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Aortic stenosis in homozygous familial hypercholesterolaemia: a paradigm shift over a century

Alexandre M Bélanger1, Leo E Akioyamen2, Isabelle Ruel1

  • 1Research Institute of the McGill University Health Centre, 1001, Boul. Décarie, Office EM1.2212, Montréal, Québec, Canada.

European Heart Journal
|July 1, 2022
PubMed

Insights

Homozygous familial hypercholesterolaemia (HoFH) patients show a decrease in aortic stenosis (AS) prevalence with statin use. The condition is shifting towards valvular aortic stenosis (VAS) due to improved survival from statins and apheresis.

Area of Science:

  • Cardiovascular Medicine
  • Genetics
  • Pharmacology

Background:

  • Homozygous familial hypercholesterolaemia (HoFH) is a severe genetic disorder characterized by extremely high LDL cholesterol levels, leading to premature atherosclerotic cardiovascular disease.
  • Aortic stenosis (AS), including supravalvular (SVAS) and valvular (VAS) types, is a common comorbidity in HoFH patients.
  • Currently, no medical treatments exist for AS in HoFH, with surgery being the only option for severe cases.

Purpose of the Study:

  • To conduct a systematic review of current evidence on aortic stenosis (AS) in patients with Homozygous familial hypercholesterolaemia (HoFH).
  • To determine the impact of pharmacological treatments, specifically statins, on the clinical presentation, phenotype, and clinical course of AS in HoFH over nine decades.

Main Methods:

  • A comprehensive literature search was conducted across multiple databases (MEDLINE, Embase, Cochrane, PubMed, AfricaWide, Scopus) from inception to November 2021.
  • Included studies were cross-sectional or retrospective, alongside individual case reports.
  • Data from 424 HoFH cases were analyzed to compare AS prevalence and type between pre-statin and long-term statin eras.

Main Results:

  • Aortic stenosis (AS) was identified in 57% of HoFH patients in the pre-statin era, compared to 35% in those reported more recently (post-2000).
  • The ratio of supravalvular aortic stenosis (SVAS) to valvular aortic stenosis (VAS) shifted from 47:53 in patients not on statins to 10:90 in patients on long-term statin therapy.
  • Increased longevity due to statins and lipoprotein apheresis was associated with this observed change in AS phenotype.

Conclusions:

  • Supravalvular aortic stenosis (SVAS) and valvular aortic stenosis (VAS) are frequent manifestations in Homozygous familial hypercholesterolaemia (HoFH).
  • The clinical phenotype of AS in HoFH appears to be shifting towards calcific valvular aortic stenosis (VAS).
  • Improvements in survival through statin therapy and lipoprotein apheresis are associated with this evolving phenotype in HoFH patients.
Abstract

Keywords:
Aortic stenosisGenetic dyslipidaemiasHomozygous familial hypercholesterolaemiaSupra-valvular aortic stenosisSystematic review

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