Stress and heart disease
I have drifted around the issue of stress and cardiovascular disease (CVD) for some time. For many years I pursued the idea that stress was the cause of CVD. Indeed, I had it all worked out, fitting all facts about CVD within this model. But…
I was at a conference in Saudi Arabia a few years ago, giving my ‘How stress causes CVD’ lectures, to great acclaim, or so I thought. However, Paul Rosch, who was also attending said to me, one evening at dinner. ‘It is all very well to show that stress is associated with heart disease, but you have not really established a mechanism.’
This, I realised, was true. I could show things such as the fact that severe depression can cause insulin resistance, even type II diabetes. Also, that depression is associated with a much higher rate of CVD, as are almost all metal health diseases. On average, someone with a mental illness can expect to die around twenty years earlier than those in the surrounding population.
I could show that psychosocial stress lead to Hypothalamic Pituitary Adrenal-axis [HPA-axis] dysfunction, which then drove the metabolic syndrome, with a much higher rate of CVD. The HPA-axis is the conductor of the entire ‘stress’ system.
At one stage I became very interested in spinal cord injury, and CVD. I discover that, the level the spinal cord injury occurred, made very significant differences to the rate of CVD. This, in turn, seemed almost entirely dependent on whether the autonomic nervous system was spared, or damaged.
The autonomic sympathetic/parasympathetic nervous system co-ordinates the ‘flight or fight’, stress, response. It runs down the spinal column before fanning out to link up to all of the organs in the body. You have little conscious control over it, which is why it is often called the ‘unconscious’ nervous system.
The sympathetic part of the autonomic system does such things as, speeding up the heart rate, constricting the bladder, redirecting blood to the muscles. Also stimulating the release of stress hormones, such as cortisol, to increase blood clotting and raise blood sugar levels – all good things in preparation for a fight.
I figured, along with many others, that if the fight or flight response was chronically activated, this would have severe and potentially damaging effects on the body. A chronic ‘dysfunctional stress response’ if you like. It appeared that much of the damage caused by a dysfunctional stress response centred around the stress hormone cortisol.
This idea was further strengthened by the looking at Cushing’s disease, a condition whereby the adrenal glands produce too much cortisol – for various reasons. People with Cushing’s disease have a spectrum of biochemical and physiological abnormalities, from raised blood pressure to severe insulin resistance, raised blood clotting factors, and suchlike.
Those with Cushing’s almost always develop the metabolic syndrome, and often frank type II diabetes. They have a vastly increased risk of dying of CVD. Around 600% (relative increase in risk). Last week I was sent a paper, looking at Cushing’s, called ‘Markers of atherosclerosis in patients with Cushing’s syndrome: a meta-analysis of literature studies.’
The authors found: ‘Cushing’s disease is associated with an increased intima-media thickness (IMT), higher prevalence of carotid plaques, and lower flow-mediated dilation as compared with controls. These data consistently suggest the need for a strict monitoring of early signs of subclinical atherosclerosis in Cushing’s patients.’1
In fact, the prevalence of atherosclerotic plaques was 988% higher (relative risk), than in controls. This is, basically, a ten-fold increase in the risk of plaques, and that moves Cushing’s Disease from association to causation.
I have also looked at people who used steroids for various medical conditions and found that they had a greatly increased risk of CVD. It is estimated that regular steroids use increases CVD risk by around 400% (relative increase in risk). For those who do not know, steroids are often called corticosteroids, because they all used cortisol as the building block. [Cortisol is also called a ‘steroid’ hormone].
PREDNISOLONE – A commonly prescribed ‘steroid’
Whilst everything was, of course, rather more complex that this, with far more strands of evidence to gather together. I had worked my way towards a pretty clear causal chain that looked something like this:
Negative psychological and/or physical stress → HPA-axis dysfunction → abnormal cortisol secretion → metabolic syndrome/type II diabetes → atherosclerosis → increased risk of CVD
Now, I think that this model is still perfectly usable, and it explains a lot. However, although I drew a simple arrow from metabolic syndrome/type II diabetes → atherosclerosis, this is the bit that Paul Rosch was talking about. What is actually happening here? It is all very well to state that something causes something else, but you still need to explain how.
I realised that I did not know how, other than in general terms. I also realised that there were many other things that ‘cause’ CVD, that are not stress related e.g. smoking, omeprazole, Kawasaki’s disease, air pollution, Avastin etc. etc. How could all these be fitted into that one small arrow. That is when I ripped up the stress hypothesis, to start again. Pretty painful, but necessary.