Advanced Lipid Testing

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Advanced lipid tests

Advanced lipoprotein tests are LDL particle numbers and particle size (pattern A & B). These advanced cholesterol tests provide a better prediction of cardiovascular disease.

Advanced lipoprotein tests

LDL particle size, number and Lp(a) better predictor of cardiovascular disease than LDL-C.

The advanced tests are:

  • LDL particle size – is grouping LDL particles based on size.
  • LDL particle number (LDL-P or Apo-B) – is measuring number of LDL particles,
  • Lipoprotein (a) – measures the number of lipoproteins (a) particle attached with LDL.

LDL particle size test

Total cholesterol of 120 mg/dL with few Large LDL (Pattern A) has a low cardiovascular risk. And an excess of small LDL (Pattern B) has high cardiovascular risk.

Test for LDL particle size can measure particle size and classify into sub-fraction. There are different methods for Lipid particle size assessment; four of them are:

  1. LDL Segmented Gradient Gel Electrophoresis available from Berkeley Heart Lab Inc. – it separates LDL particles into seven sub-fraction by size and shape.
  2. Ultracentrifugation Vertical Auto Profile (VAP) available from Atherotech Inc. – it uses the high-speed centrifuge to separate lipoprotein particles. It measures the respective distribution of cholesterol within various lipoprotein sub-fractions. It quantifies cholesterol content of VLDL, IDL, LDL, lipoprotein (a), and HDL subclasses. This test separates LDL particles based on the size into six sub-fractions. These sub-fractions are LDL-1 (most buoyant) through LDL-6 (least buoyant i.e. small dense). But does not provide concentrations of the lipoprotein particles.
  3. Nuclear Magnetic Resonance (NMR) - Lipoprofile is available from LipoScience Inc. – it is the most used test for the analysis of LDL particle size; based on their magnetic properties. This test separates LDL-P into pattern A (large, fluffy) or pattern B (small, dense). They are providing ApoB at no extra cost, although calculated not measured.
  4. Quantimetrix Lipoprint – this test uses an electrical field called tube gel electrophoresis to distinguish lipoprotein based on its size. It analyzes lipoprotein sizes and provides “LDL subfraction score”. A score less than 5.5 indicates normal risk. A score between 5.5 to 8.5 indicates intermediate risk. A score over 8.5 indicates risk for atherogenic.

A study "Disparate LDL Phenotypic Classification among 4 Different Methods Assessing LDL Particle Characteristics." Published in Clinical Chemistry, September 2006 vol. 52 no. 9 1722-1727. The measurement of LDL subclasses are becoming more important, but standardization of methods required. Complete agreement among these methods on LDL subclass occurred in only 8% of the studies. The currently available methods have vast variation. Thus unreliable as well as limits their clinical usefulness.

As per NMR test,

  • People possessing most large, fluffy LDL particles called "Phenotype A" or "Pattern A." These people are not associate with a risk for atherosclerosis.
  • People possessing most small, dense LDL particles are 'Phenotype B" or "Pattern B". These peoples are 300% greater risk towards cardiovascular diseases.

Most diabetics and people with confirmed coronary artery disease (CAD) contains "Pattern B." Most Pattern B individuals have low HDL, high triglyceride, and high blood glucose susceptibility. Pattern B is a marker for deranged metabolism.

Small LDL particles (Pattern B) easy pierce the endothelium and reaches the artery walls. Pattern B LDL can oxidize and play a role in the formation of cholesterol plaques. Only oxidized LDL enter the macrophages in the arterial lining and form cholesterol-rich plaques.

Ref: “Small LDL particles associated with the incidence of coronary artery disease in men & women.” Published in JAMA 1996; 276:875-881.

How important is LDL particle size?

Familial hypercholesterolemia is the most lethal lipid disorder, and they have large LDL particles. If not treated to lower the LDL particle number, they may die early than usual. If the larger LDL is not lethal, then why should they die prematurely?

