Introduction: Homozygous familial hypercholesterolemia (HoFH) is a rare inherited disorder characterized by markedly elevated low-density lipoprotein cholesterol (LDL-C) from birth, childhood xanthomas, and accelerated atherosclerotic cardiovascular disease. Achieving LDL-C targets remains difficult despite statins, ezetimibe, and lipoprotein apheresis, especially in patients with treatment interruption, poor adherence, or limited access to specialized lipid services. We report a female with genetically confirmed HoFH who developed severe premature coronary artery disease and showed marked lipid reduction after inclisiran therapy. Case: A 28-year-old Malay female with LDL receptor mutationconfirmed HoFH, diagnosed at age 7, had a strong family history of premature cardiovascular death. She underwent biweekly lipoprotein apheresis from ages 8 to 15 years, but later defaulted on follow-up. During pregnancy in 2021, weekly then biweekly apheresis was reintroduced for severe hypercholesterolemia, but she disengaged postpartum. In 2025, she re-presented with exertional chest pain, orthopnea, and palpitations. Examination showed widespread xanthomas. Electrocardiography demonstrated sinus tachycardia with inferolateral ST depression. Echocardiography revealed a left ventricular ejection fraction of 40%, anterior and septal akinesia, severe mitral regurgitation, moderate tricuspid regurgitation, and pulmonary hypertension. Her lipid profile showed total cholesterol 18.1 mmol/L and LDL-C 14.9 mmol/L. Coronary angiography demonstrated triple-vessel disease with left main stem involvement and critical right coronary ostial stenosis. Coronary artery bypass grafting was advised but declined. She was treated with high-dose rosuvastatin, ezetimibe, dual antiplatelet therapy, and inclisiran 284 mg. After one dose of inclisiran, total cholesterol fell to 6.78 mmol/L and LDL-C to 4.71 mmol/L, a reduction of more than 60%. Conclusion This case highlights the aggressive natural history of inadequately controlled HoFH and the importance of sustained lifelong therapy. Inclisiran may provide additional LDL-C reduction in selected HoFH patients, although long-term cardiovascular outcome data remain limited.
ALN-PCS ; Coronary Artery Disease ; Homozygous Familial Hypercholesterolemia ; Lipids

This study aims to investigate the potential effect of the water extract of fresh Rehmanniae Radix on hypercholesterolemia in mice that was induced by a high-fat and high-cholesterol diet and explore its possible mechanism from bile acid reabsorption. Male C57BL/6 mice were randomly assigned into the following groups: control, model, low-and high-dose(4 and 8 g·kg~(-1), respectively) fresh Rehmanniae Radix, and positive drug(simvastatin, 0.05 g·kg~(-1)). Other groups except the control group were fed with a high-fat and high-cholesterol diet for 6 consecutive weeks to induce hypercholesterolemia. From the 6th week, mice were administrated with corresponding drugs daily via gavage for additional 6 weeks, while continuing to be fed with a high-fat and high-cholesterol diet. Serum levels of total cholesterol(TC), triglycerides(TG), low density lipoprotein-cholesterol(LDL-c), high density lipoprotein-cholesterol(HDL-c), and total bile acid(TBA), as well as liver TC and TG levels and fecal TBA level, were determined by commercial assay kits. Hematoxylin-eosin(HE) staining, oil red O staining, and transmission electron microscopy were performed to observe the pathological changes in the liver. Three livers samples were randomly selected from each of the control, model, and high-dose fresh Rehmanniae Radix groups for high-throughput transcriptome sequencing. Differentially expressed genes were mined and KEGG pathway enrichment analysis was performed to predict the key pathways and target genes of the water extract of fresh Rehmanniae Radix in the treatment of hypercholesterolemia. RT-qPCR was employed to measure the mRNA levels of cholesterol 7α-hydroxylase(CYP7A1) and cholesterol 27α-hydroxylase(CYP27A1) in the liver. Western blot was employed to determine the protein levels of CYP7A1 and CYP27A1 in the liver as well as farnesoid X receptor(FXR), apical sodium-dependent bile acid transporter(ASBT), and ileum bile acid-binding protein(I-BABP) in the ileum. The results showed that the water extract of fresh Rehmanniae Radix significantly lowered the levels of TC and TG in the serum and liver, as well as the level of LDL-c in the serum. Conversely, it elevated the level of HDL-c in the serum and TBA in feces. No significant difference was observed in the level of TBA in the serum among groups. HE staining, oil red O staining, and transmission electron microscopy showed that the water extract reduced the accumulation of lipid droplets in the liver. Further mechanism studies revealed that the water extract of fresh Rehmanniae Radix significantly down-regulated the protein levels of FXR and bile acid reabsorption-related proteins ASBT and I-BABP. Additionally, it enhanced CYP7A1 and CYP27A1, the key enzymes involved in bile acid synthesis. Therefore, it is hypothesized that the water extract of fresh Rehmanniae Radix may exert an anti-hypercholesterolemic effect by regulating FXR/ASBT/I-BABP signaling, inhibiting bile acid reabsorption, and increasing bile acid excretion, thus facilitating the conversion of cholesterol to bile acids.
Animals ; Male ; Bile Acids and Salts/metabolism* ; Mice, Inbred C57BL ; Mice ; Diet, High-Fat/adverse effects* ; Cholesterol/metabolism* ; Drugs, Chinese Herbal/administration & dosage* ; Hypercholesterolemia/genetics* ; Receptors, Cytoplasmic and Nuclear/genetics* ; Rehmannia/chemistry* ; Liver/drug effects* ; Humans ; Cholesterol 7-alpha-Hydroxylase/genetics* ; Plant Extracts

