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Best discussion of lipids seen anywhere....ever! Size doesn't matter! Repeat. Size doesn't matter!

Member Forum >> UnKnown >> Best discussion of lipids seen anywhere....ever! Size doesn't matter! Repeat. Size doesn't matter!

jegesq

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Posted: 11/17/2009 3:01:02 AM
 
 I was perusing Jimmy Moore's message forum, searching for a post in which Jimmy Moore might have posted his most recent NMR data from his blood draw at Liposcience's headquarters on October 20, 2009-- all to no avail, since those results have evidently never been posted.   Gotta wonder why, as CADHEART asked in another thread.   But that's not the point of this post.

What I did find was an absolute gem of a discussion.  I'm going to only post the initial question and then Marc's long, long reply.   It's the reply which really matters.   If you're interested, you can read the entire thread at this link

But you don't need to read the whole thing, although I'd recommend it.  But if you read nothing else, read Marc's initial reply (quoted below).

And by the way, you should read the entire discussion, because it's a masterpiece of solid scientific reasoning from Marc dealing with almost irrational bias and misinterpretation of scientific literature from others.  In any event, Marc's initial reply is really the most cogent, solid replies I've seen anywhere.  Forget the rest of the debate on this thread.  If you read nothing else, read Marc's reply.  I don't know who "Marc" is, whether he's a member of TYP or not, whether he's a doctor or just someone interested in the science, but he's one very bright guy: 

Here goes: 

^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^
Posted by a user [name is irrelevant]

Got my NMR LipoProfile Results

Problem is I'm not quite sure how to read it. I am only at the beginning of this Low Carb journey, so I think it has a lot of room for improvement.

LDL Particle Number
LDL-P 2166
Small LDL-P 1469

Cholesterol Total: 209
LDL-C 142
HDL-C 49
Trigl 88

LDL Particle Size 20.7
Large HDL-P 4.7
Large VLDL-P 0.7

But what does it all mean? ;-)
^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^

First to reply was Jimmy Moore, who responded by saying essentially that the poster's lipid values were fine.  More or less.   

Next to reply was another poster, who's views (no offense intended by me here) weren't really very helpful in lending understanding to the original poster (or anyone else for that matter IMHO).

Next to reply was this fellow Marc.  Pay attention becaus what follows is really one of the best explanations of lipidology for the layman I've read anywhere:

^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^

RE: Got my NMR LipoProfile Results

Grab a cup of coffee and pull up a chair. This is going to be a LONG (but hopefully interesting) post!

I can help you with interpretation of the NMR LipoProfile test. Let's start with your traditional lipid values, and then we'll move on to the lipoprotein particle data:

Your Total Cholesterol (TC) is 209. This is slightly elevated according to the National Cholesterol Education Panel Adult Treatment Panel III (NCEP ATP III) guidelines, which specify TC above 200 as "high." NCEP ATP IV should be out early next year, but I doubt if the TC recommendations will change.

Your LDL-C (the cholesterol contained within low density lipoproteins) is 142. This means that you have more LDL-C than 60% of the population. If you are a "low risk" patient, then you would not qualify for treatment. If you are a "moderate risk" patient, then your LDL-C goal would be <130. If you are a "high risk" patient, then your goal would be <100. NCEP issued an addendum to ATP III in July of 2004 establishing an OPTIONAL goal of LDL-C <70 for a new category of patients deemed to have VERY high risk. The American Diabetes Association, American College of Cardiology, and some other guideline-issuing medical societies have performed independent reviews of medical literature, and generally concur with these LDL-C recommendations.

Your HDL-C (the cholesterol contained within high density lipoproteins) is 49. This is "decent" (but not great) if you are male. If you are female, then this is a borderline value. American Heart Association guidelines consider HDL-C below 40 to be "low" for men, and HDL-C below 50 to be "low" for women. Many lipidologists are uncomfortable with HDL-C <50 in men and <60 or in women, but please understand that low HDL-C is primarily viewed as a risk ASSESSMENT lab value. It is not a risk MANAGEMENT lab value like LDL-C (and non-HDL-C, and apoB, LDL-P, etc). NCEP, ADA, ACC, AHA, among others, have all concluded that there is "insufficient data" to establish a specific goal for HDL-C. Low HDL-C is a major predictor of risk, but the guidelines recommend lowering LDL-C (and non-HDL-C, apoB, and LDL-P) as the targets of therapy to reduce risk. This is a very important point - and one that many doctors don't understand.

