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Journal ArticleDOI

Reaching detection targets in familial hypercholesterolaemia: Comparison of identification strategies.

01 Jan 2020-Atherosclerosis (Atherosclerosis)-Vol. 293, pp 57-61

TL;DR: Child-parent Cascade Screening is the fastest strategy for identifying FH in the population and is applicable to any country to close the FH detection gap.
Abstract: Background and aims Familial hypercholesterolaemia (FH) is a common and preventable cause of premature heart attack but in most nations only a small proportion of FH-positive individuals have been identified. The aim of this study was to estimate the time to close this FH detection gap. Methods We developed a model to estimate the time to identify different proportions of FH in the population for three identification strategies (i) Cascade Testing (FH-mutation testing in relatives of someone with an FH mutation) (ii) Child-parent Screening (testing children for cholesterol and FH mutations during 1-year immunisation and parents of FH-positive children) and (iii) Child-parent Cascade Screening (integrating the first two methods). We used publicly available data to compare the strategies in terms of the time to identify 25%, 50% and 75% of all FH cases in the UK (current target is 25% in 5 years). For Child-parent Cascade Screening, we applied the model to other populations that have reported FH identification levels. Results In the UK, 25% of FH individuals would be identified after 47 years for Cascade Testing, 12 years for Child-parent Screening and 8 years for Child-parent Cascade Screening; 50% identification after 146, 33 and 19 years and 75% after 334, 99 and 41 years respectively. For Child-parent Cascade Screening, the times to identify 50% FH were, for Netherlands, Norway, Japan, Canada, USA, Australia/NZ, South Africa and Russia, 0, 5, 13, 15, 16, 18, 21, and 30 years respectively. Conclusions Child-parent Cascade Screening is the fastest strategy for identifying FH in the population. The model is applicable to any country to estimate the time to close the FH detection gap ( www.screenfh.com ).
Topics: Population (53%)

Summary (3 min read)

Introduction

  • Familial hypercholesterolemia (FH) is a common and preventable cause of premature ischaemic heart disease (IHD).
  • There are about 260,000 heterozygous affected individuals in the UK (prevalence 1 in 250) who have about a 100-fold excess risk of fatal myocardial infarction between ages 20 and 39 years. [1].
  • A fatal or non-fatal IHD event affects about 50% of FH-positive men before age 50 and about 30% of FH-positive women by age 60. [2].
  • How this would be delivered was not specified.
  • The authors use publicly available data to compare the time to reach 25%, 50% and 75% identification for the UK, its home nations and other countries where estimates of FH identification have been recently reported.

Cascade Testing

  • Supplementary Figure 1 gives the equation used to calculate the number of new FH individuals identified each year by Cascade Testing; the number of new FH relatives identified per known index FH mutation-confirmed case multiplied by the background number of new index FH cases identified each year from opportunistic/targeted testing (eg. high cholesterol level identified in an adult in primary care during a Health Check or in secondary care following a non-fatal cardiac event).
  • The authors assumed that all new index cases are unrelated (or else they would identify each other) to provide a best-case estimate and that all available relatives are identified within a year of identifying an index case.
  • In the model the authors reduced the number of new index cases identified per year in proportion to the population increase in FH detection each year.

Child-parent Screening

  • For Child-parent Screening a model was developed that avoids counting affected parents twice if more than one child in a family is identified as positive for FH.
  • This applies from the 3rd year of screening onwards, because the average time between births in a family is 2 years. [10].
  • The authors also avoided double-counting parents when a child, previously identified as positive, becomes a parent and has their own children screened.
  • The equations for the first 2 years of screening and from the 3rd year onwards are shown in Supplementary Figure 2.
  • The number (N) of 1-year old children (the age at screening) is the number of births per year and screening uptake (U) is the proportion attending for immunization at 1 year multiplied by the acceptance of the offer of screening among immunized children.

