15th January 2019
In this never-ending story on heart disease, I have tended to use the terms “heart disease” and “cardiovascular disease” almost interchangeably. Well, everyone else does it, so why not me? However, in this blog I shall be splitting cardiovascular disease into its two main components, heart attacks and strokes, and concentrating mainly on strokes.
The first thing to say is that there are three main causes of strokes.
- Atrial Fibrillation (ischaemic)
- A burst blood vessel in the brain (haemorrhagic)
- A blood clot (ischaemic)
[There are also cryptogenic strokes (no known cause), strokes due to a hole in the heart, strokes due to antiphospholipid syndrome, strokes due to sickle cell disease etc. etc.)
Atrial Fibrillation (AF) is a condition where the upper chambers of the heart (atria) do not contract and relax smoothly every second or so. Primarily because there is a disruption in the electrical conduction system, causing the atria to spasm and twitch in a highly irregular fashion.
When this happens, blood clots can form in the left atrium then break off and head up into the brain and get stuck. Causing a stroke. They can also travel elsewhere in the body causing a blockage to an artery in the kidneys, the leg, the arm and suchlike. If they form in the right atrium, they will end up stuck in the lungs.
These clots are usually quite small, about the size of a large grain of rice, but this is still big enough to do quite considerable damage. The treatment for AF is either to try and reverse the fibrillation or, if this does not work, to give anticoagulants such as warfarin to stop the clots forming.
A haemorrhagic stroke is when a blood vessel in the brain bursts. Blood is then forced into the brain and causes a lot of damage – leading to a stroke. Haemorrhagic strokes are usually quite severe, as you can imagine. The treatment is to NOT give an anti-coagulant of any sort. Haemorrhagic strokes are often/usually caused by a thinning of the artery wall, causing a ballooned area (aneurysm), which then bursts.
An interesting question, and I have seen different views on this is whether a small blood clot travels to the brain where it gets stuck, but does not completely block the artery, so it does not cause a stroke, but it creates an area of damage – which is then repaired – that leaves a weakness in the artery that balloons out – an aneurysm.
Anyway, the most common cause of a stroke is that large atherosclerotic plaques form in the main arteries that supply blood to the brain (carotid arteries). These plaques usually form around the base of the neck. A blood clot then forms on top of the plaque, then breaks off and travels to the brain, where it gets stuck – as with atrial fibrillation – causing a stroke. The effect is the same as with AF, but the underlying causing is completely different.
According to the American Stroke Association 87% of strokes are ischaemic.
Which means that the vast majority of strokes are caused by atherosclerotic plaques in the neck. Just as the vast majority of heart attacks are caused by atherosclerotic plaques in the coronary arteries. Therefore, you would expect that the risk factors for stroke would be exactly the same as the risk factors for heart attacks, as the underlying process is the same.
Well, many of the standard risk factors are the same. Smoking, diabetes, high blood pressure and suchlike. However, a raised LDL most certainly is not. There is a research study called the Simon Broome registry, started in the UK, that tracks the health outcomes of people diagnosed with familial hypercholesterolaemia (FH).
It is a fascinating resource which, if you decide to interpret their data through a different prism, virtually rules out the raised LDL in familial hypercholesterolaemia as a cause of CVD. One of the earlier papers in the BMJ, on the findings of the Simon Broome registry, found that:
‘Familial hypercholesterolaemia is associated with a substantial excess mortality from coronary heart disease in young adults but may not be associated with a substantial excess mortality in older patients.’1
For ‘may not be’, replace, ‘is not’. In fact, what the Simon Broome registry has found repeatedly is that, after the age of, about fifty, FH does not increase the risk of coronary heart. Thus LDL is a risk factor before the age of fifty, and not after? Which means that it cannot be a risk factor at all [the thing that kills young people with FH before the age of fifty is clotting factor abnormalities – not raised LDL]
Which is something covered in the magnificent and insightful paper: ‘Inborn coagulation factors are more important cardiovascular risk factors than high LDL-cholesterol in familial hypercholesterolemia.’2 Yes, as you may have guessed, I was a co-author.
However, if we move away from heart disease, to strokes. FH has never been found to be a risk factor for stroke – at any age. Here, for example is a study done in Norway, and published in the Journal Stroke. It was called ‘Risk of ischaemic stroke and total cerebrovascular disease in familial hypercholesterolaemia.’
