Background and Aims: The large-scale implementation and effectiveness of genetic cascade screening for familial hypercholesterolemia (FH) has been poorly studied. Based on web technologies, we aim to study a contemporary method to contact relatives to improve detection of FH.
Methods: Adults with a Dutch Lipid Clinic Network score of 6 or more points will be screened. Once a pathogenic variant in the LDLR, APOB, or PCSK9 gene will be identified, several cycles of cascade will identify first, second, and third-degree relatives. Compared to usual care, the intervention group will receive prepared email or SMS to be sent to relatives. By clicking in the text, the relative can then provide agreement to be contacted by one of the study center. The primary outcome is the difference in the yield of detection of FH between study groups. The yield of detection is the number of genetic test performed/number of contactable relatives. Secondary outcomes are changes in health behaviors, LDL-c levels and lipid-lowering drugs over 6-months.
Results: Overall, 56 families need to be included to show a significant difference of 20% in the yield of detection between the control (20%) and interventional group (40%), assuming 4 contactable relatives per family. A study network of lipid and cardiovascular clinics has been created in all linguistic regions of Switzerland. A biobank of DNA samples with family link will allow further assessment of genetic causes of dyslipidemia.
Conclusions: This large-scale implementation study will provide new evidence regarding public health, societal and clinical effectiveness of genetic cascade screening for FH.