Child-parent Cascade Screening

  • For Child-parent Cascade Screening each FH positive child also leads to the identification of their affected siblings (older siblings in the first two years of screening) and grandparent.
  • Such FH-positive individuals are counted only once in the equations in Supplementary Figure 3 (i) for the first 2 years of screening and (ii) for the 3rd year of screening onwards, which are given separately because the impact of cascade testing is greater in the first two years of screening than subsequent years, when relatives may have already been identified or not yet borne.
  • Office for National Statistics (2017) data were used for population size [12], fertility rate [13], maternal age distribution [10] and the number of deaths per year [14] and WHO/UNICEF data for immunization coverage. [15].
  • Input data are summarised in Supplementary Table 1.
  • Sensitivity analyses were performed to examine the effect of doubling the efficacy of Cascade Testing (number of new per known cases identified) and increasing the uptake of Child-parent Screening by 10% points.

Results

  • Figure 1 shows plots of FH identification for Cascade Testing, Child-parent Screening and Child-parent Cascade Screening in the UK.
  • The results show that the 25% NHS identification target is reached after 47 years, 12 years and after 8 years respectively.
  • The plots are curved, because the rate of identification declines with increasing proportions of all cases found for each strategy.
  • Comparable plots for England, Scotland, Wales and Northern Ireland are given in Supplementary Figure 4.
  • Table 2 gives the time to identify 25%, 50% and 75% of all FH cases by Child-parent Cascade Screening for 12 countries (including the 4 home nations of the UK) where current proportions of known FH have been reported.

Discussion

  • The results of this analysis show that the fastest strategy for closing the identification gap in FH is Child-parent Cascade Screening, an integration of universal screening in childhood, based on total cholesterol measurement supported by FH mutation testing during immunisation and subsequent Cascade Testing within mutation-positive families.
  • The estimate for Child-parent Cascade Screening [19] is likely to be high because it assumed a lower rate of FH identification for Child-parent Screening than was observed in practice.[8].
  • Both child, and parent benefit from such screening, from life-style interventions and the timely introduction of drug therapy (principally statins); but the child benefits twice, once by reducing his/her own risk of premature ischaemic heart disease and again by avoiding the premature death of a parent.
  • The authors projections are presented as the proportion of all cases of FH identified in the population, rather than in specified age groups, because identification targets are likely to be set for the whole population, as they have been in the UK.
  • Conflicts of Interest: None Funding: None Acknowledgements:.

Figure Legend

  • Proportion of all FH cases in the UK identified over time for Cascade Testing, Childparent Screening and Child-parent Cascade Screening (integration of first two methods), also known as Figure 1.
  • NHS 25% target denoted by horizontal dotted line.
  • Supplementary Figure 1: Flowchart for estimating the number of FH cases identified each year by Cascade Testing Supplementary Figure 2: Flowchart for estimating the number of FH cases identified each year by Child-parent Screening Supplementary Figure 3: Flowchart for estimating the number of FH cases identified by Child-parent Cascade Screening (i):.
  • In the 1st and 2nd years of Child-parent Cascade Screening (ii): Each year, in the 3rd year and onwards of Child-parent Cascade Screening Supplementary Figure 4: Time to detect proportions of all FH for England, Scotland, Wales, and Northern Ireland.

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Content maybe subject to copyright    Report

Reaching detection targets in Familial Hypercholesterolaemia; comparison of
identification strategies
David S Wald
a
and Jonathan P Bestwick
a
a
Wolfson Institute of Preventive Medicine, Queen Mary University of London
Corresponding author: DS Wald
d.wald@qmul.ac.uk
Wolfson Institute of preventive Medicine
Barts and the London School of Medicine
Charterhouse Square
London
EC1M6BQ
Key words: Familial Hypercholesterolaemia, Screening, Detection, Targets
Word count: 2658

