Latest in lipidology: is lipoprotein(a), Lp(a), "the most dangerous particle you’ve never heard of"?

Dr Attia's podcast on Lp(a), the link is here: https://peterattiamd.com/tomdayspring6/

Discussed:

- ApoB as a preferred metric over LDL-P [16:30]; Atherogenic lipoproteins (apoB/LDL-P) as front and center in pathogenesis of CVD. ApoB and LDL-P are used interchangeably, but this is not quite accurate.

- Therapeutic goals for apoB concentration [21:45]

- Lipoprotein(a)—the most dangerous particle you’ve never heard of [55:00];
preferred lab measurements [1:17:45]; 

Lipoprotein(a), or Lp(a), is a distinctive particle with 2 components: 

 - a lipoprotein core that resembles LDL
-  a shell that contains apolipoprotein(a), or apo(a)

Lp(a) is dubbed one of the final frontiers in lipid management. Elevated blood Lp(a) levels are primarily due to genetic variations in the LPA gene that encodes for apo(a) and cannot be lowered by diet, exercise or current lipid-lowering therapies. 

“By combining the atherosclerotic effects of LDL with the prothrombotic effects of apo(a), elevated Lp(a) essentially delivers a double whammy of noxious atherothrombotic effects", as per Dr Nissen. 

Normal Lp(a) levels are less than 25 mg/dL, with significant risk of atherothrombotic events beginning at levels 50-70 mg/dL and rising thereafter. And that risk is not at all rare: 64 million U.S. residents have an Lp(a) level of 60 mg/dL or higher. Over 3 million have levels of 180 mg/dL or more, which confer extremely high risks. There are no effective Lp(a)-lowering pharmacotherapies to date. That includes statins, which actually can slightly raise Lp(a) levels.

It is estimated that about one in five people in the U.S. has an Lp(a) level that puts them at risk. And, even people with a healthy level of LDL cholesterol could have a high Lp(a) level. So many people are walking around with abnormally high Lp(a) but don’t know it. Lp(a) could be a factor in the rise in heart attacks in younger, seemingly healthy adults who do not have high LDL cholesterol. The other tricky thing is that your Lp(a) level is in large part genetically wired, so things like diet and exercise won’t really change it. There are currently no FDA-approved drugs to lower it, either. Focus on strategies for lowering that risk focus on addressing other risk factors, such as high LDL cholesterol, BMI and blood pressure.

Here is Dr Nissen and Dr Cho from Cleveland Clinic on Lp(a). They discussed rosuvastatin 5 mg once a week. Dr Nissen mentioned that rosuvastatin at 1 mg per day reduced LDL by 33%. Rosuvastatin has a very long half life of 19 hours vs 14 hours for atorvastatin. Rosuvastatin is hydrophilic vs atorvastatin which is lipophilic.

 

 

References:

https://health.clevelandclinic.org/why-would-my-doctor-order-a-lipoproteina-blood-test/

https://consultqd.clevelandclinic.org/elevated-lipoproteina-is-a-long-sought-treatment-finally-on-the-way/

Mayo Clinic Lp(a) review and some nice diagrams and algorithm flow charts: https://www.mayoclinicproceedings.org/article/S0025-6196(13)00795-7/pdf