scholarly journals Familial Hypercholesterolemia (FH) in Iran: Findings from the Four-Year FH Registry

2021 ◽  
Vol 2021 ◽  
pp. 1-6
Author(s):  
Golnaz Vaseghi ◽  
Marzieh Taheri ◽  
Kiyan Heshmat-Ghahdarijani ◽  
Mohammad Rayati ◽  
Sonia Zarfeshani ◽  
...  
Keyword(s):  
Cardiovascular Disease ◽  
Familial Hypercholesterolemia ◽  
Low Density Lipoprotein ◽  
Density Lipoprotein ◽  
Degree Relative ◽  
Cascade Screening ◽  
Lipid Clinic ◽  
Premature Cardiovascular Disease ◽  
Dominant Disease ◽  
Laboratory Group

Background. Familial hypercholesterolemia (FH) is a common autosomal dominant disease. Its diagnosis in Iran was uncommon. Iran registry of FH (IRFH) has been started from 2017 from Isfahan. In this study, we report the four-year FH registry. Methods. The Iran FH registry is an ongoing study which is followed by a dynamic cohort. It has been started from 2017. The patients are selected from laboratories due to high cholesterol level and who have history of premature cardiovascular disease. The Dutch Lipid Clinic Network (DLCN) criteria are used for the detection of FH. Cascade screening is performed for detection of first-degree relative of patients. Results. Among the 997 individuals included in this registry, they were 522 (mean age 51.41 ± 12.91 year), 141 (mean age 51.66 ± 8.3 year), and 129 (mean age 41 ± 16.5 year) patients from laboratories, premature cardiovascular disease, and relatives, respectively. In total, 263 patients were diagnosed with probable or definite FH, and others were in the possible group. Low-density lipoprotein cholesterol (LDL) level was 141.42 ± 45.27   mg / dl in the laboratory group and 54.9% of patients were on LLT treatment. In patients with premature cardiovascular disease and FH, the LDL level was 91.93 ± 32.58 and was on LLT treatment. The LDL concentration in the first relative of FH patients was 152.88 ± 70.77 and 45.7% of them are on LLT therapy. Conclusions. Most of FH patients were underdiagnosed and undertreated before their inclusion in the IRFH. Cascade screening helps in the improvement of diagnosis.

scholarly journals Improving Familial Hypercholesterolemia Index Case Detection: Sequential Active Screening from Centralized Analytical Data

2021 ◽  
Vol 10 (4) ◽  
pp. 749
Author(s):  
Fernando Sabatel-Pérez ◽  
Joaquín Sánchez-Prieto ◽  
Víctor Manuel Becerra-Muñoz ◽  
Juan Horacio Alonso-Briales ◽  
Pedro Mata ◽  
...  
Keyword(s):  
Familial Hypercholesterolemia ◽  
Diagnostic Yield ◽  
Low Density Lipoprotein ◽  
Analytical Data ◽  
Genetic Diagnosis ◽  
Density Lipoprotein ◽  
Screening Strategy ◽  
Cascade Screening ◽  
Active Screening ◽  
Lipid Clinic

The majority of familial hypercholesterolemia index cases (FH-IC) remain underdiagnosed and undertreated because there are no well-defined strategies for the universal detection of FH. The aim of this study was to evaluate the diagnostic yield of an active screening for FH-IC based on centralized analytical data. From 2016 to 2019, a clinical screening of FH was performed on 469 subjects with severe hypercholesterolemia (low-density lipoprotein cholesterol ≥220 mg/dL), applying the Dutch Lipid Clinic Network (DLCN) criteria. All patients with a DLCN ≥ 6 were genetically tested, as were 10 patients with a DLCN of 3–5 points to compare the diagnostic yield between the two groups. FH was genetically confirmed in 57 of the 84 patients with DLCN ≥ 6, with a genetic diagnosis rate of 67.9% and an overall prevalence of 12.2% (95% confidence interval: 9.3% to 15.5%). Before inclusion in the study, only 36.8% (n = 21) of the patients with the FH mutation had been clinically diagnosed with FH; after genetic screening, FH detection increased 2.3-fold (p < 0.001). The sequential, active screening strategy for FH-IC increases the diagnostic yield for FH with a rational use of the available resources, which may facilitate the implementation of FH universal and family-based cascade screening strategies.