2
Abstract
Background and aims: Familial Hypercholesterolaemia (FH) is a common and preventable
cause of premature heart attack but in most nations only a small proportion of FH-positive
individuals have been identified. The aim of this study was to estimate the time to close this
FH detection gap.
Methods: We developed a model to estimate the time to identify different proportions of
FH in the population for three identification strategies (i) Cascade Testing (FH-mutation
testing in relatives of someone with an FH mutation) (ii) Child-parent Screening (testing
children for cholesterol and FH mutations during 1-year immunisation and parents of FH-
positive children) and (iii) Child-parent Cascade Screening (integrating the first two
methods). We used publicly available data to compare the strategies in terms of the time to
identify 25%, 50% and 75% of all FH cases in the UK (current target is 25% in 5 years). For
Child-parent Cascade Screening, we applied the model to other populations that have
reported FH identification levels.
Results: In the UK, 25% of FH individuals would be identified after 47 years for Cascade
Testing, 12 years for Child-parent Screening and 8 years for Child-parent Cascade Screening;
50% identification after 146, 33 and 19 years and 75% after 334, 99 and 41 years
respectively. For Child-parent Cascade Screening, the times to identify 50% FH were, for
Netherlands, Norway, Japan, Canada, USA, Australia/NZ, South Africa and Russia, 0, 5, 13,
15, 16, 18, 21, and 30 years respectively.
Conclusion: Child-parent Cascade Screening is the fastest strategy for identifying FH in the
population. The model is applicable to any country to estimate the time to close the FH
detection gap (www.screenfh.com).

3
Highlights
Familial Hypercholesterolaemia (FH) is a preventable cause of coronary heart disease.
Only a minority of individuals with FH have so far been identified
Cascade testing, Child-parent Screening and Child-parent Cascade Screening are feasible
Setting FH identification targets is important
Time to target for different strategies in different populations can be estimated.
Introduction
Familial hypercholesterolemia (FH) is a common and preventable cause of premature
ischaemic heart disease (IHD). There are about 260,000 heterozygous affected individuals in
the UK (prevalence 1 in 250) who have about a 100-fold excess risk of fatal myocardial
infarction between ages 20 and 39 years. [1] A fatal or non-fatal IHD event affects about
50% of FH-positive men before age 50 and about 30% of FH-positive women by age 60. [2]
Preventive treatment with statins is effective in reducing this high risk. [3]
Early identification of individuals with FH is therefore a public health priority but in most
populations only a small proportion of all cases have been identified. [4] In the UK, an
estimated 7% of all cases are known, leaving 93% undetected and at high risk of a
premature IHD event. [5,6] This gap in identification was highlighted in a recently published
National Health Service (NHS) Plan, and a target was set to increase the 7% to at least 25%
in 5 years. [6] How this would be delivered was not specified. Three strategies that have
been tested in practice include (i) family-based Cascade Testing, where relatives of
individuals with an FH mutation are tested for the same mutation [7] (ii) universal Child-
parent Screening, where children aged 1 year old are tested for cholesterol and FH
mutations at the time of routine immunisation and the affected parent of positive children
identified [8] and (iii) a combination of the two methods, Child-parent Cascade Screening,
where Child-parent Screening systematically identifies new unrelated index cases and leads
naturally to Cascade Testing of relatives. [9]

4
Here, we develop a model to estimate the time to identify different proportions of FH in the
population for the three identification strategies. We use publicly available data to compare
the time to reach 25%, 50% and 75% identification for the UK, its home nations and other
countries where estimates of FH identification have been recently reported.

