Diagnosing heterozygous familial hypercholesterolemia using new practical criteria validated by molecular genetics
Abstract
Heterozygous familial hypercholesterolemia (FH) is a serious disorder causing twice normal low-density lipoprotein cholesterol levels early in childhood and very early coronary disease in both men and women. Treatment with multiple medications and diet can normalize cholesterol levels in many persons with FH and prevent or delay the development of coronary atherosclerosis. Thus, there is a need for accurate and genetically validated criteria for the early diagnosis of heterozygous FH. Previously published blood cholesterol criteria greatly underdiagnosed new cases of FH among members of known families with FH in Utah and overdiagnosed FH among participants of general population screening, revealing the need for different cholesterol screening criteria in persons from these 2 different settings. The statistical concept of a priori probabilities was applied to derive 2 sets of practical screening criteria: one for persons participating in general population screening studies and another for close relatives of confirmed FH cases, showing dramatic differences. At a cholesterol level of 310 mg/dl, only 4% of persons in the general population would have FH but 95% of persons who were first-degree relatives of known cases would have FH. Detailed tables were derived to provide practical total and low-density lipoprotein blood cholesterol screening criteria for diagnosing FH in different screening settings and specific age groups. In population screening the new FH criteria require a…
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The FH patients used to build the classifier were diagnosed as probable or definite FH using existing diagnostic criteria including genetic testing information when available.
“The FH patients were followed at an FH-specific clinic and had been diagnosed as probable or definite FH using existing diagnostic criteria including genetic testing information when available.5,33–36”
From Finding missed cases of familial hypercholesterolemia in health systems using machine learning (2019) · cites this paper as [36]
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Guidelines for the diagnosis and management of heterozygous familial hypercholesterolemia
Civeira, F. (2004) · Atherosclerosis · doi:10.1016/j.atherosclerosis.2003.11.010 · Cited by 495 · see citing works
Genetic identification of familial hypercholesterolemia within a single U.S. health care system
Abul-Husn, N. S., Manickam, K., Jones, L. K., Wright, E. A., Hartzel, D. N., Gonzaga-Jauregui, C., O’Dushlaine, C., Leader, J. B., Lester Kirchner, H., Lindbuchler, D. M., et al. (2016) · Science · doi:10.1126/science.aaf7000 · Cited by 425 · see citing works
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Self-citationF. Piepoli, M. (2017) · International Journal of Behavioral Medicine · doi:10.1007/s12529-016-9583-6 · Cited by 162 · see citing works
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Finding missed cases of familial hypercholesterolemia in health systems using machine learning
Banda, J. M., Sarraju, A., Abbasi, F., Parizo, J., Pariani, M., Ison, H., Briskin, E., Wand, H., Dubois, S., Jung, K., et al. (2019) · npj Digital Medicine · doi:10.1038/s41746-019-0101-5 · Cited by 123 · see citing works
“36 The application of these criteria is done manually and takes upwards of 15 – 20 min of clinician time.”
MethodAbifadel, M., Rabès, J.-P., Jambart, S., Halaby, G., Gannagé-Yared, M.-H., Sarkis, A., Beaino, G., Varret, M., Salem, N., Corbani, S., et al. (2009) · Human Mutation · doi:10.1002/humu.21002 · Cited by 99 · see citing works
Besseling, J., Reitsma, J. B., Gaudet, D., Brisson, D., Kastelein, J. J. P., Hovingh, G. K., & Hutten, B. A. (2016) · European Heart Journal · doi:10.1093/eurheartj/ehw135 · Cited by 60 · see citing works
- Authors
- Williams, R. R., Hunt, S. C., Schumacher, M. C., Hegele, R. A., Leppert, M. F., Ludwig, E. H., & Hopkins, P. N.
- Affiliations
- St. Michael's Hospital (CA)
- Corresponding author
- Williams, Roger R.
- Venue
- The American Journal of Cardiology
- Publisher
- Elsevier BV
- Published
- 1993-07
- Volume
- 72
- Issue
- 2
- Pages
- 171-176
- ISSN
- 0002-9149 (ISSN-L)
- OpenAlex
- W2054119723
- Cited by
- 566
- References
- 0
- Citations by year
- 2026: 16 · 2025: 19 · 2024: 19 · 2023: 24 · 2022: 29 · 2021: 26 · 2020: 31 · 2019: 18 · 2018: 30 · 2017: 26 · 2016: 39 · 2015: 28 · 2014: 25 · 2013: 20 · 2012: 27
- FWCI
- 7.66
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- The American Journal of Cardiology (publishedVersion)
- PubMed (publishedVersion)
- Funders
- U.S. Public Health Service (U58-CCU803454)
- Topics
- Health Sciences › Medicine › Surgery › Lipoproteins and Cardiovascular Health
- Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Lipid metabolism and disorders
- Health Sciences › Medicine › Public Health, Environmental and Occupational Health › Health Promotion and Cardiovascular Prevention
- Keywords
- heterozygous familial hypercholesterolemia, diagnostic criteria, a priori probability, family screening, first-degree relatives, mass screening, familial combined hyperlipidemia, sensitivity and specificity
- MeSH terms
- Adolescent, Adult, Cholesterol, Diagnosis, Differential, Female, Genetic Testing, Genetic Carrier Screening, Humans, Hyperlipoproteinemia Type II, Hyperlipidemia, Familial Combined, Male, Pedigree, Probability, Utah
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