July 30, 2018

Cholesterol

#07 – Deep Dive: Lp(a) — what every doctor, and the 10-20% of the population at risk, needs to know

"Elevated Lp(a) may have conferred a survival advantage for most of human history: a better ability to deal with acute trauma, but possibly at the expense of poor handling of chronic damage. In today's environment, for many people, that's not an advantage." —Peter Attia

Read Time 11 minutes

This is our first “deep dive” episode that goes into detail on one topic. Pronounced, el-pee-little-a, this lipoprotein is simply described as a low-density lipoprotein (LDL) that has an apoprotein “a” attached to it…but Lp(a) goes far beyond its description in terms of its structure, function, and the role that it plays in cardiovascular health and disease. Affecting about 1-in-5 people, and not on the radar of many doctors, this is a deep dive into a very important subject for people to understand.

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* If you would like us to do a deep dive on a particular topic, please submit your request to the comments section of this post. Please look at the existing comments before posting, and “upvote” the topic (or topics) you want us to cover. *

Note: this podcast gets technical at times. The figures in the show notes are your friends. They truly speak more than a 1,000 words apiece. I can’t emphasize enough how helpful it is to look at the figures before, during, and/or after I try verbally walk you through things like kringle repeats, molecular weight isoforms, lysine-binding domains, and plasminogen homology, as a few examples. If you stick with it, I think you will be rewarded.

We discuss:

  • A quick primer on lipoproteins [7:30];
  • Intro to Lp(a) [11:00];
  • Lab tests for Lp(a) and reference ranges [20:00];
  • The physiologic functions of Lp(a) [31:00];
  • The problems associated with high Lp(a) [34:15];
  • Lipid-lowering therapies of Lp(a) [44:45];
  • Lp(a) modification through lifestyle intervention [1:00:45];
  • High LDL-P on a ketogenic/low-carb-high-fat diet [1:05:30]; and
  • More

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40 Comments

  1. In the show notes you mention the 2 Lp(a) SNPs but in the podcast, I didn’t hear mention of those. Can you please feature these SNPs?

  2. Please deep dive dietary ketosis especially talking about risks/benefits of short term, intermittent, and life-long adherence.

  3. I’m one of those 1 in 10 who is homozygous for at least one LPA mutation and have elevated LP(a). Big light went off when I learned this…as despite low cholesterol and not many risk factors, all four of my grandparents died of stroke or MI (although in 70s or 80s). I have known about this for about 7 years now and experimented with all sorts of interventions. I can say hands down, I am also one those people who does not do well on keto..I rarely enter ketosis despite getting 90% of fat (mostly monounsaturated as I follow a mediterranean ketogenic diet: olives, avocado, etc.) and I feel horrible. My LDL-P and fasting blood glucose go up. I think one explanation may be falling into one of the categories for Keto diet contraindications:
    Carnitine deficiency (primary)
    • Carnitine palmitoyltransferase (CPT) I or II deficiency and Carnitine translocase deficiency, CAT
    • Fatty Acid Desaturase Deficiency FADS
    • b-oxidation defects
    • Medium-chain acyl dehydrogenase deficiency (MCAD)
    • Long-chain acyl dehydrogenase deficiency (LCAD)
    • Short-chain acyl dehydrogenase deficiency (SCAD)
    • Long-chain 3-hydroxyacyl-CoA deficiency
    • Medium-chain 3-hydroxyacyl-CoA deficiency
    • Pyruvate carboxylase deficiency
    • Porphyria
    While, the autosomal recessive “xCAD” loss of function metabolic diseases are rare, being heterozygous for some of the responsible alleles is not, and I carry several of those. I suspect my ability to switch from carb to fat burning is compromised/less efficient as compared to someone without those alleles.
    Long story short: Over time what I feel best on (and is supported my significantly improved HbA1C, LDL-P, TG, total Chol, c-peptide, hsCRP) is following a whole foods, plant based diet, switching back to oral estradiol (I’m postmenopausal) and plenty of exercise.

