Universal Screening for Familial Hypercholesterolemia in Children in Kagawa, Japan.

AIM: Familial hypercholesterolemia (FH) is an underdiagnosed autosomal dominant genetic disorder characterized by high levels of plasma low-density lipoprotein cholesterol (LDL-C) from birth. This study aimed to assess the genetic identification of FH in children with high LDL-C levels who are identified in a universal pediatric FH screening in Kagawa, Japan. METHOD: In 2018 and 2019, 15,665 children aged 9 or 10 years underwent the universal lipid screening as part of the annual health checkups for the prevention of lifestyle-related diseases in the Kagawa prefecture. After excluding secondary hyper-LDL cholesterolemia at the local medical institutions, 67 children with LDL-C levels of ≥ 140 mg/dL underwent genetic testing to detect FH causative mutations at four designated hospitals. RESULTS: The LDL-C levels of 140 and 180 mg/dL in 15,665 children corresponded to the 96.3 and 99.7 percentile values, respectively. Among 67 children who underwent genetic testing, 41 had FH causative mutations (36 in the LDL-receptor, 4 in proprotein convertase subtilisin/kexin type 9, and 1 in apolipoprotein B). The area under the curve of receiver operating characteristic curve predicting the presence of FH causative mutation by LDL-C level was 0.705, and FH causative mutations were found in all children with LDL-C levels of ≥ 250 mg/dL. CONCLUSION: FH causative mutations were confirmed in almost 60% of the referred children, who were identified through the combination of the lipid universal screening as a part of the health checkup system and the exclusion of secondary hyper-LDL cholesterolemia at the local medical institutions.

Detrended fluctuation analysis can detect the impairment of heart rate regulation in patients with heart failure with preserved ejection fraction.

BACKGROUND: The impairment of short-term heart rate regulation in patients with heart failure with preserved ejection fraction (HFpEF) can cause acute hemodynamic collapse. Detrended fluctuation analysis (DFA) is a useful tool for the diagnosis of heart diseases and the prediction of mortality. In DFA, the short-term scaling exponent α is decreased in heart failure. However, its change in HFpEF patients remains unclear. METHODS: Twenty patients diagnosed with HFpEF [defined as brain natriuretic peptide (BNP) >100 pg/mL, ejection fraction (EF) ≥50%, and without significant valvular disease], 20 diagnosed with non-HFpEF (BNP > 100 pg/mL and EF < 50%), and 20 control subjects generally matched for age and gender were enrolled. Holter electrocardiography was performed, and heart rate variability was calculated. In the DFA, the scaling exponents in 1000 beats were calculated for each 15-min segment and the average of all segments was used. We compared both the short-term (<11 beats, α1) and long-term (≥11 beats, α2) scaling exponents among the three groups. RESULTS: In the HFpEF, non-HFpEF, and control groups, α1 was 0.73 ± 0.27, 0.66 ± 0.29, and 1.01 ± 0.20 (p < 0.01), and α2 was 0.95 ± 0.08, 0.88 ± 0.11, and 0.96 ± 0.07 (p < 0.01), respectively. The α1 exponent was significantly decreased in the HFpEF group (p < 0.01 vs. control) and the non-HFpEF group (p < 0.01 vs. control), while the α2 exponent was significantly decreased in the non-HFpEF group only (p < 0.05 vs. HFpEF and control). CONCLUSIONS: Short-term heart rate regulation is impaired in patients with HFpEF, while patients with non-HFpEF have both short-term and long-term impairment.

Coronary artery calcification scoring system based on the coronary artery calcium data and reporting system (CAC-DRS) predicts major adverse cardiovascular events or all-cause death in patients with potentially curable lung cancer without a history of cardiovascular disease.

The coronary artery calcium data and reporting system (CAC-DRS) is a novel reporting system based on CAC severity. Lung cancer patients have a high risk of cardiovascular disease (CVD), for which CAC severity may provide additional prognostic information. Using non-gated, non-contrast computed tomography (CT), we evaluated the CAC-DRS for predicting CVD and all-cause death in patients with potentially curable resected lung cancer. We retrospectively studied 309 consecutive patients without a history of CVD (mean age 67.4 ± 8.2 years, 61% male) who underwent curative surgery for non-small-cell lung cancer between May 2012 and March 2019 at the Japanese Red Cross Okayama Hospital. Time to incidence of major adverse cardiac events (MACEs) (non-fatal myocardial infarction, non-fatal stroke and cardiovascular death) and all-cause death was analyzed using Fine and Gray and Cox regression models. The CAC-DRS score was assessed using standard chest CT without electrocardiogram gating. During 52-months' median follow-up, 43 patients (13.4%) developed incident MACEs or died from any cause; the pathological cancer stages were Ia (n = 20), Ib (n = 8), IIa (n = 2), IIb (n = 2) and IIIa (n = 11). Patients had a graded increase in incidence of MACEs or all-cause death with increasing categories of CAC-DRS. The CAC-DRS score was significantly associated with incident MACEs or all-cause death after adjusting for confounding factors (hazard ratio 1.18; 95% confidence interval 1.10-1.25, p < 0.01). In conclusion, the CAC-DRS score on non-gated standard CT can predict incident MACEs and/or all-cause death in patients with potentially curable resected lung cancer. Lung cancer survivors with a greater CAC-DRS category may need more active management of cardiovascular risk factors.