Importance of primary dyslipidemia in the context of current dyslipidemia guidelines and current innovations in lipid therapy

Background The core of current guidelines for the prevention of cardiovascular disease is the recommendation of a risk-based intensity of LDL-cholesterol-lowering measures. Specific primary dyslipidemias might only be particulary addressed in the guidelines. Method Selective literature review on diagnosis and clinical significance of primary dyslipidemia and new lipid-lowering agents. Results Current dyslipidemia guidelines do not adequately address the importance of congenital dyslipidemia in risk stratification. This is particularly true for genetically determined elevations of triglycerides. We discuss specific aspects of the treatment of primary dyslipidemia and new lipid-lowering agents such as bempedoic acid, icosapent-ethyl, and siRNA technology-based PCSK9 inhibition with inclisiran, which have not yet been considered in the guidelines. New data on pharmacological Lp(a)-lowering as well as triglyceride- and cholesterol-lowering effects of ANGPTL3 inhibition justify the expectation that remaining therapeutic gaps will be closed in the very near future. Conclusion From the diagnosis of a genetic lipid metabolism disorder and thus lifelong increased exposure to atherogenic lipoproteins, there are prognostic and therapeutic implications for individualized therapies with the avoidance of both under- and overtreatment. New lipid-lowering agents may improve the achievement of risk-appropriate treatment goals

CaRe high - Cascade screening and registry for high cholesterol in Germany

Introduction: Familial hypercholesterolemia (FH) is an inherited disorder of the LDL metabolism, leading to cardiovascular disease, even at young age. This risk can be significantly lowered by early diagnosis and treatment. About 270,000 patients affected in Germany are not diagnosed correctly and only a small number is treated properly. To improve FH diagnosis in the general population a cascade screening and registry data is warranted, yet missing in Germany. This project aims to fill this gap. Methods: Study assistants approach physicians and lipid clinics to introduce the cascade screening and registry. The physicians identify potential FH patients and include them in the study. Patient data is acquired via questionnaires about medical history. Patients meeting at least two inclusion criteria (LDL-C > 190 mg/dl or total cholesterol > 290 mg/dl; tendon xanthomas; family history of hypercholesterolemia or early myocardial infarction) are included in the registry. Family members will be contacted and physicians get feedback about diagnosis and treatment options. Ethical approvals for all German states have been collected. Results: So far physicians, lipid clinics and patients within the Rhein-Neckar region, the Saarland, North-Rhine-Westphalia, Upper Bavaria, Bremen, Saxonia and Berlin have joined the study. We expect to include more than 3000 patients during the next two years. Conclusion: After initial patient and data collection the project aims to improve FH-diagnosis and treatment. Utilizing registry data might advance diagnostic criteria and improve detection of FH and thus prevent CVD in this population. (C) 2017 Published by Elsevier Ireland Ltd

Mathematics education today and tomorrow: Challenges and perspectives

Dieser Tagungsband dokumentiert die Ergebnisse der 29. Jahrestagung des Arbeitskreises Grundschule in der Gesellschaft für Didaktik der Mathematik (GDM), die am 11. und 12. November 2022 digital stattfand. Die Tagung stand unter dem Thema „Mathematische Bildung heute und morgen: Herausforderungen und Perspektiven“. Mathematische Bildung in der Grundschule steht vor immer wieder neuen Herausforderungen, auch aufgrund gesellschaftlicher Veränderungen. Im Rahmen der drei Hauptvorträge wurden die (1) Digitalisierung, (2) Mehrsprachigkeit und (3) Inklusion adressiert. Weiter setzten sich sieben Arbeitsgruppen mit den Themenfeldern ‚Arithmetik‘, ‚Geometrie‘, ‚Sachrechnen‘, ‚Kommunikation & Kooperation‘, ‚Lernen, Lehren und Forschen mit digitalen Medien‘, ‚Frühe mathematische Bildung‘ sowie ‚Lehrerbildung‘ intensiv mit aktuellen Forschungs- und Praxisfragen auseinander. Die zentralen Inhalte der Arbeitsgruppen sind in diesem Band ebenfalls dokumentiert.The Proceedings of the 2022 Conference of the Research Group on Primary Mathematics Education (Arbeitskreis Grundschule in der GDM) focus on current and future challenges and perspectives of mathematics education in primary school. Three invited talks addressed the main theme in each one of the aspects digitalisation, multilingualism and inclusion in plenum. Additionally, workings groups on the research areas arithmetic, geometry, modelling, as well as groups on early mathematics education, communication & co-operation, ICT education, and last not least on teacher education offered discussions on current research issues