Your Triglycerides (TG) are 88. This is a pretty good value. The current NCEP guidelines consider TG to be "borderline" if they are 150-200, "high" if they are 200-500, and "very high" if they are >500. When TG are >500, they become a goal of therapy, because very high TG can lead to pancreatitis (not a good thing). When TG are <500, LDL-C is the primary goal of therapy, but if the TG are >200, non-HDL-C becomes a secondary target of therapy. In your case, we have LDL-P data, so I'm going to gloss over non-HDL-C since LDL-P is more predictive. As I mentioned, current guidelines "allow" for TG as high as 150 (and ATP II was ok with TG up to 200). I hope ATP IV lowers the "acceptable" TG down to 125, or preferably 100. A physiologic TG value ranges from 10 to 80, with a mean of ~40. Anything above 80 (or certainly 100) is a potential problem. Why? Because TG are carried within Very Low Density Lipoprotein particles (VLDL). When excessive VLDL particles are present (especially Large VLDL), they interact with LDL particles and HDL particles, and cause these particles to become cholesterol-depleted, and/or smaller. Small HDL particles don't carry as much cholesterol as large HDL particles, and so HDL-C drops. Small HDL particles can also be passed through the kidney and renally excreted (so you start peeing out your HDL-C!). If your LDL particles are small and/or cholesterol depleted, then you have to have a HIGHER NUMBER OF THEM TO CARRY A GIVEN LEVEL OF LDL-C. Here's an important analogy, but first let's debunk a pervasive myth:

There is no such thing as "good cholesterol" and "bad cholesterol." Cholesterol is cholesterol is cholesterol. We call the cholesterol being transported inside High Density Lipoproteins (HDL-C) "good," and we call the cholesterol being transported within Low Density Lipoproteins (LDL-C) "bad." But the cholesterol itself is the same! It's the LIPOPROTEIN PARTICLES that are "good" or "bad!"

Here's the analogy:

Cholesterol is an OIL and blood is WATER-BASED. Oil and water don't mix, so in order for cholesterol to be transported through the bloodstream, it must be carried inside a hydrophyllic lipoprotein particle. Think of the cholesterol molecules as "passengers" riding inside lipoprotein particle "vehicles." If I have an LDL-C of 100 (100 passengers), how many vehicles are they in? I CAN'T KNOW! There could be 20 vehicles with 5 passengers each, or 50 vehicles with 2 passengers each, or 100 vehicles with 1 passenger each. Why do I care about the discordance? Because it's the number of VEHICLES on the road that causes the traffic jam, not the number of PASSENGERS riding inside the vehicles!

As simplistic as this analogy sounds, it is biologically accurrate. Atherosclerosis is a gradient-driven process (as are traffic jams). If you have a high number of LDL particles (LDL-P), then a strong gradient exists, and this strong gradient will force LDL particles to diffuse through the endothelial lining of the arterial wall - in other words, the LDL particles will carry cholesterol into the wall of your arteries, where they can then be retained and oxidized. The lipoprotein "vehicle" will mostly disappear, and the cholesterol that the particle carried into the artery wall will turn into foam cells, and then fatty streaks, and then atherosclerotic plaque. If the plaque ruptures, then you will have a very bad hair day - but keep in mind that it is the LDL PARTICLES (LDL-P) that messed up your hair in the first place!

So if it's the particles that are so danged important, then why are we so focused on the cholesterol inside the particles? Because technological limitations have long-prevented reliable particle number assays, so cholesterol has been used (for decades) as a surrogate marker for lipoprotein particles. We've been using cholesterol for SO LONG that we are now selling Cheerios to people on the basis of lowering their cholesterol - cholesterol is a paradigm - cholesterol is a set of blurry goggles through which most patients (and most doctors!) view cardiovascular risk. The picture becomes clearer when when cut out the surrogate and look directly at lipoprotein particle numbers (i.e. apolipoproteins such as apoB and apoA1, or the NMR LipoProfile test).

With these preliminaries out of the way, we can rapidly move through the NMR lipoprotein particle data:

Your LDL-P is 2166. This is not good. [Mine was 2009, so I can relate.]