OBJECTIVE: To investigate the gene detection results of 2 patients with familial hypercholesterolemia (FH) caused by complex heterozygous variation, and to clarify the relationship between clinical manifestations and gene variation. METHODS: Two patients (patient 1 and 2) with FH who visited Beijing Anzhen Hospital Affiliated to Capital Medical University in 2018 were selected as research subjects. A retrospective study method was used to collect clinical and family history data of the two patients. And 2 mL of peripheral venous blood from each of the two patients was collected, and genomic DNA extraction was performed on the blood samples. Sanger sequencing was used to validate the variant sites of the two patients detected by whole-exome sequencing (WES). Pathogenicity of variants was classified based on the American College of Medical Genetics and Genomics (ACMG) Standards and Guidelines for the Classification of Genetic Variants (hereinafter referred to as the "ACMG Guidelines"), and the impact of variant was analyzed using multiple bioinformatics tools including SIFT, PolyPhen-2, and SWISS-MODEL. This study has been approved by Beijing Anzhen Hospital Affiliated to Capital Medical University (Ethics No. 2024215X). RESULTS: Patient 1 initially presented with early-onset coronary heart disease, with initial lipid levels of serum total cholesterol (TC) 9.86 mmol/L (normal reference value: 3.10~5.20 mmol/L) and serum low-density lipoprotein cholesterol (LDL-C) 8.37 mmol/L (normal reference value: 1.27~3.12 mmol/L) on admission. Patient 1 initially underwent treatment with rosuvastatin combined with ezetimibe for one month, but the lipid-lowering effect was not significant. The lipid-lowering therapy was then adjusted to atorvastatin combined with ezetimibe and probucol. After one year of treatment, the patient developed paroxysmal chest pain symptoms. A follow-up lipid profile showed a serum TC level of 4.50 mmol/L and a LDL-C level of 3.55 mmol/L. The lipid-lowering regimen was continued, and the serum LDL-C levels were maintained between 2.65 and 3.66 mmol/L. Patient 2 was found to have an abnormally high blood lipid level and carotid artery hardening during physical examination, with an initial blood lipid level of serum TC 11.82 mmol/L and serum LDL-C 9.63 mmol/L. After receiving rosuvastatain therapy, the lipid-lowering effect was significant. WES revealed that patient 1 carried the heterozygous variants c.1871_1873del(p.Ile624del) and c.1747C>T (p.His583Tyr) in the LDLR gene (NM_000527.4), while patient 2 carried the heterozygous variants c.1747C>T (p.His583Tyr) in the LDLR gene and c.6936_6937inv (p.Ile2313Val) in the APOB gene (NM_000384). According to the ACMG Guidelines, the LDLR gene c.1747C>T (p.His583Tyr) was classified as a pathogenic variant (PS3+PM1+PM2_supporting+PM5+PP2+PP3), and c.1871_1873del (p.Ile624del) was classified as a pathogenic variant (PS3+PS4+PM2_supporting+PM1+PM4); the APOB gene c.6936_6937inv (p.Ile2313Val) was classified as a variant of uncertain clinical significance (PM2_supporting BP4). CONCLUSION Patients 1 and 2 in this study were patients with complex heterozygous variant FH, and their genotypic differences may be related to the differences in clinical serum LDL-C levels and the efficacy of hypolipidemic agents.
Humans ; Hyperlipoproteinemia Type II/drug therapy* ; Male ; Female ; Heterozygote ; Adult ; Middle Aged ; Receptors, LDL/genetics* ; Retrospective Studies ; Mutation ; Exome Sequencing