Estimated Prevalence of Familial Hypercholesterolemia Among Egyptian Patients with Acute Coronary Syndromes; Analysis from The Cardiorisk Project

2021 ◽  
Vol 23 (Supplement_D) ◽  
Author(s):  
Ashraf Reda ◽  
Ahmed Bendary ◽  
Ahmed Shawky Elserafy ◽  
Elsayed Farag ◽  
Tamer Mostafa ◽  
...  
Keyword(s):  
Familial Hypercholesterolemia ◽  
Acute Coronary Syndromes ◽  
Total Population ◽  
Low Density Lipoprotein ◽  
Density Lipoprotein ◽  
Cross Sectional ◽  
Lipid Clinic ◽  
Egyptian Patients ◽  
Coronary Syndromes ◽  
Premature Cad

Abstract Aims The prevalence of familial hypercholesterolemia (FH) in Egypt is largely un- known. We aimed to estimate the prevalence of FH among 3224 Egyptian patients with acute coronary syndromes enrolled from 2015 to 2018 in the nationwide cross- sectional cardioRisk project. Methods and Results We applied the Dutch Lipid Clinic criteria for the diagnosis of FH on the available data recorded for the patients enrolled in the CardioRisk project. Two main criteria were applied: the presence of premature CAD (given 2 points in the Dutch criteria), and the categorized low density lipoprotein cholesterol (LDL-C) lev- els (given 1, 3, 5, or 8 points in the Dutch criteria according to the level). From a total of 3224 patients, 2743 patients had available LDL-C levels. Among those patients, when applying the abovementioned 2 criteria, we estimated that 472 patients had at least ‘possible’ FH (17.2% of the total population). Specifically, 4 patients had ‘defi- nite’ FH (0.1%), 7 patients had ‘probable’ FH (0.25%), and 461 patients had ‘possi- ble’ FH (16.8%). Conclusion The estimated prevalence of at least ‘possible’ FH among Egyptian patients with ACS is 17%.

scholarly journals Monoclonal Antibodies in the Management of Familial Hypercholesterolemia: Focus on PCSK9 and ANGPTL3 Inhibitors

2021 ◽  
Vol 23 (12) ◽  
Author(s):  
Angela Pirillo ◽  
Alberico L. Catapano ◽  
Giuseppe D. Norata
Keyword(s):  
Monoclonal Antibodies ◽  
High Risk ◽  
Familial Hypercholesterolemia ◽  
Plasma Levels ◽  
Low Density Lipoprotein ◽  
Genetic Defect ◽  
Density Lipoprotein ◽  
Lipid Lowering ◽  
Low Density ◽  
Premature Cardiovascular Disease

Abstract Purpose of Review Familial hypercholesterolemia (FH) is a monogenic disorder characterized by high plasma levels of low-density lipoprotein cholesterol (LDL-C) since birth and a high risk of premature cardiovascular disease. The genetic defect is carried in only one allele in heterozygous FH (HeFH) or in both in the most severe homozygous FH (HoFH). Current guidelines recommend to reduce substantially LDL-C levels in these high-risk patients, with the need to use association therapy combining agents with different mechanisms of action. As most cases of FH are attributable to mutations in the gene encoding the low-density lipoprotein receptor (LDLR), statins, even in combination with ezetimibe, are less effective in reducing LDL-C plasma levels in FH patients, who require a more intensive approach with additional lipid-lowering agents. Additional targets playing key roles in regulating LDL-C levels are represented by PCSK9 and ANGPTL3. Recent Findings Two monoclonal antibodies (mAbs) targeting PCSK9, evolocumab and alirocumab, significantly reduce LDL-C levels in HeFH patients. In patients with HoFH, the efficacy of mAbs to PCSK9 is strictly related to the presence of a residual LDLR activity; thus, patients carrying null mutations do not respond to the therapy with these mAbs, whereas some effects can be appreciated in HoFH bearing defective mutations. Conversely, evinacumab, the mAb targeting ANGPTL3, is highly effective in reducing LDL-C levels even in HoFH patients carrying null LDLR mutations, thanks to its LDLR-independent mechanism of action. Summary Monoclonal antibodies inhibiting PCSK9 have shown a robust effect in FH patients presenting a residual LDLR activity, while ANGPTL3 inhibitors appear to be promising even in patients carrying null LDLR mutations.

Abstract 14681: Comparative Study Between International Guidelines in Detecting Pediatric Familial Hypercholesterolemia Through a Unique Community Health System in Kagawa, Japan

Circulation ◽  
2020 ◽  
Vol 142 (Suppl_3) ◽  
Author(s):  
Keiji Matsunaga ◽  
Asako Mizobuchi ◽  
Hayato Tada ◽  
Tsuyoshi Sasaki ◽  
Yoshihiro Asano ◽  
...  
Keyword(s):  
Health System ◽  
Community Health ◽  
Familial Hypercholesterolemia ◽  
Low Density Lipoprotein ◽  
Density Lipoprotein ◽  
Hereditary Disease ◽  
International Guidelines ◽  
Number Of Children ◽  
Lipid Clinic ◽  
Lipid Screening

