The Assessment of Carotid Atherosclerotic Plaque among Young Patients with Familial Hypercholesterolemia.

Objective Few data exist regarding when atherosclerotic changes occur among patients with familial hypercholesterolemia (FH). Carotid ultrasonography is a non-invasive method of evaluating this issue. The present study (1) compared the clinical utilities of carotid intima-media thickness (cIMT) and carotid plaque score (cPS) and (2) estimated the onset and progression of carotid atherosclerosis among patients with heterozygous FH (HeFH). Methods We retrospectively analyzed 511 patients under 30 years old who underwent carotid ultrasonography at our hospital from 2006 to 2019. We classified them into the HeFH group (n=78, 21.4±5.9 years old) and non-FH group (n=433, 23.4±6.0 years old) based on the clinical diagnosis and compared their cIMT and cPS values. In addition, we estimated the onset and progression of carotid atherosclerosis among young HeFH patients. Results There was no significant difference in the cIMT between the HeFH and non-FH groups (0.44 mm vs. 0.42 mm, p=0.25). In contrast, the cPS was significantly higher in the HeFH group than in the non-FH group (1.11 vs. 0.26, p=0.002). The regression equation for cPS of HeFH group was Y=-2.05+0.15X (r=0.37, p<0.001). Conclusion An assessment based on the cPS rather than the cIMT appears to be better to capture the progress of carotid atherosclerosis among young HeFH patients. Carotid atherosclerosis may start to develop at 14 years old in patients with HeFH.

A Case of Pulmonary Hypertension in a 67-Year-Old Woman with Thiamine Deficiency Following Partial Gastrectomy and Exacerbated by Diuretics.

BACKGROUND Thiamine deficiency often occurs in patients with alcohol abuse and unbalanced diets. However, gastric surgery and/or use of diuretics can also cause this situation. Importantly, thiamine deficiency can cause pulmonary hypertension, which is completely reversible. This report is of a case of a 67-year-old woman who presented with pulmonary hypertension and thiamine deficiency following partial gastrectomy and exacerbated by diuretics. CASE REPORT A 67-year-old woman with histories of partial gastrectomy because of non-Hodgkin lymphoma (at age 36 years) and sigmoid colectomy because of colon cancer (at age 58 years) presented with bilateral leg edema and dyspnea on exertion. Electrocardiography and right heart catheterization revealed pulmonary hypertension. Despite diuretic administration (initially indapamide, then changed to torsemide), the symptoms gradually worsened. Although she was neither an alcohol drinker nor a fussy eater, we found that her blood thiamine concentration was extremely low. We diagnosed her as having thiamine deficiency caused by gastrectomy and administered diuretics. After intravenous thiamine administration, her symptoms showed immediate improvement, associated with the normalization of the pulmonary hypertension. After detailed analysis of the cause of her pulmonary hypertension, including Swan-Ganz catheterization and echocardiography, we concluded that her pulmonary hypertension was caused by thiamine deficiency following partial gastrectomy and exacerbated by diuretics. CONCLUSIONS This case highlights the importance of recognizing that thiamine deficiency can be a cause of pulmonary hypertension, and that thiamine deficiency can be associated with gastrectomy and the use of diuretics.

Prevalence and Impact of Apolipoprotein E7 on LDL Cholesterol Among Patients With Familial Hypercholesterolemia.

Background: It has been suggested that a rare mutant apolipoprotein E7, APOE7 (p.Glu262Lys, p.Glu263Lys), has been identified to be associated with hyperlipoproteinemia in the general population. Moreover, its prevalence has been shown to be 0.005-0.06%. However, there are no prior data regarding its prevalence and impact on serum lipids in patients with familial hypercholesterolemia (FH). Methods: We recruited 1,138 patients with clinically diagnosed FH [mean age = 48, men = 512, median low-density lipoprotein (LDL) cholesterol = 231 mg/dl]. The coding regions of three FH genes (LDLR, APOB, and PCSK9) and apolipoprotein E (APOE) gene were sequenced. We investigated the prevalence and impact of APOE7 mutant on serum lipid levels in patients with FH. Results: We identified 29 patients (2.5 %) with a mutant APOE7 (heterozygote), which is apparently much higher than that of the general population. Moreover, when we focus on those without FH mutation (n = 540), we identified 21 patients (3.9 %) with a mutant APOE7. Patients with a mutant APOE7 exhibited significantly higher median LDL cholesterol and triglyceride levels compared with those without this rare mutant (249 vs. 218 mg/dl, p < 0.05, 216 vs. 164 mg/dl, p < 0.05, respectively). Moreover, LDL cholesterol levels in the APOE7-oligogenic FH individuals, with a pathogenic mutation in FH genes and APOE7 mutant, were significantly higher than that in monogenic FH patients (265 vs. 245 mg/dl, p < 0.05). Conclusion: We identified more patients with a mutant APOE7 than expected among those diagnosed with FH clinically, especially among those without FH-causing mutation. This implies a mutant APOE7 may be one of the causes FH, especially among those without FH mutations.

Prevalence, self-awareness, and LDL cholesterol levels among patients highly suspected as familial hypercholesterolemia in a Japanese community.

BACKGROUNDS: The prevalence of familial hypercholesterolemia (FH) among Japanese populations is still unclear. In addition, no prior data exist regarding the self-awareness. Accordingly, we aimed to investigate the prevalence, self-awareness, and LDL-C of patients with highly suspected as FH using data obtained in a community-based medical checkups. METHODS: This study included 52,276 subjects (18,588 men, 35.6%) aged ≥40 years who underwent the Japanese specific health checkup in Kanazawa City during 2018. We assessed the self-awareness of dyslipidemia (and the age) as well as the prevalence of patients with highly suspected as FH whose naïve LDL-C levels were ≥250 â€‹mg/dl. Naïve LDL-C levels were estimated by the adjustment (LDL-C/0.7) for those on lipid-lowering medication. We divided subjects into 3 groups based on their naïve LDL cholesterol level (≥250 â€‹mg/dl, 140-249, and ≤139 â€‹mg/dl). RESULTS: We identified 262 (0.5%) individuals highly suspected as FH whose naïve LDL-C levels were ≥250 â€‹mg/dl. Most of them (234 among 262, 89%) were under lipid-lowering medication; however, the self-awareness as dyslipidemia was not quite high (200 among 262, 76%), and their mean LDL-C level under lipid-lowering medication was 203 â€‹± â€‹35 â€‹mg/dl. Interestingly, the age of acknowledgement of dyslipidemia among the patients with highly suspected as FH was significantly younger than those in other categories (58 vs. 60/62 â€‹yrs, respectively, p â€‹< â€‹0.05 for both). CONCLUSIONS: The prevalence of patients highly suspected as FH was around 1 in 200, and their self-awareness as well as control were not still good enough among Japanese general populations.