INTRODUCTION: Early and lifelong treatment is essential in patients with familial hypercholesterolaemia (FH) due to genetically elevated low-density lipoprotein cholesterol (LDL-C) from the first years of life. In women with FH, lipid-lowering treatment is interrupted during childbearing years due to contraindication of the medication during conception, pregnancy and breastfeeding. However, little is known about the impact of breastfeeding on lipid profile and other risk markers for atherosclerotic cardiovascular disease (ASCVD) in women with FH compared with women without hypercholesterolaemia, and to what extent statins transfer into breast milk.We aim to investigate (1) the association between breastfeeding and serum lipid profile in women with and without FH; (2) the association between breastfeeding and other ASCVD risk markers in women with and without FH and (3) the concentration of statins in breast milk of women with FH. METHODS AND ANALYSIS: FH-FEMINA is a prospective study aiming to include 50 women with FH in Norway, the Netherlands and the Czech Republic. Additionally, 20 women without hypercholesterolaemia will be enrolled as a control group in Norway. Women will be included at the first study visit in gestational week 36, and follow-up visits will be scheduled at 2-4 weeks, and at 3, 6, 9 and 12 months postpartum. Information on lifestyle factors, treatment history and current and previous pregnancies will be collected. At each visit, a non-fasting blood sample, breast milk sample and information on diet, body mass index and blood pressure will be collected. Additional blood samples will be collected from the women with FH at 2, 4, 5, 7, 8, 10 and 11 months postpartum for as long as they are breastfeeding. At (re-)initiation of statin treatment, breast milk samples from women with FH will be collected for drug concentration measurements. ETHICS AND DISSEMINATION: Ethical approval will be obtained prior to study start in all three countries. Participants will be informed about the study and receive ample time to ask questions before the informed consent form is signed. The findings from this study will be disseminated to healthcare professionals, researchers and patients via peer-reviewed scientific article(s), conferences, patient organisations and social media. TRIAL REGISTRATION NUMBER: NCT05367310.

3rd Department of Internal Medicine General University Hospital 1st Faculty of Medicine Charles University Prague Czech Republic

Centre of Cardiovascular Surgery and Transplantation Brno Czech Republic

Clinic of Cardiology St Olavs University Hospital Trondheim Norway

Department of Clinical Science University of Bergen Bergen Norway

Department of Haematology Oslo University Hospital Oslo Norway

Department of Heart Disease Haukeland University Hospital Bergen Norway

Department of Internal Medicine Erasmus MC Cardiovascular Institute University Medical Center Rotterdam Rotterdam The Netherlands

Department of Nutrition Institute of Basic Medical Sciences University of Oslo Oslo Norway

Department of Pharmacology Oslo University Hospital Oslo Norway

Department of Pharmacy University of Oslo Oslo Norway

Medical Faculty Masaryk University Brno Czech Republic

National Institute for Metabolic and Cardiovascular Disease Research Brno Czech Republic

Nordland Heart Center Bodo Norway

Norwegian National Advisory Unit on Familial Hypercholesterolemia Oslo University Hospital Oslo Norway

Oslo Centre of Biostatistics and Epidemiology Department of Biostatistics Institute of Basic Medical Sciences University of Oslo Oslo Norway

The Lipid Clinic Oslo University Hospital Oslo Norway

Unit for Cardiac and Cardiovascular Genetics Oslo University Hospital Oslo Norway

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