Updated: Mar 15
Heart disease is the combination of three ailments. They are damage in the arteries called atherosclerosis, sudden events that lead to tissue death in the heart called heart attacks, and an underperforming or dysfunctional heart called heart failure. These things combined make heart disease the leading killer in the United States. While categorizing all these situations under the name heart disease makes them seem like they are one disease with one cause, I believe that there are distinct mechanisms for each one. It is of particular interest to me to show how the disease process of atherosclerosis that supposedly leads to a blockage and causes a heart attack are not as linked as we may think.
There are many forward-thinking cardiologists who have come to the conclusion that saturated fat and cholesterol in the diet does not clog arteries and is not the cause of heart disease. I am glad that the number of cardiologists that think this seems to be growing these days. However, when I hear them talk about heart health, they are still very focused on the idea that atherosclerosis in an artery is what will lead you to a heart attack. All the discussion is about dissecting out different variations in blood lipid markers and theories about what does actually cause atherosclerosis. But what if, when it comes to heart attacks, a build-up of plaque in an artery or a clot formation was rarely the cause? What if a heart attack could happen without either of those two situations happening? I believe this to be the case.
In my post called “Are Heart Attacks Caused By Blocked Arteries?” I discussed the work of the pathologist Dr. Giorgio Baroldi and illustrated how his work overwhelmingly calls into question the idea that atherosclerotic build-up or a clot formation in an artery is the cause of most heart attacks. (1) To further this point, it is also worth it to note how divided, in many different directions, the pathologists in the field of coronary artery pathology are.
In his book, Natural History of Coronary Atherosclerosis, Dr. Constantin Velican, who is Head of the Department of Pathology and Histochemistry at the Institute of Internal Medicine at Colentina Hospital in Bucharest, Romania, lists the definitions of atherosclerosis given by prominent scientists in the field. Reading through them you get the sense that there are more differences than similarities, not only in what atherosclerosis is and its cause, but also whether it is involved in the process of a heart attack. (2) How can the western medical system be so sure of the standard of care for a disease when there is such a lack of consensus among the top researchers of the disease?
Based on this, and the findings of years of searching, I would like to suggest a theory that I believe causes the vast majority of heart attacks. I have discussed this theory before in my ebook, in other blog posts, and in my heart course, but this will be my most detailed explanation to date. I will warn you it does get a bit technical and it is a bit longer than my other posts.
First, we need to understand three imbalances in the body that drive many chronic diseases. Those are the inability to readily burn fat for fuel, an excess of free radicals that leads to oxidative stress, and an imbalance in the stress response of our Autonomic Nervous System. I have discussed these in more detail in other blog posts (here, here, and here) but I will review them briefly here.
The first is the inability for our body to readily burn fat for fuel. Our bodies have the ability to burn a few different nutrients to make energy. Those nutrients are protein, fat, and carbohydrates. However, just because we can burn all three doesn’t mean that we should. Since carbohydrates are easily to burn when they are present, like when we eat them, then our body will burn them first. All good right. Not exactly. Turns out burning primarily carbohydrates is not a fast track to good health as it will result in the excess production of free radicals when we rely on them for fuel. (3,63) Our bodies are much more efficient when we burn fat and to do this, we need to restrict our carbohydrates so that our bodies can learn to burn fat, and ketones, again. This imbalance explains why eating a large amount of refined carbohydrates has been correlated with heart attack risk. (4) The most important thing to remember at this point is that the heart prefers to burn predominantly fat and ketones (5,6,7) and, as we will see, bad things happen when it is forced to burn predominantly glucose.
Secondly, let’s briefly review oxidative stress. Every time our body makes energy from a protein, fat, or carbohydrate it has to make a waste product as well. This waste product is called a free radical. As we said, burning carbohydrates (glucose) for fuel actually produces more of these free radicals (3,63) than if we were to burn a fat or a protein. (8) Burning fat is the most efficient as we make the least amount of free radicals doing this. This is important because having too many free radicals can end up causing damage to our bodies, including the lining of our arteries. (9) Other things can contribute to excess free radicals in our bodies too. Elevated blood sugar (from eating carbohydrates) (10) and excess exposure to toxins in our environment will also result in elevated free radicals in our bodies. (11,12) This imbalance tells us why smoking has such a correlation to heart attack risk (13), as it is a major toxin exposure. For now, it is important to remember that free radicals will damage the lining of our arteries and can deplete what is called Nitric Oxide (14,15).
