210 - Lp(a) and its impact on heart disease | Benoît Arsenault, Ph.D.& Peter Attia, M.D.

Benoît Arsenault is a research scientist focused on understanding how lifestyle and genetic factors contribute to cardiovascular disease risk. In this episode, the discussion casts a spotlight on Lp(a)—the single most important genetically-inherited trait when it comes to atherosclerotic cardiovascular disease (ASCVD) risk. Benoît explains the biology of Lp(a), how it’s inherited, the importance of measuring Lp(a) levels, and the diseases most associated with high Lp(a). He dives into data on the possible treatments for lowering Lp(a) such niacin, statins, and PCSK9 inhibitors, as well as the most exciting new potential therapeutic—antisense oligonucleotides.

We discuss:
0:00:00 - Intro
0:00:08 - How Benoît came to study Lp(a)—a new marker for cardiovascular risk
0:04:43 - The relationship between Lp(a) and CVD risk
0:15:08 - What genome-wide association studies (GWAS) revealed about Lp(a)
0:21:54 - Clinical tests to measure Lp(a)
0:26:11 - The biology of Lp(a)
0:29:52 - How statins lower LDL-cholesterol and why this doesn't work for an Lp(a)
0:35:20 - The structure of LDL-p and Lp(a) and what makes Lp(a) more atherogenic than an equivalent LDL particle
0:46:00 - The role of Lp(a) in aortic valve disease
0:52:24 - How greater numbers of Lp(a) particles are associated with increased risk of disease
0:56:56 - The genetics and inheritance of Lp(a) and how and when to measure Lp(a) levels
1:07:30 - Niacin and other proposed therapies to lower Lp(a), apoB, and CVD risk
1:22:46 - Why awareness of Lp(a) among physicians remains low despite the importance of managing risk factors for ASCVD
1:28:36 - The variability of disease in patients with high Lp(a)
1:37:45 - Diseases most associated with high Lp(a)
1:48:05 - The biology of PCSK9 protein, familial hypercholesterolemia, and the case for inhibiting PCSK9
2:04:58 - The variability in PCSK9 inhibitors’ ability to lower Lp(a) and why we need more research on individuals with high levels of Lp(a)
2:10:38 - Peter’s approach to managing patients with high Lp(a), and Benoît’s personal approach to managing his risk
2:13:33 - Antisense oligonucleotides—a potential new therapeutic for Lp(a)

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The Peter Attia Drive is a weekly, ultra-deep-dive podcast focusing on maximizing health, longevity, critical thinking…and a few other things. With over 40 million episodes downloaded, it features topics including fasting, ketosis, Alzheimer’s disease, cancer, mental health, and much more.

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[knatay]

I am so thankful for this information. I got a lipid panel with a wholistic MD a couple years ago as part of a wellness check and was told that all of my numbers were great, but I noticed the LP(a) number was off the chart (105 mg/dl)... When I asked my doctor about it he said it wasn’t anything to be concerned with because it was just something I inherited and couldn’t do anything about. So I never thought about it again until reading Outlive. I’m 35 years old and am so grateful to have read this book. Before reading it I was under the impression my risk for cardiovascular disease was was very low. Now that I know what I’m up against, I can pay special attention to mitigating other CVD risk factors…and stay on top of any new developments that come about

[michaelhimes]

Well, as someone who just got LPa tested at 234 nMol/L, I can say this is a much appreciated but very discouraging conversation.

[nicoad]

Wonderful discussion, thank you for addressing this big issue that the vast majority of cardiologists and GPs do not care to look into and when you ask them to do those tests mentioned they do not really want you to do. This will include the Lipid Subfractions

[erker]

good discussion
I worked in Cardiology research for 20 yrs and am glad, that Peter makes these interviews public

[traciholland]

I've listened to over 50 talks on this matter, not to mention addicted to Dr Attia's talks and it's this talk that's convinced me to subscribe to membership 🙌🏻 I must also say that I had to describe what LPa and APOb was to my doctor!!

[purpleblueunicorn]

So proud to see all this research from Quebec. Also studied engineering at Laval University, but this fascinating discussion is way above my understanding. Really grateful you do them. I'm definitely going to ask for my LPa and apoB tested. Been WFPB for 7 years and high level endurance athlete and never tested since, but all previous tests I had high LDL, so does my family.

[senseofwonder]

This is a gift! Thank you for sharing your immense knowledge.

[robertjackson]

One of your best yet. Masterfully brought the complexities of the subject to a very understandable level. Even at 1.2x speed :-)

[CarnivoreAnesthetist]

Statins definitely lower, LDL and APO B.. PSK9 inhibitors obviously do the same thing, but even more pronounced! So riddle me this, why is cardiovascular disease still the leading cause of death. It makes tjis last pandemic look like child’s play. I think it’s much more complicated. I believe clotting, Blood pressure, metabolic disease, pre-diabetes. And constantly high insulin levels played in a bigger role. When I used to do heart anesthesia, I would say 60% of my patients for coronary artery bypass graft surgery had normal LDL’s. However, they were metabolically broken. So I don’t think we have all the answers. However, not sure driving LDL down to the 30’s is a good idea. It might be. However, I don’t think it’s that simple.

[optimisticfuture]

I have elevated lipo protein A .. found out after having stents for 80+ occlusion in multiple coronary arteries. Found out after being blown off by my physicians. I’m fit thin. Ride my bike. My brother/ mother died of SCD so I pushed the issue. Now post stent am refractory to statins and on Repatha

[Peter-vnjq]

Checked my Lp(a) just recently, after hearing about it a lot. My levels were undetectable- below the threshold of the lab, at any rate. I found that quite pleasing and reassuring, ngl. I didn't even realise a "you have so little our lab equipment just throws up a zero" result was a possibility.

[AdnAwd]

Thank you so much for this informative episode, under appreciated topic indeed.

[whobdis]

I thought part of the lack of benefit from the Niacin(Niaspan) test was due to the addition of chem that reduced flushing. Either way..if something reduces LPA, and LP(a) and increases HDL yet provides no benefit one must question whether the numbers mean much of anything (at least in terms of reducing risk)

[d.e.b.]

Really helpful — thank you for posting this

[drdonavon]

what percent of all clinical atherosclerosis is caused by elevated lp(a)?

[georgesoul]

omg I'm 58 and have been waiting for a treatment for 2 decades now :( I've tried getting in the trails but there is not one near me :( I'm the oldest living male in my family by 10 years with high lpa. I guess I'm lucky to live this long... but I'm waiting for a treatment still.

[donwinston]

I've got extremely high LP(a), about 100 points above the reference as stated by Quest Diagnostics. From what I understand there's not much I can do about it (because it is almost completely genetic) except try to lower my LDL cholesterol as much as possible.

[eyera]

Most cardiologists ( nevermind other specialties) are so inadequate that it is truly embarrasing. Medical decision making over a lifetime is the leading cause of mortality and morbidity.. There is no getting around it, if you value your life and health, make properly informed choices.
Ira Goodman MD

[DrTomMD]

1:07:20 - as one who’s both parents had normal Lp(a) but mine very high, I’m totally aligned. Check before 18, and in light of the potential that estrogen may mitigate (mask/lower) levels, before first menses in girls.

[eibnt]

Very informative podcast... For info, here in the UK the experience of me and people I know is that on average GPs are extremely reluctant to offer either ApoB or LP(a), unless you get lucky with a GP who is either really open minded or up to date on the research.