of the variants. Our results highlight the lesser relative impact of APOE and differing genetic architecture of AD risk in the Amish compared to a non-Amish, general European ancestry population.

Changes in alcohol use during the COVID-19 pandemic in Europe: A meta-analysis of observational studies.

IssuesNumerous studies have examined the impact of the COVID‐19 pandemic on alcohol use changes in Europe, with concerns raised regarding increased use and related harms.ApproachWe synthesised observational studies published between 1 January 2020 and 31 September 2021 on self‐reported changes in alcohol use associated with COVID‐19. Electronic databases were searched for studies evaluating individual data from European general and clinical populations. We identified 646 reports, of which 56 general population studies were suitable for random‐effects meta‐analyses of proportional differences in alcohol use changes. Variations by time, sub‐region and study quality were assessed in subsequent meta‐regressions. Additional 16 reports identified were summarised narratively.Key FindingsCompiling reports measuring changes in overall alcohol use, slightly more individuals indicated a decrease than an increase in their alcohol use during the pandemic [3.8%, 95% confidence interval (CI) 0.00–7.6%]. Decreases were also reported more often than increases in drinking frequency (8.0%, 95% CI 2.7–13.2%), quantity consumed (12.2%, 95% CI 8.3–16.2%) and heavy episodic drinking (17.7%, 95% CI 13.6–21.8%). Among people with pre‐existing high drinking levels/alcohol use disorder, high‐level drinking patterns appear to have solidified or intensified.ImplicationsPandemic‐related changes in alcohol use may be associated with pre‐pandemic drinking levels. Increases among high‐risk alcohol users are concerning, suggesting a need for ongoing monitoring and support from relevant health‐care services.ConclusionOur findings suggest that more people reduced their alcohol use in Europe than increased it since the onset of the pandemic. However high‐quality studies examining specific change mechanisms at the population level are lacking.

European interlaboratory comparison investigations (ICI) and external quality assurance schemes (EQUAS) for the analysis of bisphenol A, S and F in human urine: Results from the HBM4EU project

The Human Biomonitoring for Europe initiative (HBM4EU) aims to study the exposure of citizens to chemicals and potentially associated health effects. One objective of this project has been to build a network of laboratories able to answer to the requirements of European human biomonitoring studies. Within the HBM4EU quality assurance and quality control scheme (QA/QC), a number of interlaboratory comparison investigations (ICIs) and external quality assurance schemes (EQUASs) were organized to ensure data consistency, comparability and reliability. Bisphenols are among the prioritized substance groups in HBM4EU, including bisphenol A (BPA), bisphenol S (BPS) and bisphenol F (BPF) in human urine. In four rounds of ICI/EQUAS, two target concentration levels were considered, related to around P25 and P95 of the typical exposure distribution observed in the European general population. Special attention was paid to the conjugated phase II metabolites known to be most dominant in samples of environmentally exposed individuals, through the analysis of both native samples and samples fortified with glucuronide forms. For the low level, the average percentage of satisfactory results across the four rounds was 83% for BPA, 71% for BPS and 62% for BPF. For the high level, the percentages of satisfactory results increased to 93% for BPA, 89% for BPS and 86% for BPF. 24 out of 32 participating laboratories (75%) were approved for the analyses of BPA in the HBM4EU project according to the defined criterion of Z-scores for both low and high concentration levels in at least two ICI/EQUAS rounds. For BPS and BPF, the number of qualified laboratories was 18 out of 27 (67%) and 13 out of 28 (46%), respectively. These results demonstrate a strong analytical capability for BPA and BPS in Europe, while improvements may be needed for BPF.

How accurate is forensic facial identification of surgically altered faces?

ABSTRACT Surgical alterations of the face have been shown to be a defining factor in alterations of physical appearance. It is estimated that 5% of the population undergo corrective procedures of the jaws for aesthetic or health purposes. To date, however, practitioners have been lacking guidelines specifying the way facial identification should be conducted. The present study explores the effect of oral and maxillofacial surgeries on landmark-based algorithms when conducted on 3D imagery. The sample composed of 50 pre-op and post-op 3D face images of individuals who had undergone corrective surgeries was tested against a set of 500 faces from the general European population. An approach based on discrete points was employed while the number of landmarks was gradually reduced to minimize intra-person and maximize inter-person variance. The results showed that the presence of surgical modifications resulted in misclassifications based on the mid-face and lower face features, particularly upper lip protrusion and shape, lower lip protrusion, and chin protrusion. The optimal set of landmarks which avoided the surgically affected regions reached an accuracy of 92% at the rank of 1% and 98% at the rank of 5. Across all tested landmark configurations, males were consistently less prone to mismatches than females.

