LDL hypercholesterolemia in children: genetic influence and response to lifestyle advice - follow-up of the Fr1dolin-trial

BACKGROUND AND AIMS: Although familial hypercholesterolemia (FH) is common and associated with significant cardiovascular morbidity, screening programs are scarce. Furthermore, the effectiveness of nutritional advice for parents on children's LDL cholesterol (LDL-C) levels is unclear, especially in FH versus non-FH hypercholesterolemia. METHODS: In the Fr1dolin study, 367 of 14,513 children in Lower Saxony and Hamburg were positively screened for LDL hypercholesterolemia with an LDL-C > 135 mg/dl (> 3.5 mmol/l). The screening was considered positive if the first finding of hypercholesterolemia was confirmed in a second sample. These 367 children were invited to a follow-up examination including an extended lipid status, nutritional counseling and genetic analysis. RESULTS: 289 out of 367 screen-positive children (57.4% girls) were followed up for 12 months; 191 (66.1%) underwent genetic testing. Children with a FH-causing pathogenic or likely pathogenic variant (n = 40, 20.9%) had significantly higher LDL-C levels than children without a variant or with a variant of uncertain significance (p < 0.001). After the nutritional counselling and after 6 and 12 months of follow-up, LDL-C levels did not improve significantly (median LDL-C at baseline 142 mg/dl, and 140 mg/dl at 6 and 12 months follow-up, respectively). CONCLUSIONS: A population-based screening program detects LDL-hypercholesterolemia in up to 2.5% of children, with a significant proportion of them having FH genetic variants, supporting early detection. One-time nutritional advice had little effect on LDL-C in general, but particularly in FH, highlighting on the one hand need for structured lifestyle programs and on the other hand early genetic testing in population based FH screening.