Thread by @Lpa_Doc

Twittorial #1; Lp(a) and the real “LDL-C”:

When one looks at your lab report, note the LDL-C says “calculated”. So, believe it or not, the most important risk factor for CVD is actually an estimated value. Hard to believe but true. 1/17

Sometimes it says direct LDL, which is an actual measurement. LDL is a complex particle containing apoB, cholesterol, cholesteryl esters, phospholipids and a bit of triglyceride. LDL-C only reflects the total cholesterol in LDL, that is why there is a “C” at end of it. 2/17

LDL particles are made of about 50% cholesterol by mass (i.e. the human body is 60% water). Lp(a) on other hand is 20-45% cholesterol. The gold standard for measuring LDL-C is ultracentrifugation. 3/17

This places your plasma in a test tube with a salt solution and ‘floats up” the lipids according density and can separate them and measure them separately. Expensive and labor intensive and not done at clinical levels. 4/17

However, because density of LDL and Lp(a) overlap, it can’t separate these so counts them together, but it can separate chylomicrons, VLDL and IDL and HDL. Think of this as swimming in a pool vs ocean, ocean is more buoyant due to salt content. 5/17

What it does not tell you is that both of these metrics are not what they seem to be. Its very difficult to actually measure the LDL without interference of Lp(a), so in general, “LDL” is actually “LDL-C + Lp(a)-C”. 6/17

We have published on this before. ncbi.nlm.nih.gov/pubmed/25943842

In rare cases another lipoprotein class IDL-C, can be in this equation, but in fasting samples it is not present except for some very rare disorders]. 7/17

Total cholesterol in blood = LDL-C + HDL-C + VLDL-C. VLDL-C is estimated by triglyceride/5 (complex topic for another time). So, the lab basically measures TC, HDL-C and estimates VLDL-C and whatever is left over is called “LDL-C”. 8/17

I think it can be appreciated that much error can be introduced with this situation. So, what does this mean for patients with elevated Lp(a)?- if ones Lp(a) is zero or close to zero then the “LDL-C is likely accurate, so no problem 9/17

However, let’s say LDL is 80 mg /dL and your doc is considering to give you more statin to get it <70 mg/dL. Lets say Lp(a) is 150 mg/dL and 30% is cholesterol, the Lp(a)-C is 50 mg/dL, but no one measured it and it is not known. 10/17

So in this subject, the “real” LDL is 30 and the Lp(a)-C is 50 and the total LDL-C is 80. The patient is not likely to respond well to more statin/ezetimibe/PCSK9i with such low LDL. Without understanding this concept, a patient will be labeled “statin resistant”. 11/17

If the Lp(a) is in nmol/L, one can estimate in mg/dL by dividing by 2.5, but this is not accurate and a rough estimate. What we need is better ways to quantitate the real LDL and to also measure Lp(a) to understand what might be happening. 12/17

It very important to know what real LDL-C in high Lp(a) patients to ultimately be able to better individualize therapy to improve outcomes. Efforts are underway in our lab to do this. At practical level, no action is currently needed outside understanding this. 13/17

Ok quiz time: Q1- 5 points
Choose the correct answer: In subjects with elevated Lp(a), one can predict that the laboratory measured LDL-C with be what compared to the real LDL-C: 14/17

Q2- 5- points
Choose correct answer regarding statin resistance:
A-Is worsened by low saturated fat/low cholesterol diet
B-Is seen in patients who take their statin daily
C-Can seen in subjects with high Lp(a)
D-There is no such thing
15/17

Bonus question: 1 point. Chose the correct answer: Which cartoon animal looks most like an Lp(a) particle when looked on straight in profile. Hint: 16/17

Happy Saturday to all, polls close next Friday morning. Feel free to suggest improvements in this forum or other topics of interest. 17/17