Universal Screening For Familial Hypercholesterolemia In Young Adults: The Young Fh Study

Introduction: Familial hypercholesterolemia (FH) is caused by genetic defects in low-density lipoprotein (LDL) receptor pathway, resulting in a persistent elevation of plasma LDL-cholesterol (LDL-C) levels as well as an increased risk of cardiovascular diseases. Early diagnosis and treatment are imperative for its management. Currently, FH patients are mainly identified by cascade screening. However, FH is underdiagnosed and undertreated, particularly in young adults, which warrants a systematic screening strategy. Hypothesis: Considering that the prevalence of FH is high (~0.4% in the general population) and that treatment of FH should be initiated earlier at the latest in young adults, we hypothesized that the universal screening of LDL-C in young adults is beneficial for early diagnosis and treatment of FH. Methods: At the University of Tokyo, plasma LDL-C levels have been measured at heath checkups for employees as well as new students. Young adults (18-30 years old) with hypercholesterolemia (LDL-C ≥ 160 mg/dL) identified by universal screening and referred to the University of Tokyo Hospital were eligible (the Young FH study). Those who have been identified by cascade screening were excluded. Mutation in FH-causing genes, as well as clinical and biochemical parameters useful for the clinical diagnosis of FH, were analyzed. The protocol was approved by the human genome, gene analysis research ethics committee of the University of Tokyo. Results: Of the total participants (n = 89, mean age 23.4 ± 3.4 years), 36 (40%) had mutations in LDLR or PCSK9 . The prevalence of mutation carriers was higher in non-obese than in obese participants (47% for body mass index (BMI) < 24 kg/m 2 vs. 26% for BMI ≥ 24). The sensitivity and specificity of clinical diagnosis were 28% and 85%, respectively, by Dutch Lipid Clinic Network Criteria (definite + probable FH), or 22% and 98%, respectively, by Japanese diagnostic criteria of FH. Conclusions: The universal screening of LDL-C effectively identifies FH high-risk patients in Japanese young adults. This screening may be beneficial in countries with low-prevalence of obesity or in non-obese populations. The use of clinical diagnostic criteria of FH for universal screening may lead to underdiagnosis.