LDL-C of 100, 130, 160, and 190 correspond to the 20th, 50th, 80th, and 95th percentiles of the U.S. population. As discussed above, your LDL-C is at the 60th percentile (you have MORE LDL-C than 60% of folks in the U.S.).

Similarly, LDL-P of 1000, 1300, 1600, and 2000 correspond to the 20th, 50th, 80th, and 95th percentiles of the population. Your LDL-P is >95th percentile. As stated above, this is not good. Numerous studies show that LDL-P is a VERY STRONG predictor of cardiovascular risk, even after multi-variate analysis including many other risk factors (including lipid measurements and ratios). A couple of studies have shown that LDL-P is not really much better than TC/HDL-C ratios, or the combination of LDL-C, HDL-C, and TG, but these studies were on people whose LDL-P was "concordant" (similar to) their LDL-C. Your LDL-P is quite a bit higher than your LDL-C would suggest (>95th percentile compared to 60th percentile), so you are "discordant," and LDL-P has a solid track record of out-predicting lipid measurements and ratios in discordant patients. This track record has been acknowledged by THREE different Expert Panels who are all advising that lipoprotein particle number measurements be added to our existing cholesterol guidelines (and all three of these Expert Panels recognize LDL-P by NMR).

I will discuss what to DO about your LDL-P at the end of this post.

Your Small LDL-P is 1469. This has clinical relevance, but NOT in the way that most people think. I will discuss this at the end of the post.

Your LDL Particle Size is "Pattern A." This means that your the average of all of your LDL particle diameters falls into the "large" category (barely). But you have a lot of Small LDL-P too, so how can this be? It's simple. You have a lot of technically "Small" LDL-P, but they're probably not "teeny tiny" - and you have enough Large LDL particles to skew the average LDL size into Pattern A (barely). None of this matters in the way that most people think, as I will discuss shortly.

Your Large HDL-P is 4.7. This is at the low end of "intermediate." If Large HDL-P drops below 4.0, then it is a more predictive marker of Metabolic Syndrome than HDL-C. [Note: There are a few different definitions of "Metabolic Syndrome," but generally speaking a person must have 3 out of 5 parameters in order to have a Metabolic Syndrome diagnosis. HDL-C is one of the 5 parameters, but low levels of Large HDL-P is actually more predictive than HDL-C. "Official guidelines" have not yet recognized this. FYI.] Either way, Large HDL-P is not a goal of therapy - LDL-P is. Worry about your LDL-P - not your Large HDL-P.

Also, data on HDL-C, HDL-P, and HDL size is all over the map. Don't get caught up in any particular "HDL" theory! HDL is a VERY confusing topic, and most doctors don't appreciate the complexities!

Your Large VLDL-P is 0.7, and this is pretty good! It's actually the best lipoprotein particle value you've got, AND it indicates that your low carb diet (and/or exercise) are working! Keep in mind, however, that having a low level of Large VLDL-P is desirable, but it is NOT a "goal of therapy," and it does NOT preclude LDL-related risk.

SO WHAT DO WE DO WITH THESE LAB VALUES?????

1. First the easy stuff. I don't care about your TC, HDL-C (even if you're female it's only 1 point low - and it's not a goal of therapy), your TG are good, Large HDL-P is ok (not great - but not a goal of therapy), Large VLDL is actually quite good (but again, not a goal of therapy).

2. Second, the confusing stuff. You've got a lot of SMALL LDL particles, and I don't care. That's right - I DON'T CARE ABOUT YOUR "small" LDL. What?!!? I'M SUPPOSED TO CARE about those evil little bastard SMALL LDL particles? Right?!!? DOESN'T SIZE MATTER????

Ummm, no.

Anyone who has read this far must clearly have an interest in learning something, so here we go:

As I tell my wife all the time, SIZE DOESN'T MATTER! Big Grin

But seriously, think about these two groups of patients:

- People with diabetes and metabolic syndrome - As a group, these folks have HIGH NUMBERS of SMALL LDL particles, and they have a lot of risk!

- People with Familial Hypercholesterolemia (FH) - This is a genetic disorder that affects 1 out of 500 people. As a group, these folks have HIGH NUMBERS of VERY LARGE LDL particles, and they have a lot of risk!

The commonality is HIGH LDL PARTICLE NUMBER - not size!

THREE Expert Panels have published data in the last 30 months on this topic, and ALL OF THEM focus on LDL particle NUMBER, not size! (ADA/ACC Consensus Statement, AACC Position Paper, 30-person/10-country panel).

