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.

Phytosterols and Cardiovascular Risk Evaluated against the Background of Phytosterolemia Cases-A German Expert Panel Statement.

Phytosterols (PSs) have been proposed as dietary means to lower plasma LDL-C. However, concerns are raised that PSs may exert atherogenic effects, which would offset this benefit. Phytosterolemia was thought to mimic increased plasma PSs observed after the consumption of PS-enriched foods. This expert statement examines the possibility of specific atherogenicity of PSs based on sterol metabolism, experimental, animal, and human data. Observational studies show no evidence that plasma PS concentrations would be associated with an increased risk of atherosclerosis or cardiovascular (CV) events. Since variants of the ABCG5/8 transporter affect the absorption of cholesterol and non-cholesterol sterols, Mendelian randomization studies examining the effects of ABCG5/8 polymorphisms cannot support or refute the potential atherogenic effects of PSs due to pleiotropy. In homozygous patients with phytosterolemia, total PS concentrations are ~4000% higher than under physiological conditions. The prevalence of atherosclerosis in these individuals is variable and may mainly relate to concomitant elevated LDL-C. Consuming PS-enriched foods increases PS concentrations by ~35%. Hence, PSs, on a molar basis, would need to have 20-40 times higher atherogenicity than cholesterol to offset their cholesterol reduction benefit. Based on their LDL-C lowering and absence of adverse safety signals, PSs offer a dietary approach to cholesterol management. However, their clinical benefits have not been established in long-term CV endpoint studies.

[Therapeutic options to reduce LDL-cholesterol beyond statins]. / Therapieoptionen zur LDL-C-Senkung zusätzlich zu Statinen.

Current dyslipidemia guidelines emphasize statins as the cornerstone of pharmacological lipid-lowering therapy. The cholesterol absorption inhibitor ezetimibe, PCSK9-antibodies, as well as bempedoic acid and inclisiran are newly available options to further reduce LDL-cholesterol. Since modern lipid-lowering therapy is characterized by an individual, "treat-to-target" approach the aim of this review is to provide a better understanding of cholesterol metabolism to guide decision-making and the rational for using early individualized combination therapies.

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 naïve LDL cholesterol (LDL-C) 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.

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.

Familial hypercholesterolemia: developments in diagnosis and treatment.

BACKGROUND: Familial hypercholesterolemia (FH) is a congenital disorder of lipid metabolism characterized by a marked elevation of the plasma concentration of LDL (low-density lipoprotein) cholesterol beginning in childhood and by the early onset of coronary heart disease. It is among the commonest genetic disorders, with an estimated prevalence in Germany of at least 1 per 500 persons. METHOD: Review of pertinent literature retrieved by a selective search. RESULTS: FH is underdiagnosed and undertreated in Germany. It is clinically diagnosed on the basis of an elevated LDL cholesterol concentration (>190 mg/dL [4.9 mmol/L]), a family history of hypercholesterolemia, and early coronary heart disease, or the demonstration of xanthomas. The gold standard of diagnosis is the identification of the underlying genetic defect, which is possible in 80% of cases and enables the identification of affected relatives of the index patient. The recommended goals of treatment, based on the results of observational studies, are to lower the LDL cholesterol concentration by at least 50% or to less than 100 mg/dL (2.6 mmol/L) (for children: <135 mg/dL [3.5 mmol/L]). The target value is lower for patients with clinically overt atherosclerosis (<70 mg/dL [1.8 mmol/L]). Statins, combined with a health-promoting lifestyle, are the treatment of choice. Lipoprotein apheresis is used in very severe cases; its therapeutic effects on clinical endpoints and its side effect profile have not yet been documented in randomized controlled trials. CONCLUSION: Familial hypercholesterolemia is a common disease that can be diagnosed simply and reliably on clinical grounds and by molecular genetic testing. Timely diagnosis and appropriate treatment can lower the risk of atherosclerosis in heterozygous patients to that of the general population.

New AHA and ACC guidelines on the treatment of blood cholesterol to reduce atherosclerotic cardiovascular risk.

After the publication of the new guidelines of the European Society of Cardiology and the European Atherosclerosis Society for the prevention and treatment of dyslipidemias (Eur Heart J 32:1769-1818, 2011; Eur Heart J 33:1635-1701, 2012), a group of authors has recently published on behalf of the American Heart Association and the American College of Cardiology guidelines on the treatment of blood cholesterol to reduce atherosclerotic cardiovascular risk (Circulation 2013). These new guidelines are supposed to replace the until now widely accepted, at least in the USA, recommendations of the National Cholesterol Education Program Adult Treatment Panel III from the years 2002 (Circulation 106:3143-3421, 2002) and 2004 (Circulation 110:227-39, 2004). Furthermore, they claim to be based mainly on hard evidence derived from the interpretation of results of prospective randomized controlled trials. This Joint Position Statement of the Society for the Prevention of Cardiovascular Diseases e.V. (D.A.CH), the Austrian Atherosclerosis Society and the Working Group on Lipids and Atherosclerosis (AGLA) of the Swiss Society of Cardiology concludes that the use of individualized prevention strategies based on specific indications and LDL cholesterol target concentrations, a strategy whose worth has been widely proven and accepted for more than a decade in Europe, should not be given up.

[Assessing the risk of HDL cholesterol]. / Erst mal Waldlauf und vernünftige Ernährung? Wie Sie das "gute Cholesterin" ankurbeln.

Low HDL cholesterol levels represent a significant cardiovascular risk factor. HDL not only has a central role in the reverse transport of cholesterol but, independently of this, presumably also has anti-oxidative, anti-inflammatory, antithrombotic and endothelium-regulating properties. The reasons for lowered HDL cholesterol levels are manifold (genetic inheritance, life style). Measures with an influence on life style can have a decisive impact on the HDL cholesterol level. Medication-based options are much less well established, and the clinical endpoints less well investigated than the corresponding options for LDL-lowering drug therapies. Among the drugs currently available, niacin has the most pronounced HDL-elevating effect.