Tag Archives: cardiovascular disease

What does cause heart disease?

(Part one of an occasional series)

So what does cause heart disease then, if it is not cholesterol?  This is question I am often asked – with varying degrees of accusation – by other doctors. Usually after I’ve given a talk dismissing raised cholesterol as a risk factor.

The simplest answer is that the most important causal factor of cardiovascular disease aka the development of plaques (thickenings) in the arteries, is stress (sorry about that rather clumsy form of words). However, as with many simple answers, explaining how stress causes ‘heart disease’ is a bit more complicated.

Which means, gentle reader, that we must go back to the beginning of the whole story, and weave a number of interconnected strands together.

The first strand here is to explain what ‘stress’ may be. I must admit that this is not easy, because few people have an agreed definition of stress. Many concepts are bandied about, and everyone has their own ideas on the subject, but most of them are rather too vague to be of any real use.

I define stress as a measurable dysfunction in the Hypothalamic-Pituitary-Adrenal axis (HPA-axis). But that may be jumping ahead rather too fast, and it requires many steps to get to this point. The first step is to attempt to break stress down into its component parts.

To do this, we have to start by accepting that stress has two basic components. There is the Stressor – the thing causing stress, and the Stressee – the individual affected by the stressor. Without making this important distinction, we will constantly mix up two concepts that need to be kept separate.

For example, many people talk about having a stressful day. I would immediately ask. Does this mean you were impacted on by lots of different stressors e.g. a traffic jam, a tight work deadline, your children getting ill. Or that you found yourself unable to cope with stressors that you would normally be able to cope with. Or both. [To be truthful I would rarely ask this, as I don’t want people shuffling away from me at the dinner table. But I might think it].

By looking at stress as having a cause, or causes, (the stressor), and then looking at their impact upon an individual (the stressee) we can start to disentangle the things that cause stress, from their actual impact.

In addition to this important distinction, there is also a need to accept that different stressors can create positive or negative effects, depending on how the person reacts to them.  Without getting too tangled in this issue, I will attempt put these first ideas into their simplest possible form

Stress has four distinct components:

  • Stressor – positive
  • Stressor – negative
  • Stressee reaction – positive
  • Stressee reaction –negative

Positive stressors could be:

  • Exercise
  • Winning the lottery
  • Giving a well-accepted speech
  • Watching your children perform on stage

Negative stressors could be:

  • Using cocaine
  • A close relative dying
  • Severe criticism at work/being bullied
  • Getting hit by a bus
  • Watching your army comrades being blown to bits by an IED

Some negative stressors are very short acting and, as such, the human psyche and physiology can cope and restore homeostasis (unless the trauma is gigantic). The problems start to arise when negative stressors act hour after hour, day after day, week after week. For example, being repeatedly physically or sexually abused as a child. Or being bullied day after day at work.

Problems created by a constant battering of negative stressors are also made significantly worse if your coping mechanisms are poor. Being bullied at work is not so bad if you have a good social life, a supportive partner, and a loving family. It also helps significantly if you are physically, fit and free from significant chronic disease.

If, however, you have no friends, no supportive family, and you have a chronic illness that weakens you, it does not take too much else to tip your system over the edge.

Unfortunately, early life trauma, and abuse, can leave people with very poor coping mechanisms. In addition, people who have suffered repeated negative stressors through their childhood often find themselves in a cycle of repeating negative behaviour. They are also likely to have poor coping skills, and difficulty with interpersonal relationships.

Effectively, therefore, the same ‘stressor’ can have very different effects on people, depending on their resilience. This resilience can be both psychologically and physically determined, and is hugely important. A ‘strong’ person can cope with stressors that might seriously damage a ‘weak’ person.

Some people say that stress can be simplified into the flight or fight response being constantly activated and eventually ‘burning’ out. Whilst it is true that a constantly stimulated flight or fight response is key to understanding the physiological damage that ‘stress’ causes, it is not the only factor in play.

A lack of social support is not the same thing as the flight or fight response. However, it can create significant problems with production of stress hormones. Depression is not the flight of fight response going wrong. Not having human contact, or touch, can damage your hormonal and autonomic/unconscious nervous systems just as much as being bullied.

In short, stress is not just determined by external factors, such as perceived – or real – threat. A vastly important aspect of stress lies within the individual, their responses to life events, and their resilience. As social animals, loneliness is just as damaging, if not more so, than someone threatening to fire you.

In my world, therefore, being depressed is a form of ‘stress’, and it causes exactly the same type of physiological damage as, say, post-traumatic  stress disorder. This is why you cannot look at an event in someone’s life e.g.  losing their job, or getting divorced, or suffering a car crash and loss of a limb, and score this from one to ten on how stressful this is.

  • Loss of job =2
  • Moving house = 3
  • Getting divorced = 4

For some people losing a job may be a blessed relief. For other a terrible humiliating shame. Others may just shrug their shoulders and move on.

For some of us, an apparently trivial event can be devastating e.g. a passing comment on our appearance.  Others will just laugh it off. Some years ago I was told by a doctor that stress couldn’t be a cause of heart disease because he had seen a well-off lady living in rose covered cottage in the country who had just had a heart attack.