5
Materials and Methods
Cascade Testing
Supplementary Figure 1 gives the equation used to calculate the number of new FH
individuals identified each year by Cascade Testing; the number of new FH relatives
identified per known index FH mutation-confirmed case multiplied by the background
number of new index FH cases identified each year from opportunistic/targeted testing (eg.
high cholesterol level identified in an adult in primary care during a Health Check or in
secondary care following a non-fatal cardiac event). We assumed that all new index cases
are unrelated (or else they would identify each other) to provide a best-case estimate and
that all available relatives are identified within a year of identifying an index case. In the
model we reduced the number of new index cases identified per year in proportion to the
population increase in FH detection each year.
Child-parent Screening
For Child-parent Screening a model was developed that avoids counting affected parents
twice if more than one child in a family is identified as positive for FH. This applies from the
3
rd
year of screening onwards, because the average time between births in a family is 2
years. [10] We also avoided double-counting parents when a child, previously identified as
positive, becomes a parent and has their own children screened. The equations for the first
2 years of screening and from the 3
rd
year onwards are shown in Supplementary Figure 2.
The number (N) of 1-year old children (the age at screening) is the number of births per year
and screening uptake (U) is the proportion attending for immunization at 1 year multiplied
by the acceptance of the offer of screening among immunized children. An FH prevalence
(P) was applied to all calculations and the median number of children per family (total
fertility rate, FR) was used to calculate the probability that a parent might have already been
identified from another child screened in previous years, since this probability increases
with the number of children in a family.
Child-parent Cascade Screening
For Child-parent Cascade Screening each FH positive child also leads to the identification of
their affected siblings (older siblings in the first two years of screening) and grandparent.
The model was developed further to avoid double-counting grandparents and siblings when

Citations
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01 Jan 2018
Abstract: BACKGROUND Since 2009, all eligible persons in England have been entitled to an NHS Health Check. Uncertainty remains about who attends, and the health-related impacts. AIM To review quantitative evidence on coverage (the proportion of eligible individuals who attend), uptake (proportion of invitees who attend), and impact of NHS Health Checks. DESIGN AND SETTING A systematic review and quantitative data synthesis. Included were studies or data reporting coverage or uptake and studies reporting any health-related impact that used an appropriate comparison group or before- and-after study design. METHOD Eleven databases and additional internet sources were searched to November 2016. RESULTS Twenty-six observational studies and one additional dataset were included. Since 2013, 45.6% of eligible individuals have received a health check. Coverage is higher among older people, those with a family history of coronary heart disease, those living in the most deprived areas, and some ethnic minority groups. Just under half (48.2%) of those invited have taken up the invitation. Data on uptake and impact (especially regarding health-related behaviours) are limited. Uptake is higher in older people and females, but lower in those living in the most deprived areas. Attendance is associated with small increases in disease detection, decreases in modelled cardiovascular disease risk, and increased statin and antihypertensive prescribing. CONCLUSION Published attendance, uptake, and prescribing rates are all lower than originally anticipated, and data on impact are limited, with very few studies reporting the effect of attendance on health-related behaviours. High-quality studies comparing matched attendees and non-attendees and health economic analyses are required.

19 citations


Journal ArticleDOI
TL;DR: Investigation of familial hypercholesterolemia can be enhanced by optimizing current diagnostic algorithms, probing electronic health records with novel information technologies and integrating universal screening of children with cascade testing of parents and other relatives.
Abstract: Purpose of review Studies reaffirm that familial hypercholesterolemia is more prevalent than initially considered, with a population frequency of approximately one in 300. The majority of patients remains unidentified. This warrants critical evaluation of existing screening methods and exploration of novel methods of detection. Recent findings New public policy recommendations on the detection of familial hypercholesterolemia have been made by a global community of experts and advocates. Phenotypic tools for diagnosing index cases remain inaccurate. Genetic testing is the gold standard for familial hypercholesterolemia and a new international position statement has been published. Correction of LDL cholesterol (LDL-C) for the cholesterol content of lipoprotein(a) [Lp(a)] may increase the precision of the phenotypic diagnosis of familial hypercholesterolemia. Cascade cotesting for familial hypercholesterolemia and elevated Lp(a) levels provides a new opportunity to stratify risk in families. Digital technology and machine learning methods, coupled with clinical alert and decision support systems, lead the way in more efficient approaches for detecting and managing index cases. Universal screening of children, combined with child-parent cascade testing, appears to be the most effective method for underpinning a population strategy for maximizing the detection of familial hypercholesterolemia. Summary Detection of familial hypercholesterolemia can be enhanced by optimizing current diagnostic algorithms, probing electronic health records with novel information technologies and integrating universal screening of children with cascade testing of parents and other relatives.

