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Higher Responsiveness to Rosuvastatin in Polygenic versus Monogenic Hypercholesterolaemia: A Propensity Score Analysis

Mickiewicz, A; Futema, M; Ćwiklinska, A; Kuchta, A; Jankowski, M; Kaszubowski, M; Chmara, M; ... Gruchała, M; + view all (2020) Higher Responsiveness to Rosuvastatin in Polygenic versus Monogenic Hypercholesterolaemia: A Propensity Score Analysis. Life , 10 (5) , Article 73. 10.3390/life10050073. Green open access

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Abstract

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 < 0.001). Adjusted model showed a lower percentage of change in LDL-C after rosuvastatin treatment in monogenic patients vs. polygenic subjects (45.9% vs. 55.4%, p < 0.001). The probability of achieving LDL-C targets in monogenic FH was lower than in polygenic subjects (0.075 vs. 0.245, 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.

Type: Article
Title: Higher Responsiveness to Rosuvastatin in Polygenic versus Monogenic Hypercholesterolaemia: A Propensity Score Analysis
Location: Switzerland
Open access status: An open access version is available from UCL Discovery
DOI: 10.3390/life10050073
Publisher version: https://doi.org/10.3390/life10050073
Language: English
Additional information: © 2020 by the Authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).
Keywords: monogenic hypercholesterolemia, polygenic hypercholesterolemia, propensity score, rosuvastatin
UCL classification: UCL
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Population Health Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Population Health Sciences > Institute of Cardiovascular Science
URI: https://discovery.ucl.ac.uk/id/eprint/10099196
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