I just replied ‘How do you know she wasn’t stressed?’ The externally idyllic existence may, in reality, be a battleground. Perhaps her smiling, smart, well-off, magistrate husband got home and beat the living daylights out of her every weekend. If so, it wouldn’t be the first time – and most certainly would not be the last.

In short, there is no point in guessing if someone is stressed. Often, there is no point asking them either. Most of us play complex internal games with regard to stress. Where it is considered a badge of honour to be ‘stressed’ and working incredibly hard – people will tell you how stressed they are. – even if they are not. Equally, if you have had a terrible upbringing, you may be so desensitised to stress that you cannot even recognise that you are suffering.

At this point I should probably attempt to bring together what makes up the concept of ‘stress’

Stress consists of stressors, and the stressee. Stressors can be positive, or negative. They can be psychological, or physical.

The same stressor can have a completely different impact on the stressee depending on their resilience.

Resilience can be damaged by such factors as:

  • Abuse in childhood
  • Long-term illness
  • A lock of supportive relationships, friends, family, church

Resilience will be improved by

  • A loving upbringing
  • Good health
  • Supportive relationships
  • Good interpersonal skills

There is no point in guessing is someone is suffering the physiological consequences of stress. Equally, there is no point in asking someone if they are stressed – they may well not know. The only way to know if someone is actually suffering from the consequences of repeated negative stressors is to measure their biochemistry and physiology.

Part two: How to measure if a person is ‘stressed’.

Does treating high blood pressure do any good?


Although I am most interested in the medical madness surrounding cholesterol lowering and statins, I have long been interested in the parallel ‘Looking Glass’ world of blood pressure lowering. During a recent on-line discussion, someone recently sent me a link to study from two or three years ago which re-ignited my interest in this area.

‘A new review has found that lowering blood pressure below the “standard” target of 140/90 mm Hg is not beneficial in terms of reducing mortality or morbidity1.’ July 2009

It confirmed, or re-confirmed, what I have long believed to be true. Unless the blood pressure is very high, lowering it seems to be an exercise in ‘sweeping a symptom under the carpet,’ rather than doing anything remotely useful. However, before discussing the management of raised blood pressure in more detail, I need to establish a little context.

The average blood pressure of an adult is around 120/70mmHg. The 120 ‘systolic’ figure represents the highest pressure reached. This happens just after the heart has finished contracting. The 70 ‘diastolic’ figure represents the lowest pressure, occurring just before the heart contracts again (there is no time for it to drop all the way down to zero).

There is no doubt that, if the pressure is very high, say 200/120, that this is associated with a greatly increased risk of stroke, heart failure and other form of cardiovascular disease. No-one disagrees with this, not even me.

There is also no argument that lowering an extremely high blood pressure can be lifesaving. But, or perhaps there are many different buts here. Things are far less straightforward when it comes to a moderately raised blood pressure.

The first question to ask is. What exactly are we ‘treating’ when we lower it? A raised blood pressure is not a disease. It is not even symptom of a disease; because a raised blood pressure does not cause any symptoms unless it is extremely high. A raised blood pressure is simply a sign, or a measurement.

What is it a sign of? It is a sign that your heart is pumping so hard that the blood pressure is raised above the ‘normal’ level. Why would the heart pump too hard? It is statement of the obvious to say that it cannot just happen for no reason at all.

In some cases, an underlying cause can be found. If you have a narrow renal (kidney) artery, for example, this reduces blood supply to the kidney. The kidney therefore believes that the blood pressure must be too low, and it releases hormones designed to raise the blood pressure. Cause and effect.

In a case like this, you can do an operation to widen the renal artery, the blood flow to the kidney increases, and the blood pressure normalises. In around five per cent of cases of high blood pressure a cause, such a renal artery stenosis, can be found. In the other ninety five per cent there is no obvious reason.

At which point, something very strange happens. Instead of calling this ‘a raised blood pressure where no cause can be found,’ the medical profession decided to turn a clinical sign into a disease. This disease is Essential Hypertension, which literally means ‘a raised blood pressure where no cause can be found.’ But you have to admit that essential hypertension sounds rather more impressive.

Once it became a de-facto disease, it can be ‘treated.’ And so it came to pass that, over time, a whole series of drugs were developed. Some reduce the blood volume, some relax the blood vessels, some block the production of hormones designed to raise blood pressure, and others prevent the heart pumping too hard.

They come by names such as thiazide diuretics, beta-blockers, alpha-blockers, angiotensin converting enzyme inhibitors, angiotensinogen II inhibitors etc. etc. After statins, these are the most prescribed type of medications. Around the world, hundreds of millions of people take them each and every day.

This mass pharmacological assault happened before anyone had actually established that lowering blood pressure was actually beneficial. There had been a couple of short term studies on people with very high blood pressure. These did show benefit.

However, when it came to moderately raised blood pressure, there were absolutely no studies at all. Yes, you did read that right. No studies. It was not until the 1970s that anyone actually set out to answer this rather fundamental question by setting up a major study. The UK Medical Research Council (MRC) study.

