LDL particle number (LDL-P)
LDL particle number counts LDL particles by NMR instead of measuring their cholesterol. Higher counts go with more cardiovascular disease, and track risk when LDL cholesterol disagrees, but in one large cohort predicted no more than standard lipids or ApoB. No guideline body's cut points could be opened for this page. Two NMR methods differed by 13% on average.
- Status
- A blood test run by nuclear magnetic resonance (NMR) spectroscopy in specialized laboratories, ordered by a clinician. FDA cleared one maker's NMR LDL particle test in 2008 and a second maker's in 2023, both under its lipoprotein test system regulation, a class I device type [1]. The 2018 US cholesterol guideline names ApoB as a risk-enhancing factor and gives no threshold for LDL particle number [2]. A working group of the American Association for Clinical Chemistry judged ApoB the preferable marker for guidelines because of its availability, scalability, standardization and relatively low cost [3].
- Measures
- The number of LDL particles in a liter of blood, estimated by NMR spectroscopy, which counts lipoprotein particles instead of measuring the cholesterol they carry [4].
- Also called
- LDL-P, LDL particle number, LDL particle count, LDL particle concentration, LDL particles, NMR LDL-P, NMR LipoProfile, NMR lipoprotein profile, LDL-PNUM, low-density lipoprotein particle number
- Tested for
- heart attack risk, cardiovascular risk, advanced lipid testing, risk when LDL cholesterol looks normal, insulin resistance, checking response to cholesterol-lowering drugs
Strong several reviews agree · Moderate one review or consistent trials · Limited one or a few small studies · Untested no study in people, listed with what it rests on
Linked in research2
- ModerateLinked to more cardiovascular disease at higher levels, about 2.5 times the rate in the top against the bottom fifth of 27,673 US women.
- ModerateLinked to coronary events when the two disagree: women with low LDL cholesterol and high LDL particle number had about 2.3 times the risk of women low on both.
Reported risks0
No risks sourced yet.
Reference ranges
Each range is the one its source published, in nmol/L. Where sources differ, each is shown.
Low LDL particle number as defined in the Multi-Ethnic Study of Atherosclerosis, 2011
Adults aged 45 to 84 free of cardiovascular disease, in a US community cohort · [5]
| Range | What the source calls it |
|---|---|
| below 1060 nmol/L | "low" |
| 1060 or above nmol/L | No name given |
A cut point defined by the authors of one cohort study, not by a guideline body. No guideline body's cut points for LDL particle number could be opened for this page, so every range here comes from a cohort study, an assay study or a review, each written with or funded by a maker of the test. The figure is the 30th percentile of LDL particle number in the cohort, chosen to match an LDL cholesterol of 100 mg/dL at the same percentile. Among people with LDL cholesterol below 100 mg/dL, 32% had an LDL particle number at or above it. Two of the authors were employees of the company that ran the test, which donated the measurements [5].
Reference interval of the NMR assay on the Vantera Clinical Analyzer, 2014
The reference group of the assay's validation study, which the abstract does not describe · [6]
| Range | What the source calls it |
|---|---|
| below 457 nmol/L | No name given |
| 457 to 2282 nmol/L | "reference interval" |
| above 2282 nmol/L | No name given |
A reference interval from the assay maker's own validation study, whose authors were all at the company. It describes where the results of a reference group fell and is not a set of risk categories. The full text was behind a paywall, so who was in the reference group and which percentiles were used could not be read. The assay measured from 300 to 3,500 nmol/L [6].
Goal applied in a systematic review of lipid-lowering trials, 2013
Adults at high cardiovascular risk on lipid-lowering treatment · [7]
| Range | What the source calls it |
|---|---|
| 1000 or below nmol/L | "goal" |
| above 1000 nmol/L | No name given |
Not a guideline goal. The review tested whether trial arms reached what it called treatment goals for high-risk patients, 1,000 nmol/L or below for LDL particle number and below 100 mg/dL for LDL cholesterol, taking the figure from an earlier paper. It also reports that a working group of the American Association for Clinical Chemistry suggested below 1,100 nmol/L beside ApoB below 80 mg/dL, a statement that could not be opened for this page. The review was funded by the company that ran the test, and both authors report payments from it [7].
How it compares with the reference method
Mixed results2
LDL particle number against ApoB
Mixed results: LDL particle number and ApoB correlated closely and predicted events about equally, yet classed a share of people differently.
The numbers and sources
- Compared with
- ApoB measured by immunoassay
- Effect
- Each LDL particle, like each other atherogenic lipoprotein particle, carries a single ApoB molecule, so ApoB counts LDL together with VLDL, intermediate-density and lipoprotein(a) particles, while the NMR test reports LDL particles [11], a count that in one cohort's method included intermediate-density particles [5]. Across 25 studies with 85 outcomes, the two markers agreed on whether an association was significant in 67 comparisons and disagreed in 18 (21.1%), and the working group called them nearly equivalent for assessing risk [3]. In 412,013 patients tested by one US laboratory, the two were highly correlated (R squared 0.79). When ApoB was below 69 mg/dL, 5% to 6% of patients were still classed as at risk by an LDL particle number of 1,073 nmol/L or above, and 6% to 7% the other way round [12]. In patients with both tests ordered together, including results from a second maker's NMR assay, the Spearman correlation was 0.83 or above and the two agreed on risk class in 85% or more, with most disagreements being a raised LDL particle number beside a normal ApoB [13]. In 27,533 women, LDL cholesterol correlated with ApoB at 0.785 and with LDL particle number at 0.692 [9].