Psychological impact of the quarantine during the COVID-19 pandemic on the general European adult population: a systematic review of the evidence.

Due to the coronavirus disease 2019 (COVID-19) different countries implemented quarantine measures to limit the spread of the virus. Many studies analysed the mental health consequences of restrictive confinement, some of which focused their attention on specific populations. The general public's mental health also requires significant attention, however. This study aimed to evaluate the effects of the COVID-19 quarantine on the general population's mental health in different European countries. Risk and protective factors associated with the psychological symptoms were analysed. A systematic search was conducted on four electronic databases (PubMed, PsycINFO, Scopus and Google Scholar). Studies published up until 20th April 2021, and following eligibility criteria were selected for this review. One thousand three hundred thirty-five (1335) studies were screened, 105 of which were included. Via network analysis, the current study investigated the pathways that underlie possible risk factors for mental health outcomes. Anxiety, depression, distress and post-traumatic symptoms are frequently experienced during the COVID-19 quarantine and are often associated with changes in sleeping and eating habits. Some socio-demographic and COVID-19-related variables were found to be risk factors for an individual's wellbeing. In particular, being female, young, having a low income, being unemployed and having COVID-19-like symptoms or chronic disorders, were found to be the most common risk factors for mental health symptoms. The COVID-19 pandemic represented an unprecedented threat to mental health globally. In order to prevent psychological morbidity and offer support tailored to short-, medium- and long-term negative outcomes, it is essential to identify the direct and indirect psychosocial effects of the lockdown and quarantine measures, especially in certain vulnerable groups. In addition to measures to reduce the curve of viral transmission, policy makers should urgently take into consideration provisions to alleviate hazards to mental health.

Usefulness of the waist-to-height ratio for predicting cardiometabolic risk in children and its suggested boundary values

Only limited information is available on the usefulness of the waist-to-height ratio (WHtR) as an abdominal obesity marker in children. Our aim was to compare the ability of a WHtR >90th percentile, a WHtR ≥0.50, a WHtR ≥0.55 and a BMI z-score ≥2 SD to predict cardiometabolic risk in children followed-up at different ages. We evaluated data from 660 children at 5, 8 and 11 years of age who participated in the Childhood Obesity Project trial in 5 European countries. We classified children with or without cardiometabolic (CMet) risk (yes vs. no) according to the presence of ≥2 parameters (blood pressure, HOMA-IR, triglyceride levels and high-density lipoprotein (HDL) cholesterol levels) ≥90th percentile. The odds ratio for CMet risk in children at all followed-up ages was statistically significant for all measures. The OR for the WHtR≥0.55 cut-off was 29.1 (5.6, 151.7) at 5 years of age, 11.8 (4.1, 33.8) at 8 year of age and 3.6 (1.7, 7.7) at 11 years of age, compared to the WHtR<0.55 cut-off. The WHtR≥0.55 cut-off showed a higher OR at younger ages than the BMI z-score ≥2SD, WHtR ≥90th percentile and WHtR≥0.50 cut-offs and a higher positive predictive value (82% at 5 years of age compared to 55%, 36% and 41%, respectively). A WHtR≥0.55 is a suitable cut-off for screening children at high cardiometabolic risk in the general young European population.

Circulating miRNAs as Potential Biomarkers for Celiac Disease Development.

