did I miss the reason for why LDL particle number (LDL-P) could be a better measure for heart disease risk compared to LDL-C? Is it just what is observed in practice? I’m curious about the mechanism that could cause this.
If LDL-C is controlled for, I would expect the outcome to be the same. Reasoning is, increased LDL-P should inversely correlate to cholesterol per particle, so even if more particles end up penetrating blood vessels, they each contain, and deposit, relatively less cholesterol than larger particles. Conversely, lager particles means fewer particles available to enter blood vessels, but when they do, they deposit relatively more cholesterol.
So it’s a wash. I guess the relationship is not linear. What gives?
As with most things, it is much more complex than this simple, linear relationship. There are a number of other variables at play. This is why we can’t intuitively deduce these kinds of things from first principles, but instead have to figure this stuff out empirically. This is how we figured out that there is indeed a clear relationship between LDL-C and heart disease risk, but that the total number of potentially atherogenic particles (measured by ApoB) provides an even better risk estimate. We also observed what happens in situations of “discordance”; that is, that even if LDL-C is lower, if ApoB remains high, risk is a bit higher. Conversely, if LDL-C is higher, but ApoB remains low, risk is a bit lower. These findings (that risk tracks better with ApoB/particle numbers) are discussed in the article series with supporting references linked in the text.