Cardiovascular Health 2025

#61

Dayspring and Attia on cardiovascular health.

This week, on episode #334 of The Drive, Peter sits down with Tom Dayspring, M.D., a world-renowned expert in clinical lipidology and a previous guest on The Drive.

In this episode, Tom explores the foundations of atherosclerosis and why atherosclerotic cardiovascular disease (ASCVD) is the leading cause of death worldwide for both men and women. He examines how the disease develops from a pathological perspective and discusses key risk factors, including often-overlooked contributors such as insulin resistance and chronic kidney disease. He breaks down the complexities of cholesterol and lipoproteins—including LDL, VLDL, IDL, and HDL—with an in-depth discussion on the critical role of apolipoprotein B (apoB) in the development of atherosclerosis. Additionally, he covers the importance of testing various biomarkers, the impact of nutrition on lipid levels, and the vital role of cholesterol in brain health, including how cholesterol is synthesized and managed in the brain, how it differs from cholesterol regulation in the rest of the body, and how pharmacological interventions can influence brain cholesterol metabolism.

They also discuss:

  • Defining atherosclerotic cardiovascular disease (ASCVD): development, risks, and physiological impact
  • The pathogenesis of ASCVD: the silent development over decades, and the importance of early detection for prevention of adverse outcomes
  • How aging and lifestyle factors contribute to rising apoB and LDL cholesterol levels, and the lifestyle changes that can lower it
  • How statins might affect brain cholesterol synthesis and cognitive function, and alternative lipid-lowering strategies for high-risk individuals
  • More
6 Likes
#62

I watched/listened today… it hurt my brain :slight_smile:

#63

If you are more or less familiar with the basics of what ApoB is and atherosclerosis, you can safely skip about the first half of this video - nothing new here that hasn’t been beaten to death. More detail and interesting information, in particular about cholesterol metabolizm in the brain is in the second half, and the closer toward the end, the more interesting it got - I certainly learned some new stuff. YMMV.

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#64

A new study found severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection was associated with the rapid growth of plaque in the coronary arteries and an increased risk of cardiovascular events. The results were published in Radiology .

More information: SARS-CoV-2 Infection Association with Atherosclerotic Plaque Progression at Coronary CT Angiography and Adverse Cardiovascular Events, Radiology (2025).

Open access paper: https://pubs.rsna.org/doi/10.1148/radiol.240876

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#65

That’s a timely release, I just tested positive for COVID this morning and I also have severe CAD.

The short summary is that it’s the inflammation that is the likely driver of that increase and that the inflammation can persist for at least 1 year (They don’t have data for a longer period). I found elsewhere that inflammation can persist for 3 years or more.

Inflammation contributed to plaque progression:
• Causal mediation analysis suggested PCAT inflammation accounted for 10.3% of total plaque growth and 5.7% of noncalcified plaque growth .
• Suggests persistent inflammation post-COVID-19 plays a role in coronary disease progression .

The whole paper is interesting BTW.

So let’s test the inflammation (hsCRP) post COVID and make sure it’s back to normal.

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#66

Agreed - the first half is a rehash of stuff already covered in this thread. But, I found the talk about the role of cholesterol in the brain very interesting. I’ve lined up the podcast for this section below:

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#67

At the end they said no one will fund statin trials to see if they prevent dementia.
The NIH is doing this with PREVENTABLE, cost $70 or 90 M iirc. STAREE in Australia.
Both testing atorvastatin to prevent dementia.

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#68

Well, insofar memory formation is implicated in dementia I am not optimistc when it comes to statins:

The Effect of Statin Treatment on Synaptogenesis in the Hippocampus

“Deranged lipid homeostasis has been implicated in neurodegenerative diseases. Cholesterol reducing compounds such as statins have received special attention for the possibility that they may be able to ameliorate or prevent cognitive loss associated with neurodegeneration. However, there is much dissension concerning the actual effect of statins on cognitive function. The aim of this study is to investigate the effects of pitavastatin on hippocampal synaptogenesis because the hippocampus is crucial for memory formation. We also evaluated the effects of pitavastatin on local hippocampal estrogen synthesized in the hippocampus itself and its effect on Brain-Derived Neurotrophic Factor (BDNF). Using a hippocampal cell line, H19-7, we found that hippocampal neurons exposed to pitavastatin demonstrate a significant reduction in the synaptic marker postsynaptic density protein 95 (psd-95). The pitavastatin treated neurons also exhibited decreased production of local estrogen and their expression of BDNF mRNA was decreased. These results suggest that statins reduce the ability of hippocampal neurons to form synapses by restricting the production of local estrogen. Because neural connections in the hippocampus are crucial for memory formation, our findings implicate statins as medications that may compromise cognitive function.”