7 citations


Journal ArticleDOI
David S. Wald1, Andrew J. Martin2Institutions (2)
TL;DR: The UK National Screening Committee (NSC) in February 2020 put thousands of families at risk of premature myocardial infarction by rejecting screening of children for familial hypercholesterolaemia (FH) to prevent ischaemic heart disease (IHD).
Abstract: The UK National Screening Committee (NSC) in February 2020 put thousands of families at risk of premature myocardial infarction by rejecting screening of children for familial hypercholesterolaemia (FH) to prevent ischaemic heart disease (IHD) FH is a silent killer of young adults There about 260 000 FH-positive individuals in the UK with only about 7% so far identified About half will have a myocardial infarction before age 50 years without treatment Prevention works if started early in life and is simple—lowering serum cholesterol, with statins, which abolishes the excess IHD risk caused by the high cholesterol1 Child-parent screening involves a heel prick blood test during routine immunisation at 1 year of age and once a child is identified the parents are tested; one will be affected since FH is inherited as an autosomal dominant and then other family members undergo cascade testing2 Such child-parent cascade screening and treatment would prevent about 4000 myocardial infarctions in the UK each year under age 50 years, about half of them fatal Why would this not be introduced as a national screening programme? The NSC came up with five reasons, all in our view, mistaken The first mistake was a failure to consider FH as a familial problem The NSC considered only the child and failed to recognise that preventing the premature death of a parent is a benefit, of course to the parent, and to the child and family The second mistake was a failure to recognise that an FH mutation is not the disorder, it is part of the …

6 citations


Journal ArticleDOI
Abstract: AIM Familial hypercholesterolaemia (FH) is a common and treatable cause of premature coronary artery disease. However, the majority of individuals with FH remain undiagnosed. This study investigated the feasibility, acceptability and cost-effectiveness of screening children aged 1-2 years for FH at the time of an immunisation. METHODS Children 1-2 years of age were offered screening for FH with a point-of-care total cholesterol (TC) test by capillary-collected blood sample at the time of an immunisation. An additional blood sample was taken to allow genetic testing if the TC level was above the 95th percentile (>5.3 mmol/L). Parents of children diagnosed with FH were offered testing. Following detection of the affected parent, cascade testing of their first-degree blood relatives was performed. RESULTS We screened 448 children with 32 (7.1%) having a TC ≥ 5.3 mmol/L. The FH diagnosis was confirmed in three children (1:150 screened). Reverse cascade testing of other family members identified a further five individuals with FH; hence, eight new cases of FH were diagnosed from screening 448 children (1:56 screened). Ninety-six percent of parents would screen future children for FH. The approach was cost-effective, at $3979 per quality-adjusted life year gained. CONCLUSION In Western Australia, universal screening of children aged 1-2 years for FH, undertaken at the time of an immunisation, was a feasible and effective approach to detect children, parents and other blood relatives with FH. The approach was acceptable to parents and is potentially a highly cost-effective detection strategy for families at risk of FH.

1 citations


Journal ArticleDOI
Abstract: Resumen Antecedentes La hipercolesterolemia familiar es la causa genetica mas frecuente de enfermedad coronaria prematura. El retraso en el diagnostico impide el correcto tratamiento precoz. No existen estrategias efectivas de cribado a nivel nacional que aseguren un correcto diagnostico. Objetivo Determinar la capacidad de un laboratorio centralizado para el diagnostico de hipercolesterolemia familiar mediante la creacion de un programa de salud para el cribado poblacional en la provincia de Huelva. Metodo Busqueda activa de pacientes con hipercolesterolemia primaria a traves de las analiticas realizadas en los laboratorios de referencia con resultados de colesterol unido a lipoproteinas de baja densidad mayor de 200 mg/dl y valoracion en la Unidad de Lipidos de Huelva para identificar casos indice, con realizacion posterior de diagnostico en cascada familiar. Resultados Se examinaron 37.440 analiticas con perfil lipidico. Tras el cribado fueron vistos en la Unidad de Lipidos 846 individuos, de los cuales fueron diagnosticados segun criterios de la Red de Clinicas de Lipidos Holandesas como posibles 654 y probables/definitivos 192 individuos, lo que supone el 1,74% y el 0,51% de la poblacion general examinada, respectivamente. Conclusiones La prevalencia puntual de hipercolesterolemia familiar en pacientes sometidos a pruebas de perfil lipidico de laboratorio fue de 1:195, mayor en comparacion con la prevalencia de hipercolesterolemia familiar en la poblacion general (basado en 1 de cada 200-300). La estrategia de busqueda oportunista del caso indice a traves de una alerta de laboratorio y cribado centralizado es una estrategia eficiente para implantar un cribado nacional para el diagnostico de hipercolesterolemia familiar.

