#41

The study showed improvement in diabetics post MI, but use may be expanding.

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#42

Thank you so much for your response. You asked if there were some other risk factors. I have genetic risk, specifically homozygous for the risk allele (C;C) on 9p21 which puts me at 1.9x risk for cardiac problems ad stroke, and also homozygous (G;G) on RS 2383206 which also raises risk for CAD, and also high blood glucose. Also family history of early stroke and cardio death. My lipids are OK except for exceptionally high HDL (125 mg/dl) – don’t know what to make of that. APOB around 90-95 and low Trigs. Heart function is good. BP is good. BMI of 19.

I had read that risk from Lp(a) starts at 30. I cannot be sure but I believe that whatever plaque I do have has resulted from 70+ years exposure to this level of Lp(a) , exacerbated by the genetics. “The9p21 gene has been shown to be a independent predictor of cardiovascular risk. Carriers have a 1.5-2.0 fold risk of CV disease (particularly stroke and abdominal aortic aeurism) compared to non carriers.” The mechanism seems to be that the aortic walls are more susceptible to damage from inflammation while also being less able to repair damage. I take lysine, proline and baby aspirin (among others) and am doing all the right things re diet and exercise. Have been for decades. Working to get inflammation down (It was down from nearly 2 to 1.1 at last reading), and also get glucose down – was mildly pre diabetic (H1AC of 5.7 but now 5.5). This also seems to be driven by the genetics. I do comprehend that my risk is “low” even with the evidence of some plaque on the LAD, and that even doubled because of genetics, the risk is not “high”. But it surprised me to discover that I had any risk at all. Before one year ago this wasn’t even on my radar. Thank you again and of course would very much appreciate your comments. It is so helpful to have your perspective.

#43

So risk is interesting. But you have a way to measure if you actually have disease. If you’ve made it to 70+ years without evidence of disease, then I’d personally be thrilled. Risk doesn’t = Disease. The problem is when you can’t measure if your risk has actually generated any disease - but here we can.
If what I know about you - and it is limited, obviously, but on the face of it, I’d be looking at having APOB in the 70’s for life and being grateful none of this risk has actually generated disease.
Naturally talk with your doctor - but if this is as presented, I’d just be doing the usual, optimized BP, no reason to go crazy on lipids, optimize glucose control/insulin sensitivity, diet, sleep, stress … and wait to be 100 or so.

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#44

Thank you so much Dr. Fraser. Your response has greatly reduced the level of worry I have been carrying. As I wrote in another post, I wish there were some model that would consider all inputs – lipids, Lp(a), BP, lifestyle, genetics, metabolic health – and grind out a data-based holistic assessment. In the absence of such a model, a response such as yours is so appreciated and so valuable. My cardiologist sees numbers and sees guidelines and wants to treat, and to be sure, I do need some meds to get APOB down. But maybe because you are not my cardiologist, you have been able to better assess my overall situation, even with the limited data I have shared. Under my pillow going forward: “Risk doesn’t = Disease.”

Thank you!

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#45

在 @DrFraser ’s point… I have a ton of risk (I actually have a lot of plaque) and even my cardiologist tells me my stress about it is more dangerous than my plaque!!!

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#46

I just asked my local cardiologist (not Dr. Tsimakas) to prescribe it to me given I was concerned about inflammation. My CRP has always been less than 1 but my GlycA score was high and I wanted to see if it could reduce GlycA. I will be able to see in next labs in June if Colchicine has impacted GlycA.

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#47

Please post your results - it would be interesting to see the results of your use of colchicine, as I’m considering it also.

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#48

This is the first I’ve ever heard about the GlycA test! My HS-CRP has always been low, but GlycA seems like a much better test. Looks like that will be next on my blood work agenda…

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#49

Hi, I’d recommend becoming a member of this group:

and sharing your story over there. Check out the pinned/featured posts.
There are some examples of folks who reversed their coronary calcification
(who also happen to be on Rapamycin). Your case is a tough one because you seem
to be doing all the right things.

#50

Let me know what your GlycA results are. I was always confident in my “inflammation” given my CRP was always low so my GlycA number (high) surprised me—hence trying to get it down and hoping the Colchicine does that.

#51

Your fasting insulin (18.8) looks high, and your HOMA-IR of 4.3 suggests you are insulin resistant. This could certainly be a contributing factor to lipid particle oxidation and heart disease. A low carb could be helpful in this regard.

Also, supplements that can potential lower LDL oxidation and have been shown to mitigate calcification growth would also be worthwhile (eg 2400mg daily of Kyolic Aged Garlic).

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#52

Are there any known downsides of the kyolic aged garlic?

Anyone else taking it / or considered taking it? I see that Bryan Johnson has been taking it.

