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Lipoproteins and LDL cholesterol

16 min

Skills you'll build3 skills
  • Choose a valid LDL-C or non-HDL-C result when triglycerides are too high for Friedewald
  • Match each lipoprotein particle to the lipid it carries and where that lipid comes from
  • Tell a high-LDL type IIa lipid profile from a triglyceride-rich profile

Try first

Try first

A lipid profile shows total cholesterol 250 mg/dL, HDL cholesterol (HDL-C) 38 mg/dL and triglycerides 460 mg/dL. The laboratory information system has calculated a Friedewald LDL cholesterol (LDL-C) of 120 mg/dL. Which cholesterol result is valid to report from this profile?

Keep going to see the reasoning.

Keep going to see the reasoning.

Right. Keep going to follow the reasoning.

Keep going to see the reasoning.

Get the idea

Use the explanation to check your first decision.

Lipoprotein transport

Lipoproteins transport lipid in plasma by three pathways:1

  1. Dietary. The intestine packages dietary triglyceride with apoB-48 into chylomicrons, which enter blood through lymph. Lipoprotein lipase hydrolyzes their triglyceride, and the liver takes up the remnants.
  2. From the liver. The liver secretes triglyceride-rich VLDL on apoB-100. Lipoprotein lipase turns it into IDL, and hepatic lipase converts IDL toward LDL, the main cholesterol-delivery particle.
  3. Back to the liver. HDL collects cholesterol from cells and returns it to the liver.

Standing plasma shows which particle is in excess. Chylomicrons float up as a cream layer after refrigerated standing. Excess VLDL leaves the plasma turbid with no cream layer.2

LDL-C and non-HDL-C

The Friedewald equation estimates LDL-C from a routine profile, in mg/dL:3

LDL-C = total cholesterol − HDL-C − triglycerides ÷ 5

Triglycerides ÷ 5 is an estimate of VLDL cholesterol. The estimate loses accuracy as triglycerides rise and LDL-C falls, and it is invalid at triglycerides of 400 mg/dL or higher.2,3 Current guidance prefers the Martin/Hopkins or Sampson/NIH equations where they apply, and a laboratory's procedure specifies the method for high triglycerides.2

Non-HDL-C = total cholesterol − HDL-C uses two measured values. It is valid in fasting and nonfasting specimens and is reported with the standard profile.4

Lipoprotein phenotypes

The Fredrickson and World Health Organization phenotypes classify hyperlipoproteinemia by the particle in excess:5

TypeParticle increasedStanding plasmaLipid results
IChylomicronsCream layer over clear plasmaTriglycerides markedly increased
IIaLDLClearCholesterol and LDL-C increased, triglycerides within the interval
IIbLDL and VLDLClear to turbidCholesterol and triglycerides increased
IIIRemnantsTurbidCholesterol and triglycerides increased, often by similar amounts
IVVLDLTurbid, no cream layerTriglycerides increased
VChylomicrons and VLDLCream layer over turbid plasmaTriglycerides markedly increased, cholesterol increased

Type IIa has triglycerides within the interval, so a raised triglyceride with a high cholesterol excludes type IIa.

Follow the bench demonstration

Sources for this step
References
  1. Feingold KR. Introduction to lipids and lipoproteins. Updated January 14, 2024. In: Feingold KR, Adler RA, Ahmed SF, et al, eds. Endotext. MDText.com, Inc; 2000-. Accessed August 29, 2026. https://www.ncbi.nlm.nih.gov/books/NBK305896/
  2. Cao J, Donato LJ, El-Khoury JM, et al. ADLM guidance document on the measurement and reporting of lipids and lipoproteins. J Appl Lab Med. 2024;9(5):1040-1056. doi:10.1093/jalm/jfae057
  3. Friedewald WT, Levy RI, Fredrickson DS. Estimation of the concentration of low-density lipoprotein cholesterol in plasma, without use of the preparative ultracentrifuge. Clin Chem. 1972;18(6):499-502. doi:10.1093/clinchem/18.6.499
  4. Blumenthal RS, Morris PB, Gaudino M, et al. 2026 ACC/AHA/AACVPR/ABC/ACPM/ADA/AGS/APhA/ASPC/NLA/PCNA guideline on the management of dyslipidemia: a report of the American College of Cardiology/American Heart Association Joint Committee on Clinical Practice Guidelines. Circulation. 2026;153:e1154-e1276. doi:10.1161/CIR.0000000000001423
  5. Beaumont JL, Carlson LA, Cooper GR, Fejfar Z, Fredrickson DS, Strasser T. Classification of hyperlipidaemias and hyperlipoproteinaemias. Bull World Health Organ. 1970;43(6):891-915. PMID:4930042

Watch one

Read each decision and its explanation.