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#69

Mechanistic, in vitro, studies are second lowest on the evidence hierarchy. It can pretty much be thrown in the garbage bin for that reason.

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#70

Which is why I don’t think it’s dispositive, but I’m not optimistic. Of course, I’m awaiting trials, but not holding my breath. YMMV.

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#71

As non-primary endpoint in trials all statin trials have either had a neutral or positive effect on dementia. The largest study ever being done in older adults in America is atorvastatin, so they have a good reason for choosing it. Who knows.

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#72

The acetyl-coa metabolism is clearly relevant to memory formation.

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#73

But if it’s not, how to drive it down? :man_shrugging:

Colchicine recently failed in a trial.

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#74

hsCRP ← IL-6 ← SASP

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#75

There are several papers on peptides like Thymosin alpha 1 for instance:
Thymosin alpha 1 restores the immune homeostasis in lymphocytes during Post-Acute sequelae of SARS-CoV-2 infection

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Here is what I got from prompting ChatGPT o3 about peptides to go along with Paxlovid for COVID:

Acute Phase (Days 1–5)
• Primary Goals:
• Focus on rest, hydration, and basic immune support.
• Peptide Focus:
• Thymosin Alpha 1: Initiate early to support a balanced immune response.
• LL-37: May be considered if early antiviral/antimicrobial support is indicated.

• Symptom Monitoring:
• Daily check of oxygen saturation, body temperature, and overall energy.
• If symptoms worsen, consider postponing additional peptides (BPC-157, Ac-SDKP, CJC-1295, Ipamorelin) until stabilization.

Subacute Phase (Days 5–14)
• Primary Goals:
• Gradually support tissue repair and reduce inflammation while monitoring recovery.

• Peptide Focus:
• BPC-157: Introduce for tissue repair if inflammatory symptoms (e.g., muscle soreness, gut discomfort) are noted.
• Ac-SDKP: Begin dosing to help mitigate fibrosis risks, especially if there are lingering respiratory or cardiovascular concerns.
• CJC-1295 & Ipamorelin: Consider initiating these to begin anabolic support and prevent muscle catabolism as activity levels slowly increase.

• Maintain Thymosin Alpha 1 if immune support remains necessary.

• Symptom Monitoring:
• Evaluate progress with markers like reduced inflammation, improved energy, and stable respiratory function.
• Continue checking vital signs (heart rate, oxygen saturation) and subjective measures (energy levels, muscle soreness).

Recovery and Return-to-Activity Phase (Day 14+)
• Primary Goals:
• Transition to a more active phase with gradual reintroduction of physical activity.

• Peptide Focus:
• Maintain CJC-1295 & Ipamorelin if anabolic support is still needed.
• BPC-157 can be tapered as tissue healing improves.
• Thymosin Alpha 1 might be reduced if immune markers are within normal limits.
• Ac-SDKP dosing can be re-evaluated based on any persistent lung or cardiac concerns.

• Symptom Monitoring:
• Monitor recovery with HRV (heart rate variability), resting heart rate, and lab tests (e.g., IGF-1 levels, inflammatory markers).
• Adjust exercise intensity based on recovery status, gradually increasing as tolerated.

I’m currently trying that along Paxlovid and I will test for hsCRP in a few weeks.

2 Likes
#76

I hadn’t seen the failed colchicine trial, so I’m glad you mentioned this. I just looked it up.

I started taking it when that study came out a couple years ago that showed it might be highly effective in reducing cardiovascular events.

On first glance, it appears that might not be the case.

Considering I’m taking it, I’d love for anyone to chime in if there is much downside to taking it anyway. In general, lowering inflammation sounds like a good thing, but perhaps there are downsides I don’t know?

