A new paper by me – please share widely

26th August 2022

And so, after a great deal of faffing about, my article on cardiovascular disease ‘Assessing cardiovascular disease: looking beyond cholesterol’ has been made free to view.

Writing an article for a medical journal is not that difficult. Trying to submit it through Kafkaesque editorial systems, now, that is tricky. They seem incapable of understanding that I am not funded by anyone. Shock, horror, I do it simply for the love of science – or something of the sort.

As for allowing the article to be open access … don’t go there. I would rather fill in a US tax form, in triplicate and, yes, I have seen US tax forms in all their incomprehensible glory. I also spent considerable time trying to explain to the editorial team that the two risk calculators I discussed in the paper could not be referenced in the approved Vancouver style.

Vancouver style: required elements:

Author. Title [Type of medium]. Place of publication: Publisher; Date of publication [Date of update/revision; Date of citation]. Availability.

I could not use Vancouver style because there was no author, place or date of publication – to start with. They were both on-line tools used to assess cardiovascular risk. Helloooo… ever heard of the Internet. Thud!

Anyway, I was invited to write the article by Dr Eric Westman, who was the guest editor for this edition of ‘Current Opinion in Endocrinology, Diabetes and Obesity.’ In truth, I get about fifty invites a day to write articles. This is not a boast, anyone who has written almost anything that has been published in a medical journal is bombarded with such requests. New journals spring up like desert flowers after the rain.

Most of the requests are, essentially, vanity publishing. You spend ages putting together a paper that you then must pay to get published – you certainly have to pay a lot to allow open access. Usually thousands of dollars. The publisher meanwhile gains copyright. Then hardly anyone ever reads it. But, hey, you can send a copy to your mum – who will be very proud. If none the wiser what you are trying to say.

Thus, I do not respond to such requests normally. But in this case, I did. Eric Westman is a staunch ally in the crusade to look at different causal models of cardiovascular disease. Models not based on LDL/cholesterol levels.

For this edition he also invited others e.g., David Diamond to write other articles casting doubt on the LDL/cholesterol hypothesis – in the proper scientific manner. Dr Westman then paid to make them open access. A cost running into many thousands of dollars. Good man.

Anyway, here it is.

For those who have read my blog assiduously, or have read ‘The Clot Thickens’, none of this is new, or any surprise. However, I hope that it does add some more scientific credibility.  Here is the abstract.


Purpose of review

The low-density lipoprotein (LDL)-cholesterol level is a weak predictor of developing cardiovascular (CV) disease and can only explain a small proportion of CV risk. It is not used to determine CV risk on either the atherosclerotic cardiovascular disease (ASCVD) calculator in the United States, or the Qrisk3 in the UK.

A study in JAMA in 2022 suggested that ‘the absolute benefits of statins are modest and may not be strongly mediated through the degree of LDL reduction’. Perhaps it is time to look beyond cholesterol to a different causal model – the ‘thrombogenic’ model of ASCVD.

Recent findings

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV2) pandemic demonstrated that infectious agents damage the endothelium and the glycocalyx – the glycoprotein layer protecting underlying endothelial cells. There are numerous other conditions leading to this kind of damage, which can trigger thrombus formation, causing strokes and myocardial infarctions.

Although these are acute events, they highlight a mechanism for the development of ASCVD which centres on endothelial damage and thrombus formation as both the primary causal mechanism for acute events, and the driver behind progression towards atherosclerotic plaque development.


The cholesterol hypothesis, that a raised LDL is directly causal for ASCVD, does not adequately explain cardiovascular risk in individuals, or populations. An alternative ‘thrombogenic’ hypothesis is proposed as a more valid causal model.

Here are the key points


  • Low-density lipoprotein (LDL)-cholesterol is a weak predictor of cardiovascular risk
  • Factors that drive endothelial damage and thrombus formation greatly increase atherosclerotic cardiovascular disease (ASCVD) risk.
  • The thrombogenic can explain a number of causal risk factors that do not fit within the LDL-cholesterol hypothesis, including type II diabetes, smoking and systemic lupus erythematosus.
  • The thrombogenic hypothesis, that endothelial damage and subsequent clot formation underlies the formation and growth of plaques, may represent a better model for ASCVD.
  • There is a need to research the thrombogenic hypothesis in more depth.

Stripping away the scientific obfuscation which is now required of all scientific writing. If anyone understands what you are trying to say, you lose. The two points that I was trying to make were the following:

  • The LDL/cholesterol hypothesis is most likely wrong. It is a weak predictor of risk, at best, and cannot explain how many factors known to increase the risk of cardiovascular disease, actually cause cardiovascular disease.
  • There is an alternative hypothesis, the ‘thrombogenic’ hypothesis which can explain how, and why, many different, apparently unconnected factors actually do cause cardiovascular disease.

I hope that the readers of this blog can make as much noise about it as possible and share it as widely as possible. You may even want to read the entire paper. It is not very long, and it is not too technical. At least I don’t think so.

Thank you.

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