Marks Daily Apple
Serving up health and fitness insights (daily, of course) with a side of irreverence.
28 Dec

How to Interpret Advanced Cholesterol Test Results

After last week’s post on interpreting traditional lipid tests, I promised a follow-up post on interpreting the advanced VAP and NMR Lipoprofile tests that provide measurements of particle size and all the various sub-fractions of HDL and LDL particles. I even hinted that it might be worth bypassing the traditional test entirely and going straight to the advanced stuff if you were going to get your cholesterol measured anyway, because of the greater accuracy and more detailed picture of your lipids the VAP and NMR tests provide.

Well, I’m going to have to reevaluate my stance on the matter and rethink that original suggestion. Recent evidence shows and commentary from researchers concludes that the various advanced lipoprotein particle classification tests can produce wildly disparate results on the same samples to the point of rendering them unreliable (sound familiar?), especially if we’re going to be evaluating our health based on the results. A 2009 systematic review found that the available LDL subfraction literature “does not provide adequate data about comparability in terms of test performance to choose one or another method to serve as a standard nor are data on comparability in terms of predicting CVD outcomes.” In short, it could – and probably does – have diagnostic value, but there are no real standards for measurement or analysis that would allow us to use the information. Yet.

The only study with a full text available examined four different methods for testing LDL subfraction size. Authors took blood samples from 10 females and 30 males, all healthy and ranging from ages 23 through 61 years, which were then sent out to the labs for testing. Four samples from each person (taken one after the other without any lag time in between) were sent out. Each lab used a different type of LDL fractionation and particle size analysis:

  1. LDL Segmented Gradient Gel Electrophoresis – separates LDL particles into 7 subfractions by size and shape
  2. Vertical Auto Profile-11, or VAP – separates LDL particles into 6 subfractions by size, LDL-1 (most buoyant) through LDL-6 (least buoyant)
  3. NMR Lipoprofile – separates LDL particles into A (large, fluffy, buoyant) or B (small, dense)
  4. Quantimetrix Lipoprint LDL System (sounds like a drug from a Philip K. Dick novel), or tube gel electrophoresis – analyzes lipoprotein sizes and assigns either a normal (less than 5.5), intermediate risk (5.5 to 8.5), or atherogenic (over 8.5) “LDLSF score”

The results “varied considerably among the methods.” According to tube gel electrophoresis, 79% of the people sampled fell into large, fluffy pattern A LDL, while VAP found that only 8% of samples were pattern A. Both VAP and NMR stuck 54% of the people into pattern B, but tube gel electrophoresis classified just 5% (two people) as pattern B. As for type A/B (a roughly equal mix of small, dense LDL and fluffy LDL), VAP classified 2.5 times more samples as A/B than did tube gel electrophoresis and gradiant gel electrophoresis (NMR doesn’t do A/B). For a nice visual of the discrepancies, check out the LDL phenotype distribution data in graph form.

When all was said and done, the four methods agreed on the classification of a mere three people whose lipids they measured. NMR matched the other methods the most and VAP the least, for what it’s worth.

And while it’s true that LDL-C measurements were very different across the different methodologies (as this graph shows), the within-patient relative measurement of LDL-C was maintained across all methodologies; the same was not true for LDL particle size measurements.

I think determining LDL particle size will be helpful in assessing a person’s risk for heart disease. I just don’t think we can use the tests that are currently available to do it, not reliably at least. Which do you choose – VAP or NMR or one of the electrophoresis methods? According to the data, NMR’s more likely to put you in pattern A than VAP, but that’s an indictment of the variability in accuracy of the various methods. Relying on that is just trying to game the system. It might be more or less reliable than VAP, but we can’t know that yet.

Beyond the traditional lipid tests, however, there is a measure that’s worth looking into: Apolipoprotein B.