The third imbalance is a dysfunctional stress response in our Autonomic Nervous System. Our evolved stress response is supposed to work by being activated only when it needs to be, like when our life is in danger. However, because of the mismatch in how our stress response evolved and the current environment we modern humans live in, our stress response can become imbalanced. This means that instead of healthily going back and forth between a stress response and a non-stress state we can get stuck in a stress response that causes our bodies to be on constant high alert. This can alter the signaling of our Autonomic Nervous System to our body. (16) This imbalance explains why heart attacks are more prevalent on stressful days of the year (17) and why Mondays are the most common day for heart attacks to occur. (18) For now, remember that our ANS is always supposed to send a balanced signal to our heart cells and if this is interfered with it can trigger a series of events that can lead to a heart attack.
Now, how do these imbalances directly cause a heart attack? Let’s dig into it. As we said, the heart prefers to burn predominantly fat and ketones for fuel (5,6,7) and the body has mechanisms in place that ensure that this happens. One being that the fat we eat is packaged into chylomicrons and then delivered, more or less, directly to the heart by way of the lymphatic system before it can be used by other tissues giving the heart first dibs. Another being that the heart has a signaling pathway that allows it to communicate directly to fat cells. (21) The heart takes burning fat pretty seriously, and I believe that the majority of heart attacks happen when a series of events takes place that forces it to switch to burning predominantly glucose for fuel.
The Standard American Diet (SAD) that is full of refined carbohydrates is not a diet that is going to help our body run on fat for fuel. Like we said, our body does things to make sure the heart still gets to burn predominantly fat we do eat even if we are eating many refined carbohydrates as well. It is very interesting that most of the body will burn glucose first if it is present, which is why we have to restrict carbohydrates to get ourselves in ketosis, yet the heart doesn’t do this and will burn fat and ketones even if glucose is present. (5) Despite our heart being special, not making sure our body is adapted to burning fat can predispose our heart to suffering a heart attack when the other imbalances we have talked about happen too.
So, let’s say that someone is living life with a high stress job and is so consumed by that job that there is just no time to care about eating for optimal health and avoiding toxins. This is unfortunately the case for many people in our fast-paced modern world. It is the exact scenario that, combined with getting older as we will discuss, leads to us suffering many diseases, but especially a heart attack.
Due to the mismatch between our evolved stress response and our modern human environment, combined with our higher-level thinking, humans can put themselves in a chronic low-grade stress response just by thinking something bad is going to happen. When a human has a stress response it increases function to parts of the body that will help it get away from or fight off a threat (muscles, senses), but it is only supposed to do this while in a stressful situation. Dr. Robert Sapolsky, who has spent his life studying the difference between the stress response of mammals in their natural environment compared to the stress response of humans in the modern world, states it well, “Mobilizing energy while sprinting for your life helps save you. Do the same thing chronically because of a stressful thirty-year mortgage, and you’re at risk for metabolic problems like diabetes and high blood pressure”. (22)
What does this have to do with a heart attack? Well, it turns out that a chronic low-grade stress response with periodic bursts of very high stress responses over time can lead to the imbalance in our autonomic nervous system we talked about. Our autonomic nervous system consists of two parts. There is the “rest and digest”, or parasympathetic, which is more active in a non-stress situation. Then there is the “fight or flight”, or sympathetic, reserved for those times when a stress response is necessary. These two states should be in balance and a surge in one normally includes a lesser surge of the other. (23) The signal for this system is conducted through the vagus nerve. Many believe this nerve only affects the right atrium, where the hearts pacing signal is receive from the nervous system. However, research has shown that this nerve reaches all areas of the heart and can therefore affect the whole heart. (24) While there are a combination of factors that have to happen for a heart attack to occur, when this system gets out of balance it is one of the key players that triggers a heart attack.