1 citations


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21 Jul 2004-JAMA
TL;DR: Two years of pravastatin therapy induced a significant regression of carotid atherosclerosis in children with familial hypercholesterolemia, with no adverse effects on growth, sexual maturation, hormone levels, or liver or muscle tissue.
Abstract: ContextChildren with familial hypercholesterolemia have endothelial dysfunction and increased carotid intima-media thickness (IMT), which herald the premature atherosclerotic disease they develop later in life. Although intervention therapy in the causal pathway of this disorder has been available for more than a decade, the long-term efficacy and safety of cholesterol-lowering medication have not been evaluated in children.ObjectiveTo determine the 2-year efficacy and safety of pravastatin therapy in children with familial hypercholesterolemia.DesignRandomized, double-blind, placebo-controlled trial that recruited children between December 7, 1997, and October 4, 1999, and followed them up for 2 years.Setting and ParticipantsTwo hundred fourteen children with familial hypercholesterolemia, aged 8 to 18 years and recruited from an academic medical referral center in the Netherlands.InterventionAfter initiation of a fat-restricted diet and encouragement of regular physical activity, children were randomly assigned to receive treatment with pravastatin, 20 to 40 mg/d (n = 106), or a placebo tablet (n = 108).Main Outcome MeasuresThe primary efficacy outcome was the change from baseline in mean carotid IMT compared between the 2 groups over 2 years; the principal safety outcomes were growth, maturation, and hormone level measurements over 2 years as well as changes in muscle and liver enzyme levels.ResultsCompared with baseline, carotid IMT showed a trend toward regression with pravastatin (mean [SD], −0.010 [0.048] mm; P = .049), whereas a trend toward progression was observed in the placebo group (mean [SD], +0.005 [0.044] mm; P = .28). The mean (SD) change in IMT compared between the 2 groups (0.014 [0.046] mm) was significant (P = .02). Also, pravastatin significantly reduced mean low-density lipoprotein cholesterol levels compared with placebo (−24.1% vs +0.3%, respectively; P<.001). No differences were observed for growth, muscle or liver enzymes, endocrine function parameters, Tanner staging scores, onset of menses, or testicular volume between the 2 groups.ConclusionTwo years of pravastatin therapy induced a significant regression of carotid atherosclerosis in children with familial hypercholesterolemia, with no adverse effects on growth, sexual maturation, hormone levels, or liver or muscle tissue.

