Positive Predictive Values of Familial Hypercholesterolemia Diagnoses in the Danish National Patient Registry and the Danish Familial Hypercholesterolemia Registry – A Validation Study

Jakob Knold,1,2 Christian Bork,3,4 Martin Snoer,5 Merete Heitmann,6,7 Lia Evi Bang,8 Helle Kanstrup,9,10 Kristoffer Lund Hansen,11 Berit Storgaard Hedegaard,12 Kristian Korsgaard Thomsen,2,13 Bo Kobberø Lauridsen,14 Ann Bovin,15 Alberte Aspaas Lundquist,16 Hassan Kussai Salem Al Tamimi,17 Jens Uffe Brorholt-Petersen,18 Thomas Emil Christensen,19 Mette Lykke Norgaard Bertelsen,20 Thomas Gohr,21 Annie Ellermann,22 Camilla Plambeck Hansen,23 Anette Weis,23 Philip Rising Nielsen,23 Erik Berg Schmidt,3,4 Henning Bundgaard,7,8 Finn Lund Henriksen1,2 On behalf of the Danish Familial Hypercholesterolemia Study Group1Department of Cardiology, Odense University Hospital, Odense, Denmark; 2Clinical Institute, University of Southern Denmark, Odense, Denmark; 3Department of Cardiology, Aalborg University Hospital, Aalborg, Denmark; 4Department of Clinical Medicine, Aalborg University, Aalborg, Denmark; 5Department of Cardiology, Zeeland University Hospital, Roskilde, Denmark; 6Department of Cardiology, University Hospital Bispebjerg-Frederiksberg, Copenhagen, Denmark; 7Institute for Clinical Medicine, University of Copenhagen, Copenhagen, Denmark; 8Department of Cardiology, Rigshospitalet, Copenhagen University Hospital, Copenhagen, Denmark; 9Department of Cardiology, Aarhus University Hospital, Aarhus, Denmark; 10Department of Clinical Medicine, Aarhus University, Aarhus, Denmark; 11Department of Cardiology, Hospital of Southern Jutland, Aabenraa, Denmark; 12Department of Cardiology, Viborg-Silkeborg-Skive Regional Hospital, Viborg, Denmark; 13Department of Cardiology, Hospital of Southwest Jutland, Esbjerg, Denmark; 14Department of Cardiology, Herlev-Gentofte Hospital, Copenhagen, Denmark; 15Department of Cardiology, Hospital of Lille Baelt, Vejle, Denmark; 16Department of Paediatrics and Adolescent Medicine, Rigshospitalet, Copenhagen University Hospital, Copenhagen, Denmark; 17Department of Cardiology, Naestved, Slagelse, Ringsted Hospital, Slagelse, Denmark; 18Department of Cardiology, Goedstrup Hospital, Goedstrup, Denmark; 19Department of Cardiology, Amager-Hvidovre Hospital, Copenhagen, Denmark; 20Department of Cardiology, North Zeeland University Hospital, Hilleroed, Denmark; 21Department of Cardiology, Lille Baelt Hospital, Kolding, Denmark; 22Department of Pediatrics, Holbaek Hospital, Holbaek, Denmark; 23The Danish Healthcare Quality Institute, Aalborg, DenmarkCorrespondence: Jakob Knold, Email [email protected]: The Danish Familial Hypercholesterolemia (FH) Registry (DFH) was established in 2020 to monitor the detection rate of FH and quality of care provided among patients with FH. DFH is nationwide, and together with the Danish National Patient Registry (DNPR) includes more than 10,000 registered cases of FH. However, the validity of FH diagnoses in the DNPR and DFH is unknown.Purpose: We aimed to investigate the positive predictive value of FH cases registered in the DNPR and DFH.Methods: We retrospectively retrieved a nationwide random sample of 800 patients with an FH diagnosis registered in the DNPR between 1st of January 2020 and 1st of May 2023. Subsequently, we retrieved information on cases also registered in the DFH, and validated all registered cases based on medical records. Individuals with a Dutch Lipid Clinical Network-score ≥ 6 were considered valid FH cases. Positive predictive values with 95% confidence intervals were used to assess the validity of the registered diagnoses.Results: We found a positive predictive value of 63.8% (95% CI: 60.7; 67.0) for an FH diagnosis recorded in the DNPR (510/800), and 88.1% (95% CI: 82.2; 92.3%) for those diagnosed with genetic FH (141/160). A primary diagnosis of FH registered by cardiological departments had a positive predictive value of 71.0% (95% CI: 67.2; 74.6%) (417/587), and 88.3% (95% CI: 82.6; 92.8%) for genetic FH (113/128), respectively. The positive predictive value of FH cases registered in the DFH was 83.0% (95% CI: 78.9; 86.5) (318/383).Conclusion: The validity of FH cases in the DFH was high, while the validity of an FH diagnosis in the DNPR was relatively low. However, restricting the analysis to a primary diagnosis obtained from cardiological departments may be used to improve the validity of FH diagnoses in the DNPR.Keywords: validity, epidemiology, lipidology, familial hypercholesterolemia