To explain this, I will have to get a bit technical, so bear with me. The control of the balance of the autonomic nervous system in cardiac cells, and many other cells, relies on two messenger molecules called cAMP and cGMP. cAMP levels rise in the heart cells when we have a stressful response to something, and cGMP levels rise when we are in a relaxation state. The only difference is that when it comes to cGMP, the relax molecule, something else is also needed to increase its levels. That something else is nitric oxide, NO (25), which is produced in the cells of the walls of arteries called endothelia. These two molecules—cAMP and cGMP—keep each other in check within heart cells. When we experience a stressful response and the nervous system causes spikes in cAMP within the heart then cGMP, provided there is enough NO, also has an increase just to keep the system more in balance. (26) This is depicted in the image below.
But the system can become unbalanced. When we have prolonged periods in our life with many surges of stress responses that increase levels of cAMP and not enough stimulation of the relax response then we can lose the ability to effectively move between these two states and can get stuck in our stress state. This is called decreased vagal tone because the vagus nerve is the nerve that carries the non-stress signals. The best measure of balance in our stress response is Heart Rate Variability (HRV), the higher your HRV the more balanced you are. In one study, Heart Rate Variability has been shown to be completely suppressed preceding 95% of ischemic events. (27)
When this imbalance of our stress response happens the failsafe within the cardiac cells is that those consistently high levels of cAMP are balanced by also rising levels of cGMP. But remember that cGMP can only do this if NO is present. If NO gets depleted, it is really bad news. Having high free radicals, or oxidative stress can deplete our NO. (28) Free radicals are molecules with an unpaired electron and they do not like to be unpaired. Because of this, the free radicals go running around the body like the looney tunes Tasmanian devil trying to find another electron to make a pair. One place it can find another electron is NO. (29) This decreases the NO available for cGMP simulation. Also, oxidative stress causes damage to the lining of an artery causing atherosclerosis. (30) Since the lining of the artery is where our NO is made, and damaged arteries can’t make it, this can also result in lower NO levels.
Now that we have set the stage, it is time for the big event. When humans experience decreased vagal tone for long periods of time while also experiencing decreases in NO levels, this can cause a surge in the stress response and subsequent elevation in cAMP in our heart cells without the balanced rise in cGMP. (31) This is shown in the image below.
When this happens the cascade of events that is a heart attack plays out. The sudden unchecked rise in adrenaline from the stress response has been shown to cause an increase in lactic acid production within cardiac cells. (32) This happens because the heart usually prefers to burn ketones—a product of burning fat—but in this situation the body thinks it needs to burn energy quicker. Since it is quicker to burn glucose the heart cells revert to burning it rather than burning the more efficient and preferred energy source of fats and ketones. (33) Burning glucose causes the build-up in lactic acid and hydrogen ions within the heart cells creating a state of acidity. Studies have shown that the production of lactic acid is increased by a factor of eight in this situation, and that no change in oxygen levels is seen during these events. (32) This is similar to when you do a sprint or a hard, fast workout, lactic acid builds up in the muscles causing the muscle to have that burning feeling, but oxygen levels are not affected.
When this happens in a muscle in the legs or arms, we can just stop moving it and the lactic acid will move along stopping the build-up and the burning. Since the heart can’t just stop contracting the lactic acid quickly builds up causing a major problem. The presence of acid in the heart tissue prevents calcium from being able to bind to muscle fibers to create contraction of heart muscles. (34) It has been shown that low calcium in heart cells results in slower conduction velocity and elevated arrhythmia risk. (35) This eventually leads to decreased muscle tension and contractility which then causes a stretching of the wall of the heart that leads to increased pressure. (36,37) This increase in pressure in the tissue prevents blood supply from getting to the tissue. (38) This results in very quick tissue death before any drop in oxygen is seen in heart tissue. In other words, a heart attack.
Only this series of events accounts for all the observations we see in a heart attack, as well as for certain associated risk factors of heart attacks. It clears up many of the interesting phenomenon associated with heart attacks. To further illustrate the validity of this theory let’s discuss some of them.
