Can Statins Cause Heart Attacks?!
Statins are one of the most lucrative and widely used drugs to lower cholesterol. In recent years, more of its problems are coming to light.
Metabolic Machinery
It is no secret that I am not a fan of statins.
In fact, I am generally opposed to artificially suppressing cholesterol. Not least because cholesterol is one of the most important molecules in all of mammalian physiology.
Cholesterol is involved with:
Cell structure, fluidity and repair
Signaling, proliferation, migration and trafficking
Hormone production and balance
The list goes on.
Although you can continue to argue about the merits of lowering cholesterol for some survival benefit, there is no cholesterol therapeutic approach as harmful as statins.
If you are like most people (including doctors), you may think that statins simply lower cholesterol. This could not be further from the truth.
Statins (or HMG-CoA Reductase inhibitors) block an enzyme upstream to some of the most important functions of the cell. You can see from the diagram below that HMG-CoA Reductase is responsible for the production of all sorts of different molecules, in addition to all of the molecules derived from sterols (which are in the thousands).
One of the most well known molecules that statins deplete is Coenzyme-Q10 or Ubiquinone.
CoQ is an anti-oxidative protein that is part of the electron transport chain in our mitochondria. Mitochondria are responsible for making energy, and they does so by a process called oxidative phosphorylation facilitated by this transport chain.
Statins also block the production of Heme A. Heme A is a functional component of cytochrome c oxidase (Complex 4 in the electron transport chain).
Cells rely on mitochondria’s ability to generate ATP (energy) in order to survive & thrive.
Thus, anything which impairs optimal function of mitochondria will lead to cell dysfunction. As you can see, statins heavily inhibit the optimal function of our mitochondria.
Cells of the heart (cardiomyocytes) contain more mitochondria than any other organ in the human body. Which makes sense - the heart has a hard task, and it’s working nonstop.
From this information alone, it is completely reasonable to assume that any substance which interferes with energy production in this manner, will ultimately result in organ dysfunction.
Troponin & Heart
It would appear that some researchers share my concerns, and put this hypothesis to the test.
Now, the content of this experiment centers around changes in serum troponin levels.
Troponins are proteins which are integral to the normal function of muscle. In cardiology, we measure serum (blood) troponin levels in the diagnosis of heart attacks or other causes of damage to heart muscle.
The premise is that as heart muscle gets damaged (either by inflammation or ischemia), the cell leaks troponins into the bloodstream. Once we detect it, we become suspicious of heart damage.
There are different types of Troponins, measured by different tests. One of the more common tests is high sensitivity Troponin T (hsTnT). This is the troponin assay that was used in the study.
hsTNT is diagnostic of myocardial infarction (heart attack) when 22 ng/L in men, and 14 ng/L in women.
Additional data supports that in the healthy general population, levels 6 ng/L confers increased risk of cardiovascular disease/dysfunction.
Study Design
The authors recruited 56 patients without history of coronary artery disease, cardiac pathology or recent admission related to acute chest pain.
Information to note about this cohort:
Baseline characteristics were rather well balanced between the two groups including similar rates of: diabetes, hypertension, smoking status, and family history
The only difference (statistically significant) was the total cholesterol and LDL, which was lower in the group that was on statins (as we’d expect).
Both groups underwent moderate intensity exercise, which consists of 5 mins of treadmill at 2.5 km/hour (brisk walk), followed by 30 minutes at 5.5 km/hour (jog). Serum troponin was measured before and 4 hours after exercise.
Results
As you can see, the Statin users demonstrated a significant increase in hsTNT after exercise. Let’s review the numbers:
Average hsTNT after exercise in control group was 7.74 ng/L, highest of 13.5 ng/L, and an average increase of about 7.1%
Average hsTNT after exercise in the statin group was 11.4 ng/L, highest of 26.6 ng/L, and an average increase of about 43.8%
When comparing to reference ranges of hsTNT, you can see that some participants in the statin group demonstrate a level that is compatible with a heart attack (>22 ng/L).
The authors then applied a rule-out limit, which involves repeating the hsTNT after an hour to see if it is still high or returns back to baseline. When applying this rule, they found that 38% of statins users had consistently elevated hsTNT sufficiently high to suggest ischemia to the heart. Fundamentally, an indicator of damage to heart muscles. In the control group, only 10% demonstrated a similar increase (p=0.024).
What Does This Mean?
As we established, statins interrupt the mitochondrial and cellular machinery needed to properly generate energy & function.
When you exercise, you place an elevated metabolic demand (or stress) on your cells and organs.
But, if there is a discrepancy between the stress load (in this case, moderate exercise) and capacity to meet this demand…we begin to experience cellular dysfunction.