Lipid-modifying therapy and low-density lipoprotein cholesterol goal attainment in patients with familial hypercholesterolemia in Germany: The CaReHigh Registry

Background and aims: Familial hypercholesterolemia (FH) is amongst the most common genetic disorders encountered in primary care. Yet, only a minority of affected patients is diagnosed and treated. This interim analysis of the CaRe High Registry aims at examining the state of treatment and attainment of lipid goals in German FH patients. Methods: The CaRe High registry includes FH patients from lipid clinics and private practices. Data have been collected using questionnaires filled in by the recruiting physicians and by interviewing the participating patients. Results: We examined 512 F H patients diagnosed according to clinical criteria. Median age at the time of the first FH diagnosis was 39 (25th and 75th percentile: 27-50) years, median treatment naive LDL cholesterol (LDLC) was 239.4 mg/dl (6.19 mmol/l), 25th to 75th percentile 191.8-342.5 mg/dl (4.96-8.86 mmol/l). 27% of the participants did not receive lipid-lowering drugs. Among the patients treated with lipid-lowering drugs, 19% received a PCSK9 inhibitor (PCSK9i) in combination with a statin, 9% were treated with a PCSK9i alone and 3% were treated with a combination of PCSK9i and a non-statin drug. Patients with pre-existing CVD were more likely to be treated with lipid-lowering drugs and more likely to receive a PCSK9i, but LDL-C targets were only achieved by a minority of patients (<20%). Gap to target LDL-C was lowest and the median achieved LDL-C reduction was 1.4 times higher with PCSK9i treatment than with (oral) lipid-lowering therapy without PCSK9i. Conclusions: The Care High registry has included patients with the typical clinical features of familial hypercholesterolemia. PCSK9i treatment in addition to standard therapy allows attainment of target values in many patients with initially very high LDL-C

The German CaRe high registry for familial hypercholesterolemia – Sex differences, treatment strategies, and target value attainment

Background and aims: Familial hypercholesterolemia (FH) is among the most common genetic disorders in primary care. However, only 15% or less of patients are diagnosed, and few achieve the goals for low-density lipoprotein cholesterol (LDL-C). In this analysis of the German Cascade Screening and Registry for High Cholesterol (CaRe High), we examined the status of lipid management, treatment strategies, and LDL-C goal attainment according to the ESC/EAS dyslipidemia guidelines. Methods: We evaluated consolidated datasets from 1501 FH patients diagnosed clinically and seen either by lipid specialists or general practitioners and internists. We conducted a questionnaire survey of both the recruiting physicians and patients. Results: Among the 1501 patients, 86% regularly received lipid-lowering drugs. LDL-C goals were achieved by 26% and 10% of patients with atherosclerotic cardiovascular disease (ASCVD) according to the 2016 and 2019 ESC/EAS dyslipidemia guidelines, respectively. High intensity lipid-lowering was administered more often in men than in women, in patients with ASCVD, at higher LDL-C and in patients with a genetic diagnosis of FH. Conclusions: FH is under-treated in Germany compared to guideline recommendations. Male gender, genetic proof of FH, treatment by a specialist, and presence of ASCVD appear to be associated with increased treatment intensity. Achieving the LDL-C goals of the 2019 ESC/EAS dyslipidemia guidelines remains challenging if pre-treatment LDL-C is very high