A fasting lipid profile arrives for verification. The laboratory information system has calculated a Friedewald LDL-C. The serum is turbid, with no cream layer.

Which cholesterol results can be released?

TestResultReference intervalFlag
Total cholesterol232 mg/dL High<200 mg/dL<200High
HDL-C41 mg/dL>40 mg/dL>40
Triglycerides428 mg/dL High<150 mg/dL<150High
LDL-C, calculated105 mg/dL High<100 mg/dL<100High

Specimen: H 4, L 180, I 1. Fasting 12 hours; serum turbid with no cream layer

  1. Check the triglycerides first. At 428 mg/dL they are above 400 mg/dL.

    The triglyceride result determines whether the Friedewald equation can be used.

  2. Set the calculated LDL-C aside. The calculation gives 232 − 41 − 428 ÷ 5 = 232 − 41 − 85.6 = 105 mg/dL, but the equation is invalid at this triglyceride, so this number cannot be released.

    The equation assumes VLDL cholesterol is triglycerides ÷ 5, and that assumption fails here.

  3. Calculate non-HDL-C: 232 − 41 = 191 mg/dL.

    Non-HDL-C uses two measured values and stays valid when triglycerides are high.

  4. Report the profile with non-HDL-C, and add the comment that LDL-C is not calculated at triglycerides of 400 mg/dL or higher. Any LDL-C comes from the method your procedure specifies, such as a direct LDL-C assay.

    The procedure specifies the LDL-C method for high triglycerides, and the report comment refers the reader to it.

Release total cholesterol, HDL-C, triglycerides and a non-HDL-C of 191 mg/dL. The calculated LDL-C is withdrawn with a comment.

Practice this skill

Your turn

Problem 1 of 3 · Hints available

A fasting lipid profile has triglycerides of 520 mg/dL. Which cholesterol result remains valid to report from the routine profile?

Correct. Non-HDL-C uses two measured values, works with fasting and nonfasting specimens, and is particularly useful when triglycerides are elevated.

Incorrect. Friedewald becomes invalid at triglycerides of 400 mg/dL (4.5 mmol/L) or higher, and fasting does not change that limit.

Incorrect. Triglycerides ÷ 5 is the Friedewald estimate of VLDL cholesterol, and that assumption is invalid at 400 mg/dL or higher.

Hint
  1. Check the triglyceride against the Friedewald limit first.
  2. Fasting helps the Friedewald estimate only below its triglyceride limit.
  3. Look for the result calculated only from measured values.

Review LDL-C and non-HDL-C

Problem 2 of 3 · Hints available

Which particle initially carries long-chain dietary lipid from the intestine through lymph into blood?

Incorrect. The liver secretes very-low-density lipoprotein (VLDL) on apoB-100 to carry endogenous triglyceride.

Correct. Enterocytes package re-esterified long-chain fatty acids with apoB-48 into chylomicrons, which enter blood through intestinal lymph.

Incorrect. Low-density lipoprotein (LDL) forms from VLDL in the endogenous pathway and is the major cholesterol-delivery particle.

Hint
  1. The particle leaves the intestine through lymph, before the liver processes the lipid.
  2. Which particle contains apoB-48?

Review Lipoprotein transport

Problem 3 of 3 · On your own

A fasting profile shows total cholesterol 296 mg/dL, HDL-C 42 mg/dL, triglycerides 240 mg/dL and a calculated LDL-C of 206 mg/dL. After refrigerated standing, the plasma is slightly turbid with no cream layer. Which phenotype fits?

Type IV raises VLDL and triglycerides. An LDL-C of 206 mg/dL shows LDL raised as well.

