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Brief Report
October 16, 2019

Association of Low-Density Lipoprotein Cholesterol With Risk of Aortic Valve Stenosis in Familial Hypercholesterolemia

Author Affiliations
  • 1The Lipid Clinic, Oslo University Hospital, Oslo, Norway
  • 2Division of Internal Medicine, Nordland Hospital, Bodø, Norway
  • 3Department of Clinical Medicine, University of Tromsø, Tromsø, Norway
  • 4Department of Health and Social Science, Centre for Evidence-Based Practice, Western Norway University of Applied Science, Bergen, Norway
  • 5Department of Global Public Health and Primary Care, University of Bergen, Bergen, Norway
  • 6Oslo Centre for Biostatistics and Epidemiology, Department of Biostatistics, University of Oslo, Oslo, Norway
  • 7Department of Nutrition, University of Oslo, Oslo, Norway
  • 8National Advisory Unit on Familial Hypercholesterolemia, Oslo University Hospital, Oslo, Norway
  • 9Unit for Cardiac and Cardiovascular Genetics, Oslo University Hospital, Oslo, Norway
  • 10Division of Mental and Physical Health, Norwegian Institute of Public Health, Bergen, Norway
JAMA Cardiol. Published online October 16, 2019. doi:https://doi.org/10.1001/jamacardio.2019.3903
Key Points

Question  Are patients with genetically proven familial hypercholesterolemia at risk of aortic valve stenosis compared with the general population?

Findings  In this registry-based cohort study of all Norwegian genotyped patients with familial hypercholesteremia, during 18 300 person-years of follow-up, an increased incidence of aortic valve stenosis was observed compared with the total Norwegian population stratified by sex and age.

Meaning  A significantly higher incidence of aortic valve stenosis was observed in patients with familial hypercholesterolemia compared with the total Norwegian population.


Importance  Aortic valve stenosis (AS) is the most common valve disease. Elevated levels of low-density lipoprotein (LDL) cholesterol are a risk factor; however, lipid-lowering treatment seems not to prevent progression of AS. The importance of LDL cholesterol in the development of AS thus remains unclear. People with familial hypercholesterolemia (FH) have elevated LDL cholesterol levels from birth and until lipid-lowering treatment starts. Thus, FH may serve as a model disease to study the importance of LDL cholesterol for the development of AS.

Objective  To compare the incidence of AS per year in all genetically proven patients with FH in Norway with the incidence of these diseases in the total Norwegian population of about 5 million people.

Design, Setting, and Participants  This is a registry-based prospective cohort study of all Norwegian patients with FH with regard to first-time AS between 2001 and 2009. All genotyped patients with FH in Norway were compared with the total Norwegian populations through linkage with the Cardiovascular Disease in Norway project and the Norwegian Cause of Death Registry regarding occurrence of first-time AS. Data were analyzed between January 1, 2018, and December 31, 2018.

Main Outcomes and Measures  Standardized incidence ratios.

Results  In total, 53 cases of AS occurred among 3161 persons (1473 men [46.6%]) with FH during 18 300 person-years of follow-up. Mean age at inclusion and at time of AS were 39.9 years (range, 8-91 years) and 65 years (range, 44-88 years), respectively. Total standardized incidence ratios were 7.9 (95% CI, 6.1-10.4) for men and women combined, 8.5 (95% CI, 5.8-12.4) in women, and 7.4 (95% CI, 5.0-10.9) in men, respectively, indicating marked increased risk of AS compared with the general Norwegian population.

Conclusions and Relevance  In this prospective registry study, we demonstrate a marked increase in risk of AS in persons with FH.