@DrFraser ?

#77

Adding some info on LL-37 which looks useful for the COVID acute phase from undermind.ai:

LL-37 shows promise as a therapeutic peptide in mitigating inflammation and addressing immune dysfunction in COVID-19, with strong antiviral and immunomodulatory properties supported by preclinical studies and limited clinical evidence ([1], [3], [7]); however, no direct data exist on its clinical efficacy in post-COVID-19 patients or its long-term effects on inflammation resolution.

Critical Summary of Findings: 1. Evidence Supporting LL-37’s Antiviral and Immunomodulatory Effects:

  • Antiviral Properties:
    • LL-37 inhibits SARS-CoV-2 spike protein-ACE2 binding and disrupts viral membranes, effectively reducing infection in vitro and in animal models ([7], [8], [9]).
    • Vitamin D and niacinamide upregulate LL-37, enhancing its efficacy against SARS-CoV-2 across multiple variants ([5], [8], [9]).
  • Immune Modulation:
    • LL-37 reduces pro-inflammatory cytokines (e.g., IL-6, TNF-α) by modulating NF-κB and TLR4 pathways ([2], [6]) and inhibits neutrophil extracellular trap (NET) formation, mitigating thrombotic complications ([2], [4]).
    • LL-37 expression inversely correlates with COVID-19 severity, indicating its key role in immune regulation and outcome prediction ([3], [5]).

2. Clinical Evidence for LL-37 in COVID-19 Context:

  • A clinical study of oral LL-37 in hospitalized COVID-19 patients shortened viral RNA clearance time and improved recovery when administered early ([1]).
  • Observational studies link higher serum LL-37 levels to better disease outcomes, suggesting its potential as a biomarker or therapeutic adjunct ([3], [10]).

3. Gaps in Post-COVID-19 Applications:

  • No studies directly examine LL-37’s effect on chronic inflammation, tissue repair, or clinical outcomes in post-COVID-19 patients specifically.
  • Its potential to clear persistent viral antigens or modulate endothelial dysfunction in post-COVID-19 remains unexplored.

4. Remaining Challenges and Risks:

  • Safety concerns arise with prolonged LL-37 exposure, including risks of immune overmodulation or insufficient dosages ([1], [6]).
  • Translational gaps exist between acute COVID-19 and post-COVID contexts, requiring tailored clinical trials.

Concluding Insights:

LL-37 holds significant promise for modulating inflammation and supporting recovery in acute COVID-19 but lacks targeted research specific to the chronic inflammation and systemic repair challenges of post-COVID-19 conditions. Expanding clinical trials to focus on post-COVID-19 patients is critical to validate its potential in this context.

1 Like
#78

I like LL37 too. Have not tried, but don’t like needles and risk. I’m sure the risk is very small, but to me needles make risk.

Risk free options for Covid, or at least spike protein: Nattokinase, lumbrokinase I’ve taken a lot of this sort of a rotation, always taking one. I hesitate to type Ivermectin, but there it is. It is said to break down the spike, downside=0. The latest to claim defense against the dreaded spike is Pectasol, which is a no brainer since it kills cancer and heart disease (also ties up and eliminates heavy metals) and now ties up the spike protein receptors whatever that means. I’d like pectasol for the ITP, should work like mad. If it didn’t I’d stop taking it. Final one off the top of my head is Stamets mushroom defense, antiviral and boosts the NK. In the same vein, AHCC Kinoko platinum which brags on the label that 30 clinical studies show it maintains peak NK activity and immune response.

You can do these all at once, I do.

I like the stuff with low risk first. Good luck in any case,

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#79

I would like to see more research being done on Desmosterol and what else lowers/raises it.

#80

I’m not sure what failed trial this was. If for Covid-19 or lowering HsCRP in Covid-19, not an issue, as I’ve never had it on my list of things to do for Covid-19.

The discussion in an AHA Journal has a reasonable take on it in the context of those with CAD or even theoretically for those with need for primary prevention of CAD - it looks like a reasonable thing to be on, so long as no side/adverse effects.

The article goes through a nice history of colchicine and concludes “Colchicine lowers hsCRP and may decrease coronary artery plaque volume.”

1 Like