Type V includes excess chylomicrons, which float up as a cream layer. This plasma has none.

In type IIa, triglycerides are within the interval. A triglyceride of 240 mg/dL and turbid plasma show VLDL raised too.

Read high cholesterol and triglycerides as type IIa

Type IIa raises total cholesterol and LDL-C with triglycerides within the reference interval. When triglycerides rise as well, VLDL or remnant particles are increased, which fits type IIb or type III. Labeling the specimen IIa misses the triglyceride-rich particles that the lipid results and standing plasma show.

LDL-C is high and triglycerides are raised, with turbid plasma and no cream layer. LDL and VLDL are both increased.

Review Dyslipidemia patterns

Use it

Read the case evidence, then make each decision. The step is complete without it.

  • A lipid profile for a 47-year-old man, MRN 6093127, waits in the verification queue. The laboratory information system has calculated a Friedewald LDL-C.
  • The lipemia index is within the limits for these methods, and QC is acceptable.
TestResultReference intervalFlag
Total cholesterol262 mg/dL High<200 mg/dL<200High
HDL-C36 mg/dL Low>40 mg/dL>40Low
Triglycerides610 mg/dL High<150 mg/dL<150High
LDL-C, calculated104 mg/dL High<100 mg/dL<100High

Specimen: H 6, L 240, I 1. Fasting 12 hours; thin cream layer over turbid plasma after refrigerated standing

Decision 1 of 3

What does the cream layer show?

Chylomicrons are the largest, lightest particles and float to the top. A cream layer after a 12-hour fast shows they are clearing slowly.

Excess VLDL makes plasma turbid without a cream layer. Here VLDL explains the turbid plasma below the layer.

Confused dietary chylomicrons with hepatic VLDL

Chylomicrons carry dietary triglyceride from the intestine through lymph on apoB-48. VLDL carries triglyceride made in the liver on apoB-100. A cream layer on standing plasma marks chylomicrons, and VLDL excess gives turbidity with no cream layer. If the two are confused, the standing-plasma test is misread.

LDL particles are small and dense. They stay mixed through clear plasma.

Review Lipoprotein transport

Decision 2 of 3

What do you do with the calculated LDL-C?

At triglycerides of 610 mg/dL, the Friedewald estimate is invalid, and a wrong LDL-C would reach the chart.

Reported Friedewald LDL-C at triglycerides ≥400 mg/dL

The Friedewald equation estimates VLDL cholesterol as triglycerides ÷ 5. That assumption loses accuracy as triglycerides rise and LDL-C falls. The equation fails at triglycerides of 400 mg/dL or higher. Non-HDL-C is calculated from two measured values and stays valid in fasting and nonfasting specimens.

The measured total cholesterol, HDL-C and triglycerides are valid, and only the LDL-C calculation is invalid.

Non-HDL-C, 262 − 36 = 226 mg/dL, uses two measured values. The comment explains the missing LDL-C, and any LDL-C comes from the method your procedure specifies.

The equation is invalid for this specimen's lipoproteins at any dilution, and the result is multiplied back to 610 mg/dL.

Review LDL-C and non-HDL-C

Decision 3 of 3

Which phenotype does this fasting specimen fit?

Type IV raises VLDL alone and shows no cream layer.

In type IIa, triglycerides are within the interval and plasma is clear. This specimen has markedly raised triglycerides and a cream layer.

Read high cholesterol and triglycerides as type IIa

Type IIa raises total cholesterol and LDL-C with triglycerides within the reference interval. When triglycerides rise as well, VLDL or remnant particles are increased, which fits type IIb or type III. Labeling the specimen IIa misses the triglyceride-rich particles that the lipid results and standing plasma show.

Type I shows a cream layer over clear plasma. The plasma below this layer is turbid.

A cream layer over turbid plasma means chylomicrons and VLDL are both increased, with markedly raised triglycerides and a raised cholesterol.

Review Dyslipidemia patterns

The triglyceride of 610 mg/dL is above the Friedewald limit, so the calculated LDL-C was withdrawn and non-HDL-C was reported. The cream layer over turbid plasma showed that chylomicrons and VLDL were both increased.

For reference

Sources checked