Objective:b> To identify and analyze 3D architecture of the mutational sites of susceptible genes in a pedigree with familial hypercholesterolemia-like phenotype (FHLP). Methods:b> This is a case series study. A pedigree with suspected familial hypercholesterolemia was surveyed. The proband admitted in Beijing Anzhen Hospital in April 2019. Whole-exome sequencing was performed to determine the mutational sites of susceptible genes in the proband. Polymerase chain reaction (PCR) sequencing was used to verify the pathogenic variant on proband's relatives. The structural and functional changes of the proteins were analyzed and predicted by Discovery Studio 4.0 and PyMol 2.0. Results:b> The patients in the pedigree showed abnormal lipid profiles, especially elevated levels of total cholesterol(TC). The genetic screening detected the c.1330C>T SNP in the exon 8 of lipase C (LIPC) gene, this mutation leads to an amino acid substitution from arginine to cysteine at position 444 (Arg444Cys), in the proband and proband's father and brother. In this family, members with this mutation exhibited elevated TC, whereas lipid profile was normal from the proband's mother without this mutation. This finding indicated that LIPC: c.1330C>T mutation might be the mutational sites of susceptible genes. The analysis showed that Arg444Cys predominantly affected the ligand-binding property of the protein, but had a limited impact on catalytic function. Conclusion:b> LIPC: c.1330C>T is a new mutational site of susceptible genes in this FHLP pedigree.
Humans ; Male ; Hyperlipoproteinemia Type II/genetics* ; Lipase/genetics* ; Lipids ; Mutation ; Pedigree ; Phenotype ; Proteins

Objective:b> To analyze the status of excess heart age and its risk factors among Chinese residents aged 35 to 64 years. Methods:b> The study subjects were Chinese residents aged 35 to 64 years who completed the heart age assessment by WeChat official account "Heart Strengthening Action" through the internet from January 2018 to April 2021. Information such as age, gender, body mass index (BMI), blood pressure, total cholesterol (TC), smoking history, and diabetes history was collected. The heart age and excess heart age were calculated according to the characteristics of individual cardiovascular risk factors and the heart aging was defined as excess heart age≥5 years and 10 years respectively. The heart age and standardization rate were calculated respectively based on the population standardization of the 7th census in 2021.CA trend test was used to analyze the changing trend of excess heart age rate and population attributable risk (PAR) was used to calculate the contribution of risk factors. Results:b> The mean age of 429 047 subjects was (49.25±8.66) years. The male accounted for 51.17% (219 558/429 047) and the excess heart age was 7.00 (0.00, 11.00) years. The excess heart age rate defined by excess heart age≥5 years and ≥10 years was 57.02% (the standardized rate was 56.83%) and 38.02% (the standardized rate was 37.88%) respectively. With the increase of the age and number of risk factors, the excess heart age rate of the two definitions showed an upward trend according to the result of the trend test analysis (<i>Pi><0.001). The top two risk factors of the PAR for excess heart age were overweight or obese and smoking. Among them, the male was smoking and overweight or obese, while the female was overweight or obese and having hypercholesterolemia. Conclusion:b> The excess heart age rate is high in Chinese residents aged 35 to 64 years and the contribution of overweight or obese, smoking and having hypercholesterolemia ranks high.
Humans ; Male ; Female ; Overweight ; Hypercholesterolemia/epidemiology* ; Risk Factors ; Obesity/epidemiology* ; Body Mass Index ; China/epidemiology*