Background & AimsCeliac disease (CeD), an immune-mediated disease with enteropathy triggered by gluten, affects ~1% of the general European population. Currently, there are no biomarkers to predict CeD development. MicroRNAs (miRNAs) are short RNAs involved in post-transcriptional gene regulation, and certain disease- and stage-specific miRNA profiles have been found previously. We aimed to investigate whether circulating miRNAs can predict the development of CeD.MethodsUsing next-generation miRNA-sequencing, we determined miRNAs in >200 serum samples from 53 participants of the PreventCD study, of whom 33 developed CeD during follow-up. Following study inclusion at 3 months of age, samples were drawn at predefined ages, diagnosis (first anti-transglutaminase antibody (TGA) positivity or diagnostic biopsy) and after the start of a gluten-free diet (GFD). This allowed identification of circulating miRNAs that are deregulated before TGA positivity. For validation of the biomarkers for CeD and GFD response, two additional cohorts were included in subsequent meta-analyses. Additionally, miRNAs were measured in duodenal biopsies in a case-control cohort.Results53 circulating miRNAs were increased (27) or decreased (26) in CeD versus controls. We assessed specific trends in these individual miRNAs in the PreventCD cohort by grouping the pre-diagnostic samples of the CeD patients (all had negative TGA) by how close to seroconversion (first sample positive TGA) the samples were taken. 8/53 miRNAs differed significantly between controls and samples taken <1 year before TGA positivity: miR-21-3p, miR-374a-5p, 144-3p, miR-500a-3p, miR-486-3p let-7d-3p, let-7e-5p and miR-3605-3p. 6/26 downregulated miRNAs reconstituted upon GFD, including miR-150-5p/-3p, whereas no upregulated miRNAs were downregulated upon GFD. 15/53 biomarker candidates also differed between CeD biopsies and controls, with a concordant direction, indicating that these circulating miRNAs might originate from the intestine.ConclusionsWe identified 53 circulating miRNAs that are potential early biomarkers for CeD, of which several can be detected more than a year before TGA positivity and some start to normalize upon GFD.

Genetic risk score for Alzheimer's disease in the Amish highlights differences in the genetic architecture compared to other European ancestry populations.

Alzheimer's disease is the most prevalent type dementia and has a strong genetic component. Much of AD genomic research has focused on identifying risk variants, primarily in European ancestry populations. After immigration to the United States, the Amish experienced a genetic bottleneck, making it likely that their underlying genetic architecture is different from the broader European ancestry population. Here, we compare the genetic risk for Alzheimer's disease in an Amish and general European ancestry population using genetic risk scores (GRSs). 1,981 adults were recruited from Amish communities in Indiana and Ohio. A non-Amish population of 2,470 adults were recruited from clinics in Tennessee, North Carolina, and Florida as a comparison group. Subjects were screened for cognitive impairment and further evaluated for AD and dementia. Genotype data were collected using Illumina genotyping chips. Imputation was performed based on a 1,000 Genomes reference panel. GRSs were generated using genome-wide significant variants from Kunkle et al., (2019), weighted by their log-odds ratios. We compared the GRSs by source population and case status. Further, we evaluated their predictive ability on AD status with and without sex, age, and APOE genotype covariates. The results indicated that there exists less variation in GRSs among the Amish population. This is evident in how the four highest GRSs belonged to non-Amish individuals. The median GRS of Amish cases was also moderately lower overall among Amish cases (0.0163) compared to non-Amish cases (0.0171). In the Amish population, area under curve (AUC) of the GRS model was strengthened considerably from 0.541 to 0.872 by inclusion of the sex and age covariates and slightly (AUC=0.883) by further inclusion of APOE genotype. In the non-Amish group, inclusion of sex and age improved AUC from 0.583 to 0.697 and to 0.817 by subsequent inclusion of APOE genotype. These results suggest that the Amish have a different genetic architecture than a general European-ancestry population, manifesting itself in less overall variation but also a lower relative importance of APOE. Since the prevalence of dementia in the Amish is similar to the general European population, this suggests the Amish may harbor unique AD genetic risk variants.

Recurrence of Graves' Disease: What Genetics of HLA and PTPN22 Can Tell Us.

BackgroundApproximately half of patients diagnosed with Graves’ disease (GD) relapse within two years of thyreostatic drug withdrawal. It is then necessary to decide whether to reintroduce conservative treatment that can have serious side effects, or to choose a radical approach. Familial forms of GD indicate a significant genetic component. Our aim was to evaluate the practical benefits of HLA and PTPN22 genetic testing for the assessment of disease recurrence risk in the Czech population.MethodsIn 206 patients with GD, exon 2 in the HLA genes DRB1, DQA1, DQB1 and rs2476601 in the gene PTPN22 were sequenced.ResultsThe risk HLA haplotype DRB1*03-DQA1*05-DQB1*02 was more frequent in our GD patients than in the general European population. During long-term retrospective follow-up (many-year to lifelong perspective), 87 patients relapsed and 26 achieved remission lasting over 2 years indicating a 23% success rate for conservative treatment of the disease. In 93 people, the success of conservative treatment could not be evaluated (thyroidectomy immediately after the first attack or ongoing antithyroid therapy). Of the examined genes, the HLA-DQA1*05 variant reached statistical significance in terms of the ability to predict relapse (p=0.03). Combinations with either both other HLA risk genes forming the risk haplotype DRB1*03-DQA1*05-DQB1*02 or with the PTPN22 SNP did not improve the predictive value.Conclusionthe DQA1*05 variant may be a useful prognostic marker in patients with an unclear choice of treatment strategy.

