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1/ Interesting timing, @LDLSkeptic -- @siobhan_huggins and I are coauthoring a post that lays out the "lipoprotein-centric" vs "lipid profile-centric" schools of thought.
But since this has come up a lot in the last 24 hours, I'll do a twitter thread on the overview... https://twitter.com/LDLSkeptic/status/1294686742210125825
But since this has come up a lot in the last 24 hours, I'll do a twitter thread on the overview... https://twitter.com/LDLSkeptic/status/1294686742210125825
2/ Almost everyone takes the "lipoprotein-centric" view of risk. That is to say, most believe there's a particular lipoprotein metric to watch for. The troublemaker, as it were.
For conventional medicine, that's all ApoB-containing lipoproteins (remnants and LDL, of course)...
For conventional medicine, that's all ApoB-containing lipoproteins (remnants and LDL, of course)...
3/ For many in the low carb space it's a subset of LDL. Specifically, the "small dense" particles, rather than the "large buoyant" particles with the latter generally considered safe.
Also, and related, many point to oxidized LDL (oxLDL) or glycated LDL as the true troublemaker.
Also, and related, many point to oxidized LDL (oxLDL) or glycated LDL as the true troublemaker.
4/ But as I say in many of my presentations, I'm very skeptical that any lipoprotein starts out as inherently atherogenic.
Rather, I believe the levels of lipids being discussed are frequently a *reflection* of a broken system - such as diseases resulting in chronic inflammation
Rather, I believe the levels of lipids being discussed are frequently a *reflection* of a broken system - such as diseases resulting in chronic inflammation
5/ I often bring up atherogenic dyslipidemia (AD), which is where one has low HDL-C and high triglycerides (TG)
And this typically results in that predominance of small dense LDL particles (sdLDLp) @LDLSkeptic mentions above.
And this typically results in that predominance of small dense LDL particles (sdLDLp) @LDLSkeptic mentions above.
6/ But the reference range for sdLDL levels is an absolute number (≥500 nmol/L) rather than a percentage of the total.
People who are very fat adapted with high HDL and low TG (the reverse of AD) will often have 0-30% of their total LDLp as smLDLp.
People who are very fat adapted with high HDL and low TG (the reverse of AD) will often have 0-30% of their total LDLp as smLDLp.
7/ Yet I see these same percentages in people who are on a high carb, low fat diet. They might have an LDLp of 810 with smLDLp of 220, for example.
This is one of the massive reasons we need to be studying *healthy* low carbers to confirm this context.
This is one of the massive reasons we need to be studying *healthy* low carbers to confirm this context.
8/ Look at these two profiles:
(a) I have someone within my family who has an HDL < 30, TG > 1000, with LDLp of 700, and sdLDLp of 600 (on cholesterol lowering Rx)
(b) I have a LMHR friend with HDL >80, TG <50, LDLp 3,500, smLDLp of 1,000
Who do you think is more at risk?
(a) I have someone within my family who has an HDL < 30, TG > 1000, with LDLp of 700, and sdLDLp of 600 (on cholesterol lowering Rx)
(b) I have a LMHR friend with HDL >80, TG <50, LDLp 3,500, smLDLp of 1,000
Who do you think is more at risk?
9/ No question, I'm far more worried about the family member with AD, even if their smLDLp is nearly half of the LMHR friend (in absolute num), it's a difference of 85% of the total vs 28%
But in case you were looking to codify this as my new preferred risk ratio, think again...
But in case you were looking to codify this as my new preferred risk ratio, think again...
10/ The whole point of this thread is to get away from seeing a single metric (or ratio).
If the "lipid profile" comprising the pattern of multiple markers (such as AD) are much stronger in association of risk than a single metric, we have to think of this systemically.
If the "lipid profile" comprising the pattern of multiple markers (such as AD) are much stronger in association of risk than a single metric, we have to think of this systemically.
11/ For example, if we know T2D often results in both (1) more of an atherogenic dyslipidemic lipid profile, and (2) more cardiovascular disease risk...
...why start with the assumption (1) caused (2)?
Or put differently, how do we know T2D *didn't* result in both (1) and (2)?
...why start with the assumption (1) caused (2)?
Or put differently, how do we know T2D *didn't* result in both (1) and (2)?
12/ Many of you may remember the #LCCholesterolChallenge that focused on exactly this.
As irony would have it, it was two years ago yesterday that I posted an #LDLBounty to go along with it, which is still unclaimed, btw. https://cholesterolcode.com/lccholesterolchallenge-six-month-update/
As irony would have it, it was two years ago yesterday that I posted an #LDLBounty to go along with it, which is still unclaimed, btw. https://cholesterolcode.com/lccholesterolchallenge-six-month-update/
13/ Even when just keeping it to three metrics: 
LDL-C, HDL-C, and 
TG, I find this is commonly associated with longevity in NHANES.
It doesn't tell us everything -- but it certainly appears to tell us a lot more than one of these metrics by itself. https://twitter.com/DaveKeto/status/1123239136322674688?s=20
LDL-C, HDL-C, and TG, I find this is commonly associated with longevity in NHANES.It doesn't tell us everything -- but it certainly appears to tell us a lot more than one of these metrics by itself. https://twitter.com/DaveKeto/status/1123239136322674688?s=20
14/ In short, I feel trying to identify a lipid metric without looking at the whole is problematic. And the reason for this is that I believe lipid profiles are generally more about the heath status association with atherosclerosis than being the independent cause of it
