Advanced Lipid Testing – when “bad cholesterol” isn’t good enough

In an earlier post, I reviewed the new ACC/AHA guidelines for treating cholesterol.  These guidelines recommend basing treatment solely on LDL-c or the “bad cholesterol”, treating when it is high but not to a specific target.  Over the last several decades, lowering levels of LDL-c has resulted in a decreased rate of heart disease that combined with advances in treatment has also reduced the death rate from heart disease.

Despite these advances, heart disease remains the number one killer of Americans.  A 2009 study from ULCA demonstrated that half of people who have heart attacks have relatively “normal” levels of LDL-c cholesterol.  What are we missing in these people?  Is their another marker we could measure to more accurately predict risk?  

What is Cholesterol testing?

Low Density Lipoprotein is the “sticky stuff” that clogs arteries.  Cholesterol is a carrier for the lipoproteins that circulate in our blood.  The more lipoproteins in you blood, the greater your risk for heart disease.  Historically we have used the measurement of LDL cholesterol to act as a surrogate measure of these sticky proteins because it was the best we had.  We have had a tremendous impact on heart disease by treating cholesterol.

The problem with LDL-c measurement is that it is a calculation based on certain assumptions about how the sticky proteins are distributed in the system.  The model breaks down when triglycerides (another component of a cholesterol panel) are elevated.  When this occurs, the sticky proteins are not distributed evenly and you have a lower level of LDL-c than the true level of sticky proteins that cause plaque.  The result is that the traditional LDL-c reading will underestimate the risk of heart disease – helping to account for the “half of heart attack victims with normal cholesterol.”

What other markers are there for lipid testing?

Many measurements have been evaluated to see if there are better predictors of heart disease than LDL-c.  3 of the most promising are Non-HDL-c, Apo-B and LDL particle number (LDL-p).  

Non-HDL-c is a calculation that simply subtracts the HDL-c level from the Total Cholesterol level in a standard lipid panel.  For those at highest risk of heart disease, a non-HDL-c level over 130mg/dl is associated with increased risk of heart disease regardless of what the usual LDL-c is.  The advantage of this reading is that it can be determined at no additional cost from a standard lipid panel.  Disadvantages are variability based on fasting state and that it may not predict how well medication is reducing risk.

Apo-B is a protein that is deposited in the walls of arteries to create plaque.  It is carried through the system by cholesterol.  The more Apo-B in your system the greater your risk of heart disease.  Each particle of low density lipoprotein contains 1 molecule of APO-B.  Studies have shown that Apo-B levels can remain elevated even in setting of “normal” cholesterol levels.

LDL-p directly measures the particles of low density lipoprotein that account for the risk of heart disease.  Studies have shown that LDL-p can be elevated even when cholesterol levels are normal.  Information presented at the most recent American Cardiology Conference demonstrated that treating patients to a normal LDL-p had a 22-25% reduction in heart attacks than those treated to traditional goal cholesterol values.

How does this affect my practice?

I see patients at increased risk of heart disease on a daily basis.  I generally order a traditional cholesterol panel on all patients.  When their history indicates an increased risk of heart disease – due to family history, diabetes, hypertension or obesity, I will order an LDL-p as well.  I will also order an LDL-p if their traditional cholesterol panel shows high triglycerides.  I find this test to be one of the easiest to interpret as there are direct values that correlate with risk.  It also does not require fasting – making it a very convenient test indeed!

So while not everyone needs to have their LDL-p measured, it is important not to simply accept a cholesterol reading at face value.  Like all tests, it needs to be interpreted in the setting of your individual risk factors and other medical conditions.  Knowing your real risk of heart disease is a necessary initial step towards improving your health!

The path to wellness begins with a proper diagnosis. 

Author: Eric Goldberg, MD, FACP

I am a Board Certified Internal Medicine physician. I currently practice at and am the Medical Director of NYU Langone Internal Medicine Associates. Posts are my opinion and not medical advice or an official position of NYU Langone Medical Center.

What are your thoughts?