Aims: Familial hypercholesterolemia (FH) is a genetic disorder characterized by elevated low-density lipoprotein cholesterol (LDL-C) levels, which increases the risk of premature coronary artery disease. Early detection and treatment are vital, especially in children. To improve FH diagnosis in children, the Japan Atherosclerosis Society (JAS) released new guidelines in July 2022. This study assessed and compared the sensitivity and specificity of the clinical diagnostic criteria from the JAS pediatric FH guidelines of 2017 and 2022. Methods: From September 2020 to March 2023, 69 children with elevated plasma LDL-C levels (≥ 140 mg/dL) were included in a pediatric FH screening project in Kagawa. The children were evaluated using genetic testing alongside the clinical diagnostic criteria from the JAS pediatric FH guidelines of 2017 and 2022. Results: Using the JAS pediatric FH 2017 criteria, eight children were diagnosed as FH-positive and 61 children as FH-negative. The JAS pediatric FH 2022 criteria identified 15 children with definite FH, 31 with probable FH, and 23 with possible FH. Genetic testing detected FH pathogenic variants in 24 children. The sensitivity and specificity for the JAS pediatric FH 2017 criteria were 0.292 and 0.978, respectively. For the JAS pediatric FH 2022 criteria, the sensitivity was 0.542 for definite FH with a specificity of 0.956, and 0.917 for probable FH with a specificity of 0.467. Conclusion: The clinical diagnostic criteria of the JAS pediatric FH 2022 guidelines demonstrated improved diagnostic efficiency compared with those of 2017, as evidenced by the increased sensitivity while preserving specificity.

The aim of this study is to evaluate the discriminative properties of the Multidimensional Quality of Life Questionnaire for HIV infection (MQoL-HIV) and to determine those factors contributing to the health-related quality of life (HRQoL) of HIV-1 infected persons living in Japan. The MQoL-HIV, the Nottingham Health Profile (NHP) as a generic instrument, and the Center for Epidemiologic Studies-Depression Scale (CES-D) as a psychological measure were administered in 375 patients as a multiple-centre study. The score distribution of the MQoL-HIV showed a unimodal distribution. The Cronbach's α coefficient scored more than 0.7 in seven out of 10 domains, but was low in both the physical functioning and sexual functioning domains. There was a strong correlation between the CES-D and MQoL-HIV index scores (R-0.73). Relatively high coefficient values were found between psychiatric and nervous symptoms and the index score (R = -0.60). In total, the MQoL-HIV may possess discriminative properties.

Background: The Friedewald equation, commonly used to calculate low-density lipoprotein cholesterol (LDL-C), occasionally yields inaccurate estimations for very-low-density lipoprotein cholesterol, suggesting the need for an alternative method such as the Martin equation. In this study, we aimed to evaluate the discrepancies between the Friedewald and Martin equations, particularly in the context of pathogenic variants associated with familial hypercholesterolemia (FH).Methods and Results: We evaluated the discrepancies between LDL-C levels calculated using the Friedewald and Martin equations, and for the presence of pathogenic variants of FH in 53 children with hypercholesterolemia detected through universal lipid screening. Genetic testing revealed pathogenic variants of FH in 24 of the 53 children. Chi-squared tests indicated a significant difference in the presence of pathogenic variants of FH between the “Friedewald ≥ Martin” and “Friedewald < Martin” groups (χ2=11.348, P<0.001). Even in 37 children with LDL-C <180 mg/dL, discrepancies between the equations were still associated with the presence of pathogenic FH variants (Fisher’s exact test, P=0.028).Conclusions: Discrepancies in LDL-C levels measured by the Friedewald and Martin equations might serve as a useful predictive marker for identifying pathogenic variants of FH, especially in cases of LDL-C <180 mg/dL, which are often challenging to diagnose.

Aim: Familial hypercholesterolaemia (FH), an autosomal-dominant disorder, requires early diagnosis to prevent atherosclerosis in children and coronary artery disease (CAD) in their parents. This study aimed to evaluate the effectiveness and barriers of reverse cascade screening (RCS) combined with universal cholesterol screening (UCS) for paediatric FH. Methods: We performed RCS combined with UCS for paediatric FH between January 2018 and July 2023. Family pedigree was evaluated in second-degree relatives, using a child with a genetic diagnosis of FH as the proband. Based on the 2022 Japan Atherosclerosis Society clinical guidelines, cases with suspected FH were classified into four categories: “Definite”, “Probable”, “Possible”, or “Unlikely”. Those who did not complete the diagnostic process were evaluated based on the reasons, including challenges such as “Untested lipids in children”, “Bereavement”, “CAD with unspecified details”, “Dyslipidaemia with unspecified low-density lipoprotein cholesterol (LDL-C) levels”, and “No information on CAD or dyslipidaemia”. Results: Of 252 patients suspected of having FH, 94 completed the diagnostic process. Among them, 49 were classified as “Definite” FH cases, predominantly among first-degree relatives. In contrast, 158 patients did not complete the diagnostic process, with the most common barriers being “Dyslipidaemia with unspecified LDL-C levels” and “No information on CAD or dyslipidaemia”, particularly among second-degree relatives. Conclusion: RCS combined with UCS for paediatric FH using genetic testing is effective for the early diagnosis of FH in asymptomatic cases. However, addressing barriers that hinder FH diagnosis, such as difficulties in approaching second-degree relatives, is critical for improving diagnosis rates.