- Population
- 25 clinical studies [3]. 412,013 patients of one laboratory and 1,411 patients at 6 US clinics [12]. Patients with simultaneous orders for the three tests, whose number the abstract does not give [13]. 27,533 women [9].
- Sources
- [11], [3], [12], [13], [9]
- Caveats
- The sources state no threshold for agreement. The laboratory study was written by staff of the laboratory that sold both tests, and its cut points are percentiles of its own patients [12].
Agreement between NMR methods
One independent study found two NMR methods correlated above 0.9 for LDL particle number while one read 13% higher on average.
The numbers and sources
- Compared with
- A second maker's NMR method run on the same samples
- Effect
- In serum from 150 people measured by two widely used NMR methods, LDL particle concentrations correlated above 0.9, and the mean was 1,330 nmol/L with one method and 1,176 nmol/L with the other, 13% apart. Agreement was weaker for particle subclasses, and the authors concluded that harmonization would be needed for particle results to be comparable [14]. In one maker's validation study, results from its two analyzers correlated at an R squared of 0.96, and coefficients of variation within and between runs were 2.6% to 5.8% [6]. A 2009 review noted that advanced lipoprotein tests had not been standardized and that several could be performed only by the company marketing them, limiting independent information on test performance [15].
- Population
- Serum samples from 150 people [14]. Serum pools at low, medium and high LDL particle number [6].
- Sources
- [14], [6], [15]
- Caveats
- The comparison study states no threshold for agreement, so the result is given as numbers only. A cut point set with one NMR method may not carry over to a result from another [14].
What studies tie it to
Linked in research2
Heart attack, stroke and other cardiovascular disease in cohort studies
Linked to more cardiovascular disease at higher levels, about 2.5 times the rate in the top against the bottom fifth of 27,673 US women.
The numbers and sources
- Effect
- In initially healthy US women, the adjusted hazard ratio for cardiovascular disease in the top against the bottom fifth was 2.51 (95% CI 1.91 to 3.30) for LDL particle number, 2.57 (1.98 to 3.33) for ApoB, 2.52 (1.95 to 3.25) for non-HDL cholesterol and 1.74 (1.40 to 2.16) for LDL cholesterol. Adding LDL particle number to a model with the total to HDL cholesterol ratio and other risk factors reclassified essentially no one, and the authors called its prediction comparable but not superior to standard lipids or apolipoproteins [4]. In a multi-ethnic US cohort, the hazard ratio per standard deviation was 1.32 (95% CI 1.19 to 1.47) for LDL particle number and 1.20 (1.08 to 1.34) for LDL cholesterol [5]. In a later analysis of that cohort, the top against the bottom quarter had a hazard ratio for coronary heart disease of 1.77 (95% CI 1.21 to 2.58), which weakened after adjustment for the standard lipid panel [8]. A laboratory medicine working group reviewed 25 studies with 85 outcomes in which both markers were measured, and found LDL particle number and ApoB each significantly associated with the outcome in 50 comparisons and neither in 17 [3].
- Population
- 27,673 women followed 11 years, 1,015 events [4]. Participants in a cohort of 6,814 adults aged 45 to 84, 319 events over 5.5 years [5]. 4,679 participants of the same cohort [8]. 25 clinical studies [3].
- Sources
- [4], [5], [8], [3]
- Caveats
- Observational. None of the studies here assigned treatment by LDL particle number, so they do not show what happens to events when it is lowered. The multi-ethnic cohort analysis was written with employees of the company that ran the test [5].
Heart disease when LDL particle number and LDL cholesterol disagree
Linked to coronary events when the two disagree: women with low LDL cholesterol and high LDL particle number had about 2.3 times the risk of women low on both.
The numbers and sources
- Effect
- Among 27,533 healthy women split at the medians, 24.3% had LDL particle number and LDL cholesterol on opposite sides. Among women with LDL cholesterol below the median of 121 mg/dL, those with LDL particle number at or above its median had an age-adjusted hazard ratio for coronary events of 2.32 (95% CI 1.88 to 2.85) against women low on both. Among women with LDL cholesterol at or above the median, those with a low LDL particle number had a hazard ratio of 0.42 (0.33 to 0.53). The same pattern held for ApoB (2.48 and 0.34) and non-HDL cholesterol (2.92 and 0.40) [9]. In a multi-ethnic cohort, among people whose two values differed by 12 percentile points or more, LDL particle number was associated with cardiovascular events (HR 1.45 per standard deviation, 95% CI 1.19 to 1.78) and LDL cholesterol was not (1.07, 0.88 to 1.30) [5]. In the Framingham Offspring cohort, people below the 25th percentile of LDL particle number had 59 events per 1,000 person-years, against 81 for those equally low on LDL cholesterol [10].
