Abstract 20310: Cardiovascular Risk Markers in a Large Cohort of Children With Genetically Verified FH Show No Inheritance-Related but LDL Receptor Mutation-Type and Family History of CVD-related Variance
Introduction: Familial hypercholesterolemia (FH) is an autosomal dominant disease caused primarily by mutations in the low density lipoprotein (LDL) receptor gene. FH patients have increased total- and LDL cholesterol leading to accelerated atherosclerosis and premature cardiovascular disease (CVD). In an FH pregnancy the absolute rise in lipid levels are often much higher than in healthy pregnancies, and this maternal hypercholesterolemia
may thus contribute to an unfavorable in utero environment potentially increasing susceptibility of adult CVD. Few studies have investigated whether maternal FH is associated with an unfavorable phenotype in offspring compared with paternal FH inheritance.
Hypothesis: The aim of the present study was to investigate the impact of maternal vs. paternal FH on pre-treated plasma lipids. In addition, the effect of LDL receptor mutation types and Family history of early CVD in FH children was evaluated
Methods: We included 1063 children with FH (0-19 years) in the study. Five-hundred had inherited FH maternally and 563 paternally. Furthermore, 624 children with FH had an LDL receptor negative mutation and 332 of the FH children had an FH grandparent suffering from early CVD whereas the remaining children had an FH grandparent with late or no CVD. Differences were tested for using a random intercept mixed model taking account for between-family variation.
Results: Children with maternal FH did not have different levels of total-, LDL- or HDL-cholesterol, triglycerides, apoA1, apoB, lipoprotein (a) compared with children With paternal FH. Moreover, children with LDL receptor negative mutations had higher levels of total- and LDL cholesterol in addition to apoB, and concomitantly lower levels of HDL-cholesterol and apoA-1 than children with other LDL receptor mutations. Finally, children with an FH grandparent with early CVD had significant higher LDL-cholesterol levels than children without.
Conclusions: Maternal FH does not lead to a more unfavorable
phenotype in untreated FH children. However, both FH children with LDL receptor negative mutation and FH children with early CVD in family had a more unfavorably phenotype. Hence statin treatment should potentially be initialized earlier in this group.
Author Disclosures: I. Narverud: None. J.R. van Lennep: None. J.J. Christensen: None. J. Versmissen: None. J.M. Gran: None. P.O. Iversen: None. L. Ose: None. P. Aukrust: None. B. Halvorsen: None. T. Ueland: None. S.M. Ulven: None. M.B. Veierød: None. E. Sijbrands: None. K. Retterstøl: None. K.B. Holven: None.
- © 2014 by American Heart Association, Inc.