How Stress Causes Heart Disease

dr_malcolm_kendrick_m.d._134by Malcom Kendrick, M.D.

Acute stress
It has long been recognised that fatal heart attacks can follow stressful events. The ‘stressor' can be physical, or emotional. After blizzards, there is always a spike in deaths as people shovel the snow away from their property. After major earthquakes, there is always an increase in deaths in the affected area from the worry and anxiety caused.

A study in the USA ‘The Hound of the Baskervilles effect: natural experiment on the influence of psychological stress on timing of death' demonstrated that people of Chinese/Asian origin were more likely to die on the fourth of the month. The number four is considered very unlucky in this population. It has also been shown that after major sporting events heart attack deaths go up, or down, depending on whether the team wins or loses.

Quite how acute psychological stress kills is not certain. Do the arteries go into spasm? Does the blood clot more readily in the coronary arteries? Does the electrical conduction system go haywire? Does the heart beat harder causing it to build up lactic acid, leading to muscle damage and death? The answer to all of these questions is probably, yes.

Indeed, with enough acute stress it does seem that perfectly healthy, happy, hearts can run into real problems, leading to an acute myocardial infarction (MI), or ‘heart attack.' Some people admitted to hospital with ‘heart attacks', and who have died, have shown no sign of any underlying coronary artery disease. No thickening of the arteries, no build up of atherosclerosis. Just acute psychological stress, then, bang.

Longer term problems with stress
However, the final event in heart disease is not what I am really talking about here. The more complex, and therefore the more interesting question, is whether or not long term psychological stress can cause the gradual build up of atherosclerosis, leading to widespread cardiovascular disease. Narrowing the arteries in the heart, the neck, the aorta, the kidneys, wherever.

I strongly believe that it can, and that the evidence is robust. Clearly though, suggesting that, for example, a lack of social support, leading to chronic negative stress, can eventually lead to an atherosclerotic plaque developing in an artery in the heart requires more than one step to be explained. So, how does it work?

The HPA-axis, plus the sympathetic nervous system
The best place to start is at a very basic, and primitive, system that controls our responses to threat, stress... whatever you want to call it. Deep down, there is a vastly complex neuro-hormonal system at work, one which we have very little real control over. It consists of the hypothalamic-pituitary-adrenal axis (HPA-axis), plus the autonomic (unconscious) nervous system.

This system was designed, in large part, to allow us to survive in situations of extreme danger. When danger threatens, a whole set of hormones are released, epinephrine (adrenaline), nor-epinephrine, cortisol, growth hormone etc. At the same time the sympathetic nervous system lights up, sending messages to the heart to pump harder, blood supply to direct to the muscles etc. We are ready to go, run, do battle - whatever is needed.

This is the ‘flight or fight' response, and most people have heard of it. It is clearly a good thing, in many ways, as it allows us to escape from dangerous situations without having to consciously speed our heart rate up, and divert blood to muscle cells. However, it is increasingly clear that if this system is activated too often, and for too long, things can start to go wrong.

What sort of things can cause this to happen? Well, the first thing I have to say is that the effects of ‘stress' and the damage it can cause vary hugely from person to person. One person may enjoy the cut and thrust of the financial trading floor, the shouting and yelling and pressure. Another may find it intolerable, and have a nervous breakdown.

So, creating hard and fast rules about what causes a breakdown in the HPA-axis, in any given individual, is not possible. However, there are certain situations that are likely to create more breakdowns in more people e.g. loss of job, a bullying boss, forced relocation, breakdown of social ties.

A Harvard biologist called Sapolsky has done some very interesting work on Baboons in Africa. He has studied their social hierarchy, and has found that those lower down the pecking order are regularly picked on, threatened and ‘bullied' by bigger, stronger baboons. As a result they show deranged levels of stress hormones in their blood - and a defective immune response. They become post-traumatic stress baboons.

The long-term damage caused by fear, and bullying seems to happen to people as well. Recent research in Chicago has found that social isolation, and a fear of crime, cause an overload of stress hormones that actually changes cell biology (Cancer cause and control, vol 18, p 323). In this case, they have found that this then drives a very high risk of breast cancer in women, not heart disease.