- Population
- 27,533 women, median follow-up 17.2 years, 1,070 coronary events [9]. Participants in a cohort of 6,814 adults, 319 events [5]. 3,066 middle-aged white adults followed a median 14.8 years, 531 events [10].
- Sources
- [9], [5], [10]
- Caveats
- Observational. High and low were defined by each cohort's own medians or percentiles, not by a fixed cut point. After adjustment for HDL cholesterol, triglycerides and other factors, risk in the women's cohort remained under or overestimated by about 20% to 50% [9].
Sources
- US Food and Drug Administration. 510(k) premarket notification records K063841 (NMR LipoProfile assay, LipoScience, cleared July 23, 2008) and K210801 (AXINON LDL-p Test System, Numares AG, cleared July 19, 2023), both under 21 CFR 862.1475, Lipoprotein test system, read through the openFDA device API. https://open.fda.gov/apis/device/510k/
- Grundy SM, Stone NJ, Bailey AL, et al. 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. Circulation. 2019. https://doi.org/10.1161/CIR.0000000000000625
- Cole TG, Contois JH, Csako G, et al. Association of Apolipoprotein B and Nuclear Magnetic Resonance Spectroscopy-Derived LDL Particle Number with Outcomes in 25 Clinical Studies: Assessment by the AACC Lipoprotein and Vascular Diseases Division Working Group on Best Practices. Clinical Chemistry. 2013. https://doi.org/10.1373/clinchem.2012.196733
- Mora S, Otvos JD, Rifai N, et al. Lipoprotein Particle Profiles by Nuclear Magnetic Resonance Compared With Standard Lipids and Apolipoproteins in Predicting Incident Cardiovascular Disease in Women. Circulation. 2009. https://doi.org/10.1161/CIRCULATIONAHA.108.816181
- Otvos JD, Mora S, Shalaurova I, et al. Clinical implications of discordance between low-density lipoprotein cholesterol and particle number. Journal of Clinical Lipidology. 2011. https://doi.org/10.1016/j.jacl.2011.02.001
- Matyus SP, Braun PJ, Wolak-Dinsmore J, et al. NMR measurement of LDL particle number using the Vantera Clinical Analyzer. Clinical Biochemistry. 2014. https://doi.org/10.1016/j.clinbiochem.2014.07.015
- Rosenson RS, Underberg JA. Systematic Review: Evaluating the Effect of Lipid-Lowering Therapy on Lipoprotein and Lipid Values. Cardiovascular Drugs and Therapy. 2013. https://doi.org/10.1007/s10557-013-6477-6
- Steffen BT, Guan W, Remaley AT, et al. Use of Lipoprotein Particle Measures for Assessing Coronary Heart Disease Risk Post-American Heart Association/American College of Cardiology Guidelines: The Multi-Ethnic Study of Atherosclerosis. Arteriosclerosis, Thrombosis, and Vascular Biology. 2015. https://doi.org/10.1161/ATVBAHA.114.304349
- Mora S, Buring JE, Ridker PM. Discordance of Low-Density Lipoprotein (LDL) Cholesterol With Alternative LDL-Related Measures and Future Coronary Events. Circulation. 2014. https://doi.org/10.1161/CIRCULATIONAHA.113.005873
- Cromwell WC, Otvos JD, Keyes MJ, et al. LDL particle number and risk of future cardiovascular disease in the Framingham Offspring Study: Implications for LDL management. Journal of Clinical Lipidology. 2007. https://doi.org/10.1016/j.jacl.2007.10.001
- Soffer DE, Marston NA, Maki KC, et al. Role of apolipoprotein B in the clinical management of cardiovascular risk in adults: An Expert Clinical Consensus from the National Lipid Association. Journal of Clinical Lipidology. 2024. https://doi.org/10.1016/j.jacl.2024.08.013
- Varvel SA, Dayspring TD, Edmonds Y, et al. Discordance between apolipoprotein B and low-density lipoprotein particle number is associated with insulin resistance in clinical practice. Journal of Clinical Lipidology. 2015. https://doi.org/10.1016/j.jacl.2014.11.005
- Kroner GM, Yuzyuk TN, Zuromski LM, Johnson LM. Retrospective comparison of results for simultaneous orders for LDL particle count, apolipoprotein B, and LDL-C. Clinica Chimica Acta. 2021. https://doi.org/10.1016/j.cca.2021.03.004
- Rief M, Raggam R, Rief P, et al. Comparison of Two Nuclear Magnetic Resonance Spectroscopy Methods for the Measurement of Lipoprotein Particle Concentrations. Biomedicines. 2022. https://doi.org/10.3390/biomedicines10071766
- Mora S. Advanced Lipoprotein Testing and Subfractionation Are Not (Yet) Ready for Routine Clinical Use. Circulation. 2009. https://doi.org/10.1161/CIRCULATIONAHA.108.819359