Martine Paquette, Armen Erzingatzian, Isabelle Ruel, Zobaida Al-Baldawi, Leslie Brown, Mark H Sherman, Nathalie Laflamme, Jean Bergeron, Patrick Couture, Diane Brisson, Miriam Larouche, Daniel Gaudet, Lubomira Cermakova, Darryl Wan, Nathaniel Moulson, Gordon A Francis, G B John Mancini, Brooke A Kennedy, Robert A Hegele, Gary F Lewis, Brian W McCrindle, Barbara Cifra, Thomas Ransom, Ruth McPherson, Jacques Genest, Liam R Brunham, Iulia Iatan, Alexis Baass
This is the first systematic evaluation within a national HoFH registry to report the univariable and multivariable predictors of AS in patients with HoFH. An external validation of our results in an international cohort of HoFH is warranted.
BACKGROUND: Homozygous familial hypercholesterolemia (HoFH) is a rare genetic disease of low-density lipoprotein cholesterol (LDL-C) metabolism. This disease is associated with a major risk of both atherosclerotic cardiovascular disease and aortic stenosis (AS). The predictors of AS in this population are not well established.
OBJECTIVE: To investigate the univariable and multivariable predictors of AS in patients from the Canadian HoFH registry.
METHODS: Individuals from the Canadian HoFH registry were included in this retrospective longitudinal study. Clinical data were obtained from the treating physicians using a standardized questionnaire. Cox proportional hazards models were used to investigate the predictors of AS. The observed lifetime risk of AS was calculated using Kaplan-Meier estimates.
RESULTS: Among the 67 patients with HoFH, 25 (37%) developed AS. The mean age at baseline was 22 ± 17 years and women represented 57% of the cohort. The independent predictors of AS were the baseline LDL-C (hazard ratio [HR] 1.22 [1.09-1.35], P = .0003) as well as the presence of at least 1 null genetic variant (HR 3.73 [1.41-9.86], P = .008). Having a baseline LDL-C value above 13 mmol/L was associated with an observed lifelong risk of developing AS approaching 100% within this cohort, whereas having a value below this threshold was associated with a risk of 27% (P = .0002).
CONCLUSION: This is the first systematic evaluation within a national HoFH registry to report the univariable and multivariable predictors of AS in patients with HoFH. An external validation of our results in an international cohort of HoFH is warranted.