Repeat after me: Size doesn't matter, Size doesn't matter, oh, but it sort of matters....bear with me....

Ok, so what do we DO with an LDL-P of 2100+????

If you recall my earlier statements, LDL-P of 2000 = 95th percentile. In other words, 95% of folks have fewer LDL particles bombarding their arterial walls. LDL-P this high is BAD. Period. End of story.

I don't care about the well-meaning-but-ill-informed folks who want to post "their special theory" about lipids or inflammatory markers (i.e. hs-CRP) or imaging techniques like CIMT, EBT, MRI, CT, etc. LDL-P of 2100+ is a PROBLEM. PERIOD. END OF STORY.

Do lipid ratios and/or non-HDL-C predict risk better than LDL-C? Yes!

Do inflamatory markers like hs-CRP or the PLAC-test provide additive risk prediction? Yes!

Do imaging techniques like CIMT, EBT, MRI, and CT have some usefullness? Yes!

Do any of the aforementioned tests give you a get-out-of-jail-free-card for an LDL-P of 2100+? NO!!!!

Jimmy is correct that a low carb diet will improve your LDL particle number, and that is the good news. The BAD news is that you probably need to reduce your LDL-P by ~35% (if you are a moderate risk patient) or by ~55% (if you are a high risk patient). Your risk status should be determined by your doctor.

Low carb diets DO improve lipoproteins, but you are unlikely to get a 35% reduction in LDL-P by diet alone (possible - but not common). And if you are a "high risk" patient, then it will be virtually impossible for you to get your LDL-P <1000 by diet alone.

With an LDL-P of 2100+, I recommend either Vytorin (10/20 or 10/40), or Crestor 10 (with a possible titration to 20). If you doctor is a die-hard Lipitor fan, then ask him to start you with the 20mg dose (although this would be my third choice based upon my review of the outcomes data).

IF you are taking a decent dose of a potent statin such as Crestor (preferred) or Lipitor, or a statin/ezetimibe combination like Vytorin (preferred), and your LDL-P is STILL TOO HIGH, THEN SIZE MATTERS!

If you're taking an above-listed product, and doing your diet and exercise, and you still have a high LDL-P, AND a high Small LDL-P, then add niacin or a fibrate. If you still have a high LDL-P but your Small LDL-P is not high, then titrate the statin, or switch to a more potent statin, or add Zetia or WelChol.

In other words, LDL particle size helps to predict Metabolic Syndrome, and also helps with selecting appropriate pharmacotherapy. LDL particle NUMBER is a goal of therapy - particle SIZE helps to inform treatment decisions.

Now keep reading while I take Jimmy to task: Tongue

JIMMY - Your LDL-P of 1400+ is NOT GOOD! I love what you're doing by promoting the low carb lifestyle, but please realize that LDL-P of 1400+ STILL CONFERS A LOT OF CARDIOVASCULAR RISK! Try generic simvastatin 20mg for $4 per month from Wal-Mart or other competitive pharmacies - please! This low-dose, generic, affordable, SAFE and well-tolerated statin is supported by a HUGE number of outcomes studies. Low carb diets DO IMPROVE LIPOPROTEINS, but a lot of folks need more than just diet and exercise. Please don't talk people out of statins! (and no, I don't have any financial interest in statin sales - I just know the medical literature!) BOTH diet AND pharmacotherapy are important!

In closing, this is an IMPORTANT TOPIC, and I am happy to speak with anyone who has questions. Just call me at the number listed below (between 9am and 9pm EST).

Best Regards,

Marc
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LynneC

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Posted: 11/17/2009 8:01:53 AM
 
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Posted: 11/17/2009 9:14:22 AM
 
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Posted: 11/17/2009 9:34:02 AM
 
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Posted: 11/17/2009 9:41:14 AM
 

Well, to be fair CAD, not everyone clicks on the links you post.  I know that in that particular thread, I sure didn't.  Too bad because I would have found Marc's response sooner.

