Are patients with genetically proven familial hypercholesterolemia at risk of aortic valve stenosis compared with the general population?
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.
A significantly higher incidence of aortic valve stenosis was observed in patients with familial hypercholesterolemia compared with the total Norwegian population.
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.
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.
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.
Mundal LJ, Hovland A, Igland J, et al. Association of Low-Density Lipoprotein Cholesterol With Risk of Aortic Valve Stenosis in Familial Hypercholesterolemia. JAMA Cardiol. Published online October 16, 2019. doi:https://doi.org/10.1001/jamacardio.2019.3903
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