Lab Interpretation

Cholesterol Particle Size Testing: The Complete FM Practitioner Guide

What cholesterol particle size and particle number testing measure, what the outcome studies show, how NMR and ApoB compare, and where the evidence stops.

By Peter Kozlowski, MDReviewed by Andrew Le, MDMarch 7, 20266 min read

Cholesterol particle size testing measures the number and size of LDL particles in the blood, alongside the amount of cholesterol on a standard lipid panel. In the Framingham Offspring cohort, LDL particle number was related more strongly to future cardiovascular disease than LDL cholesterol, and in the ARIC study, small dense LDL cholesterol predicted coronary heart disease. Results are interpreted by the treating clinician in the context of the whole patient.

The number printed as "LDL cholesterol" on a standard lipid panel measures the amount of cholesterol carried in LDL particles. Because the cholesterol content per particle varies, LDL-C and LDL particle number often disagree, and particle testing is built to show that gap.

Why Particle Number Can Matter More Than LDL-C

In the Framingham Offspring Study of 3,066 adults, people with a low LDL particle number had fewer cardiovascular events than people with an equally low LDL-C or non-HDL-C. In MESA, among people whose two measures disagreed, only LDL particle number was associated with incident cardiovascular disease.

The case has limits. In the Women's Health Study of 27,673 women, NMR lipoprotein profiles predicted cardiovascular disease comparably to standard lipids and apolipoproteins, without being superior.

→ Deep dive: LDL Pattern A vs Pattern B: What It Means for CV Risk

LDL Pattern A vs Pattern B

Pattern B describes a predominance of small, dense LDL particles, part of an atherogenic lipoprotein phenotype associated with excess adiposity and high-carbohydrate diets. Pattern A describes predominantly larger LDL particles.

In ARIC, small dense LDL cholesterol was strongly correlated with an atherogenic lipid profile, was higher in people with diabetes, and predicted coronary heart disease even in people considered low risk by their LDL-C.

Particle size and particle number answer different questions, so clinicians read them together.

How Particle Size and Number Are Tested

NMR LipoProfile

The LabCorp NMR LipoProfile reports LDL particle number, small LDL particle number, LDL size, HDL particle number, an insulin resistance score and a standard lipid panel.

Apolipoprotein B (ApoB)

ApoB measures atherogenic particles directly. A 2009 position statement called apo B a better measure of LDL particle number and a more reliable risk indicator than LDL-C, and a 2013 review of 25 clinical studies found apo B and NMR LDL particle number nearly equivalent in assessing cardiovascular risk.

→ Full comparison: NMR Lipoprofile vs Standard Lipid Panel

Interpreting an NMR Report

Each marker answers a different question, and the ordering lab's reference ranges are the starting point for every one of them.

LDL particle number: the Framingham Offspring analysis found it a stronger predictor than LDL-C.
LDL size and small LDL particles: read alongside particle number, since small dense LDL cholesterol predicted risk in ARIC.
HDL particles: in the Women's Health Study, HDL particle concentration was not significantly associated with cardiovascular disease after adjustment, while larger HDL size was associated with lower risk.
VLDL particles: in the same study, higher VLDL particle concentration was associated with higher risk.

Who Gets Tested

The 2018 AHA/ACC cholesterol guideline lists elevated apolipoprotein B and elevated lipoprotein(a) among risk-enhancing factors that can inform statin decisions in adults at borderline or intermediate risk. Who to test, and which test to use, is a decision for the treating clinician.

How Treatment Is Framed

Pattern B can change with metabolic change. In a weight loss trial, losing about 9 kg converted Pattern B to Pattern A in 58 percent of men who started with Pattern B.

On the prescription side, icosapent ethyl lowered ischemic events in statin-treated patients with elevated triglycerides in REDUCE-IT. Agent selection, dosing, combinations and timing are prescribing decisions for the treating clinician.

Lp(a)

Lipoprotein(a) is an LDL-like particle that the 2018 cholesterol guideline lists as a risk-enhancing factor, with values reported in either mg/dL or nmol/L. Check which unit the lab used before comparing results over time.

Monitoring Over Time

Clinicians often repeat advanced lipid testing to see whether particle number, particle size, triglycerides and HDL are moving in the right direction. The retest interval and targets are decisions for the treating clinician.

FAQ

Can you have Pattern B LDL with normal cholesterol levels?

Yes. LDL-C measures cholesterol mass, and in the ARIC study small dense LDL cholesterol predicted coronary heart disease even in people considered low risk by their LDL-C.

What's the difference between LDL-P and ApoB?

Both estimate the number of atherogenic particles by different methods. A review of 25 clinical studies found them nearly equivalent in assessing cardiovascular risk.

Is NMR better than a standard lipid panel?

Not always. In the Women's Health Study, NMR lipoprotein profiles predicted cardiovascular disease comparably to standard lipids and apolipoproteins, without being superior.

Can Pattern B change?

In one trial, weight loss converted Pattern B to Pattern A in 58 percent of men who started with Pattern B.

Is the NMR LipoProfile covered by insurance?

Coverage varies by insurer, plan and clinical indication. Check with the lab and the plan before ordering.

Citations

Cromwell WC, Otvos JD, Keyes MJ, et al. LDL particle number and risk of future cardiovascular disease in the Framingham Offspring Study. J Clin Lipidol. 2007, 1(6):583-592. PMID 19657464
Contois JH, McConnell JP, Sethi AA, et al. Apolipoprotein B and cardiovascular disease risk: position statement from the AACC. Clin Chem. 2009, 55(3):407-419. PMID 19168552
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. Clin Chem. 2013, 59(5):752-770. PMID 23386699
Hoogeveen RC, Gaubatz JW, Sun W, et al. Small dense low-density lipoprotein-cholesterol concentrations predict risk for coronary heart disease: the ARIC study. Arterioscler Thromb Vasc Biol. 2014, 34(5):1069-1077. PMC3999643
Krauss RM, Blanche PJ, Rawlings RS, Fernstrom HS, Williams PT. Reversal of small, dense LDL subclass phenotype by normalization of adiposity. Obesity (Silver Spring). 2009, 17(9):1768-1775. PMC2837149
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, 119(7):931-939. PMID 19204302
Bhatt DL, Steg PG, Miller M, et al. Cardiovascular risk reduction with icosapent ethyl for hypertriglyceridemia (REDUCE-IT). N Engl J Med. 2019, 380(1):11-22. PMID 30415628
Otvos JD, Mora S, Shalaurova I, et al. Clinical implications of discordance between low-density lipoprotein cholesterol and particle number. J Clin Lipidol. 2011, 5(2):105-113. PMID 21392724
Grundy SM, Stone NJ, et al. 2018 AHA/ACC guideline on the management of blood cholesterol. Circulation. 2019, 139(25):e1082-e1143. PMID 30586774
LabCorp. NMR LipoProfile with Lipids.

HANS is a clinical AI copilot that runs beside your EMR. It reads NMR LipoProfile, ApoB and Lp(a) results alongside the rest of the chart and helps you document your assessment faster. See how HANS works.