While heart attacks are seen across many age groups, they are more prevent in the elderly. Let’s use these three imbalances to explain why that may be. It has been shown that the heart cells become less efficient at burning fat and ketones for fuel just through the process of aging. (19) Also, an older person has had a longer period of time to build-up toxins in their body that can contribute to oxidative stress. Lastly, the unfortunate truth is that many elderly people feel socially isolated. Way back when, elderly people were the purveyors of knowledge and wisdom and this information was vitally important for the survival of future generations. These days the way of life is changing so rapidly that the life experience of an older person isn’t always as relevant in the modern-day. Plus, the information people need can often times be looked up on the relatively new thing called the internet. I believe that this has led to many elderly people feeling socially isolated from others and society and somewhat removed them from their natural purpose of providing wisdom and guidance. Social isolation has been shown to increase the risk of recurring heart attacks. (20) Heart rate variability is also known to decline naturally as we age (64) at least when studied in our modern population.
Another interesting observation is that nearly 100% of heart attacks happen in the left ventricle. (39) Which is curious because severe stenosis and clots are evenly distributed among the vessels of the heart supplying all areas of the heart. However, when we take into account that the series of events described above eventually leads to a change in pressure that restricts blood flow then an area of the heart that is under the most pressure already would be more prone to any changes in pressure. It is well known that the left ventricle is under the most pressure making it more susceptible to the changes in pressure cause by the stretching and decreased contractility that happens once lactic acid builds up and interferes with calcium.
This theory also explains the observation that oxygen usage of the heart muscle is largely unchanged during the event of a heart attack. You would think that if the idea that a blockage of blood flow causes a heart attack that oxygen levels would drop. Studies have shown that a shift in metabolism after the stimulation of a stress response in heart cells can lead to the events described above without any effect on oxygen consumption in heart cells. (40,41)
It is also well known that males suffer from heart attacks more than females. (42) Could this be explained by the fact that women generally have a healthier vagus nerve compared to men, especially before menopause? (43) And could the stimulation of the vagus nerve due to menstrual cycles creating healthy cardiac rhythms and HRV being giving females an advantage? (44). Perhaps the fact that men tend to suffer from heart attacks earlier in life than women do (45) is because of this “protective” effect of parasympathetic stimulation of a monthly cycle for women so that their HRV stays more balanced until after menopause.
It is also interesting that heart disease patients tend to have a more difficult time in winter, and we see more deaths of these patients in winter. (46) It is no surprise then that we also see lower HRV during the winter months than we do in the summer months. (47) This most likely due to decreased exposure to nature in the winter months.
We already mentioned earlier in the article that heart attacks are more prevalent during stressful times (17) (holidays, Mondays, sporting events) and happen more commonly in elderly people. It is not hard to imagine the increase in sympathetic dominance during those stressful times and it has been observed that HRV does decline as we age. (48,49,50) Again, many different associations between life factors and incidence of heart attacks become clearer when looking at this through the lens of this theory.
Lastly, there are some heart disease drugs that while not specifically used to prevent a heart attack have been shown to do so. Some of the heart attack prevention effects of beta blockers are probably due to the fact that they have been shown to have a desirable effect on HRV. (58,59,60) The same goes for ACE inhibitors. (61) Also, nitroglycerin tablets used to treat angina are thought to dilate the blood vessels and restore blood flow to an area and relieve the angina. However, I have written in other posts how blocked arteries are fully compensated by collateral arteries and blood flow is not compromised. Therefore, it is more logical to conclude that the effect we see as relief from angina by nitroglycerin is due to it helping the body restore NO levels. As we have said, decreased NO will lead to a dysfunctional signaling of the autonomic nervous system in heart cells via cGMP. Nitroglycerin has been shown to increase the expression of cGMP in tissues. (62)
We will close with some action steps. To prevent a heart attack focus on correcting three imbalances in the body. Be sure that you are fat adapted by utilizing carbohydrate restriction and intermittent fasting to make it less likely that your heart will ever convert to burning more glucose in any situation. Reduce your oxidative stress by becoming a fat burning machine and learning what substances in your environment are toxic to you and how you can avoid them. Lastly, be in contact with nature (51), do not suppress feelings (52), be part of a community (52), practice mindfulness (53), expose your body to heat and cold (54,55), have sex (56), and have meaningful loving relationships (57). These are all things that will increase HRV and balance your stress response.
Stay healthy out there!
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