Child-Parent Screening for Familial Hypercholesterolemia

doi:10.1016/j.jpeds.2011.06.006

The Journal of Pediatrics

Volume 159, Issue 5, November 2011, Pages 865-867

https://doi.org/10.1016/j.jpeds.2011.06.006 Get rights and content

A pilot study of child-parent screening for familial hypercholesterolemia was undertaken in children aged 1 to 2 years coming for immunization. Of 214 parents asked, 200 agreed to screening (94%). Simultaneous immunization-cholesterol measurement was successful in all children. Population child-parent screening is feasible and acceptable when combined with pediatric immunization.

Section snippets

Methods

Children aged 1 to 2 years requiring routine immunization were identified from the register of a London general practice. Parents were asked whether their child could be screened for FH. To avoid distressing children twice, once from the immunization and again from the blood sampling, the immunization (left thigh) and blood spot (left heel, with 2-mm Tenderfoot lancet; ITC, Edison, New Jersey) were performed simultaneously by two clinical staff members. Blood was collected with capillary tubes,

Results

Of 214 parents asked, 200 (94%) agreed to FH screening. Concurrent heel prick and immunization was successful in all children, yielding approximately 200 μL of blood and adding approximately 2 minutes to the immunization procedure.

Figure 1 shows the total cholesterol distribution in 198 children (two Cholestech measurements failed); the median cholesterol level was 3.8 mmol/L (147 mg/dL; log SD, 0.078). No child had a cholesterol level >2.0 MoM (7.6 mmol/L or 297 mg/dL). The Cholestech results

Discussion

Our results show that child-parent screening for FH is feasible and acceptable in clinical practice. Screening can be done at the same time as childhood immunization and requires no new clinical facilities; immunization clinics and arrangements for systematically seeing children aged 1 to 2 years already exist. There was no indication that screening adversely affected immunization rates, which were, for Haemophilus Influenza B/Meningitis-C, 71% in the year preceding the study and 84% during the

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Familial hypercholesterolemia
Mortality in treated heterozygous familial hypercholesterolemia: implications for patient management
Atherosclerosis
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Risk of fatal coronary heart disease in familial hypercholesterolaemia
BMJ
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There are more references available in the full text version of this article.

Cited by (37)

