scholarly journals Stakeholder Views on Active Cascade Screening for Familial Hypercholesterolemia

Healthcare ◽  
2018 ◽  
Vol 6 (3) ◽  
pp. 108 ◽  
Author(s):  
Carla van El ◽  
Valentina Baccolini ◽  
Peter Piko ◽  
Martina Cornel
Keyword(s):  
The Netherlands ◽  
Familial Hypercholesterolemia ◽  
Screening Program ◽  
Family Members ◽  
Preventive Strategy ◽  
Cascade Screening ◽  
Privacy Regulation ◽  
Psychological Burden ◽  
Roles And Responsibilities ◽  
Screening Programs

In familial hypercholesterolemia (FH), carriers profit from presymptomatic diagnosis and early treatment. Due to the autosomal dominant pattern of inheritance, first degree relatives of patients are at 50% risk. A program to identify healthy relatives at risk of premature cardiovascular problems, funded by the Netherlands government until 2014, raised questions on privacy and autonomy in view of the chosen active approach of family members. Several countries are building cascade screening programs inspired by Dutch experience, but meanwhile, the Netherlands’ screening program itself is in transition. Insight in stakeholders’ views on approaching family members is lacking. Literature and policy documents were studied, and stakeholders were interviewed on pros and cons of actively approaching healthy relatives. Sociotechnical analysis explored new roles and responsibilities, with uptake, privacy, autonomy, psychological burden, resources, and awareness as relevant themes. Stakeholders agree on the importance of early diagnosis and informing the family. Dutch healthcare typically focuses on cure, rather than prevention. Barriers to cascade screening are paying an own financial contribution, limited resources for informing relatives, and privacy regulation. To benefit from predictive, personalized, and preventive medicine, the roles and responsibilities of stakeholders in genetic testing as a preventive strategy, and informing family members, need to be carefully realigned.

Population-Based Screening in Children For Early Diagnosis and Treatment of Familial Hypercholesterolemia: Design of The VRONI Study

2021 ◽  
Author(s):  
Veronika Sanin ◽  
Raphael Schmieder ◽  
Sara Ates ◽  
Lea Dewi Schlieben ◽  
Jens Wiehler ◽  
...  
Keyword(s):  
Familial Hypercholesterolemia ◽  
Screening Program ◽  
Molecular Genetic ◽  
Population Based ◽  
Molecular Genetic Analysis ◽  
Cascade Screening ◽  
Screening Programs ◽  
Pathogenic Variants ◽  
Risk Indices ◽  
Training Courses

Abstract Background: Heterozygous Familial Hypercholesterolemia (FH) represents the most frequent monogenic disorder with an estimated prevalence of 1:250 in the general population. Diagnosis during childhood enables early initiation of preventive measures, reducing the risk of severe consecutive atherosclerotic manifestations. Nevertheless, population-based screening programs for FH are scarce.Methods: In the VRONI study children aged 5 to 14 years in Bavaria are invited to participate in a FH screening program during regular pediatric visits. The screening is based on LDL-C measurements from capillary blood. If exceeding 130 mg/dl (3.34 mmol/l), i.e. the expected 95th percentile in this age group, subsequent molecular genetic analysis for FH is performed. Children with FH pathogenic variants enter a registry and are treated by specialized pediatricians. Furthermore, qualified training centers offer FH-focused training courses to affected families. For first degree relatives, reverse cascade screening is recommended to identify and treat affected family members.Results: Implementation of VRONI required intensive prearrangements for addressing ethical, educational, data-safety, legal and organisational aspects, which will be outlined in this paper. Recruitment started in January of 2021, within two months more than 280 pediatricians screened over 1,150 children. Approximately 60,000 children are expected to be enrolled in the VRONI study until 2024. Conclusion: VRONI aims to test the feasibility of a population-based screening for FH in children in Bavaria, intending to set the stage for a nation-wide FH screening infrastructure. Further we aim to validate genetic variants of unclear significance, detect novel causative mutations, and contribute to polygenic risk indices. (German Clinical Trials Register: DRKS00022140; registered August 21st2020.)

scholarly journals Quality Assessment of the Genetic Test for Familial Hypercholesterolemia in The Netherlands

Cholesterol ◽  
2013 ◽  
Vol 2013 ◽  
pp. 1-8 ◽  
Author(s):  
Iris Kindt ◽  
Roeland Huijgen ◽  
Marieke Boekel ◽  
Kristiaan J. van der Gaag ◽  
Joep C. Defesche ◽  
...  
Keyword(s):  
The Netherlands ◽  
Familial Hypercholesterolemia ◽  
Screening Program ◽  
Reference Laboratory ◽  
Test Results ◽  
Cascade Screening ◽  
Dna Test ◽  
Increased Risk ◽  
A Prospective Study ◽  
Positive Results