While this study was on breast cancer, it is the first (that I am aware of) to show that chronic isolation leading to fear/stress can create a measurable change in cell biology.

What I was also interested in was the finding that women who were more socially isolated had a ‘flatline' cortisol response. By which I mean that the normal flexible pattern of cortisol secretion had gone - completely.

Cortisol is a key stress hormone, and a flatline response is a key indicator that the neurohormonal system has been badly damaged. Some people refer to this as HPA-axis ‘burnout.' This pattern is seen in post-traumatic stress disorder, severe depression, and other forms of psychiatric illness, including myalgic encephalomyelitis (ME) otherwise known as chronic fatigue syndrome (CFS) and post viral fatigue syndrome.

In effect, this study adds to a large and rapidly growing body of research which demonstrates that long term psychological stressors, including; social isolation, bullying, and lack of social support all lead to HPA-axis dysfunction. Which can be detected by a flatline cortisol secretion.

Once this happens, a whole spectrum of physiological abnormalities inevitably follows.
In a shortened version, these include:

  • Insulin resistance
  • Abdominal obesity
  • Raised blood sugar levels
  • Raised blood pressure
  • Raised fibrinogen levels (a blood clotting factor)

Some of you may recognise this as the metabolic syndrome, or syndrome X, or Reaven's syndrome, or insulin resistance syndrome (yes, it has many names). Whatever you call it, this spectrum of abnormalities greatly increases the risk of cardiovascular disease (CVD).

What I find interesting, and strangely little remarked upon, is that this group of abnormalities is also found in a condition called Cushing's disease. In this disease, usually caused by a tumour in the pituitary gland, there is chronically increased production of cortisol. A flatline cortisol response.

Once this happens you see exactly the same set of metabolic abnormalities as you see in metabolic syndrome. When I say exactly, I mean exactly (although often a bit more extreme). Cushing's disease also greatly increases the risk of dying of CVD.

Further support that cortisol may be the key hormone involved in the widespread metabolic disruption that leads to coronary heart disease (CHD) comes from research on steroids. Normally steroids are used for their powerful anti-inflammatory effects, and are prescribed in conditions such as asthma, rheumatoid arthritis and inflammatory bowel disease. However if you give people long-term steroids, they will develop Cushing's syndrome. [Steroids are all synthetically based cortisol, which is why they are sometimes called corticosteroids]. 

In the short-term steroids are almost magically powerful. In the long term they lead to

  • Insulin resistance
  • Abdominal obesity
  • Raised blood sugar levels
  • Raised blood pressure
  • Raised fibrinogen levels (a blood clotting factor)

Yes, you may recognise this list. It is exactly the same as metabolic syndrome, and it is exactly the same set of abnormalities that you see in Cushing's disease.

Recent evidence has demonstrated that long-term steroid use greatly increases the risk of developing insulin resistance, type II diabetes, and then dying of heart disease.

Stress and cortisol and metabolic syndrome - and heart disease
To me, the links in the chain between stress and heart disease have all been proven, beyond reasonable doubt.

  • We now know that long term negative stressors e.g. bullying, social isolation, fear of crime can create measurable damage to the HPA-axis, and the autonomic nervous system.
  • The most obvious damage is to cortisol secretion, which becomes flattened and unresponsive.
  • We have evidence from both Cushing's disease and steroid use that abnormal cortisol levels lead to metabolic syndrome
  • Recent studies have shown that metabolic syndrome is a major risk of CHD

Perhaps most importantly, there are many studies now demonstrating the entire causal chain. The INTERHEART study, done in hundreds of different countries to look at causes of CHD, found that psychosocial stress was a major risk factor. The Whitehall study in the UK has consistently found low position in social hierarchy to be the single most important factor in causing a high risk of CHD (and shorter life expectancy).

I do not think that there can be the slightest doubt that stress is an extremely important factor in causing coronary heart disease. I think that it is the most important factor of all, as it can cause both the build up of atherosclerosis, and it can trigger the final event that kills you.

Dr. Malcolm Kendrick (MbChB MRCGP) M.D.
Dr. Kendrick has worked in family practice for almost twenty years.
He has specialized in heart disease and set up the online educational website for the European Society of Cardiology.
He is a peer-reviewer for the British Medical Journal. 
April 2010

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