Search

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., Competing Interests: The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: NS was project lead of the CaRe High registry, which is financed in cooperation with Amgen GmbH and Sanofi-Aventis GmbH. IaH reports lecture fees from Synlab. NS reports non-financial support from Amgen GmbH during the conduct of the study. AD is employed by the CaRe High registry. TBG, AB, ACK, WR, CK, MM, KSJ, JLK, and CBO have nothing to disclose. IGB has received honoraria for consulting and/or lecture fees from Amgen, Sanofi-Aventis, Aegereon, Regeneron, Novartis, Pfizer, Synlab, Akcea Therapeutics, and Daiichi-Sankyo and institutional support from Amgen, Sanofi-Aventis, Akcea Therapeutics, DACH, and Novartis. HH reports lecture fees from Amgen, Berlin-Chemie, Daiichi-Sankio, Pfizer, and Sanofi-Aventis. SK received honoraria as a speaker and member of advisory boards from Amgen, AstraZeneca, Berlin Chemie, Boehringer Ingelheim, Daiichi Sankyo, Medical Association North Rhine Germany, Novartis, Roche, Sanofi-Aventis, and Servier. FUB reports lecture fees from Amgen, Sanofi-Aventis, and Synlab outside the submitted work. UK reports grants from D.A.C.H. Society for Prevention of cardiovascular disease during the conduct of the study; others from Amgen, Sanofi-Aventis, Alexion, Berlin Chemie, and Fresenius Medical Care outside the submitted work. GK reports lecture/advisory board fees from Akcea, Amgen, BMS, MSD, Sanofi-Aventis, and Synlab outside the submitted work. UJ reports honoraria from Aegerion, Akcea, Amgen, Chiesi, Sanofi-Aventis, Kaneka, Diamed, and Fresenius Medical Care outside the submitted work. WK reports personal fees from AstraZeneca, Novartis, Pfizer, The Medicines Company, DalCor, Kowa, Amgen, Corvidia, Berlin-Chemie, and Sanofi-Aventis, and grants and non-financial support from Beckmann, Singulex, Abbott, and Roche Diagnostics outside the submitted work; BO reports lecture/advisory board fees from Amgen, Amryt, Berlin Chemie, Hexal, MSD, and Sanofi-Aventis outside the submitted work. UL reports personal honoraria for lecture fees and other from Amgen, BerlinChemie, MSD, and Sanofi-Aventis outside the submitted work. EST received speakers' honoraria for presentations, advisory board activities, and funding of research projects by Fresenius Medical Care Germany, Amgen, Sanofi-Aventis, and Berlin Chemie. HS reports personal fees from AMGEN, Sanofi-Aventis, and MSD SHARP&DOHME outside the submitted work. KP reports personal fees from Akcea, Amarin, Amgen, Berlin-Chemie, Boehringer-Ingelheim, MSD, Daiichi-Sankyo, and Sanofi-Aventis outside the submitted work. AV reports lecture/advisory board fees from Aegerion, Amgen, Berlin Chemie, Fresenius, MSD, Regeneron/Sanofi-Aventis, and Synlab outside the submitted work. DMW received honoraria as speaker and member of advisory boards from Amarin, Amgen, AstraZeneca, Bayer, Boehringer Ingelheim, MSD, Novo Nordisk, Novartis, Sanofi-Aventis, and Sanofi-Pasteur. US reports honoraria for consultancy and lecturing from Amgen, Amarin, AstraZeneca, Berlin Chemie, Boehringer Ingelheim, Daiichi Sankyo, MSD, Sanofi-Aventis, Synlab, Novartis, and NovoNordisk.WM reports grants and personal fees from Sanofi-Aventis during the conduct of the study; grants from Siemens Healthineers, Astra-Zeneca, Bayer Vital GmbH, bestbion dx GmbH, Boehringer Ingelheim Pharma GmbH Co KG, Immundiagnostik GmbH, Merck Chemicals GmbH, MSD Sharp and Dohme GmbH, Novartis Pharma GmbH, and Olink Proteomics, grants and personal fees from Aegerion Pharmaceuticals, AMGEN, Alexion Pharmaceuticals, BASF, Abbott Diagnostics, Numares AG, Berlin-Chemie, and Akzea Therapeutics, and other from Synlab Holding Deutschland GmbH outside the submitted work., (© 2023 The Authors.)

The R219K polymorphism in the ATP-binding cassette transporter 1 gene ( ABCA1) has been associated with reduced severity of atherosclerosis, fewer coronary events, decreased triglycerides and a trend to increased HDL in men with coronary heart disease (CHD). This study examined the frequency and the effect on CHD and plasma lipids of the polymorphism in patients of both sexes attending a lipid out-patient clinic. The overall frequency of the K allele was 0.26. It was lower in patients with CHD (0.21) than in those without (0.27) but this was not statistically significant. Amongst patients with elevated Lp(a) the frequency of the K allele was significantly lower in those with CHD (0.16) than in those without (0.29). There were no statistically significant differences in total cholesterol, LDL, HDL, apoB or apoAI between carriers and non-carriers. When patients with probable secondary hypertriglyceridaemia (triglycerides >1000 mg/dl), type 2 diabetes and carriers of lipoprotein lipase polymorphisms associated with hypertriglyceridaemia were excluded, the K allele was significantly associated with reduced triglycerides but only in patients with apoE 3/3 genotype. In conclusion, we provide additional evidence that the R219K polymorphism in the ABCA1 gene either directly or as a result of linkage disequilibrium with additional functional variant(s), has a protective effect against CHD and is associated with lower plasma triglycerides in sub-groups of patients with hyperlipidaemia.