Cholesterol Experts Say Everyone Needs a LP(a) Test

#41

No as interventions currently are not supposed to make any substantive difference.

Both my wife and I and 35-40% of my patients on Quest CardoIQ are simply <10 mg/dL

There are a smattering in the middle and then a group well north of 75 mg/dL.

I guess this continuum must be addressed as there is no cutoff and simply being low I’d great.

If higher, it just increases relative risk.

I’d really encourage folks to listen to the latest Simon Hill on The Proof Podcast with the lipidolgist and the lean keto . I thought it would add much to my knowledge . I was wrong. Added a real appreciation for monitoring through imaging rather than necessary treating if no evidence of vascular disease.

Spend the time looking at this … it is a fascinating education. The point isn’t the ketogenic diet. The point is how to assess vascular disease risk.

Also, the concept of citizen scientist. This is so relevant to this platform. This fellow has no formal medical training and is an incredible expert. We have individuals on this platform who aren’t dissimilar.

Https://youtu.be/gfzxnz1sdi0

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#42

What a fantastic conversation. The 1.5 hours (at 2 x speed), will pay some dividends throughout life along with some other podcasts like the ones Peter Attia had with Allan Sniderman and Thomas Dayspring. The way I heard it is that Cromwell was for treatment even if no evidence yet of detected disease multiple times although he did remark a few times that taking CAC can be used in that way. Parts of the conversation are to different audiences. Those skeptical of LDL and are LMHR going to astronomical LDL it is better they start treatment because of positive CAC than if not. Positive CAC is advanced disease according to Sniderman and I would rather try to prevent or delay getting a positive CAC. He is basically telling a smoker to quit smoking when they get lung cancer, which is good when there are a large audience who believes smoking doesn’t cause lung cancer.

image

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#43

First - can I get the source of those graphs. I need them for my database!

You are right - this is a fascinating conversation, and is actually going to have me tweak my approach here and offer patients a reasonable alternative to saying that we must treat bad lipids. I will tell them much like Dr. Cromwell that I think it is safest to goal a lifelong apoB of 70 if Lp(a) is negative, and 50 if Lp(a) is positive so long as there is no established vascular disease.

However, for those who for whatever reason – and I still don’t understand the social contagion that has led to this, don’t want to manage this - then there is a sensible second option - but once there is evidence of plaque … my advice will become more intense to manage this before it becomes symptomatic.

Just a great discussion between these two really smart individuals.

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#44

I was searching for this awhile ago and couldn’t find any, until I realized Google Images understands what is in the images in its database (including graphs), it seems, so then it became easier.

https://www.researchgate.net/figure/Distribution-of-coronary-artery-calcium-scores-among-men-and-women-on-a-logarithmic_fig1_8383857

This one seems also good:

https://www.newportbodyscan.com/ebt-coronary-calcium-scoring-guide/

CACWomen
CACMen

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#45

Well, I, for one, HATE those graphs :slight_smile: But i have a CAC of almost 500 (and by now, probably greater… grrrr)…

Any ideas for me?

I’m on repatha, eat a WFPB diet, have eliminated almost all coconut oil for it’s sat fat, have significantly reduced most added sugars, trying to eat for fewer large glucose spikes, great weight… I should exercise more … other than that, is there anything aside from prayer?

#46

Wow! A year ago Lp(a) wasn’t even on the radar of most of us and our doctors, and now it is A THING! I credit Peter Attia with first alerting me to it. Got tested and found it was 40 mg/dl. Here’s some N=1 experience since that time:

–Got a CAC score: 0.96. I am sure it would have been zero if not for having had the higher Lp(a) working on me for 74 years. Other lipids were good. Lifestyle/behavior all what they are supposed to me. I am sure my cardio situation is 100% genetic.

–Started Repatha which lowered Lp(a) to 29. But – glucose which had already been a little high (for years) now higher and Hb A1C into pre diabetes so asked for insulin and C peptide measurements. Which came back off the charts low. Message – if you are lucky enough to get on to Repatha – monitor your glucose and insulin. Driving down PCSK9 can impact the pancreas. The sequence by which an endogenous too-low level of PCSK9 causes the pancreas to reduce insulin is well documented. But that this can happen if you reduce exogenously with PCSK9i/Repatha --not so much. Tom Dayspring has said there are no risks to taking Repatha. Not. I am sure this is what happened to me as now numbers are starting to creep back up but still low, after having stopped the Repatha. (I do think that the Repatha might have further provoked what I feel might be a simmering LADA, which I have to get confirmed).

