#1

Imaging studies and other tests provide evidence that statins promote atherosclerotic plaque calcification.

However, statins may also promote a more uniform distribution of the calcified plaque, thus lowering the risk of cardiac events.

As noted in the paper linked below:

“Most studies using imaging modalities and/or biomarkers have demonstrated that statins promote atherosclerotic plaque calcification in coronary and peripheral arteries in the long term, especially at high doses. Although such an effect seems detrimental at first sight, it has been associated with higher plaque stability and less adverse cardiovascular events. Presumably, statins promote favorable arterial and atherosclerotic calcification, which do not expand atherosclerotic lesions and attenuate their vulnerability.”

This suggests that statins actually promote premature but more uniform aging of the cardiovascular system. Reducing the risk of sudden cardiac events may come at a cost of accelerated aging.

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#2

I wonder if there is a threshold below which statin would not exhibit this effect.

#3

If you don’t take them your own body will naturally promote premature aging of your cardiovascular system :slight_smile:

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#4

:grin: (plus the required characters)

#5

cleerly-plaque-ischemia-11082024.pdf (561.3 KB)
CAC vs CCTA and Cleerly.pdf (716.6 KB)

I’ve copied 2 items I was sent from Cleerly that I think is useful in this discussion.

So if you look at the low risk through high risk plaques … the low density non-calcified is extremely high risk, the non-calcified (not low density) is the progression of the plaque getting stable and then calcified is the more stable plaque. For this reason - when looking at the second document, you’ll see why I’ve abandoned CT Cardiac Calcium testing; as it isn’t a useful study. It misses all the high risk plaque.

I particularly find the second paragraph in this document to have useful information, in the 31% of major cardiac events occur in patients with a CAC score of 0. Also, in patients (in these studies) with a CAC of zero, 41-53% of patients had significant plaque. So I no longer see any value from getting a CAC score and no longer advise it.

Statins convert unstable plaques to stable plaques, and I currently have patients with non-calcified significant amounts of plaque who are doing a year of Nattokinase, and statin and we will have to see what their repeat CCTA’s show at 1 year. It will be fascinating!

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#6

I have always had a love hate relationship with statins. For now I will continue to take atorvastatin because the bulk of the evidence is very positive.

I asked Gemini pro:

Please critique this paper and give me your opinion on whether or not I should continue taking atovastatin. I am not overweight, BMI of 21. I am able to keep my lipids in the low range by diet alone.

The main excerpts:

1. Critique of the Paper (Ghanim et al., 2024)

Title: The Effect of Atorvastatin on Pancreatic β-Cell Function and Gene Expression in Type 2 Diabetes

Summary of Findings: This small clinical study investigated the effects of high-dose atorvastatin (80 mg/day) on pancreatic β-cell function in patients with Type 2 Diabetes (T2D). The study found that after 12 weeks, atorvastatin therapy led to:

  • An increase in insulin resistance (HOMA-IR).
  • An increase in fasting plasma glucose and HbA1c.
  • A reduction in glucose-stimulated insulin secretion.
  • Changes in gene expression in pancreatic islets that are “likely associated with β-cell dysfunction.”

Strengths of the Paper:

  • Direct Investigation: It uses a well-designed protocol (hyperglycemic clamp) to directly measure insulin secretion, which is a more accurate method than relying solely on fasting blood tests.
  • Molecular Insight: It goes beyond clinical markers by looking at gene expression, offering a potential mechanism for why atorvastatin might affect blood sugar.
  • Specific Population: It focuses on patients who already have T2D, a group known to be at higher risk for statin-related glycemic issues.

Weaknesses & Limitations:

  • Very Small Sample Size: The study had only 13 participants. This is a major limitation. A study this small is considered exploratory. Its findings cannot be definitively generalized to the entire population.
  • No Placebo Group: The study was an “open-label, baseline-controlled” study, not a randomized, double-blind, placebo-controlled trial. This means there was no comparison group taking a dummy pill, and both patients and researchers knew they were taking the drug. This introduces potential bias.
  • High Dose: The study used 80 mg of atorvastatin, which is the maximum daily dose. The effects observed at this high dose may not be the same as those at lower, more common doses (e.g., 10mg, 20mg, or 40mg).
  • Short Duration: The study only lasted 12 weeks. It does not provide information on long-term effects.
  • Population Specificity: The participants were obese (mean BMI of 35.9) and already had T2D. You mentioned your BMI is 21 and you are not overweight. It’s unclear if these findings apply to someone with your profile, especially if you do not have T2D.

Overall Critique: This is an interesting, hypothesis-generating pilot study that provides some mechanistic evidence for a known side effect of statins (worsening blood sugar). However, its small size and lack of a control group mean it should not be used as the sole basis for making major clinical decisions. It confirms what large epidemiological studies have already shown—statins can raise blood sugar—but adds a potential biological explanation.

2. Contextualizing Your Situation

Now, let’s relate this to your situation, keeping in mind I am providing information for you to discuss with your doctor, not medical advice.

The “Statin and Diabetes” Dilemma: It is well-established in medical literature that statin therapy is associated with a small increase in the risk of developing new-onset diabetes and can slightly worsen glycemic control in people who already have diabetes.

  • The Trade-off: The general medical consensus, supported by major guidelines (like those from the American College of Cardiology and American Heart Association), is that the cardiovascular benefits of statins (preventing heart attacks and strokes) far outweigh the small risk of increased blood sugar in most patients. A heart attack is generally considered a much more immediate and severe risk than a slight increase in HbA1c.
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#7

I did an LLM search relating to the links between acetylation and CVD

It is an interesting thought that statins create more calcified arteries, but that may be a side effect of having less cholesterol.

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#8

As someone who genuinely is statin-intolerant, I take 1mg pitavastatin 6 days a week which appears to be low enough to avoid the side effects while still providing a roughly 20% LDL-C reduction from baseline to ~60 mg/dL. At that dose and frequency I experience absolutely no muscle pain and even my liver values have stabilized (with the help of reta and some supplements). I’m assuming my body is just very inefficient at breaking down statins so concentrations build up too high with regular doses.

I can understand being wary of other statins but pitavastatin has the most favorable side effect profile. Even steroid shops like Driada Medical have started to sell it as cycle support.

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#9

I can understand that. There are some statins I can’t tolerate. Atorvastatin has worked well for me and has other benefits:

Atorvastatin Specifically

Atorvastatin:

  • Has strong LDL-lowering potency
  • Produces robust CRP reduction
  • Has extensive evidence in:
    • Secondary prevention
    • Stroke reduction
    • High-risk elderly populations

So it exhibits pleiotropic effects, but its benefit still scales primarily with LDL reduction.

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