Importance of the triglyceride level in identifying patients with a Type III Hyperlipoproteinemia phenotype using the ApoB algorithm
Abstract
Background Hyperlipoproteinemia Type III (HLP3), also known as dysbetalipoproteinemia, is defined by cholesterol and triglyceride (TG) enriched remnant lipoprotein particles (RLP). The gold standard for diagnosis requires demonstration of high remnant lipoprotein particle cholesterol (RLP-C) by serum ultracentrifugation (UC), which is not readily available in daily practice. The apoB algorithm can identify HLP3 using total cholesterol (TC), plasma triglyceride (TG), and apoB. However, the optimal TG cutoff is unknown. Objective We analyzed apoB algorithm defined HLP3 at different TG levels to optimize the TG cutoff for the algorithm. Methods 128,485 UC lipid profiles in the Very Large Database of Lipids (VLDbL) were analyzed. RLP-C was assessed at TG ≥ 133 mg/dL, ≥175 mg/dL, ≥200 mg/dL, and ≥ 250 mg/dL. Sensitivity (Sn), specificity (Sp), positive predictive value (PPV), negative predictive value (NPV), and prevalence adjusted and bias-adjusted kappa (PABAK) were calculated against UC Criterion (VLDL-C/TG ≥ 0.25) for HLP3. Results The median age (IQR) was 57 years (46-68). 45% were men, 20.1% had diabetes, and 25.5% had hypertension. The median RLP-C level for the TG cutoffs (mg/dL) of ≥ 133, ≥ 175, ≥ 200, and ≥ 250 were 34, 43, 50, and 62 mg/dL, respectively, compared to 67 mg/dL in UC defined HLP3. TG ≥ 133 mg/dL yielded optimal results (Sn 29.5%, Sp 98.5%, PABAK 0.96, PPV 13.6%, NPV 99.4%). Conclusion TG ≥ 133 mg/dL allows for high sensitivity in screening for HLP3. Higher…
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Previous studies have shown that a TG cutoff of ≥1.5 mmol/L is optimal for identifying carriers of the ε2ε2 genotype and FD.
“Previous studies have shown that a TG cutoff of ≥1.5 mmol/L is optimal for identifying carriers of the ε2ε2 genotype and FD [10,51].”
From Spectrum and Prevalence of Rare APOE Variants and Their Association with Familial Dysbetalipoproteinemia (2024) · cites this paper as [51]
Cites
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ApoB, LDL-C, and non-HDL-C as markers of cardiovascular risk
Sehayek, D., Cole, J., Björnson, E., Wilkins, J. T., Mortensen, M. B., Dufresne, L., Pencina, K. M., Pencina, M. J., Thanassoulis, G., & Sniderman, A. D. (2025) · Journal of Clinical Lipidology · doi:10.1016/j.jacl.2025.05.024 · Cited by 20 · see citing works
Self-citationBlokhina, A. V., Ershova, A. I., Kiseleva, A. V., Sotnikova, E. A., Zharikova, A. A., Zaicenoka, M., Vyatkin, Y. V., Ramensky, V. E., Kutsenko, V. A., Garbuzova, E. V., et al. (2024) · International Journal of Molecular Sciences · doi:10.3390/ijms252312651 · Cited by 8 · see citing works
- Authors
- Varghese, B., Park, J., Chew, E., Sajja, A., Brownstein, A., Pallazola, V. A., Sathiyakumar, V., Jones, S. R., Sniderman, A. D., & Martin, S. S.
- Affiliations
- Johns Hopkins University (US)
- McGill University Health Centre (CA)
- Corresponding author
- Martin, Seth S.
- ORCID
- Venue
- Journal of Clinical Lipidology
- Publisher
- Elsevier BV
- Published
- 2021-01
- Volume
- 15
- Issue
- 1
- Pages
- 104-115.e9
- ISSN
- 1876-4789 (ISSN-L)
- 1933-2874
- OpenAlex
- W3094458672
- Cited by
- 12
- References
- 3
- Citations by year
- 2026: 1 · 2025: 3 · 2024: 1 · 2023: 2 · 2022: 4 · 2021: 1
- FWCI
- 1.60
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Journal of clinical lipidology (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Novo Nordisk
- American Heart Association
- Strålsäkerhetsmyndigheten
- Sanofi
- National Institutes of Health
- Aetna Foundation
- Quest Diagnostics
- Topics
- Health Sciences › Medicine › Surgery › Lipoproteins and Cardiovascular Health
- Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Lipid metabolism and disorders
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Diabetes, Cardiovascular Risks, and Lipoproteins
- Keywords
- type III hyperlipoproteinemia, dysbetalipoproteinemia, remnant cholesterol, sensitivity and specificity, triglyceride levels
- MeSH terms
- Adult, Aged, Algorithms, Apolipoproteins B, Female, Humans, Hyperlipoproteinemia Type III, Male, Middle Aged, Phenotype, Triglycerides
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