Introduction. Familial hypercholesterolemia (FH) is an inherited disorder associated with a severely increased risk of cardiovascular disease. Although DNA test results in FH are associated with important medical and ethical consequences, data on accuracy of genetic tests is scarce. Methods. Therefore, we performed a prospective study to assess the overall accuracy of the DNA test used in the genetic cascade screening program for FH in The Netherlands. Individuals aged 18 years and older tested for one of the 5 most prevalent FH mutations, were included consecutively. DNA samples were analyzed by the reference and a counter-expertise laboratory following a standardized procedure. Results. 1003 cases were included. In the end, 317 (32%) carried an FH mutation, whereas in 686 (69%) samples no mutation was found. The overall accuracy of the reference laboratory was 99.8%, with two false positive results identified by the counter-expertise laboratory. Conclusion. The currently used mutation analysis is associated with a very low error rate. Therefore, we do not recommend routine use of duplicate testing.

Cascade screening program for familial hypercholesterolemia

2018 ◽  
Vol 65 (5) ◽  
pp. 280-286
Author(s):  
Patricia Rubio-Marín ◽  
Alfredo Michán-Doña ◽  
Juan Maraver-Delgado ◽  
Raquel Arroyo-Olivares ◽  
Rosalía Barrado Varea ◽  
...  
Keyword(s):  
Familial Hypercholesterolemia ◽  
Screening Program ◽  
Cascade Screening

Abstract 15779: Quality of Life in a Cohort of Familial Hypercholesterolemia Patients Undergoing Molecular Cascade Screening in Brazil

Circulation ◽  
2015 ◽  
Vol 132 (suppl_3) ◽  
Author(s):  
Ana Cristina Souto ◽  
Alexandre Pereira ◽  
Cinthia E Jannes ◽  
Julia Fukushima ◽  
Jose E Krieger ◽  
...  
Keyword(s):  
Quality Of Life ◽  
Familial Hypercholesterolemia ◽  
Linear Models ◽  
Screening Program ◽  
Short Form ◽  
Smoking Habit ◽  
Genetic Diagnosis ◽  
Cascade Screening ◽  
Social Demographic

Introduction:: Familial hypercholesterolemia (FH) is an underdiagnosed and undertreated disease associated with elevated risk of early cardiovascular disease (CVD) and thus can reduce quality of life. The present health related quality of life (HRQL) investigation, evaluated patients personal interpretation of morbidity burden in daily life. Methods: The study included a total of 1,032 adult individuals participating in a FH molecular cascade-screening program. The involved individuals were index cases (IC n=363), with genetic diagnosis or FH and their first-degree relatives (FDR, n=669). All patients were evaluated at the first session of the molecular diagnosis process. HRQL measurements, mental (MCS) and physical (PCS) component scores, was carried out with the Medical Outcomes Study (MOS) 12-Item Short-Form Health Survey (SF-12) questionnaire. Results: IC were older (52±13.1 vs. 46±16.2 years, P<0.05) and presented lower PCS than FDR (44.7±9.3 vs. 49.2±8.4, P<0.05). No differences were seen on the MCS component. Overall, generalized linear models showed that smoking habit (11.9% prevalence, P=0.006), previous diagnosis of hyperlipidemia (78.6%, P=0.020) and depression (13.5% prevalence, P<0.000) were significant predictors of MCS. The presence of heart failure (6.5%, P=0.018), angina pectoris (12.9%, P=0.005), previous myocardial infarction (12.3%, P=0.012), hypertension (33.9%, P=0.018) and obesity (12.8%, P<0.000) were all predictors of PCS. The presence of arrhythmias (10.7% prevalence) predicted both MCS and PCS (P=0.042 and P=0.00, respectively). Male gender (42.4%, P<0.000) and education level (< 9 years of background, 28% P<0.000) were social-demographic aspects predictive of differences in MCS and PCS, respectively. Conclusions: Reductions in the individuals’ reported quality of life were explained by differences in social-demographic characteristics but mainly by inadequate health/disease status, such as risk factors and previous CVD. Active FH genetic cascade diagnosis by promoting early and adequate medical care and thus preventing early CVD, may improve substantially the subjective appraisal of HRQL.

scholarly journals Cascade screening for familial hypercholesterolemia-identification of the C308Y mutation in multiple family members and relatives for the first time in mainland China

2019 ◽  
Vol 20 (1) ◽  
Author(s):  
Weirong Jin ◽  
Qiuwang Zhang ◽  
Bei Wang ◽  
Lili Pan ◽  
Hongyou Qin ◽  
...  
Keyword(s):  
Dna Sequencing ◽  
Familial Hypercholesterolemia ◽  
Low Density Lipoprotein ◽  
Family Members ◽  
Mainland China ◽  
Density Lipoprotein ◽  
Low Density ◽  
Lipid Profiling ◽  
Cascade Screening ◽  
First Time

