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LDL Management in a 34 Year Old with Familial Hypercholesterolemia

Here is a patient question sent by an excellent cardiologist.

Question from a physician — I just met a 34-year-old male who has a heterozygous LDL receptor defect. Father MI at age 53. Patient is a non-diabetic, non-smoker without hypertension. He had an LDL pre-Statin of about 400. He has been on statin for 20 yrs. He is now on Crestor 40 and Zetia 10. His most recent laboratory values are: total cholesterol 201, HDL 39, triglycerides 97, LDL 141. His Lpa is normal and his apoprotein B is 113. I have no objective imaging at his age and don’t know if it would help. He is far beyond 50% reduction from his baseline. I was going to leave him alone. Let me know if you think otherwise.

My Response — The New ACC/AHA Guidelines suggest adding therapy to a statin and ezetimibe when the LDL-C is >100 (if pre-treatment was >190) or when the LDL is >130 (if pre-treatment LDL-C was >220). I find the Guidelines confusing and hard to remember so here is how I think about these cases. Also, they do not consider how long the LDL has been high.

Your patient has been treated for 20 years, which is good, but we never know how adherent kids are to the therapy. I am much more aggressive with folks with familial hyperlipidemia who have been untreated for years because they have a lot of “cholesterol mg years”, just like pack years of smoking. The longer left untreated, the more risk. His treatment relaxes me, somewhat. On the other hand, an LDL of 141 is not ideal and clearly above the 130 mentioned above. The FOURIER trial, used PCSK9 inhibitor evolocumab, in high risk CAD patients to lower median LDL-C from 92 to 30 mg/dl and produced a 1.5% absolute reduction in CAD events over a median duration of only 2.2 years. This supports the concept that even lower is better. With your patient I would scour him looking for corneal arcus, tendon zanthoma, anything that would suggest that he has deposited cholesterol in inappropriate places despite your treatment. I would even get a coronary calcium scan. If he has even trivial calcium, at his age, I would definitely be even more aggressive by adding a PCSK9 inhibitor. So, leaving him alone is not necessarily “wrong”, but I am biased toward getting his LDL even lower and would look for justification. Granted some “lipid experts” would not, but I would. Of course, this depends on the patient’s thoughts as well.