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Posted: 11/17/2009 9:45:47 AM
 
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Posted: 11/17/2009 10:18:00 AM
 
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Posted: 11/17/2009 11:24:50 AM
 
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Posted: 11/17/2009 11:32:15 AM
 
I did see that Jimmy Moore said this about his own small particle LDL  "small LDL-P being a minuscule 30".
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Posted: 11/17/2009 12:31:10 PM
 
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Posted: 11/17/2009 12:42:38 PM
 
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Posted: 11/17/2009 12:58:09 PM
 
Ralph, any chance to get it done in NJ or other state near you?  (using a friend's address, etc)


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Posted: 11/17/2009 1:09:32 PM
 
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Posted: 11/17/2009 1:38:18 PM
 

Ralph:  while you will need a doctor Rx for it, i am sure you can probably get it done at NYU medical center



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Posted: 11/17/2009 2:07:12 PM
 
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Posted: 11/17/2009 4:17:50 PM
 
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Posted: 11/17/2009 7:10:06 PM
 
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Posted: 11/17/2009 8:28:55 PM
 
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Posted: 11/17/2009 8:29:54 PM
 
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Posted: 11/17/2009 8:40:24 PM
 
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Posted: 11/17/2009 8:45:36 PM
 

LindyBill

who gots the NMR 11/17/2009.  Marc Garber, You, Berserkertooth?

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Posted: 11/17/2009 8:54:36 PM
 
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Posted: 11/17/2009 9:56:06 PM
 
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Posted: 11/17/2009 10:18:26 PM
 
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Posted: 11/17/2009 10:26:47 PM
 
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Posted: 11/17/2009 10:48:06 PM
 
Cadheart:

Jimmy's brother's arteries were totally clogged with plaque at the age of 32. Jimmy is in his middle 40's.  His heart scan score is zero. Saturated fats certainly seems to be protective in his case.
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Posted: 11/17/2009 10:51:58 PM
 
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Posted: 11/17/2009 10:56:21 PM
 
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Posted: 11/17/2009 11:03:12 PM
 
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Posted: 11/17/2009 11:05:17 PM
 
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Posted: 11/18/2009 6:35:14 AM
 
If the trump card on the TYP forum is that CAC scores of zero are meaningless, then we might as well just  discuss who mskes the best flavor of cocao and the forum's ISP response time.
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Posted: 11/18/2009 7:58:38 AM
 
To All:

Fantastic discussion!  I gotta get the WIKI finished to we can better catalog all this info and observation!

HH
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Posted: 11/18/2009 8:12:30 AM
 
So what's more important, calcium score, or LDL-P? I thought the former, but lately sentiment on here seems to be the latter (is this track your LDL?).


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Posted: 11/18/2009 9:02:54 AM
 
I bet he's a great salesman!   : )-
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Posted: 11/18/2009 10:24:26 AM
 
Let us not forget that you get cardiac events from the Plaque in your system. Not from your Lipids. The evidence from a chart showing the increase in events compared to your plaque score is overwhelming, IMO.
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Posted: 11/18/2009 1:42:58 PM
 

Todd.  I don't disagree.  And I'd still like to know who Dr. BG and Dr. T are as well.

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Posted: 11/18/2009 6:15:30 PM
 
Jeg, thanks for a great post.


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Posted: 11/18/2009 8:32:57 PM
 
When Jeg stops posting is when I'll stop reading.  Very valuable, thought provoking "stuff."  Thanks, Jeg.


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Posted: 11/19/2009 9:07:06 AM
 
Well, I was thinking about what Dr. Davis said about the whether Marc is a drug rep. 

My family practice doctor explained lipids in the EXACT same fashion........so, he probably heard it from a drug
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Posted: 11/19/2009 8:14:59 PM
 
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Posted: 11/19/2009 8:24:36 PM
 
Here's another wild suggestion:  Why not also invite Jimmy Moore to drop in from time to time as well.  I think he would benefit from the discussion and we would as well.


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Posted: 11/20/2009 9:38:22 AM
 
Jeg, you may be right regarding where Marc works.    Perhaps his message, since it is very easy to understand, is used 
by a doctors to explain to his patients.   I am glad I read this, though.
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Posted: 11/20/2009 11:28:35 AM
 
I thought I'd heard it here from you!


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Posted: 11/20/2009 1:55:47 PM
 
jeg, I think you are taking too much credit! As I remember G made that statement in a long thread in which several of us took her to task not just to you, though I do admit that you are the mastermind behind many hidden things.:) JJ


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Posted: 11/21/2009 9:14:19 AM
 
Thank you Dr. Davis for the clarification, and apologies that you had to address this issue at all.
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