Recruitment started in 1973. Seven hundred thousand people were contacted, and half a million people accepted an invitation to participate.  As is the way with such things, this enormous initial number was whittled down to just under eighteen thousand people who had a diastolic blood pressure between 90 – 109, and a systolic pressure below 200.

The eagerly awaited results were released in 1985. I remember the year well, as I was at a cardiovascular conference at the time. Everyone was convinced that that there would be major benefits.

And what were the results? Well, if you get down to the most important outcome of all, which is overall mortality, there were 248 deaths in the treated group and 253in the placebo group2. Or to put this another way: 248 out of 9000 died in the treatment arm died, and 253 out of 9000 died in the placebo arm:

Overall mortality: 248/9000 = 2.75% (treatment group)

Overall mortality: 253/9000 = 2.81% (placebo)

The total difference in deaths was seven. The absolute percentage difference in deaths was 0.06% over five years. There was no difference in the death rate from heart disease.

I remember thinking at the time. ‘Blimey that should throw the cat amongst the pigeons. We are going to have to re-think this area.’ How wrong could one man be? Because the result of the MRC study was that absolutely nothing changed. There was no re-think, no fundamental review, nothing.

Men occasionally stumble over the truth, but most of them pick themselves up and hurry off as if nothing ever happened.’ Sir Winston Churchill.

Actually, it is not entirely true to say that nothing happened. Within the world of anti-hypertensive therapy a subtle, but critically important, change did take place. Whilst there was no benefit on heart disease, or life expectancy, there was a small, but statistically significant, effect on stroke. One stroke delayed for around nine hundred years of treatment.

At this point, the research community started to combine stroke and heart disease under the heading ‘cardiovascular disease’. It was then reported that blood pressure treatment reduced total deaths from cardiovascular disease. Which is true. The fact that there was no impact on Coronary Heart Disease and/or overall mortality was gradually pushed into the background

Nowadays, when people report on blood pressure lowering, the discussion is almost entirely focussed on cardiovascular mortality (which basically means stroke).

In a parallel move, researchers started to move away from outcome data e.g. death from stroke and heart disease, and began to use a mathematical model (the log-linear model) to define the success of lowering blood pressure3.

Once you decide that the lower you get the blood pressure the better this is, you no longer need measure death from heart disease and stroke and suchlike. You just measure the blood pressure reduction, feed these data into the log-linear model, then you can establish the clinical benefit you must have had.

There is just one slight problem. This model doesn’t actually work in practice. Twenty years ago Ancel Keys – the man who created the diet-heart hypothesis – concluded that the linear model was useless. Twelve years ago, a group of medical statisticians re-analysed the original data which underpinned the log-linear model and they concluded the following:

‘Shockingly, we have found that the Framingham data in no way supported the current paradigm to which they gave birth. In fact…. The paradigm MUST be false4.’

They went on to make the following statement:

‘No randomised trial has ever demonstrated any reduction of risk either overall, or cardiovascular death by reducing systolic blood pressure to below 140mmHg.’

The effect of their analysis was, as you may expect, a deafening silence. This was despite the fact that these researchers had just proved that everything that everybody believed about lowering blood pressure was wrong. The log linear model rules, lowering blood pressure is beneficial.

Nine years later, another analysis appeared. The one mentioned at the start of this article. It exactly the same thing…. again:

‘A new review has found that lowering blood pressure below the “standard” target of 140/90 mm Hg is not beneficial in terms of reducing mortality or morbidity1.’ July 2009

During that twelve year period between these two studies, the thresholds for ‘treating’ blood pressure became lower and lower. For diabetics, essential hypertension has now fallen to a systolic of 115mmHg. This definition was created from combined end-point cardiovascular data, and the log-linear model. The one that has been proved ‘shockingly’ to be false. I wasn’t that shocked.

In fact, only one thing shocks me. It is fact that you cannot get anyone to change their minds in this area. A raised blood pressure is bad, and must be lowered, full stop. Whilst I would agree that a raised blood pressure is ‘bad’ in that it is associated with and increased risk of premature death. I cannot find evidence that lowering the blood pressure does any good, no matter what the level.

The simple fact is that when blood pressure is raised, it is raised for a reason. The reason is an underlying ‘disease’. And just because you cannot find it, does not mean that it doesn’t’ exist.

Lowering the blood pressure will certainly get rid of an annoyingly high measurement, but it cannot (unless by complete coincidence), have any impact on the underlying disease…… the thing causing you to die. So, unless it is startlingly high, what good can lowering blood pressure actually do?

The answer my friend, is not blowin in the wind. The answer is ‘no good at all.’

1: http://www.medscape.com/viewarticle/705670?src=mp&spon=2&uac=97302DZ

2: MRC trial of treatment of mild hypertension: principal results. Medical Research Council Working Party: BMJ 1985;291(6488):97

3: Stamler J. Blood pressure and high blood pressure, aspects of risk. Hypertension 1991; 18(Suppl I): I–95 – I – 107

4: Port S, Garfinkel A, Boyle N:  There is a non-linear relationship between mortality and blood pressure. EHJ (2000) 21 p 1635-1638