Clinical impact of early vs. late treatment in familial hypercholesterolaemia: a systematic review
Abstract
Background: Familial hypercholesterolaemia (FH) is an inherited condition characterised by very high lifelong levels of low-density lipoprotein cholesterol (LDL-C), leading to an increased risk of atherosclerotic cardiovascular disease (ASCVD). FH has a high prevalence yet is underdiagnosed. Unless detected by cascade testing or opportunistically, FH is commonly only identified after a cardiovascular (CV) event. To inform decision-making on preventive public health measures for FH in Ireland, and given a lack of direct universal screening evidence in children, a systematic review of the clinical effectiveness and safety of early compared with late diagnosis and or treatment was undertaken.
Methods: Electronic searches were conducted in November 2025 across seven databases, from inception with no language restrictions, supplemented by grey literature searches. Outcomes of interest were morbidity, mortality, surrogate markers, quality of life. Screening, data extraction and quality appraisal were performed independently by two reviewers.
Reviewers: Of 7,758 records identified and 299 full texts screened, 12 observational studies met the inclusion criteria. Heterogeneity in defining early versus late treatment limited comparability between studies. Studies reported that earlier diagnosis and treatment was associated with improved clinical outcomes such as a reduced risk of ASCVD and probability of, or death from, a major CV event. Studies reported that treatment in childhood was protective against ASCVD events and or death compared with later treatment as an adult. Studies identified a positive association between surrogate outcomes in children, such as thinner carotid intima media thickness and lower cumulative LDL-C exposure, and earlier treatment.
Conclusions: The direction of effect across multiple studies suggests that earlier diagnosis and or treatment of FH is associated with improved surrogate outcomes in children and improved CV outcomes in adulthood.
Key messages: • Evidence suggests that earlier diagnosis and or treatment of FH, as a proxy for screening evidence, is associated with improved surrogate outcomes in children and cardiovascular outcomes in adults.
• There was substantial heterogeneity in the study contexts and the applied definition of early versus late diagnosis or treatment, limiting comparability between studies.
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BibTeX
@article{umeokwoaka2026clinical,
title = {{Clinical impact of early vs. late treatment in familial hypercholesterolaemia: a systematic review}},
author = {VC Umeokwoaka and LE Comber and OM Jenkins and A Maher and M O’Neill and M Ryan},
journal = {The European Journal of Public Health},
year = {2026},
month = oct,
doi = {10.1093/eurpub/ckag169.1926},
url = {https://doi.org/10.1093/eurpub/ckag169.1926},
note = {CC BY-NC 4.0},
}
RIS
TY - JOUR
TI - Clinical impact of early vs. late treatment in familial hypercholesterolaemia: a systematic review
AU - VC Umeokwoaka
AU - LE Comber
AU - OM Jenkins
AU - A Maher
AU - M O’Neill
AU - M Ryan
PY - 2026
DA - 2026/10/01
JO - The European Journal of Public Health
DO - 10.1093/eurpub/ckag169.1926
UR - https://doi.org/10.1093/eurpub/ckag169.1926
AB - Background: Familial hypercholesterolaemia (FH) is an inherited condition characterised by very high lifelong levels of low-density lipoprotein cholesterol (LDL-C), leading to an increased risk of atherosclerotic cardiovascular disease (ASCVD). FH has a high prevalence yet is underdiagnosed. Unless detected by cascade testing or opportunistically, FH is commonly only identified after a cardiovascular (CV) event. To inform decision-making on preventive public health measures for FH in Ireland, and given a lack of direct universal screening evidence in children, a systematic review of the clinical effectiveness and safety of early compared with late diagnosis and or treatment was undertaken. Methods: Electronic searches were conducted in November 2025 across seven databases, from inception with no language restrictions, supplemented by grey literature searches. Outcomes of interest were morbidity, mortality, surrogate markers, quality of life. Screening, data extraction and quality appraisal were performed independently by two reviewers. Reviewers: Of 7,758 records identified and 299 full texts screened, 12 observational studies met the inclusion criteria. Heterogeneity in defining early versus late treatment limited comparability between studies. Studies reported that earlier diagnosis and treatment was associated with improved clinical outcomes such as a reduced risk of ASCVD and probability of, or death from, a major CV event. Studies reported that treatment in childhood was protective against ASCVD events and or death compared with later treatment as an adult. Studies identified a positive association between surrogate outcomes in children, such as thinner carotid intima media thickness and lower cumulative LDL-C exposure, and earlier treatment. Conclusions: The direction of effect across multiple studies suggests that earlier diagnosis and or treatment of FH is associated with improved surrogate outcomes in children and improved CV outcomes in adulthood. Key messages: • Evidence suggests that earlier diagnosis and or treatment of FH, as a proxy for screening evidence, is associated with improved surrogate outcomes in children and cardiovascular outcomes in adults. • There was substantial heterogeneity in the study contexts and the applied definition of early versus late diagnosis or treatment, limiting comparability between studies.
SN - 1101-1262
SN - 1464-360X
ER -