Isabelle Ruel1, Sumayah Aljenedil1, Iman Sadri1, Émilie de Varennes1, Robert A Hegele2, Patrick Couture3, Jean Bergeron3, Eric Wanneh4, Alexis Baass4,5,6, Robert Dufour7, Daniel Gaudet8, Diane Brisson8, Liam R Brunham9,10,11, Gordon A Francis9,10,11, Lubomira Cermakova12, James M Brophy13, Arnold Ryomoto14, G B John Mancini14, Jacques Genest15. 1. Research Institute of the McGill University Health Centre, Royal Victoria Hospital, Montreal, QC, Canada. 2. Departments of Medicine and Biochemistry, Schulich School of Medicine and Robarts Research Institute, Western University, London, ON, Canada. 3. Lipid Research Centre, CHU de Québec-Université Laval, Quebec City, QC, Canada. 4. Division of Experimental Medicine, Department of Medicine, McGill University, Montreal, QC, Canada. 5. Nutrition, Metabolism, and Atherosclerosis Clinic, Institut de recherches cliniques de Montréal, QC, Canada. 6. Division of Medical Biochemistry, Department of Medicine, McGill University, QC, Canada. 7. Department of Nutrition, Université de Montréal, Montreal, QC, Canada. 8. Lipidology Unit, Community Genomic Medicine Centre and ECOGENE-21, Department of Medicine, Université de Montréal, Saguenay, QC, Canada. 9. Healthy Heart Program Prevention Clinic, St. Paul's Hospital, Vancouver, BC, Canada. 10. Department of Medicine, University of British Columbia, Vancouver, BC, Canada. 11. Centre for Heart Lung Innovation, Providence Health Care Research Institute, University of British Columbia, Vancouver, BC, Canada. 12. Department of Pathology and Laboratory Medicine, University of British Columbia, Vancouver, BC, Canada. 13. McGill University, Royal Victoria Hospital, Montreal, QC, Canada. 14. Department of Medicine, Division of Cardiology, University of British Columbia, Vancouver, BC, Canada. 15. Research Institute of the McGill University Health Centre, Royal Victoria Hospital, Montreal, QC, Canada; jacques.genest@mcgill.ca.
Abstract
BACKGROUND: Familial hypercholesterolemia (FH) is the most frequent genetic disorder seen clinically and is characterized by increased LDL cholesterol (LDL-C) (>95th percentile), family history of increased LDL-C, premature atherosclerotic cardiovascular disease (ASCVD) in the patient or in first-degree relatives, presence of tendinous xanthomas or premature corneal arcus, or presence of a pathogenic mutation in the LDLR, PCSK9, or APOB genes. A diagnosis of FH has important clinical implications with respect to lifelong risk of ASCVD and requirement for intensive pharmacological therapy. The concentration of baseline LDL-C (untreated) is essential for the diagnosis of FH but is often not available because the individual is already on statin therapy. METHODS: To validate a new algorithm to impute baseline LDL-C, we examined 1297 patients. The baseline LDL-C was compared with the imputed baseline obtained within 18 months of the initiation of therapy. We compared the percent reduction in LDL-C on treatment from baseline with the published percent reductions. RESULTS: After eliminating individuals with missing data, nonstandard doses of statins, or medications other than statins or ezetimibe, we provide data on 951 patients. The mean ± SE baseline LDL-C was 243.0 (2.2) mg/dL [6.28 (0.06) mmol/L], and the mean ± SE imputed baseline LDL-C was 244.2 (2.6) mg/dL [6.31 (0.07) mmol/L] (P = 0.48). There was no difference in response according to the patient's sex or in percent reduction between observed and expected for individual doses or types of statin or ezetimibe. CONCLUSIONS: We provide a validated estimation of baseline LDL-C for patients with FH that may help clinicians in making a diagnosis.
BACKGROUND:Familial hypercholesterolemia (FH) is the most frequent genetic disorder seen clinically and is characterized by increased LDL cholesterol (LDL-C) (>95th percentile), family history of increased LDL-C, premature atherosclerotic cardiovascular disease (ASCVD) in the patient or in first-degree relatives, presence of tendinous xanthomas or premature corneal arcus, or presence of a pathogenic mutation in the LDLR, PCSK9, or APOB genes. A diagnosis of FH has important clinical implications with respect to lifelong risk of ASCVD and requirement for intensive pharmacological therapy. The concentration of baseline LDL-C (untreated) is essential for the diagnosis of FH but is often not available because the individual is already on statin therapy. METHODS: To validate a new algorithm to impute baseline LDL-C, we examined 1297 patients. The baseline LDL-C was compared with the imputed baseline obtained within 18 months of the initiation of therapy. We compared the percent reduction in LDL-C on treatment from baseline with the published percent reductions. RESULTS: After eliminating individuals with missing data, nonstandard doses of statins, or medications other than statins or ezetimibe, we provide data on 951 patients. The mean ± SE baseline LDL-C was 243.0 (2.2) mg/dL [6.28 (0.06) mmol/L], and the mean ± SE imputed baseline LDL-C was 244.2 (2.6) mg/dL [6.31 (0.07) mmol/L] (P = 0.48). There was no difference in response according to the patient's sex or in percent reduction between observed and expected for individual doses or types of statin or ezetimibe. CONCLUSIONS: We provide a validated estimation of baseline LDL-C for patients with FH that may help clinicians in making a diagnosis.
Authors: Uma Ramaswami; Marta Futema; Martin P Bogsrud; Kirsten B Holven; Jeanine Roeters van Lennep; Albert Wiegman; Olivier S Descamps; Michal Vrablik; Tomas Freiberger; Hans Dieplinger; Susanne Greber-Platzer; Gabriele Hanauer-Mader; Mafalda Bourbon; Euridiki Drogari; Steve E Humphries Journal: Atherosclerosis Date: 2019-11-15 Impact factor: 5.162
Authors: Latifah Alothman; Magdaline Zawadka; Sumayah Aljenedil; Mahesh Kajil; David Bewick; Daniel Gaudet; Robert A Hegele; Eva Lonn; Daniel Ngui; Isabelle Ruel; Michelle Tsigoulis; Narendra Singh; Jacques Genest; Milan Gupta Journal: CJC Open Date: 2019-06-07