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

Agnieszka Mickiewicz1, Marta Futema2, Agnieszka Ćwiklinska3

  • 1Department of Cardiology I, Medical University of Gdansk, Dębinki 7, 80-211 Gdańsk, Poland.

Life (Basel, Switzerland)
|May 24, 2020
PubMed

Insights

Familial hypercholesterolemia (FH) patients with polygenic causes respond better to rosuvastatin than those with monogenic mutations. Polygenic FH patients are more likely to achieve LDL-cholesterol targets with this treatment.

Area of Science:

  • Cardiovascular Medicine
  • Genetics
  • Pharmacology

Background:

  • Familial hypercholesterolemia (FH) is a genetic disorder characterized by high LDL-cholesterol (LDL-C).
  • Monogenic defects account for approximately 40% of FH cases, while polygenic factors contribute to hypercholesterolemia in the majority of mutation-negative individuals.
  • Understanding the genetic basis of FH is crucial for predicting treatment response.

Purpose of the Study:

  • To investigate the association between the underlying genetic cause (monogenic vs. polygenic) of FH and the response to rosuvastatin treatment.
  • To compare the efficacy of rosuvastatin in achieving LDL-C targets between monogenic and polygenic FH populations.

Main Methods:

  • FH patients were genotyped for mutations in LDLR and APOB genes.
  • A polygenic risk score (PRS) was utilized to identify polygenic hypercholesterolemia in mutation-negative patients.
  • Rosuvastatin treatment was administered, and patients were followed for 8 months, with propensity score analysis used to assess treatment response variables.

Main Results:

  • Monogenic FH subjects exhibited higher baseline LDL-C levels compared to polygenic subjects (7.6 ± 1.5 mmol/L vs. 6.2 ± 1.2 mmol/L).
  • Rosuvastatin treatment resulted in a significantly lower percentage change in LDL-C in monogenic patients compared to polygenic subjects (45.9% vs. 55.4%).
  • The probability of achieving LDL-C targets was lower in monogenic FH (0.075) versus polygenic subjects (0.245), with polygenic patients being more likely to reach goals (OR 3.28).

Conclusions:

  • FH patients with a polygenic cause demonstrate a substantially higher responsiveness to rosuvastatin compared to those with monogenic mutations.
  • Polygenic hypercholesterolemia is associated with a greater likelihood of achieving therapeutic LDL-C goals with rosuvastatin treatment.
  • These findings highlight the importance of considering the genetic etiology in tailoring lipid-lowering therapies for FH.

Keywords:
monogenic hypercholesterolemiapolygenic hypercholesterolemiapropensity scorerosuvastatin

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