Abstract Background Familial hypercholesterolemia (FH), an autosomal dominant genetic disorder, is underdiagnosed and undertreated. The majority of FH cases are caused by low density lipoprotein receptor (LDL-R) gene mutations. The C308Y mutation in LDL-R results in approximately 70% loss of LDL-R activity, leading to the elevation of low density lipoprotein-cholesterol (LDL-C) and an increased risk of premature coronary heart disease (CHD). The aim of this study was to identify FH cases by cascade screening in family members and relatives of a 37-year old male with premature CHD and hypercholesterolemia. Methods Clinical exam, blood lipid profiling and genomic DNA sequencing of all exons of LDL-R were performed for the proband and his 14 family members and relatives. FH diagnosis was carried out using the Dutch Lipid Clinic Network (DLCN) criteria. Results Lipid profiling showed that 9 individuals, including the proband, had hypercholesterolemia. All these 9 subjects had a G > A substitution at nucleotide 986 in exon 7 resulting in the C308Y mutation as determined by DNA sequencing, and all those carrying the mutation were diagnosed as having definite FH under the DLCN criteria. However, most (7/9) did not have suggestive clinical manifestations of CHD. Conclusions The C308Y mutation was discovered in multiple family members and relatives for the first time in mainland China. Cascade screening is key for the confirmatory diagnosis of FH. Our hypothesis that the C308Y is a common variant in the population of Southern China origin warrants further validation by screening for the C308Y mutation in a large population.

Mo1706 Optimizing Screening Programs by Real-Time Monitoring: Outcomes of the National Colorectal Cancer FIT-Based Screening Program of the Netherlands

2016 ◽  
Vol 150 (4) ◽  
pp. S757-S758
Author(s):  
Esther Toes-Zoutendijk ◽  
Monique van Leerdam ◽  
Evelien Dekker ◽  
Frank van Hees ◽  
Folkert van Kemenade ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
The Netherlands ◽  
Real Time ◽  
Screening Program ◽  
Real Time Monitoring ◽  
Screening Programs

Abstract 15576: Cardiovascular Disease in Elderly Familial Hypercholesterolemia Individuals Attending a Cascade Screening Program

Circulation ◽  
2020 ◽  
Vol 142 (Suppl_3) ◽  
Author(s):  
elaine coutinho ◽  
Marcio H Miname ◽  
Viviane Z Rocha ◽  
Marcio S Bittencourt ◽  
Cinthia Jannes ◽  
...  
Keyword(s):  
Cardiovascular Disease ◽  
Familial Hypercholesterolemia ◽  
High Intensity ◽  
Screening Program ◽  
Coronary Revascularization ◽  
Genetic Diagnosis ◽  
Lipid Lowering ◽  
Lipid Lowering Therapy ◽  
Cvd Risk ◽  
Cascade Screening

Introduction: Familial hypercholesterolemia (FH) is associated with early onset of cardiovascular disease (CVD) and mortality. Lipid lowering treatment (LLT) may change the natural history of FH, however there is scant information about elderly individuals (older than 60 years) with FH. This study describes characteristics of elderly FH individuals presenting or not CVD. Hypothesis: Monogenic defects are important markers of CVD risk and initiation and long-term use of lipid lowering therapy (LLT) is relevant to minimize this risk. Methods: Cross-sectional analysis of clinical and laboratory of molecularly proven elderly FH (FH+) and non-affected (FH-) individuals attending a cascade screening program. FH+ were divided in those presenting or not CVD (defined as previous myocardial infarction or ischemic stroke, carotid or coronary revascularization and angina with stenosis ≥50% on angiography). Results: From 4,111 genotyped individuals, 462 (11.2%) elders were included (198 FH+ and 264 FH-). There was predominance of females in either groups, however with more men in FH+ 37.4% vs. 24.2%, p=0.002. No differences were seen between FH+ and FH- regarding age, [median (%25;75%)] 66 (62;71) and 66 (63;71) years, p=0.68; use of LLT 88.5% vs. 91.5%, p=0.29 and high intensity LLT 61.7 % vs. 55.8%, p=0.20, respectively. Despite longer LLT duration in FH+ 11(7;20) vs. 7 (3;13) years, p<0.001, in either groups LLT was started late, at 54 (47;61) and 59 (52;64) years, p <0.001, respectively in FH+ and FH-. FH+ had higher LDL-C at diagnosis, 243 (179;302) vs. 228 (209;251) mg/dL, p=0.013, as well as greater frequencies of previous CVD 40.9% vs. 27.3%, p=0.002, and early CVD 22.2% vs. 9.0%, p<0.001. In FH+, male sex [OR (95%CI)] 5.29 (2.25-12.45), p<0.001, and use of high intensity LLT 2.51 (1.08-5.87), p=0.03, were independently associated with CVD. Conclusions: The genetic diagnosis of FH was associated with higher rates of CVD and early CVD vs. FH- hypercholesterolemics. Elders with FH+ who survived despite late LLT initiation have a worse CVD history than FH- elders, emphasizing the relevance of a monogenic defect as cause of long-lasting hypercholesterolemia and CVD risk, particularly in men.

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