Specialized lipid testing, sometimes called lipoprotein particle testing, is ordered by doctors to further check risk status.  Doctors look for the presence of a “discordance” between the LDL cholesterol level on a standard lipid profile and risk.  Another test to assess this is the ApoB (apolipoprotein B) level.  Discordance occurs almost always if someone has high triglycerides, and is typically seen in people who are overweight or have diabetes.


What do we mean by “discordance?”

Discordance occurs when the LDL cholesterol does not estimate risk as well as other lipid measures.  This can occur in up to 20% of people.  Most of these people are overweight or obese or have diabetes.


Should individuals with familial hypercholesterolemia (FH) get specialized lipid testing?

The short answer is no.  In FH there is almost never discordance between LDL cholesterol levels and risk.  Additional testing that helps in risk stratification for FH includes genetic testing and measuring Lp(a). If you want to learn more, read.on.


What causes discordance?

Triglycerides and cholesterol are carried around in the blood on particles that combine proteins and fat. VLDL particles carry a lot of triglyceride and LDL particles carry a lot of cholesterol.  When triglycerides are high, LDL particles have less cholesterol (for many reasons) and thus, become smaller. When this happens, and because LDL particles are smaller, there are more LDL particles at any given level of LDL cholesterol. Since LDL particles cause atherosclerosis, studies have shown that the more LDL particles that are present, the higher the risk.  This higher risk may also be measured as a higher non-HDL cholesterol (a measure of all the lipid particles combined other than HDL), higher apolipoprotein B (apoB) level, or is also called excess “small LDL.”


Does discordance occur in FH?

This “discordance” almost never occurs in familial hypercholesterolemia.  Patients with FH usually do not have high triglycerides.

In FH, the LDL cholesterol is an accurate reflection of risk and total particle number.  You should remember that all LDL particles will cause plaque to build up in the arteries regardless of size. Patients with FH have more LDL particles than those without FH. No LDL particle is good for you. It remains controversial whether or not the smaller particles cause more atherosclerosis than bigger particles.