Familial hypercholesterolemia (FH) is a genetic autosomal disease, characterized by high levels of cholesterol since birth, that leads to a very high cardiovascular (CV) risk. In patients with the heterozygous FH (HeFH), in case of a maternal transmission, fetus is exposed to high maternal cholesterol levels during pregnancy. Based on the Developmental Origins of Health and Disease concept, our objective was to study the effect of heritability of genetic FH mutation on the occurrence of CV events in adults with HeFH.

We included 138 HeHF patients with a genetic diagnosis and a clear familial history of hypercholesterolemia among 513 patients included in the Marseille's REFERCHOL register. Occurrence of CV events were compared by maternal (MH group, 64 patients) or paternal (PH group, 74 patients) heritability. The logistic regression method was used to determine the predictors of CV events.

At inclusion, parameters were comparable between groups except more hypertension (25% vs. 9.4%, P=0.01), more treatment by anti-PCSK9 (20.3 vs. 5.4%, P=0.008) and less familial early CV events (28.6 vs. 51.4%, P=0.007) in the MH group. Regarding CV events, 35.9% of MH patients and 27% of PH patients had a CV event (P=0.26). Predictive factors of CV event were sex (P=0.0004), age at start of statins (P=0.0003), maximal LDL-c (P=0.009) and Lp(a) (P=0.007). On multivariate analysis, heritability was not statistically associated with CV risk (PH risk vs. MH risk: OR=0.34, P=0.076). Sex, age at start of statins and Lp(a) were still associated with CV events occurrence (OR=0.3, P=0.044 for female; OR=1.08, P=0.001 for a later start of statins; OR=6.98, P=0.0096 for Lp(a)).

Heritability has no significant effect on the occurrence of CV event during adulthood although paternal heritability seems to be protective. We are recruiting all HeFH patients from French FH register to improve the power of the study and confirm the observed trend.