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In summary
* This is the first of a two-part note reviewing the classic Ference et al consensus statement on LDL and ASCVD, which was published in 2017.
* The publication claimed that low density lipoproteins (LDL) (one of the five major carriers of lipids) cause atherosclerotic cardiovascular disease (ASCVD).
* This first note examines the mechanism by which LDL is claimed to cause ASCVD. It’s a slippery mechanism to review because one minute it’s LDL, then it’s apoB-containing lipoproteins more generally, then it’s very small apoB-containing lipoproteins specifically.
* Ference et al used the Bradford Hill criteria to move from the claim that LDL and ASCVD are associated, to LDL causes ASCVD. This first note presents their list of eight of the nine criteria and their claim for how each criterion has been met.
* For four of the eight Bradford Hill criteria, Ference et al use Familial Hypercholesterolemia (FH) as evidence. FH is a (rare to extremely rare) genetic condition that impairs the body’s ability to remove LDL from the blood stream, resulting in consistently high levels of LDL. FH also results in heart disease, but only in certain age groups and in certain circumstances. The claim that LDL is high in people with FH and ASCVD is high in people with FH and therefore LDL causes ASCVD does not withstand scrutiny.
Please note, there is a glossary at the end of this note for terms used within it (ASCVD, LDL apoB-containing lipoproteins etc). This note does get technical in places – not least because the claim that LDL causes ASCVD gets technical and so the rebuttal also gets technical. On my final read-through of this note, I found that the most technical bits are the verbatim extracts (in italics) from the Ference paper and other papers. Hopefully, my narrative either side is simpler, so skip bits as suits you to follow the arguments.
Zoe
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