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.

Separating Fact from Fiction in the Diagnosis and Management of Food Allergy

Separating Fact from Fiction in the Diagnosis and Management of Food Allergy

Association of glycated haemoglobin A1c levels with cardiovascular outcomes in the general population: results from the BiomarCaRE consortium

Abstract Background Glycated haemoglobin A1c (HbA1c) is used to monitor the quality of diabetes treatment; however, its role in predicting cardiovascular outcomes in the general population remains uncertain. Purpose The additional use of glycated haemoglobin A1c (HbA1c) as a biomarker might highlight subjects of the general population with an increased risk for cardiovascular outcomes with cardiovascular disease, cardiovascular mortality or overall-mortality. Methods Data from six prospective population-based cohort studies across Europe comprising 36,180 participants were analysed. HbA1c was evaluated in conjunction with classical cardiovascular risk factors (CVRFs) for association with cardiovascular mortality, cardiovascular diseases (CVD), and overall mortality in the study population, in non-diabetic (N=32,477), and diabetic participants (N=3,703). Results Kaplan-Meier curves showed higher event rates with increasing continuous log-transformed HbA1c levels. Cox regression analysis revealed significant associations between HbA1c (in mmol/mol) log-transformed divided by interquartile range and the examined outcomes, with a hazard ratio (HR) of 1.12 (95% confidence interval (CI): 1.04–1.20, p=0.0019) for cardiovascular mortality, 1.10 (95% CI: 1.04–1.16, p&amp;lt;0.001) for CVD, and 1.09 (95% CI: 1.05–1.14, p&amp;lt;0.001) for overall mortality per one unit increase. An increased risk of CVD was observed in subjects without diabetes with increased HbA1c levels (HR 1.09; 95% CI: 1.01–1.16, p=0.021). An HbA1c cut-off value of 39.89 mmol/mol (5.8%), 36.62 mmol/mol (5.5%), and 38.80 mmol/mol (5.7%) for cardiovascular mortality, CVD, and overall mortality, respectively, was determined for selecting individuals at an increased risk. Conclusion HbA1c was demonstrated to be an independent prognostic biomarker for all investigated outcomes in the general European population. An approximately linear relationship was observed between an increase of HbA1c levels and the outcomes. Elevated HbA1c levels were also associated with the outcomes in participants without diabetes (i.e. HbA1c levels &amp;lt;6.5% (&amp;lt;48mmol/mol) which underlines the importance of HbA1c levels in the overall population. Funding Acknowledgement Type of funding sources: Public grant(s) – EU funding. Main funding source(s): European Union Seventh Framework ProgrammeEuropean Union FP 7 project CHANCES Kaplan-Meier curves for the outcomesPenalised cubic splines HbA1c/time event

Targeted exome analysis of Russian patients with hypertrophic cardiomyopathy.

BackgroundHypertrophic cardiomyopathy (HCM), described as the presence of hypertrophy of left ventricular, is the most prevalent heritable cardiovascular disease with predominantly an autosomal dominant type of inheritance. However, pathogenic alleles are not identified in at least 25% of patients with HCM, and the spectrum of pathogenic variants that contribute to the development of HCM in Russia has not been fully described. Therefore, the goal of our study was to identify genetic variants associated with the etiopathogenesis of HCM in Russian patients.MethodsThe study cohort included 98 unrelated adult patients with HCM. We performed targeted exome sequencing, an analysis using various algorithms for prediction of the impact of variants on protein structure and the prediction of pathogenicity using ACMG Guidelines.ResultsThe frequency of pathogenic and likely pathogenic variants in all HCM‐related genes was 8% in our patients. We also identified 20 variants of uncertain significance in all HCM‐related genes.ConclusionsThe prevalence of individual pathogenic variants in HCM‐related genes in Russian population appears to be lower than in general European population, which could be explained by ethnic features of Russian population, age characteristics of our sample, or unidentified pathogenic variants in genes previously not linked with HCM.

Lead (Pb) and neurodevelopment: A review on exposure and biomarkers of effect (BDNF, HDL) and susceptibility.