We typically think of a heart attack as a scenario in which there is not enough oxygen getting to the heart, usually because of a blockage of the coronary arteries.
But oxygen (O2) is just another electron transport vehicle, which accepts the electrons from Complex 4 to ultimately form water (H2O).
The end result is the same! Whether you are low on oxygen or low on Cytochrome C Oxidase, or low on CoQ-10…it doesn’t matter. This is simply a question of where the bottleneck is.
In both cases, the end-result is mitochondrial dysfunction and an inability to make enough ATP (energy) to meet the demands of physiologic stress.
If this imbalance is persistent, you get ischemia of heart muscles, which eventually starts to die and…release troponins into the bloodstream.
To strengthen this framework, take the case of another form of heart attacks called Takostubo cardiomyopathy, aka stress-related cardiomyopathy, aka broken heart syndrome.
These are all different names for the same process. Some sort of physiologic stress overwhelms the hearts capacity to deal with demand…and it acutely fails.
What is interesting about this cohort?
According to a multi-center study of 2429 patients with Takostubo, statins provide no survival benefit.
Which is exactly what we would expect. If anything, statins may make it worse.
Criticism & Limitations
There have been a couple of knee-jerk reactions when I initially shared this study on Twitter.
One person pointed out that the study is not a randomized control trial. This is a classic go-to argument for anyone who dislikes the findings of a study.
Although this is a limitation, it does not automatically negate their findings. Nor does it address the mechanisms which support the findings.
In my opinion, there is one legitimate criticism here.
Like I said in the beginning, Troponins are found in muscles. Specifically, in skeletal muscle and heart muscle.
Which means that, it is possible that the hsTnT in the blood also came from skeletal muscle. Assuming this is true, it brings up two interesting points.
First, the impact of statins on mitochondrial function are so potent that generally healthy adults walking and jogging on the treadmill for 35 minutes is enough stress to lead to muscle cell death.
Which is not at all surprising. After all, one of the most frequently reported side effects of statin use is muscle pain and fatigue. Completely accounted for by the mechanism I outlined above.
Second, if the statin is having this impact on skeletal muscle…why would it not have a similar impact on heart muscle?
Therefore, best case scenario for statin-apologists is that moderate exercise is leading to both skeletal and heart muscle cell death.
Worst case scenario, this is only the damage caused to muscles with one-time 35 minutes of treadmill activity. Imagine how much more damage you can cause by higher intensity, longer duration, and more frequent exercise.
Not exactly the win they were hoping for.
Counter-Point
Which brings me to what is most frustrating about this whole debate.
What I laid out for you in the first half of this article is precisely the groundwork and understanding you need to predict and verify the physiologic consequence of statin use on metabolically active organs.
What we have here is a scenario in which there is tinder, kindling, logs, and fuel all laid out exactly as needed.
Then, we introduce a lit match (in this case the Statin) to make a roaring fire.
How do the modern medicine apologists respond? Well, we have to rule out other causes before we can definitively say that the lit match started the fire!
Let’s do some randomized control trials…just to make sure.
Knock yourself out.
On the other hand, if you find this line of reasoning convincing…and the findings of this study concerning, then I would suggest learning more about statins and cholesterol.
Cherry On Top
Here I am spending thousands of words and hours of my life trying to outline a thorough argument.
But, what you may not appreciate is the average doctor, even the average cardiologist…maybe even pharmacologist…does not know these things.
Most of them believe statins are merely a “cholesterol lowering agent” which has revolutionized the care of patients with cardiovascular disease. This falls under secondary prevention. Preventing repeat occurrences of cardiovascular events.
But, they don’t stop there. They also believe it is a revolution in care of all patients. So they prescribe in an effort to prevent a first event. Primary prevention.
With this contrasting position that most centralized physicians take, it is both disconcerting and entertaining to read the conclusion from the authors of this study.
…statin therapy can cause a significant increase in hsTnT after moderate exercise.
It is therefore important to consider these effects of statins to prevent misdiagnosis or unnecessary hospitalizations.
From my reading, the authors are suggesting that if we appropriately apply the rule-out algorithm for diagnosis of heart muscle ischemia/death, we may inappropriately diagnose heart damage in people who take statins and exercise.
The amount of apologism for this bunk ideology is deafening.
For those of your genuinely interested in understanding cholesterol as well as statins, I would humbly recommend this article:
Or, if you would prefer to hear some of my thoughts on the modern mainstream understanding of atherosclerotic disease, check out this recent audio session:
Your point about troponin in muscle is valid. Perhaps they need to repeat the study also measuring CK fractionation, like we did in the old days before we measured troponin.
Printing this out for future reference!