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Joan Slack1Institutions (1)
TL;DR: The life experience of 104 patients with Fredrickson's type-II hyperbetalipo-proteinaemia has been compared with 41 patients with hyperlipoproteinaemia associated with hypertriglyceridaemia and the risks were lower but the risk of peripheral vascular disease was increased.
Abstract: The life experience of 104 patients with Summary Fredrickson's type-II hyperbetalipo-proteinaemia has been compared with 41 patients with hyperlipoproteinaemia associated with hypertriglyceridaemia (Fredrickson's types III, IV, and v hyperlipoproteinsemia). Of 21 male index patients with type-II hyperbetalipoproteinaemia 15 developed ischaemic heart-disease (I.H.D.) at mean age 42.7 years, and 2 have died. 20 out of 30 biochemically affected male relatives developed I.H.D. at mean age 43.8 years with 12 deaths. Of 23 female index patients 20 developed I.H.D. at mean age 48.4 years with 4 deaths. 9 out of 30 affected female relatives developed I.H.D. at mean age 57.1 years with 2 deaths. Of the group of 29 male index patients and 5 affected male relatives with types III, IV, and v hyperlipoproteinaemia, 12 developed at mean age 48.7 years, 10 having intermittent claudication and none have died. The 7 female patients are all alive, 5 developed I.H.D. at mean age sixty-five. For men with type-II hyperbetalipoproteinaemia the chance of a first attack of I.H.D. was 5.4% by age thirty, 51.4% by age fifty, and 85.4% by age sixty. For women the risks were 0, 12.2%, and 57.5% respectively. For men with types III, IV, and v hyperlipoproteinaemia the risks were lower (0, 30, and 53.3%) but the risk of peripheral vascular disease was increased.

529 citations


Journal ArticleDOI
David S. Wald1, Jonathan P. Bestwick1, Joan K. Morris1, Ken Whyte1  +2 moreInstitutions (1)
TL;DR: Child-parent screening was feasible in primary care practices at routine child immunization visits and 8 persons were identified as having positive screening results for familial hypercholesterolemia and were consequently at high risk for cardiovascular disease.
Abstract: BackgroundChild–parent screening for familial hypercholesterolemia has been proposed to identify persons at high risk for inherited premature cardiovascular disease. We assessed the efficacy and feasibility of such screening in primary care practice. MethodsWe obtained capillary blood samples to measure cholesterol levels and to test for familial hypercholesterolemia mutations in 10,095 children 1 to 2 years of age during routine immunization visits. Children were considered to have positive screening results for familial hypercholesterolemia if their cholesterol level was elevated and they had either a familial hypercholesterolemia mutation or a repeat elevated cholesterol level 3 months later. A parent of each child with a positive screening result for familial hypercholesterolemia was considered to have a positive screening result for familial hypercholesterolemia if he or she had the same mutation as the child or, if no mutations were identified, had the higher cholesterol level of the two parents. Re...

177 citations


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TL;DR: In this study, initiation of statin therapy during childhood in patients with familial hypercholesterolemia slowed the progression of carotid intima-media thickness and reduced the risk of cardiovascular disease in adulthood.
Abstract: Background Familial hypercholesterolemia is characterized by severely elevated low-density lipoprotein (LDL) cholesterol levels and premature cardiovascular disease. The short-term efficac...

162 citations


Journal ArticleDOI
20 Sep 2007-BMJ
TL;DR: The proposed strategy of screening children and parents for familial hypercholesterolaemia could have considerable impact in preventing the medical consequences of this disorder in two generations simultaneously.
Abstract: Objective To develop a population screening strategy for familial hypercholesterolaemia. Design Meta-analysis of published data on total and low density lipoprotein (LDL) cholesterol in people with and without familial hypercholesterolaemia according to age. Thirteen studies reporting on 1907 cases and 16 221 controls were used in the analysis. Included studies had at least 10 cases and controls with data on the distribution of cholesterol in affected and unaffected individuals. Main outcome measures Detection rates (sensitivity) for specified false positive rates (0.1%, 0.5%, and 1%) in newborns and in age groups 1-9, 10-19, 20-39, 40-59, and ≥60 years. Results Serum cholesterol concentration discriminated best between people with and without familial hypercholesterolaemia at ages 1-9, when the detection rates with total cholesterol were 88%, 94%, and 96% for false positive rates of 0.1%, 0.5%, and 1%. The results were similar with LDL cholesterol. Screening newborns was much less effective. Once an affected child is identified, measurement of cholesterol would detect about 96% of parents with the disorder, using the simple rule that the parent with the higher serum cholesterol concentration is the affected parent. Conclusions The proposed strategy of screening children and parents for familial hypercholesterolaemia could have considerable impact in preventing the medical consequences of this disorder in two generations simultaneously.

135 citations