Introduction: Familial hypercholesterolemia (FH) is an autosomal hereditary disease found in patients who have elevated low-density lipoprotein cholesterol (LDL-C) from birth. Early detection and treatment of FH during childhood potentially reduces the risk of premature cardiovascular events. In Kagawa prefecture, a unique community health system, involving three steps, has been conducted to prevent lifestyle-related diseases for 10-year-old children. This system includes universal lipid screening, selection by pediatricians, and next-generation sequencing (NGS) of FH-related genes in hospitals. The aim of this study is to compare 3 international guidelines to detect pediatric FH with this unique community health system in Kagawa. Methods: In Kagawa prefecture, the universal lipid screening of approximately 8,000 children at 10 years of age is performed annually, covering over 90% of the target group. After excluding secondary hypercholesterolemia, pediatric clinics introduced children with LDL-C >140mg/dL to 4 designated hospitals to perform NGS. We applied the guidelines of the Dutch Lipid Clinic Network (DLCN), Simon Broome (SB), and the Japanese Atherosclerosis Society (JAS) to children who received NGS in the unique community health system in Kagawa. Results: We performed NGS for 46 children from January 2018 to February 2020 (LDL-C 186.0±50.3 mg/dL; Male/F 27/19) and 26 (57%) had FH genetic mutations (23 LDL-R and 3 PCSK9 mutations). Seventeen children met FH criteria for DLCN (35%), 10 for Simon Broome (22%), and 11 for JAS (24%), respectively. The combination of NGS and either of the 3 guidelines increased the number of children diagnosed as FH up to 31 (67%). Conclusion: International guidelines detected only half of pediatric FH who were diagnosed by the unique community health system in Kagawa. Further investigation will be required to build an effective universal screening system for pediatric FH.

Differences in phenotype, genotype and cardiovascular events between patients with probable and definite heterozygous familial hypercholesterolemia

2019 ◽  
Vol 16 (6) ◽  
pp. 467-478
Author(s):  
Ye-Xuan Cao ◽  
Bing-Yang Zhou ◽  
Di Sun ◽  
Sha Li ◽  
Yuan-Lin Guo ◽  
...  
Keyword(s):  
Familial Hypercholesterolemia ◽  
Cardiovascular Events ◽  
Oxidized Ldl ◽  
Low Density Lipoprotein ◽  
Survival Rates ◽  
Gene Mutations ◽  
Density Lipoprotein ◽  
Heterozygous Familial Hypercholesterolemia ◽  
Lipid Clinic ◽  
Kaplan Meier

Aim: To investigated the potential differences between probable and definite heterozygous familial hypercholesterolemia (HeFH) patients diagnosed by Dutch Lipid Clinic Network criteria. Methods: Clinical characteristics, lipid profile, severity of coronary artery stenosis and gene mutations were compared. Kaplan–Meier curve was performed to evaluate the cardiovascular events. Results: Overall, 325 participants were included and divided into two groups: probable (n = 233) and definite HeFH (n = 92). Definite HeFH patients had higher low-density lipoprotein cholesterol (LDL-C), oxidized-LDL and proprotein convertase subtilisin/kexin 9 levels, and higher prevalence of tendon xanthomas. The incidence of genetic mutations was statistically higher in definite HeFH than probable HeFH patients. The coronary stenosis calculated by Gensini score was statistically severer in definite HeFH patients. The best LDL-C threshold for predicting mutations was 5.14 mmol/l. Definite HeFH had lower event-free survival rates. Conclusion: Definite HeFH patients had higher severity of phenotype and genotype, and higher risk of cardiovascular events.

scholarly journals Two Novel Disease-Causing Mutations in the LDLR of Familial Hypercholesterolemia

2021 ◽  
Vol 12 ◽  
Author(s):  
Haochang Hu ◽  
Tian Shu ◽  
Jun Ma ◽  
Ruoyu Chen ◽  
Jian Wang ◽  
...  
Keyword(s):  
Familial Hypercholesterolemia ◽  
High Throughput Sequencing ◽  
Low Density Lipoprotein ◽  
Density Lipoprotein ◽  
Bioinformatic Analysis ◽  
Genetic Mutations ◽  
Missense Mutations ◽  
Autosomal Dominant Disorder ◽  
Lipid Clinic

As an autosomal dominant disorder, familial hypercholesterolemia (FH) is mainly caused by pathogenic mutations in lipid metabolism-related genes. The aim of this study is to investigate the genetic mutations in FH patients and verify their pathogenicity. First of all, a pedigree investigation was conducted in one family diagnosed with FH using the Dutch Lipid Clinic Network criteria. The high-throughput sequencing was performed on three family members to explore genetic mutations. The effects of low-density lipoprotein receptor (LDLR) variants on their expression levels and activity were further validated by silico analysis and functional studies. The results revealed that LDLC levels of the proband and his daughter were abnormally elevated. The whole-exome sequencing and Sanger sequencing were used to confirm that there were two LDLR missense mutations (LDLR c.226 G &gt; C, c.1003 G &gt; T) in this family. Bioinformatic analysis (Mutationtaster) indicated that these two mutations might be disease-causing variants. In vitro experiments suggested that LDLR c.226 G &gt; C and c.1003 G &gt; T could attenuate the uptake of Dil-LDL by LDLR. In conclusion, the LDLR c.226 G &gt; C and c.1003 G &gt; T variants might be pathogenic for FH by causing uptake dysfunction of the LDLR.

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