A systematic review of cost-effectiveness analysis of different screening strategies for familial hypercholesterolemia
2024, Journal of Clinical Lipidology
Diagnosis rate of familial hypercholesterolemia (FH) remained less than 10 % globally and the economic evaluation results of different FH screening strategies varied. This study aimed to systematically review the methodology and results of cost effectiveness analysis (CEA) of FH screening, which will provide evidence support for health-related decision-making.
The Medline/PubMed, Embase, Cochrane Library, Web of science, National Health Service Economic Evaluation Database (NHSEED) and CEA Registry databases were electronically searched to collect full economic evaluation from the establishment of the databases to June 30, 2022. The quality of included studies was evaluated by the Consolidated Health Economic Evaluation Reporting Standards statement 2022 (CHEERS 2022) checklist.
Among 232 retrieved studies, 18 economic evaluations were included and all of them are from developed countries, with an average quality score of 0.73. The decision tree model and/or Markov model were constructed by thirteen articles (72 %). Twelve studies (67 %) adopted the healthcare perspective and the lifetime horizon to compare the costs and health outcome of different screening strategies. The results of eight studies indicated that cascade screening was a cost-effective strategy compared with no screening, which was more pronounced in younger adults. Universal screening in young adults aged 16 years or 18-40 years (n=3) and in children aged 1-2 years combined with reverse cascade screening (n=3) are both cost-effective. The probability of being cost-effective for cascade screening (n=6) and universal screening (n=1) of young aged 18-40 years were greater than 95 %.
Our review demonstrated the economic advantages of cascade screening, universal screening of young adults, and universal screening of newborns combined with reverse cascade screening. Further health economic evaluation is needed in children and in low- and middle-income countries.
2018 AHA/ACC/AACVPR/AAPA/ABC/ACPM/ADA/AGS/APhA/ASPC/NLA/PCNA Guideline on the Management of Blood Cholesterol: Executive Summary: A Report of the American College of Cardiology/American Heart Association Task Force on Clinical Practice Guidelines
2019, Journal of the American College of Cardiology
2018 AHA/ACC/AACVPR/AAPA/ABC/ACPM/ADA/AGS/APhA/ASPC/NLA/PCNA Guideline on the Management of Blood Cholesterol: A Report of the American College of Cardiology/American Heart Association Task Force on Clinical Practice Guidelines
2019, Journal of the American College of Cardiology
Improving the detection of familial hypercholesterolaemia
2019, Pathology
Familial hypercholesterolaemia (FH) is a dominantly inherited disorder of low-density lipoprotein (LDL) catabolism, which if untreated causes lifelong elevated LDL-cholesterol (LDL-c), accelerated atherosclerosis and premature cardiovascular disease. Recent evidence suggests the prevalence of heterozygous FH is ∼1:220, making FH the most common autosomal dominant condition. Lowering LDL-c with statin and lifestyle therapy reduces the risk of cardiovascular events. Furthermore, proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors significantly lower LDL-c in addition to statin therapy, and early outcome data suggest improved vascular outcomes with these agents in FH patients in addition to statins. However, the vast majority of people with FH still remain undiagnosed. The onus is on clinicians to identify kindreds with FH, as PCSK9 inhibitors, although expensive, are funded for patients with FH in Australia. Multiple strategies for detecting FH have been proposed. The detection of index cases can be achieved through applying electronic screening tools to general practice databases, universal screening of children during immunisation, and targeted screening of patients with premature cardiovascular disease. Advances in genomic technology have decreased costs of genetic testing, improved the understanding of the pathogenesis of FH and facilitated cascade screening. However, awareness of FH amongst clinicians and the general public still requires optimisation. This review outlines recent advances in FH detection, including emerging strategies and challenges for the next decade.
Universal screening of children for familial hypercholesterolaemia: Value for money?
2018, Atherosclerosis
Universal screening at age 1–2 years as an adjunct to cascade testing for familial hypercholesterolaemia in the UK: A cost-utility analysis
2018, Atherosclerosis
Familial hypercholesterolaemia (FH) is widely underdiagnosed. Cascade testing (CT) of relatives has been shown to be feasible, acceptable and cost-effective in the UK, but requires a supply of index cases. Feasibility of universal screening (US) at age 1–2 years was recently demonstrated. We examined whether this would be a cost-effective adjunct to CT in the UK, given the current and plausible future undiagnosed FH prevalence.
Seven cholesterol and/or mutation-based US ± reverse cascade testing (RCT) alternatives were compared with no US in an incremental analysis with a healthcare perspective. A decision model was used to estimate costs and outcomes for cohorts exposed to the US component of each strategy. RCT case ascertainment was modelled using recent UK CT data, and probabilistic Markov models estimated lifetime costs and health outcomes for the cohorts screened under each alternative. 1000 Monte Carlo simulations were run for each model, and average outcomes reported. Further uncertainty was explored deterministically. Threshold analysis investigated the association between undiagnosed FH prevalence and cost-effectiveness.
A strategy involving cholesterol screening followed by diagnostic genetic testing and RCT was the most cost-effective modelled (incremental cost-effectiveness ratio (ICER) versus no US £12,480/quality adjusted life year (QALY); probability of cost-effectiveness 96·8% at £20,000/QALY threshold). Cost-effectiveness was robust to both deterministic sensitivity analyses and threshold analyses that modelled ongoing case ascertainment at theoretical maximum levels.
These findings support implementation of universal cholesterol screening followed by diagnostic genetic testing and RCT for FH, under a UK conventional willingness-to-pay threshold.

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: Funded by a grant from the British Medical Association. Alere Ltd provided the Cholestech analyzer for cholesterol measurement, and Elitech UK Ltd provided the Tenderfoot lancets. Neither the funder nor industry had any role in the design, conduct, or writing up of the study. D.W. has a patent (GB2414186A) for a medical device that combines medical injection and blood sampling. The remaining authors authors declare no conflicts of interest.

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Clinical and Laboratory ObservationChild-Parent Screening for Familial Hypercholesterolemia

Section snippets

Methods

Results

Discussion

Familial hypercholesterolemia

Mortality in treated heterozygous familial hypercholesterolemia: implications for patient management

Atherosclerosis

Risk of fatal coronary heart disease in familial hypercholesterolaemia

BMJ

Clinical and Laboratory Observation
Child-Parent Screening for Familial Hypercholesterolemia