Lead (Pb) is a ubiquitous environmental pollutant and a potent toxic compound. Humans are exposed to Pb through inhalation, ingestion, and skin contact via food, water, tobacco smoke, air, dust, and soil. Pb accumulates in bones, brain, liver and kidney. Fetal exposure occurs via transplacental transmission. The most critical health effects are developmental neurotoxicity in infants and cardiovascular effects and nephrotoxicity in adults. Pb exposure has been steadily decreasing over the past decades, but there are few recent exposure data from the general European population; moreover, no safe Pb limit has been set. Sensitive biomarkers of exposure, effect and susceptibility, that reliably and timely indicate Pb-associated toxicity are required to assess human exposure-health relationships in a situation of low to moderate exposure. Therefore, a systematic literature review based on PubMed entries published before July 2019 that addressed Pb exposure and biomarkers of effect and susceptibility, neurodevelopmental toxicity, epigenetic modifications, and transcriptomics was conducted. Finally included were 58 original papers on Pb exposure and 17 studies on biomarkers. The biomarkers that are linked to Pb exposure and neurodevelopment were grouped into effect biomarkers (serum brain-derived neurotrophic factor (BDNF) and serum/saliva cortisol), susceptibility markers (epigenetic markers and gene sequence variants) and other biomarkers (serum high-density lipoprotein (HDL), maternal iron (Fe) and calcium (Ca) status). Serum BDNF and plasma HDL are potential candidates to be further validated as effect markers for routine use in HBM studies of Pb, complemented by markers of Fe and Ca status to also address nutritional interactions related to neurodevelopmental disorders. For several markers, a causal relationship with Pb-induced neurodevelopmental toxicity is likely. Results on BDNF are discussed in relation to Adverse Outcome Pathway (AOP) 13 ("Chronic binding of antagonist to N-methyl-D-aspartate receptors (NMDARs) during brain development induces impairment of learning and memory abilities") of the AOP-Wiki. Further studies are needed to validate sensitive, reliable, and timely effect biomarkers, especially for low to moderate Pb exposure scenarios.

Drug Therapy and Adherence in Patients With Coronary Heart Disease: Results of the Russian Part of the EUROASPIRE V International Multicenter Study.

Aim To study the practice of drug treatment of ischemic heart disease (IHD) and the consistency of this practice with the established guidelines.Material and methods Results of the Russian part of the EUROASPIRE V study were compared with the general European population of the study. At ≥6 mos. and &lt;2 years after the discharge from the hospital, patients were invited to visit the site for an interview. The drug therapy recommended upon discharge and taken by patients in the long-term as well as the patients' compliance with the treatment were analyzed. In Russian centers, 699 patients were registered, and 399 of them visited the centers for the interview.Results Upon discharge from the hospital, patients of the Russian cohort and of the entire study population were prescribed acetylsalicylic acid or other antiplatelet drugs (99.2% and 94.1%, respectively); beta-blockers (87.2 and 81.6%, respectively); angiotensin-converting enzyme (ACE) inhibitors (69.9% and 61.1%, respectively); sartans (16.5% and 14.2 %, respectively); calcium channel blockers (19.3 and 19.4 %, respectively); nitrates (8.0% and 22.5 %, respectively); diuretics (31.1 and 32.5 %, respectively); statins (98.0% and 85.0 %, respectively); and anticoagulants (6.6 and 8.3 %, respectively). For the long-term treatment, patients of the Russian cohort and of the entire study population took antiplatelets (94.7 % and 92.5 %, respectively); beta-blockers (83.2% and 81.0 %, respectively); ACE inhibitors (60.2% and 57.3 %, respectively); sartans (19.3% and 18.4 %, respectively); calcium antagonists (21.1% and 23.0 %, respectively); nitrates (9.0% and 18.2 %, respectively); diuretics (31.8% and 33.3 %, respectively); statins (88.2% and 80.8 %, respectively); and anticoagulants (8.8% and 8.2 %, respectively). High intensity hypolipidemic therapy was prescribed to 54.0 % of patients in Russian centers and 60.3 % of patients in the entire study. Both Russian and international patients evaluated their compliance with the prescribed medication as high.Conclusion According to results of the EUROASPIRE V study as compared to earlier studies, the practice of drug therapy in Russian patients with IHD has significantly approached European indexes. Further optimization is possible by a more extensive use of high intense hypolipidemic treatment and antidiabetic drugs with a documented positive effect on prognosis of cardiovascular diseases.