Abstract 19911: Markers of Survival in Septuagenarians and Octogenarians With Heterozygous or Homozygous Familial Hypercholesterolemia
Objective: Familial hypercholesterolemia (FH) is an autosomal dominant trait characterized by elevated low-density lipoprotein-cholesterol (LDL-C) concentrations appearing at birth and is associated with an increased risk of premature atherosclerotic cardiovascular disease (CAD). Some homozygous (Ho) FH subjects survive over 80 years of age and a proportion of heterozygous (He) FH subjects aged over 70 years have never experienced CAD symptoms. The objective of this study consists in identifying genetic, clinical and/or environmental factors associated with survival over 70 years in FH.
Methods and Results: The familial analysis of 1,860 French-Canadian FH individuals carrying either the French-canadian Type 1 (15KB deletion) or the French-canadian Type 2, (W66G), which are both FH-causing mutations in the LDLR gene, was performed to identify HoFH and HeFH subjects over 70 years of age. Out of this number, we were able to list a total of 112 subjects (among which 2 HoFH aged 72 and 84 years with baseline cholesterol 18 and 21 mmol/L respectively). Multivariate regression analyses revealed that the gender, high-density lipoprotein-cholesterol (HDL-C) level, the proportion of LDL-C decrease under therapy and the type of mutation in the LDLR gene were significant contributory factors of survival over 80 years or of CAD-free survival over 70 years (p-value under 0.001). In these models, the contribution of HDL-C was independent from that of LDL-C reduction. Notably, HDL-C and gender were shown to be significant covariates of survival among HoFH relatives. Fine phenotyping and exome sequencing analyses are ongoing.
Conclusion: Based on a monogenic model of high LDL-C and premature CAD, these results demonstrated that despite the reduction of LDL-C, several other covariates would probably constitute major targets for cardiovascular disease (CVD) risk management.
Author Disclosures: É. Khoury: None. D. Brisson: None. G. Tremblay: None. K. Tremblay: None. D. Gaudet: None.
- © 2015 by American Heart Association, Inc.