    • I am also someone with Super high LPa. 374 nmols is my norm. On statins it went up to low 500’s nmols. I too feel better on a Mainly all plant based diet. I add in some sardines and fish here and there and some nuts and red wine. But trying to mainly stick to the all plant based. There are some promising Trials right now, with an siRNA drug. I have no inflammation issues, at least based on my blood work, and the results so far. I have always be “fit”, had no symptoms, but long story short when I found out about my high LPa I insisted on a CT Calcium score. That was high at 490. Then had a Nuclear Stress test. That is where they saw a potential block. Next I had 2 Angioplasities (so many blocks they couldn’t do it in one) and a Rotoblation (one aretery so blocked they had to drill it out) and 6 stents. I went from thinking I was the Picture of health to omg, I could have died. LAD 95 to 99% blocked, RCA (drilled out one) close to 100% blocked, 4 stent just in the RCA, and CX-80% (not as bad). They believe my body created new pathways and that is why I had no symptoms. Anyway, it has been a journey and I feel good and like you, I think mostly plant based is the way to go, at least for me. And exercise is super important. When those things are “all in check” I feel very good. I am 58 years old, as a side note.

      • Thanks for posting. I just recently was sent to a Cardiologist, for rising BP, and high cholesterol, and found out that I too have high LPa. 228. The Dr that discovered it, doesn’t even normally do that test, and he doesn’t know how to treat it. He had me start Repatha, which is a shot that I am supposed to give myself every 2 weeks, for high cholesterol. I’m on my 3rd day after shot, and it has made me very sick.
        I can’t take Statins, they break down my muscles, so this shot was an alternative.
        I haven’t been feeling well, and been experiencing a lot of dizziness, even prior to the shot. I too have always worked out, I’m not overweight, and I’ve been a Vegetarian for years. I do occasionally eat fish.
        Based on your experience, what test do you think I should ask for first? I too am 58. I have a 23 yr old son, and I would like to see him get married one day, and possibly be a Grandparent. Thanks for any help you can give me.

      • Thank you, Katherine for sharing your journey. I am starting the same process you went through. I have family history of heart disease so, I decided to ask general physician for Peter’s recommended blood tests. I had to educate him on the tests. It turns out, my LP(a) is over 400. I seem to be healthy on the outside with a BMI of 23, but have elevated cholesterol, blood sugar, joint pain and extreme fatigue. I am scheduled for a CAC this week. I’m scared and this is a learning journey for me but I’m thankful I can be proactive.

    • “…switching back to oral estradiol” – would love to hear more about that! I am on transdermal estradiol, so far no beneficial impact on my elevated lp(a). Wondering whether switching is worth the added risks…?

    • Hi Mims,
      After listening to podcast #42, I just started HRT, after 4 years of menopause. I decided to go with Premarin (0.5mg) and Progesterone(100mg). I see that you are taking estradiol? Do you have any feedback on my choices?

      Best,
      Helena

  4. Friends, I am in the same camp as you all… A physically fit, 50 year old…. Mom of o seven year old…. family history of strokes, brain hemorrhages, cvd. I started to request my own blood work when I started to see the elevated cholesterol fearing that something more wasn’t right because my diet as an athlete has been well controlled, mainly whole foods, some lean protein. It seemed unlikely that the rising number were due to diet or lack of exercise. As I dug a little deeper and got my lp(a) number ( 390), I got really worried and sought out a cardiologist. Like you Debra, I had always seen myself as the picture of health but suddenly I find myself on high doses of Lipitor and niacin with a baby aspirin in the side. I have played with keto before, but like a couple of you said, it makes the situation worse for me. I have gotten to the point of measuring my oil and going fully plant based except for occasional fish… To the other extreme…. It is helpful to hear what other interventions you all have tried. I am starting to wonder if limiting my oil so drastically is counterproductive as my HDL is dropping precipitously now. Like you Debra, I desperately want to see my son grow up and graduate. It has been a hard road but it makes me feel more supported to know that there are others of you out there. Anything you can offer is appreciated as is this podcast. (I always learn so much here). This is such valuable information and not as well publicized in general media outlets as it should be

  5. In the intro to lipoproteins, you state that LDL is about 20 nm in size, which is easily able to pass through the endothelium. However, I am having difficulty understanding this as the endothelium is connect by adherens junctions, which prevent the passage of proteins 3.6 nm or larger [1]. It seems to me more plausible that they enter through the vasa vasorum, where there are fenestrations that allow the passage of proteins up to 50-60 nm [1]. Also histologic slides of the coronary arteries show that the endothelium is multiple layers thick [2-3], contrary to the commonly held idea that it is only 1 layer thick, making it further implausible that the lipoproteins enter from the endothelium. Can you elaborate on your statement that LDL easily passes through the endothelium?

    1. https://www.ncbi.nlm.nih.gov/books/NBK54116/
    2. https://www.sciencedirect.com/science/article/pii/S1359644616301921
    3. https://tbiomed.biomedcentral.com/articles/10.1186/1742-4682-9-11

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