Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Review
. 2023 Jun 12:53:6-15.
doi: 10.1016/j.athplu.2023.06.001. eCollection 2023 Sep.

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

Winfried März  1   2   3   4 , Nina Schmidt  1 , Ira An Haack  1 , Alexander Dressel  1 , Tanja B Grammer  2   5 , Marcus E Kleber  2   6 , Andrea Baessler  7 , F Ulrich Beil  8 , Ioanna Gouni-Berthold  9 , Ulrich Julius  10 , Ursula Kassner  11 , Julius L Katzmann  12 , Gerald Klose  13 , Christel König  14 , Wolfgang Koenig  15   16 , Ann-Cathrin Koschker  17 , Ulrich Laufs  12   18 , Martin Merkel  19 , Britta Otte  20 , Klaus G Parhofer  21 , Wibke Hengstenberg  15 , Heribert Schunkert  15 , Ksenija Stach-Jablonski  2 , Elisabeth Steinhagen-Thiessen  11 , Christoph B Olivier  22 , Harry Hahmann  23 , Stefan Krzossok  24 , Anja Vogt  21 , Dirk Müller-Wieland  25 , Ulrike Schatz  10
Affiliations
Review

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

Winfried März et al. Atheroscler Plus. .

Abstract

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.

Keywords: Adherence; Cardiovascular risk; Cascade screening; Familial hypercholesterolemia; Low-density lipoproteins; Patient registry; Treatment.

PubMed Disclaimer

Conflict of interest statement

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.

Figures

Fig. 1
Fig. 1
Status, availability and results of genetic analyses of FH patients participating in the CaRe High registry.
Fig. 2
Fig. 2
Lipid-lowering therapy (LLT) of patients with FH at the time of study inclusion: a) no LLT, b) statins alone; c) combinations without PCKS9i, i.e. two or more of the following agents: statins, ezetimibes, fibrates, bile acid sequestrants; d) oral monotherapy without statins and without PCSK9 inhibitors (PCSK9i); e) PCSK9i alone or in combination with other lipid-lowering agents; f) apheresis alone or in combination with other lipid-lowering therapy.
Fig. 3
Fig. 3
LDL-C goal attainment according to EAS/ESC dyslipidemia guidelines 2016 (A), 2019 (B). Treatment goals were: (A) less than 100 mg/dl (2.6 mmol/l) without pre-existing CVD and less than 70 mg/dl (1.8 mmol/l) for FH patients with pre-existing CVD; (B) less than 70 mg/dl (1.8 mmol/l) for FH without pre-existing CVD or any other cardiovascular risk factor and less than 55 mg/dl (1.4 mmol/l) for FH with pre-existing CVD or another cardiovascular risk factor.
Fig. 4
Fig. 4
Multivariate logistic-regression analysis of therapy intensity adjusted for age, gender, ASVD, obesity, DM, hypertension, corrected LDL-C and genetic test result. The odds ratios (with 95% CIs) to the binary outcomes are shown. ∗ indicates the reference category.
See this image and copyright information in PMC

Similar articles

See all similar articles

Cited by

References

    1. Brænne I., Kleinecke M., Reiz B., Graf E., Strom T., Wieland T., Fischer M., Kessler T., Hengstenberg C., Meitinger T., Erdmann J., Schunkert H. Systematic analysis of variants related to familial hypercholesterolemia in families with premature myocardial infarction. Eur J Hum Genet. 2016;24:191–197. doi: 10.1038/ejhg.2015.100. - DOI - PMC - PubMed
    1. Goldberg A.C., Hopkins P.N., Toth P.P., Ballantyne C.M., Rader D.J., Robinson J.G., Daniels S.R., Gidding S.S., De Ferranti S.D., Ito M.K., McGowan M.P., Moriarty P.M., Cromwell W.C., Ross J.L., Ziajka P.E. Familial hypercholesterolemia: screening, diagnosis and management of pediatric and adult patients: clinical guidance from the national lipid association expert panel on familial hypercholesterolemia. J. Clin. Lipidol. 2011:133–140. doi: 10.1016/j.jacl.2011.03.001. - DOI - PubMed
    1. Whitfield A.J., Barrett P.H.R., Van Bockxmeer F.M., Burnett J.R. Lipid disorders and mutations in the APOB gene. Clin Chem. 2004 doi: 10.1373/clinchem.2004.038026. - DOI - PubMed
    1. Defesche J.C., Pricker K.L., Hayden M.R., Van Der Ende B.E., Kastelein J.J.P. Familial defective apolipoprotein B-100 is clinically indistinguishable from familial hypercholesterolemia. Arch Intern Med. 1993 doi: 10.1001/archinte.1993.00410200071008. - DOI - PubMed
    1. Abifadel M., Varret M., Rabès J.P., Allard D., Ouguerram K., Devillers M., Cruaud C., Benjannet S., Wickham L., Erlich D., Derré A., Villéger L., Farnier M., Beucler I., Bruckert E., Chambaz J., Chanu B., Lecerf J.M., Luc G., Moulin P., Weissenbach J., Prat A., Krempf M., Junien C., Seidah N.G., Boileau C. Mutations in PCSK9 cause autosomal dominant hypercholesterolemia. Nat Genet. 2003 doi: 10.1038/ng1161. - DOI - PubMed

LinkOut - more resources