Advanced lipoprotein testing and subfractionation are not (yet) ready for routine clinical use
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Neither LDL size nor the concentration of small, dense LDL particles adds to CVD prediction in multiple variable analysis beyond standard lipid risk factors, although small LDL particles predict cardiovascular risk in univariate analysis.
“Neither LDL size nor the concentration of small, dense LDL particles adds to CVD prediction in multiple variable analysis beyond the standard lipid risk factors, although small LDL particles predict cardiovascular risk in univariate analysis (35)(36)(37).”
From Evaluation and Treatment of Hypertriglyceridemia: An Endocrine Society Clinical Practice Guideline (2012) · cites this paper as [36]
In §1.B (page unavailable), the paper reports that LDL size was no longer significantly associated with CVD after adjustment for LDL particle concentration and other risk factors, supporting that part of the claim. It also reports associations between small LDL and CVD risk, but does not establish that small, dense LDL particle concentration adds nothing to prediction beyond standard lipid risk factors; it says both small and large LDL subclasses remained associated with CVD events after accounting for lipoprotein correlations. (LLM, conf=0.86)
Experimental — accuracy not yet measuredAll LDL particles are atherogenic, but their concentration is not always reflected by LDLC measurement because the cholesterol content in the particles can vary widely between individuals according to the continuous remodeling of lipoproteins in blood.
“All LDL particles are atherogenic, but their concentration is not always reflected by LDLC measurement because the cholesterol content in the particles can vary widely between individuals according to the continuous remodeling of lipoproteins in blood [10].”
From Quantifying atherogenic lipoproteins for lipid-lowering strategies: Consensus-based recommendations from EAS and EFLM (2020) · cites this paper as [10]
In §1.B (page not supplied), the paper says small and large LDL particles are similarly atherogenic and illustrates that two people can have the same LDL cholesterol level but different LDL particle concentrations because smaller particles contain less cholesterol. The passage does not attribute this variation to continuous remodeling of lipoproteins in blood, so that causal explanation is unsupported. (LLM, conf=0.88)
Experimental — accuracy not yet measuredThe number of LDL particles (LDLP) measured by lipoprotein subfractionation techniques is more strongly causally related to ASCVD than the cholesterol content of the particles.
“This residual risk indicates that a focus solely on the measurement of LDLC is not an optimal strategy for all patients, in part explained by accumulating evidence that the number of LDL particles (LDLP) measured by lipoprotein subfractionation techniques is more strongly causally related to ASCVD than the cholesterol content of the particles [9,10].”
From Quantifying atherogenic lipoproteins for lipid-lowering strategies: Consensus-based recommendations from EAS and EFLM (2020) · cites this paper as [10]
Section 1.A says CVD risk is more closely associated with NMR LDL particle concentration than with LDL cholesterol. That supports the comparison, but the paper describes an association, not a stronger causal relationship to ASCVD; it also says the clinical value of particle testing remains uncertain. The indexed passages provide no page numbers. (LLM, conf=0.90)
Experimental — accuracy not yet measuredMeasurement of apolipoprotein B (apoB) or advanced measurement of LDLP can be used to assess the number of LDL particles.
“Measurement of apolipoprotein B (apoB), the major protein component of LDL, or advanced measurement of LDLP (not yet widely available) can also be used to assess the number of LDL particles [10,12].”
From Quantifying atherogenic lipoproteins for lipid-lowering strategies: Consensus-based recommendations from EAS and EFLM (2020) · cites this paper as [10]
All LDL particles are atherogenic, regardless of size.
“While earlier studies emphasized the atherogenicity of small LDL particles, it is now recognized that all LDL particles are atherogenic, regardless of size [10].”
From Quantifying atherogenic lipoproteins for lipid-lowering strategies: Consensus-based recommendations from EAS and EFLM (2020) · cites this paper as [10]
Risk of ASCVD is more directly related to the number of apoB-containing particles (reflected by apoB measurement) than to the cholesterol content of lipoproteins.
“This is consistent with the notion that risk of ASCVD is more directly related to the number of apoB-containing particles (reflected by apoB measurement) than to the cholesterol content of lipoproteins [10].”
From Quantifying atherogenic lipoproteins for lipid-lowering strategies: Consensus-based recommendations from EAS and EFLM (2020) · cites this paper as [10]
Epidemiological studies have not provided conclusive evidence that measurement of HDL size contributes to risk prediction.
“Epidemiological studies have not provided conclusive evidence that measurement of HDL size contributes to risk prediction (36, 50 -55).”
From Evaluation and Treatment of Hypertriglyceridemia: An Endocrine Society Clinical Practice Guideline (2012) · cites this paper as [36]
The CVD Risk Assessment section discusses whether LDL particle size adds risk information, not whether HDL size does. Searches for HDL particle size and HDL subfractions found no passage in our copy assessing their contribution to risk prediction. (LLM, conf=0.72)
Experimental — accuracy not yet measured
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References 57 · Cited by 89
- Authors
- Mora, S.
- Affiliations
- Brigham and Women's Hospital (US)
- Corresponding author
- Mora, Samia
- ORCID
- Mora, Samia
- Venue
- Circulation
- Published
- 2009-05-05
- Volume
- 119
- Issue
- 17
- Pages
- 2396-2404
- ISSN
- 0009-7322 (ISSN-L)
- 1524-4539
- PMC
- PMC2735461
- OpenAlex
- W2031055477
- Cited by
- 89
- References
- 57
- Citations by year
- 2026: 3 · 2025: 1 · 2024: 7 · 2022: 3 · 2021: 7 · 2020: 7 · 2019: 3 · 2018: 10 · 2017: 5 · 2016: 2 · 2015: 5 · 2014: 9 · 2013: 8 · 2012: 8
- FWCI
- 1.01
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Circulation (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Heart, Lung, and Blood Institute (K08HL094375)
- Topics
- Health Sciences › Medicine › Surgery › Lipoproteins and Cardiovascular Health
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Diabetes, Cardiovascular Risks, and Lipoproteins
- Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Lipid metabolism and disorders
- Keywords
- clinical implementation, dyslipidemia, cardiovascular risk assessment
- MeSH terms
- Cardiovascular Diseases, Cell Fractionation, Humans, Lipoproteins, Triglycerides, Clinical Laboratory Techniques
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