I had a massive heart attack when I was 39 years old. This was completely unexpected because I had not noticed any symptoms and all the previous annual blood tests and physical examinations had not alerted me to any immediate risks. It’s still an unsolved problem – heart attacks are the first shocking revelation of an underlying disease for many young and seemingly fit people. (The deaths of young public figures in the past few years serve as grim reminders.) Asymptomatic and otherwise fit people, well into middle age, worry about the risk of such a sudden event. Surprisingly, the generally available information on reducing cardiovascular risk for this population is still limited to major lifestyle changes such as diet, exercise, and smoking cessation. Sometimes counter-productive unnecessary testing is also recommended.
Understanding the mechanisms of these unexpected heart attacks is essential to go beyond clichéd recommendations. My research suggests that in addition to big-picture lifestyle changes, daily decisions to avoid overlapping stressors such as sleep deprivation, physical and mental stress are critical to reducing this risk. Furthermore, frequent tests (other than basic blood tests) are not helpful.
Why are these attacks happening?
There are three contributing factors. One is the presence of plaque in the coronary arteries – commonly known as blockages. Coronary arteries are blood vessels that supply blood to the heart and enable it to pump properly. Blockages block this blood supply and damage the heart.
If these blockages are large, people may experience symptoms such as chest pain and shortness of breath, especially during any exertion, and may seek medical attention before an attack occurs.
A common misconception is that blockages occur when fats (lipids, cholesterol) and cells build up in the walls of arteries—like blocks in a house’s plumbing. This is wrong. The figure below illustrates this false view.
Blockages are the result of cells and cholesterol particles breaking through the barrier of endothelial cells and infiltrating the artery lining. As a result, a pimple-like bump forms on the artery wall. This is called plaque or stenosis. Percent (%) stenosis is usually measured as the percentage of blocked artery diameter. Plaque does not swell in the artery but can flow out (called positive remodeling). See the picture below.
Sudden attacks are triggered by small disturbances. These are “therapeutically silent” and do not restrict blood flow (and, therefore, cause no symptoms) but cause problems if they rupture. This is the second factor. The break-up and blockage of such blockages within the coronary arteries, as shown in the figure below, initiates the blood clotting mechanism to “repair” the injury from the plaque blockage.
The third factor is the intensity of clotting. Severe clotting can cause massive blockages in arteries and lead to heart attacks. Thus, the clot – and not the plaque – blocks blood flow. If the clotting is less severe, smaller clots form. These are sufficient for injury repair and do not affect blood flow. Surprisingly, this type of plaque breakup – with small clot formation – is very common. According to a 2015 article in the Journal of the American College of Cardiology (JACC), millions go through such events without any symptoms. These people avoid sudden attacks due to low clotting ability.
Can testing help?
So, three things need to be detected: the presence of small plaques, the possibility of plaque disruption (known as fragility), and the intensity of blood clotting. Reliable non-invasive diagnostic tests are available to detect only the first – small plaques. However, testing for each of these (even if it is available) does not provide a guaranteed window into the future because all three factors depend on lifestyle and environmental conditions.
New plaques may develop and existing ones may change in size. A weak plaque may become fixed and reversible. And, blood clotting intensity changes depending on factors like time of day, content of previous meal, emotional state of the person and many others. Changes occur in seconds or may not be noticed for months. This dynamic aspect makes it impossible to predict these sudden attacks because the problem is not limited to identifying individuals at risk from the three contributing factors. In addition to marking the person at risk, one must also identify the “blockage flash point” for that person – a time when these three elements come together and lead to a sudden attack.
The logical conclusion is that the presence of only one or two elements is not an immediate threat. The data above—indicating that many people are undergoing plaque blockage without symptoms—support the hypothesis. Further support comes from population statistics. A 2021 article in Circulation reported a study of nearly 30,000 people between the ages of 50 and 64 in Sweden without a diagnosis of coronary disease. It showed that nearly 42 percent carried some plaque! All these people seem to be living without awareness of the disease. Furthermore, approximately 0.3 percent of the population suffers from heart attacks annually (2019 statistics).
The implication for the test is that the benefit of detecting plaque (only one of the three elements) in an asymptomatic population has been questioned. In particular, because the risk of heart attack over 10 years can be estimated from a review of lifestyle factors and blood tests. Risky tests such as computed tomography (CT) tests that use X-rays must show evidence that the test ultimately results in heart attack prevention—an effort that is still in progress. Current American Heart Association (AHA) guidelines advocate a limited role for testing in asymptomatic patients (only CT calcium score testing is recommended for specific populations).
So is daily life suspenseful?
Does the knowledge that a sudden attack is an event requiring the combination of three factors provide some relief? Or, should individuals be concerned about being in a population subgroup that faces attacks? In addition to following AHA guidance, insights based on the flash point concept can help further reduce risk. As this quote from a research article by Falk et al [1995, Circulation: 92-657] Explains: “Onset of acute coronary syndrome [heart attacks] does not arise randomly; A large portion seems to be triggered by an external factor or situation.” Examples are mornings, Mondays, strenuous exercise, cold weather and emotional stress.
Triggers can be thought of as events that create optimal conditions for flash point development. Generally, the triggers are stress that causes inflammation. Inflammation “activates” various body systems and is one of the causes of plaque formation, plaque disruption, and clotting. The conceptual graphic below shows some of the triggers that affect the body’s “activation” state over a 24-hour period. Beyond a certain threshold, plaque disruption and extensive clotting are triggered due to sudden attacks.
The visual shows the cumulative activation state as the sum of baseline and stressors such as sleep deprivation, daily (circadian) body cycles. Variable daily events and triggers are added on top. An important note is that although some triggers are known to increase inflammation, there are no data to indicate the magnitude and shape of these trend lines and threshold levels. Still, the visual helps inform and impress that the overlapping of stressors leads to a higher activation state and moves the person closer to the flash point.
A heart attack can result from a “the-straw-that-breaks-the-commel’s-back” type of situation where a seemingly normal activity, such as morning exercise, or an emotionally difficult conversation, if accompanied by an already high activity level, leads. to attack suddenly. I had a heart attack in the afternoon during my routine, moderate intensity gym workout. This was “on top” of a busy travel schedule and several nights of poor sleep over the previous ten days.
Action is possible on two fronts based on the graphic. Baseline can be thought of as contributing risk factors such as genetics, age, diabetes, high blood pressure, lipid levels, obesity, smoking, and now, possibly, Covid. This risk can be reduced through major lifestyle changes and medications. Techniques such as meditation and yoga can also help.
The second risk is from daily stress and is managed by ensuring that these stressors do not overlap. Some practical tips include avoiding a succession of late nights, not exercising late at night or with an intense travel schedule, and understanding one’s emotional stressors. Also, remember that baseline risk increases with age. Therefore, any exercise regimen should be adjusted (with medical input) as you age. Unexpected heart failure is a reality that is not fully understood and therefore, not yet eliminated. Repeated testing does not eliminate this risk. A lifestyle with a few rules of thumb to avoid flash points can reduce daily stress and anxiety.
Disclaimer: The above does not constitute medical advice. Individuals should consult with physicians to decide on treatments and interventions. Dr Tushar Gore is the Managing Director of Resonance Laboratories, a niche pharmaceutical manufacturer. He studied at IIT-Bombay and University of Minnesota and has worked at McKinsey and Novo Nordisk. His focus area is medicine