Some of you may have noticed this study, others may not. The amazing ‘wonderdrug’ trial proving that cholesterol lowering drugs have unparalleled benefits on preventing stroke. Here is just one headline from the Daily Express. A major newspaper in the UK.
Statins slash stroke risk by 30 per cent: Millions more should be given drug, say experts
New research has found that the wonderdrugs – which include statins and fibrates – can slash the risk of suffering a stroke by a third in the elderly. And experts now say there is clear evidence that even among the over-75s – a group not routinely prescribed statins – people can benefit from the life-saving drugs.
It is yet more evidence that the cholesterol-lowering drugs are lifesavers and that their benefits outweigh the potential side effects. Lead researcher Christophe Tzourio, Professor of Epidemiology at the University of Bordeaux and Inserm, said: “A one third reduction in stroke risk, if confirmed, could have an important effect on public health.”1
And so on and so forth.
Colleagues of mine love to wave articles like this at me with a triumphant smirk. ‘Seems you’re wrong about cholesterol lowering after all.’ What do you say to that? Eh..’ I usually ask them if they actually read the study. ‘Primary prevention with lipid lowering drugs and long term risk of vascular events in older people: population based cohort study.’2 I ask them this question, but I know that they’ve not. I find it rare to come across a doctor who would ever deign do such a thing as read a scientific paper.
However, when studies like this come out, I do feel the need to raise my enthusiasm to a sufficient level to have a peek at the paper. In this case it was rather easy. This paper was published in the British Medical Journal (BMJ), and I get it delivered to me every week by post. What a quaint thing, actual physical reading material.
My first problem, before I even started reading this study, is that I knew beforehand that a raised cholesterol level is not a risk factor for stroke. Never has been, not anywhere, not in any study I have read. Whilst you can find studies claiming that a raised cholesterol level (LDL) is a risk factor for heart disease [ and you can find others that show the opposite], I have yet to find any study demonstrating any association between raised cholesterol and stroke.
Here, for example, is a short extract from one massive study, the biggest, which looked at four hundred and fifty thousand people over seven million years of observation. It was published in the Lancet:
‘The associations of blood cholesterol and diastolic blood pressure with subsequent stroke rates were investigated by review of 45 prospective observational cohorts involving 450 000 individuals with 5-30 years of follow-up (mean 16 years, total 7·3 million person-years of observation), during which 13 397 participants were recorded as having had a stroke.
Most of these were fatal strokes in studies that recorded only mortality and not incidence, but about one-quarter were from studies that recorded both fatal and non-fatal strokes. After standardisation for age, there was no association between blood cholesterol and stroke except, perhaps, in those under 45 years of age when screened. This lack of association was not influenced by adjustment for sex, diastolic blood pressure, history of coronary heart disease, or ethnicity (Asian or non-Asian).3 [My bold].
Now, if you are unable to find an association between cholesterol levels and stroke in seven point three million years of observation then, you know what, it just ain’t there. In fact, I challenge anyone reading this blog to provide any evidence that cholesterol levels are associated with overall stroke risk. Gulp, that makes me hostage to fortune.
This is why stroke associations struggle when they talk about cholesterol and stroke. They seem desperate to say that raised cholesterol levels cause stroke, but just can’t. Here is how the National Stroke Association fudges the issue.
‘High cholesterol may raise your risk for stroke by increasing your risk for heart disease, a stroke risk factor.4’
Whilst it is, of course, true that having heart disease does increase your risk of stroke, and vice-versa, the rest of this statement reveals a yawning gap in logic [For the sake of this argument, let us assume it is true that a raised cholesterol causes heart disease].
A (raised cholesterol) → B (heart disease) →C (Stroke)
A does not → C
Question. If A does not lead to C, how does A lead to B, then leading to C? I shall ask for this to become a question in the Oxford and Harvard entrance exams.
[BTW, if you can work this one out, then please feel free to let me know how it works. Exactly.]
Anyway. We find a study demonstrating that two cholesterol lowering drugs, in this case statins and fibrates, significantly reduce the risk of stroke. But a raised cholesterol level is not a risk factor for stroke. Which means that there can be no possibility that the benefit seen can have been due to cholesterol lowering? That, my friends, is simple logic. No need for Oxford and Harvard to get involved at all. This could be discussed on entrance to kindergarten.
Now, just to add to my short analysis this study I would like to draw your attention to something not remarked upon by the popular press at all. However, I thought that you may find it interesting. It was the following statement from the paper:
‘We found no association between lipid lowering drug use and coronary heart disease (hazard ratio 1.12, 0.90 to 1.40).’ [For those who hate figures/confidence intervals, sorry, I left them in for those who like them].
This was the dog that did not bark in the night.
In summary, here we have a study showing that cholesterol lowering reduced the risk of stroke, when a raised cholesterol level is not a risk factor for stroke. On the other hand, it failed to show any benefit on reducing the risk of heart disease. Some would consider that a study such as this raises more questions than answers. However, with wearisome inevitability, it has been twisted around to provide further proof that everyone should be taking statins. Sigh.
2: Alperovitch et al: BMJ 25 May 2015 pp12.
3: Cholesterol, diastolic blood pressure, and stroke: 13 000 strokes in 450 000 people in 45 prospective cohorts The Lancet Volume 346, Issues 8991–8992, 30 December 1995, Pages 1647–1653