Child–Parent Familial Hypercholesterolemia Screening in Primary Care

TLDR

Child‑parent screening for familial hypercholesterolemia is proposed to identify individuals at high risk for inherited premature cardiovascular disease. The study evaluated the efficacy and feasibility of child‑parent screening for familial hypercholesterolemia in primary care during routine immunization visits of 10,095 children aged 1–2 years. Screening involved measuring capillary cholesterol and testing for mutations, with a positive result defined by an elevated cholesterol (≥1.53 MoM) plus a mutation or repeat elevation, and an alternative strategy using a 1.35 MoM cutoff plus mutation or two ≥1.50 MoM values. The screening identified 28 children (0.3 %) with positive results, 17 additional mutation carriers with lower cholesterol, an overall mutation prevalence of 1 in 273, and using an alternative cutoff identified 40 children and 40 parents, yielding 8 high‑risk individuals per 1,000 screened. Funded by the Medical Research Council.

Abstract

Child-parent screening for familial hypercholesterolemia has been proposed to identify persons at high risk for inherited premature cardiovascular disease. We assessed the efficacy and feasibility of such screening in primary care practice.We obtained capillary blood samples to measure cholesterol levels and to test for familial hypercholesterolemia mutations in 10,095 children 1 to 2 years of age during routine immunization visits. Children were considered to have positive screening results for familial hypercholesterolemia if their cholesterol level was elevated and they had either a familial hypercholesterolemia mutation or a repeat elevated cholesterol level 3 months later. A parent of each child with a positive screening result for familial hypercholesterolemia was considered to have a positive screening result for familial hypercholesterolemia if he or she had the same mutation as the child or, if no mutations were identified, had the higher cholesterol level of the two parents.The use of a prespecified cholesterol cutoff value of 1.53 multiples of the median (MoM, corresponding to a percentile of 99.2) identified 28 children who had positive screening results for familial hypercholesterolemia (0.3% of the 10,095 children; 95% confidence interval [CI], 0.2 to 0.4), including 20 with a familial hypercholesterolemia mutation and 8 with a repeat cholesterol level of at least 1.53 MoM. A total of 17 children who had a cholesterol level of less than 1.53 MoM also had a familial hypercholesterolemia mutation. The overall mutation prevalence was 1 in 273 children (37 in 10,095; 95% CI, 1 in 198 to 1 in 388). The use of an initial cholesterol cutoff value of 1.35 MoM (95th percentile) plus a mutation, or two cholesterol values of at least 1.50 MoM (99th percentile), identified 40 children who had positive screening results for familial hypercholesterolemia (0.4% of the 10,095 children, including 32 children who had a familial hypercholesterolemia mutation and 8 who did not have the mutation) and 40 parents who had positive screening results for familial hypercholesterolemia.Child-parent screening was feasible in primary care practices at routine child immunization visits. For every 1000 children screened, 8 persons (4 children and 4 parents) were identified as having positive screening results for familial hypercholesterolemia and were consequently at high risk for cardiovascular disease. (Funded by the Medical Research Council.).