Objective:b> To summarize the genotypes and clinical characteristics of homozygous family hypobetalipoproteinemia (Ho-FHBL) caused by apolipoprotein B (APOB) gene variations. Methods:b> The clinical, laboratory, genetic, and liver histology data of a boy with Ho-FHBL managed in the hepatology ward of the Children's Hospital of Fudan University in May 2021 were retrospectively analyzed. The literature was searched from China National Knowledge Infrastructure, Wanfang Data Knowledge Service Platform, China VIP database, China Biology Medicine disc and PubMed database (up to May 2022) with "familial hypobetalipoproteinemia" or "hypobetalipoproteinemias" or "hypo beta lipoproteinemia" or "hypolipoproteinemias" as the search terms. All relevant literatures were reviewed to summarize the clinical and genetic features of Ho-FHBL caused by APOB gene variations. Results:b> The male patient was admitted to the hospital due to abnormal liver function tests for 8 months at the age of 4 years and 6 months. Blood biochemistry showed transaminitis and abnormally low serum levels of lipids. Liver biopsy revealed fatty liver with inflammation and early cirrhosis (Brunt score was F3G2S4). Whole exome sequencing revealed two novel variants of APOB gene (c.3745C>T, p.Q1249 * from the father and c.4589_4592delinsAGGTAGGAGGTTTAACTCCTCCTACCT, p.T1530Kfs * 12 from the mother). He was diagnosed as Ho-FHBL caused by APOB gene compound heterozygous variations. Literature search retrieved 36 English literatures and 0 Chinese literature. A total of 55 (23 males and 32 females) Ho-FHBL cases, including this one, were caused by 54 APOB gene pathogenic variants (23 frameshift, 15 nonsense, 7 missense, 8 splice and 1 gross deletions). The age of the last follow-up was between 1 month and 75 years. Among them, 28 cases had lipid malabsorption, 19 cases had early dysplasia, 12 cases had no symptoms. Twenty-one patients had symptoms related to fat soluble vitamin deficiency, including 14 cases of acanthocytosis, 10 cases of neurological symptoms, and 6 cases of ocular lesions. Thirty-four patients had liver involvement, including 25 cases of elevated transaminase, 21 cases of fatty liver, 15 cases of hepatomegaly, 9 cases of liver fibrosis, 3 cases of liver cirrhosis, 1 case of hepatic hemangioma and 1 case of liver neoplastic nodule. Conclusions:b> The variants of APOB gene in Ho-FHBL are mainly frameshift and nonsense variations. Patients may have lipid malabsorption and (or) early dysplasia, or symptom-free. Liver involvement is common.
Child ; Female ; Humans ; Male ; Child, Preschool ; Infant ; Abetalipoproteinemia/diagnosis* ; Retrospective Studies ; Hypobetalipoproteinemias/diagnosis* ; Fatty Liver/genetics* ; Apolipoproteins B/genetics* ; Lipids

Familial hypercholesterolemia (FH) is an autosomal dominant inherited disease caused by abnormal lipoprotein metabolism. Patients with FH have a significantly increased risk of coronary artery disease (CAD) due to long-term exposure to high levels of low-density lipoprotein (LDL). The diagnosis of FH relies heavily on gene detection, and examination of LDL receptor (LDLR) function is of great significance in its treatment. This review summarizes the current advances in the screening, diagnosis, and treatment of FH and functional analysis of LDLR gene mutations.
Humans ; Hyperlipoproteinemia Type II/therapy* ; Coronary Artery Disease ; Lipoproteins, LDL ; Mutation

This report presents a case of a male infant, aged 32 days, who was admitted to the hospital due to 2 days of bloody stools and 1 day of fever. Upon admission, venous blood samples were collected, which appeared pink. Blood biochemistry tests revealed elevated levels of triglycerides and total cholesterol. The familial whole genome sequencing revealed a compound heterozygous variation in the <i>LPLi> gene, with one variation inherited from the father and the other from the mother. The patient was diagnosed with lipoprotein lipase deficiency-related hyperlipoproteinemia. Acute symptoms including bloody stools, fever, and bloody ascites led to the consideration of acute pancreatitis, and the treatment involved fasting, plasma exchange, and whole blood exchange. Following the definitive diagnosis based on the genetic results, the patient was given a low-fat diet and received treatment with fat-soluble vitamins and trace elements, as well as adjustments to the feeding plan. After a 4-week hospitalization, the patient's condition improved and he was discharged. Follow-up showed a decrease in triglycerides and total cholesterol levels. At the age of 1 year, the patient's growth and psychomotor development were normal. This article emphasizes the multidisciplinary diagnosis and treatment of familial hyperlipoproteinemia presenting with symptoms suggestive of acute pancreatitis, including bloody ascites, in the neonatal period.
Humans ; Infant ; Male ; Acute Disease ; Ascites ; Cholesterol ; Hyperlipoproteinemia Type I/genetics* ; Hyperlipoproteinemias ; Lipoprotein Lipase/genetics* ; Pancreatitis ; Triglycerides