A total of 46 cases (19 women and 27 men) of cerebrovascular disease were observed in the cohort of people with FH, with no increased risk of cerebrovascular disease compared with the general population (standardized incidence ratio, 1.0; 95% CI, 0.8–1.4). Total number of ischemic strokes in the cohort of people with FH was 26 (9 women and 17 men), with no increased risk compared with the general population (standardized incidence ratio, 1.0; 95% CI, 0.7–1.5).3
In 2010 the Lancet published a major study looking at risk factor for stroke in the non-FH population3. They used the term population attributable risk factors (PAF), which ‘weights’ the factors, depending on how prevalent they are (i.e., how many people have got the various risk factors). Their list of PARs for stroke was as follows:
- 51.8% – Hypertension (self-reported history of hypertension or blood pressure >160/90mmHg)
- 18.9% – Smoking status
- 26.5% – Waist-to-hip ratio
- 18.8% – Diet risk score
- 28.5% – Regular physical activity
- 5% – Diabetes mellitus
- 3.8% – Alcohol intake
- 4.6% – Psychosocial stress
- 5.2% – Depression
- 6.7% – Cardiac causes (atrial fibrillation, previous MI, rheumatic valve disease, prosthetic heart valve)
- 24.9% – Ratio of ApoB to ApoA (reflecting cholesterol levels)
You will see that LDL is not in that list. The ratio of ApoB to ApoA is. However, this is primarily the ratio of VLDL (triglycerides) to HDL (‘good’ cholesterol), which is an accurate reflection of ‘insulin resistance’ and bears no relationship to LDL. As I always say to people who ask me for advice on reviewing clinical research…’the most important thing to focus on is not what is there, it is what is not there.’
Any study on CVD will be examining LDL levels very closely. If a relationship were found it would be shouted from the rooftops. The fact that you hear nothing about LDL in this paper means that there was no correlation – at all.
You can, if you wish, try to find some evidence that the risk of stroke is increased by a raised LDL level. I must warn you that you will look for a long time, because there is no evidence, anywhere – at all. It has interested me for many years that this issue is simply swept under the carpet.
Now, write out one hundred times:
- Raised LDL is not a risk factor for stroke
- Raised LDL is not a risk factor for stroke
- Raised LDL is not a risk factor for stroke….
Then, ask yourself the question. How can a raised LDL be a risk factor for heart disease and not stroke – as the two conditions are, essentially, the same condition? Atherosclerotic plaques in medium sized arteries with the critical/final event being the formation of a blood clot – on top of the plaque.
Then, ask yourself another question. If a raised LDL is not a risk factor for stroke, how can lowering the LDL level provide any benefit? The correct answer is that… it cannot. Yet statins do provide benefit in stroke (Usual proviso here. Not by a great amount in absolute terms, but the benefit does appear to exist).
‘A meta-analysis of randomized trials of statins in combination with other preventive strategies, involving 165,792 individuals, showed that each 1-mmol/l (39 mg/dl) decrease in LDL-cholesterol equates to a reduction in relative risk for stroke of 21.1 (95% CI: 6.3-33.5; p = 0.009)’ 4
Just to repeat the main point here. A raised LDL is not, and has never been, a risk factor for stroke. Yet it is claimed that lowering the LDL level reduces the risk of stroke? In reality, the evidence from the statin trials prove, beyond any doubt, that any benefit achieved by statins cannot be through lowering the LDL level.
The logic stripped down is, as follows:
- A raised level of factor A does not cause disease B
- Thus lowering factor A cannot reduce the risk of disease B
- Thus, you cannot claim that lowering factor A can have any possible effect on disease B
However, every single cardiovascular expert seems delighted to inform us, in all seriousness, that lowering factor A does, indeed, reduce the risk of disease B. Despite this breaking the very fabric of logic in two.
“Alice laughed: “There’s no use trying,” she said; “one can’t believe impossible things.”
“I daresay you haven’t had much practice,” said the Queen. “When I was younger, I always did it for half an hour a day. Why, sometimes I’ve believed as many as six impossible things before breakfast.” Alice in Wonderland.