–Drive down inflammation – important for all health metrics, but especially for Lp(a) which is less harmful in the setting of very low overall inflammation. Depends of course on how high Lp(a) is. I exercise daily but am turning it up and swimming/using hot whirlpool three times a week instead of two. Of all the interventions, I personally have found that exercise and the heat shock proteins seem to be the most effective for reducing inflammation. (but have also stopped all alcohol and doubled down everywhere I can).

–Tell your children to get the Lp(a) checked. My son, it turns out, has it worse than I do.

–consider getting genetics tested. I did, after I discovered the Lp(a), and I found I had a 9p21 (C;C) variant: meaning homozygous for the risk allele, meaning --unusually susceptible from damage to arterial wall from inflammation and epithelial inability to repair. Don’t know it this is tied to the Lp(a) or a further additional instigator. from Promethease: " a recent study has shown that genetic variants in 9p(21) interfere with the interferon signaling pathway and effect the repair response of vascular epithelial cells to inflammation thus accelerating the pathological process of atherosclerosis leading to CAD." This single mutation puts me at 1.9x risk for cardio events.

–Surprised by all of this, as prior to the Lp(a) discovery, and subsequent genetics testing and CAD score I did not have a clue, other than some family history-- grandmother with diabetes and father died early from stroke – which I conveniently ignored as having been repeatedly told by doctors that my numbers were great and I was so healthy.

–I don’t know how to calibrate my overall risk – the contribution of (my overall very good)lifestyle versus (my abysmal) genetics for me personally – and would welcome any suggestions about this-- where to go for assessment.

–once again, N=1, YMMV, as they say. Hope this information may be helpful . . . .

PS: Rapamycin delivered a few days ago and debating whether to start . . . .even the very smallest dose.

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#47

I had my second dose last week and so far smooth sailing for me… fwiw!

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#48

Beth - yes, lots of things you can do. Do you have a specialist you see that understands all this? I can’t give individual medical advice on the board unfortunately. If you are in one of the states I’m licensed, I’d be happy to take a quick review of data (off board) and give you some free formal advice, but if you are outside of the 4 states I’m licensed in, I’d not be able to do more than provide general approach advice. Either way, message me and I can at least give you some general input, or if you are in AZ, CA, KY, TN then I can give you specific advice.

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#49

Just finished watching that 3hr youtube discussion and yes, I learned a lot. Cromwell was excellent…clear, logical and to the point…the other 2 - not so much. Just brief mentions of Lp(a). But clear on the importance of other factors, mainly metabolic syndrome (BMI), blood glucose control, inflammation and blood pressure. And clear on the progression over time…that LDL may fluctuate up and down but that it’s the amount of time that it stays high that matters.
I unfortunately don’t have any blood tests from before my recent ones to know my history of LDL/ApoB levels, so I would need a CT coronary angiogram to really know my plaque levels. That might help me decide if I should be taking a daily low dose aspirin. All my other risk factors - blood pressure, HbA1c, HsCRP, BMI - look good and my ApoB/ApoA1 ratio is an acceptable .587. So, like @Deborah_Hall , if I hadn’t gotten an Lp(a) test, I would have been unaware of any problem.
How does the CAC test compare to the CT coronary angiography in terms of cost and difficulty?

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#50

I’m in CA… I’ll pm you :slight_smile: And thank you!

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#51

I also have just received my rapamycin and acarbose but decided to wait and assess the effects of just starting atorvastatin on my lipids and/or possible side effects before complicating it with rapamycin.
Here’s an article on the relationship between Lp(a) and blood pressure:
“Upon analysis, results indicated there was no increase in risk for cardiovascular disease events for those with elevated Lp(a) and no hypertension relative to their counterparts without elevated Lp(a) and no hypertension in fully adjusted models (HR, 1.09 [95% CI, 0.79-1.50]).”

https://www.hcplive.com/view/elevated-lp-a-can-increase-cardiovascular-risk-in-people-with-high-blood-pressure

Also this one on aspirin:
" Conclusions
Aspirin use was associated with a significantly lower risk for CHD events in participants with lipoprotein(a) >50 mg/dL without baseline CVD. The results of this observational propensity‐matched study require confirmation in studies with randomization of aspirin use."

https://www.ahajournals.org/doi/10.1161/JAHA.123.033562

#52

CAC score is inexpensive and mine was covered. Have not had angiography. It is expensive. Had echo cardiogram with normal results. This shows function as in ejection fraction