Background and Objective: Dyslipidemia in hypothyroidism results from the effects of thyroid hormones on lipid metabolism. These, in combination with hypothyroidism-induced hemodynamic changes, are risk factors for cardiometabolic diseases. We determined the prevalence of metabolic syndrome (MS) among adult Filipinos with hypothyroidism and compared clinical and laboratory characteristics of those with versus without MS. Methods: This is a retrospective study of 105 patients with biochemically confirmed hypothyroidism. A review of records obtained anthropometric measurements, blood pressure, fasting blood glucose, lipid profile, and thyroid hormones. Clinical and laboratory characteristics were then compared between MS and those without. Significant differences were determined by two-way ANOVA, while heterogeneity of categorical variables was determined by chi-square or Fisher exact test. All data analyses were performed using Stata version 17.0 with a significance level of p<0.05. Results: The prevalence of MS is 36.19% (95%CI: 27.04%,46.15%). Body mass index (BMI) peaks at obese class I among those with MS. There is a significantly higher proportion of patients diagnosed to have diabetes (28.95% vs. 7.46%; p=0.003) and hypertension (52.63% vs. 14.93%; p<0.001) in the MS group. No significant differences were noted between groups regarding age, sex, etiology of hypothyroidism, blood pressure, fasting glucose, lipid profile, and thyroid hormone levels. Conclusion Our study showed that the prevalence of MS in adult Filipinos with hypothyroidism is increased at 36.19%. Only BMI, presence of diabetes, and hypertension were shown to be significantly higher. Emphasis must be placed on early screening among hypothyroid patients at high risk of developing MS. A prospective study using waist circumference and clinical and metabolic parameters is needed to validate these findings.
dyslipidemia ; hypothyroidism ; metabolic syndrome ; prevalence

Background: Cardiovascular disease (CVD) is a leading cause of death around the world including the Philippines. Dyslipidemia and lifestyle have been considered as important modifiable risk factors. Experts in the Philippines have recommended that among individuals with dyslipidemia, lifestyle modification should be advised regardless of their present condition or risk profile. However, a key limitation of the most recent guidelines is the lack of studies on lifestyle interventions involving Filipinos. Objective: This study aimed to provide preliminary evidence for the use of a lifestyle medicine intervention program in the management of dyslipidemia as risk factor for cardiovascular disease. Methods: This study employed a mixed method of quantitative and qualitative research designs. The tools used were selfadministered questionnaires, collecting and examining documents. Measures to improve validity in qualitative studies have also been employed such as respondent validation and rival explanation. Triangulation with the findings from the other qualitative methodologies was also employed. Ethical approval was granted. Results: The first part of the study has a total of 66 participants who underwent a lifestyle intervention program in a single clinic, comprising of 26 male and 40 female subjects were selected through convenient sampling method. Around 50% of the participants were 40-59 years old, 42.4% were 30-39 years old, and only 7.6% were 60-89 years old. The knowledge of the respondents had an overall mean of 7.73 (SD=1.16) which is interpreted as high knowledge. The attitude of the respondents had a mean of 3.58 (SD=0.50) which is interpreted as very positive. The respondents also had a good lifestyle practice with overall mean of 2.76 (SD=0.49). The second part of the study consisted of eight participants with 3 males and 5 females who were chosen through purposive sampling. All participants experienced reduction of their LDL-C and total cholesterol levels after the 12-week lifestyle intervention. Two participants had increased triglyceride levels. The select group also showed reduction in the blood glucose levels and body mass index. Conclusion This study revealed that participants had good knowledge and attitude regarding cardiovascular diseases and its risk factors. Yet, there is still a high number of those who do not efficiently practice healthy lifestyle and diet. Additional information should be extracted to establish the dietary intake of participants which contributed to the increase in triglyceride levels of some select participants.
lifestyle ; ischemic heart disease ; dyslipidemia