Thread by @TheCuriousAhmed

Both ApoB and LDL-P measure the same target i.e LDL particle concentration, yet discordance between the two metrics usually occur.

An example, this study (Krauss et al) we analyzed earlier, SFA significantly increased ApoB, but not LDL-P.
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https://mobile.twitter.com/TheCuriousAhmed/status/1065745460839759873

On the other hand, in this study (Maki et al), MUFA decreased ApoB, yet increased LDL-P.

This study seem to indicate that LDL-P doesn't necessarily go with the same direction as ApoB.
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https://mobile.twitter.com/TheCuriousAhmed/status/1065789387143811072

Also another example is this study (Jarauta et al), which compared the difference in lipoproteins between Familial Hypercholesterolemia (FH) and Familial Combined Hyperlipidemia (FCH).
ncbi.nlm.nih.gov/m/pubmed/21196…
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In this study, FCH had similar or slightly higher LDL-P than FH, yet lower ApoB than FH.

ApoB is unlikely to be a marker of remnant lipoproteins (such as IDL or VLDL), since FCH also had higher levels of these lipoproteins than FH, yet ApoB was lower.
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So, how could two metrics that measure the same thing could be discordant?

My hypothesis is that, ApoB assay don't seem to capture smaller LDL particles, particularly very small LDL particles (LDL IV or LDL4).
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We found that in Krauss et al study, SFA feeding decreased very small LDL particles and increased larger particles.
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In Maki et al study, MUFA seemed to decrease larger particles and increase smaller particles, although not statistically significant. Overall, these particles don't carry much cholesterol, so any increase may not be so observable using LDL-C.
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LDL-C/LDL-P ratio is also decreased in this study, this suggests that MUFA decreased LDL-C in this study by decreasing particle size.
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(Note: the effect of MUFA in the previous study is the opposite to Krauss et al study, where smaller LDL particles decreased and larger LDL particles increased, therefore average particle size increased and LDL-P decreased)
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In Jarauta et al study, people with FCH had higher concentration of smaller LDL particles and lower concentration of larger LDL particles compared to people with FH.
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The discordance between LDL-P and ApoB was investigated in this study by Dayspring (@DrLipid) et al
ncbi.nlm.nih.gov/m/pubmed/25911…
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@Drlipid It was found that low ApoB, but high LDL-P (LDL-P > ApoB) is associated with smaller LDL particles (and also IR and other characteristics of MetS), whereas high ApoB, but low LDL-P (ApoB > LDL-P) is associated with larger LDL particles.
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@Drlipid So, in discordant situations, LDL-P is more usuful than ApoB.

That probably explains why LDL-P is more predictive than ApoB, as @kevinnbass pointed out.
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https://mobile.twitter.com/kevinnbass/status/1061639265334018049

@Drlipid @kevinnbass Although SFA probably increase ApoB in some cases (since SFA increase particle size increase), but not necessarily LDL-P?

In Virta, there was a statistically significant reduction in LDL-P but not for ApoB, probably because very small LDL decreased and large LDL increased?
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@Drlipid @kevinnbass Very small LDL particles (LDL IV) -similar to Lp(a)- are unique on their own, their clearance is regulated by Sortilin protein rather than LDLr.
Genetic mutations in Sortillin that increase the levels of this LDL subtype is associated with CHD risk.
lipid.org/sites/default/…
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@Drlipid @kevinnbass Interestingly, insulin inhibit sortilin secretion via mTORC1 pathway, though this pathway also upregulate LDLr.

ncbi.nlm.nih.gov/pmc/articles/P…

@Drlipid @kevinnbass LDLr regulates the clearance of larger LDL particles, whereas sortilin regulates the clearance of smaller LDL particles (as hypothesized by Krauss).

This is probably a noval mechanism by which the reduction of insulin decrease smaller LDL particles and increase the larger ones.