Higher Responsiveness to Rosuvastatin in Polygenic versus Monogenic Hypercholesterolemia: A Propensity Score Analysis
Agnieszka Mickiewicz,
Marta Futema,
Agnieszka Ćwiklinska,
Agnieszka Kuchta,
Maciej Jankowski,
Mariusz Kaszubowski,
Magdalena Chmara,
Bartosz Wasąg,
Marcin Fijałkowski,
Miłosz Jaguszewski,
Steve E. Humphries,
Marcin Gruchała
Affiliations
Agnieszka Mickiewicz
Department of Cardiology I, Medical University of Gdansk, Dębinki 7, 80-211 Gdańsk, Poland
Marta Futema
Centre for Heart Muscle Disease, Institute of Cardiovascular Science, University College London, London WC1E 6BT, UK
Agnieszka Ćwiklinska
Department of Clinical Chemistry, Medical University of Gdansk, Dębinki 7, 80-211 Gdańsk, Poland
Agnieszka Kuchta
Department of Clinical Chemistry, Medical University of Gdansk, Dębinki 7, 80-211 Gdańsk, Poland
Maciej Jankowski
Department of Clinical Chemistry, Medical University of Gdansk, Dębinki 7, 80-211 Gdańsk, Poland
Mariusz Kaszubowski
Institute of Statistics, Department of Economic Sciences, Faculty of Management and Economics, Gdansk University of Technology, 80-233 Gdańsk, Poland
Magdalena Chmara
Department of Biology and Genetics, Medical University of Gdansk, Dębinki 1, 80-211 Gdańsk, Poland
Bartosz Wasąg
Department of Biology and Genetics, Medical University of Gdansk, Dębinki 1, 80-211 Gdańsk, Poland
Marcin Fijałkowski
Department of Cardiology I, Medical University of Gdansk, Dębinki 7, 80-211 Gdańsk, Poland
Miłosz Jaguszewski
Department of Cardiology I, Medical University of Gdansk, Dębinki 7, 80-211 Gdańsk, Poland
Steve E. Humphries
Centre for Cardiovascular Genetics, British Heart Foundation Laboratories, Institute of Cardiovascular Science, the Rayne Building University College London, London WC1E 6JF, UK
Marcin Gruchała
Department of Cardiology I, Medical University of Gdansk, Dębinki 7, 80-211 Gdańsk, Poland
Background: The monogenic defect in familial hypercholesterolemia (FH) is detected in ∼40% of cases. The majority of mutation-negative patients have a polygenic cause of high LDL-cholesterol (LDL-C). We sought to investigate whether the underlying monogenic or polygenic defect is associated with the response to rosuvastatin. Methods: FH Individuals were tested for mutations in LDLR and APOB genes. A previously established LDL-C-specific polygenic risk score (PRS) was used to examine the possibility of polygenic hypercholesterolemia in mutation-negative patients. All of the patients received rosuvastatin and they were followed for 8 ± 2 months. A propensity score analysis was performed to evaluate the variables associated with the response to treatment. Results: Monogenic subjects had higher mean (±SD) baseline LDL-C when compared to polygenic (7.6 ± 1.5 mmol/L vs. 6.2 ± 1.2 mmol/L; p p p = 0.004). Polygenic patients were more likely to achieve LDL-C goals, as compared to those monogenic (OR 3.28; 95% CI: 1.23–8.72). Conclusion: Our findings indicate an essentially higher responsiveness to rosuvastatin in FH patients with a polygenic cause, as compared to those carrying monogenic mutations.