Conversely, people with diabetes and advanced metabolic syndrome have small LDL particles. Still, they managing to live well for 50 to 70 age, before succumbing to heart disease.  

From this, you can understand:

High LDL-P number is the important predictor of cardiovascular risk than its size.

LDL particle number testing

LDL Particle number measures LDL particles number in nmol/L. LDL-P is a stronger predictor of heart risk than LDL-C. About 30 to 40% people with low LDL may have elevated LDL-P. That is why; many people suffer from a heart attack even though they do not have elevated LDL-C levels.

ApoB is two main variants; apoB 48 and apoB 100. ApoB 48 is in chylomicrons and synthesized by the small intestine. One molecule of ApoB 100 is in VLDL, IDL, LDL and LP(a) particles and synthesized by the liver. ApoB 100 most probably pierce arterial walls. Thus, it is important to assess cardiovascular risk. Elevated apoB number would be the initiation factor of atherosclerosis.

Framingham study shows people with lowest LDL-C has 37% more heart disease than lowest LDL-P.


ApoB and LDL-P are better heart risk predictors than LDL-C. Apo-B and LDL-P are two different methods to measure LDL particle number.

Merits of Apo-B vs. LDL-P are not clear. So you can choose based on its availability, cost and clinician preference.

Reference range for LDL-P

  • Optimal: less than 1000 nmol/L
  • Low/No risk: 1000 to 1299 nmol/L
  • High risk: more than equal to 1300 nmol/L

There is an increased chance towards cardiovascular risk if LDL-P is above the normal range.

Reference range for apoB

  • ​Optimal: less than 60 mg/dL (<0.6 g/l)
  • Moderate risk: 60 to 80 mg/dL (0.6 to 0.8 g/l)
  • High risk: more than 80 mg/dL (>0.8 g/l)

There is increased chance towards cardiovascular risk. If the ApoB number is above normal healthy range.

Lipoprotein (a)

Lipoprotein (a) is an LDL particle attached to a special protein called apo(a).

The Lp(a) level in the blood is genetically inherited. Elevated levels of Lp(a) associated with inflammation in the arterial wall. Those without or with very low Lp(a), seems healthy.

Thus, plasma Lp(a) is not necessary; at least under normal conditions. Lp (a) circulates and does restorative work on damaged blood vessels. The Lp(a) concentrate is around the damaged blood vessel. It binds with the amino acids and promotes oxidized LDL deposits in the wall. This deposits leads to more inflammation and can develop plaque.

"Elevated Plasma L (a) & Coronary Heart Disease in Men Aged 55 Years & Younger." Published in JAMA 1996; 276(7):544-548. The study shows high Lp(a) is an independent risk factor for the development of premature CHD in men.

Who should take Lp(a) test?

Patients who have the below-noted risk may need to take Lp(a) test.

  • Your family member had heart disease, heart attacks, or heart problems before age 55.
  • High cholesterol or LDL-C levels not responding to the treatment.

How to perform Lp(a) test? Lp(a) blood test should take after 12 hours of fasting. That is not eating or drinking anything except water.

Reference range for Lp(a)

  • Optimal: less than 20 mg/dL (<50 nmol/l)
  • Moderate risk: 20 to 30 mg/dL (50 to 75 nmol/l)
  • High risk: more than 30 mg/dL (>75 nmol/l)

If Lp(a) is above normal range, then increased risk towards atherosclerosis and heart attack.

Many people do not have detectable levels of Lp (a) in their bloodstream.

What are the health conditions that increase Lp(a)?

Certain health conditions may increase Lp(a), these conditions are:

  • Low-estrogen,
  • Hypercholesterolemia,
  • Severe hypothyroidism,
  • Uncontrolled diabetes,
  • Renal failure, and
  • Nephrotic syndrome (kidney disorder with protein loss).

The commercial Lp(a) testing may not have the same accuracy. Measuring and treating elevated Lp(a) cholesterol levels are not widely followed.

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