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#53

Yes, one of the few things I still believe in. I still take 250mg Niacin with meals too. Of course tree bark and gotu cola.

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#54

Do you perceive any benefits from the gotu kola?

#55

No, I’m going on faith in the papers I’ve read. French Maritime pine bark and gotu cola is pretty well researched.

#56

As always, thanks for the info.

#57

Discussed a bit more below - and cheap via labcorp / Marek it seems

#58

Lp(a): Your significantly elevated Lp(a) level (285 nmol/L) is likely a major contributor to your ongoing risk. Lp(a) is an independent risk factor for coronary artery disease and is not effectively lowered by statins or lifestyle changes. The Olpasiran trial you participated in, which lowered your Lp(a) to 179 nmol/L, is promising, but levels below 75 nmol/L are considered optimal. Perhaps consider PCK9-i for some additional drop, which can reduce Lp(a) levels by 20–25%.

LDL-C: Your current regimen of high-intensity statin and ezetimibe is a good start, but consider discussing with your doctor whether additional lipid-lowering therapies (such as PCSK9 inhibitors) may be appropriate to further reduce your LDL-C to less than 30. You can try replacing Ezetimibe with this one.

High Insulin and HOMA-IR: Consider insulin sensitizing drugs like metformin, low dose pioglitazone, acarbose etc., which also might be life extending in general.

What tests can I do to catch the progress of plaque proactively?

  • Carotid Intima-Media Thickness Test (CIMT) can be used to measure the thickness of the inner two layers of the carotid artery, giving an indication of atherosclerosis.
  • Intravascular Ultrasound (IVUS) and Optical Coherence Tomography (OCT) are two advanced imaging techniques that can provide detailed images of the inside of the arteries, helping to assess plaque buildup and characteristics more accurately than traditional imaging.
  • Regular CT angiograms or stress tests can also help monitor the condition of your arteries and heart function.

Supplements:

  • I’m a big fan of supplements like 3-4g fish oil (to control inflammation), digestive enzymes (to help with loss of proteolysis) – they have some evidence of plaque reversal,
  • Track and control inflammation. Ideal HS-CRP is negligible (<0.2). Anything above can be further treated to bring it lower.
  • I personally take Kyolic Garlic Extract which has some evidence of slowing down plaque buildup.

Many many references in the Facebook group mentioned above (Heart Disease - Optimal Prevention and Management).

Best.

5 Likes
#59

Thx for the rich post

Can you discuss this a bit more

#60

Proteolysis, the enzymatic breakdown of proteins, is vital for cellular health and function. Its decline is linked to several age-related issues. A primary effect is the loss of muscle mass, or sarcopenia, which occurs as damaged proteins in muscle cells accumulate due to reduced proteolytic activity. This leads to muscle weakness and loss (Source 1, Source 2).

Decreased proteolytic activity also contributes to protein aggregation in neurodegenerative diseases like Alzheimer’s, characterized by the buildup of misfolded proteins. Normally, these proteins are degraded by proteolytic enzymes. A reduction in this activity results in the formation of plaques typical of various neurodegenerative diseases (Source 1, Source 2).

Additionally, impaired cellular function can stem from a reduction in proteolytic activity with age. Proteolysis is crucial for degrading damaged or obsolete proteins, maintaining cellular balance. When this function declines, protein buildup impairs cellular operations, contributing to aging and related diseases (Source 1, Source 2).

Proteolytic activity also impacts atherosclerosis, or arterial plaque formation. Proteolytic enzymes are essential for degrading the arterial wall’s extracellular matrix. A balance disruption in these enzymes can lead to plaque development, arterial thickening, and reduced elasticity, exacerbating atherosclerosis (Source 1, Source 2).

Nattokinase, a proteolytic enzyme, is linked to plaque reversal at high doses and interacts with plasminogen activator inhibitor-1 (PAI-1), influencing longevity. Less PAI-1 production correlates with a 7-year increase in lifespan. Overactivation of PAI-1, which inhibits proteolysis, is common in numerous diseases. Inhibiting PAI-1 can significantly alleviate conditions like fatty liver and dyslipidemia, activate the longevity molecule FGF21 fivefold, and reduce PCSK9 (Source 1, Source 2, Source 3).

Success stories about reversing plaque (CAC score) by lowering LDL levels and using high-dose nattokinase supplements have been reported. Moreover, products like Wobenzym have shown potential in lowering elevated TGF-beta, found to be rejuvenating in mice (Source 1, Source 2).

In conclusion, maintaining robust proteolytic activity is essential for managing age-related conditions such as sarcopenia, neurodegenerative diseases, cellular dysfunction, and atherosclerosis. Targeting molecules like PAI-1 and using proteolytic enzymes like nattokinase might offer viable therapeutic strategies to enhance longevity and healthspan.

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