#53

Thanks. What was unclear in my reading about Lp(a) was whether the reduction in Lp(a) that you get from taking PCSK9 inhibitors actually resulted in a reduction in heart disease events or ACM compared to reducing ApoB (lipids) with a statin, bempedoic acid, ezetimibe or combination to get your ApoB to around 50. (even if Lp(a) went up slightly)

#54

In the ODYSSEY OUTCOMES trial in patients with recent acute coronary syndrome (ACS), the proprotein convertase subtilisin/kexin type 9 inhibitor alirocumab reduced lipoprotein(a), low-density lipoprotein cholesterol (LDL-C), and cardiovascular events compared with placebo. This post hoc analysis determined whether baseline levels and alirocumab-induced changes in lipoprotein(a) and LDL-C [corrected for lipoprotein(a) cholesterol] independently predicted total cardiovascular events.

Alirocumab-induced reductions in lipoprotein(a) (median −5.0 [−13.6, 0] mg/dL) and corrected LDL-C (median −51.3 [−67.1, −34.0] mg/dL) independently predicted lower risk of total cardiovascular events. Each 5-mg/dL reduction in lipoprotein(a) predicted a 2.5% relative reduction in cardiovascular events.

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#55

Looked into a bit more - does look light this might work in a big way, at least in some populations:

While earlier studies suggested that Lp(a) serum levels are mostly determined by genetic factors (7., 8.), several recent reports indicate that Lp(a) is also induced by mediators of the innate immune system (9., 11.).

IL-6 blockade might be a potential therapeutic option to treat elevated Lp(a) serum concentrations in humans and might be a noninvasive alternative to lipid apheresis in the future.

In a recent clinical study of our group, we have shown that TCZ lowers Lp(a) serum levels in RA patients by up to 50% (14.). This was confirmed recently in an independent cohort (15.). Due to this finding, one may consider modern anti-cytokine therapies as a new promising approach for lowering Lp(a) levels in affected patients as an alternative to the much more invasive lipid apheresis.

@DrFraser @Davin8r - any thoughts on whether this might be something to look into more?

Especially now that generics/biosimulars are coming online and the price hence likely to drop a lot.

Additional papers i found below and earlier post here: Cholesterol Experts Say Everyone Needs a LP(a) Test - #40 by Neo

IL-6 blockade by monoclonal antibodies inhibits apolipoprotein (a) expression and lipoprotein (a) synthesis in humans

https://www.jlr.org/article/S0022-2275(20)31243-8/fulltext

Effects of inhibition of interleukin-6 signalling on insulin sensitivity and lipoprotein (a) levels in human subjects with rheumatoid diseases

Effect of interleukin-6 receptor blockade on surrogates of vascular risk in rheumatoid arthritis: MEASURE, a randomised, placebo-controlled study

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#56

Thanks for a rich post. Can you talk more to the part I quoted above - is it a known risk of PCSK9i?

#57

From Journal of Biological Chemistry, 2022 “Proprotein convertase PCSK9 Affects Expression of Key Surface Proteins in Human Pancreatic Beta Cells…”

After discussing the role of (endogenous) PCSK9 in the pancreas, the authors state “It would be interesting to determine if PCSK9 monoclonal antibodies or siRNA affect levels of expression of LDLR and VLDR …in pancreatic beta cells.”

So no, there is only conjecture, to be fair, that the PCSK9i meds would have a similar effect as an endogneous reduction of PCSK9. It has not been demonstrated.

Except perhaps my me? While still on Repatha, I asked to have insulin measured on 4/11. It was <2. Stopped Repatha, On April 15, Insulin was 3 and CPeptide was 1. By April 29th Insulin was 5 and C Peptide was 1.2. Glucose went down as well. So insulin still low but coming back.

So, am I unique, a rare outlier? or a canary?

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#58

And no there is no connection between the PCSK9i and LADA – I just meant that I think I may have had or have a very indolent case of LADA for a very long time, that has been undiagnosed, and that the Repatha may have exacerbated it? or may-be just focused my attention to the extremely low insulin? but the fact that the insulin and C Peptide seem to be normalzing now that I have been off the Repatha suggests that the Repatha had an impact on the pancreas independent of any existing underlying type 1 diabetes thing that I may or may not have going on. To be continued . . .

#59

Il-6 is part of SASP also it drives CRP so reducing senescence could cut lp(a)

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#60

I’m not sure I understand, doesn’t insulin or C-peptide only matter in relation to how much glucose you had at the same time? Were you also fasting exactly 12 hours before each test (not longer or shorter as it influences the result)?