Apolipoprotein B is a protein residing in LDL particles. In fact, every single LDL particle has a single ApoB, making ApoB an effective measurement of LDL particle count. By all accounts I could find, ApoB is reliable and accurate. Every LDL particle has one ApoB, and along with TC:HD ratio, ApoB count is a strong predictor of heart disease risk (again, with the caveat that these studies are on populations leading a decidedly unPrimal and highly inflammatory lifestyle). If you have a lot of ApoB, you have a lot of LDL particles, which could mean the LDL receptor activity is down-regulated. Or, it could mean you’re losing weight, which can affect lipid values in multiple ways. Or, it could mean that today was a particularly “high ApoB day” and that getting it tested next week will give a different result – simply due to natural fluctuations. You just don’t know.

What I’d really like to see is a little high-def moving graphical representation of your arterial health. Like, instead of getting a single snapshot of the state of your blood lipids, you’d go into the doctor’s office and strap on a non-invasive device (which, if required for its operation, applies the perfect dose of ionizing radiation to provoke a hormetic response, rather than a pathogenic one) that monitors your blood lipid activity. You’d wear it for maybe a week, during which time it would monitor your blood, download the data, and give you a play-by-play summary of what exactly happened in your body. It would even convert it into visual form, so you could watch a nice Pixar-quality video at the end showing cartoon LDL particles with frowny faces oxidizing (or not), interacting with receptors (or not), happy-faced ones delivering cholesterol to be turned into sex hormones, increasing because thyroid health is compromised and LDL receptors down-regulate, decreasing because they’re making more deliveries to cells (good), decreasing because you had a stressful four days of no sleep and low-nutrient junk food and the resulting systemic inflammation was oxidizing them and they ended up as atherosclerotic plaque and no longer in your bloodstream to be measured. Such a device would be great and truly useful.

We don’t have that (yet), but what we do have, while imperfect, isn’t totally useless. Using a traditional lipid test and ApoB, we can still get clues. Next time we talk about this stuff, I’ll go over some strategies for responding to these numbers – if any response is warranted.

Thanks for reading, and be sure to leave a comment in the comment board telling us of your experience with advanced lipid tests, especially if you’ve had several done using different methods (did they agree with each other?).

You want comments? We got comments:

Imagine you’re George Clooney. Take a moment to admire your grooming and wit. Okay, now imagine someone walks up to you and asks, “What’s your name?” You say, “I’m George Clooney.” Or maybe you say, “I’m the Clooninator!” You don’t say “I’m George of George Clooney Sells Movies Blog” and you certainly don’t say, “I’m Clooney Weight Loss Plan”. So while spam is technically meat, it ain’t anywhere near Primal. Please nickname yourself something your friends would call you.

  1. This is why we need the Primal philosophy. It helps us cut through the details and BS and puts sensible decisions within the grasp of mortal man. No wonder we’re all so easily baffled by BS.

    Grokitmus Primal wrote on December 28th, 2011
  2. Many of us are interested in the amount of large , fluffy, buoyant LDL particles vs the less buoyant/dense particles. since the latter are associated with artherosclerosis. I think what ever test was used (no matter how inconsistent the results between various tests) we should stick to one test and track the progress. so far I had 2 tests in the past 12 months, time for a third. is this a plausible strategy???

    PaleoDentist wrote on December 28th, 2011
  3. This is why I focus on triglycerides and VLDL.

    Arty wrote on December 28th, 2011
  4. Its all so irritating, so often these tests they use to prescribe dangerous medications are useless because they cannot get the same results twice in a row! So CW says go ahead and take that messed up medication but we need to advocate for ourselves more and believe them less and this shows that. I think I will just listen to my body more and the doctor less.

    EZ wrote on December 28th, 2011
    • Statins do not work on particle size anyways. So if someone has 260 total cholesterol but with 30 triglycerides, most or probably ALL of the particles are billowy, fluffy.

      So one would start taking drugs to literally RUIN someones perfect health!

      Arty wrote on December 28th, 2011
  5. This is why you should focus on the basics: quality food, quality sleep, lots of activity (including plenty of play!), and quality, real-life social interactions with people you care about.

    The rest is fluff. Health is quality of life, not a number on a lab test.

    Uncephalized wrote on December 28th, 2011
    • That’s right. Mark has gone too deep, so that we don’t have to (Thankyou, Mark).

      Mike wrote on December 28th, 2011
    • Amen, do the right things and f**k the

      Paul wrote on December 29th, 2011
  6. Thanks Mark – good info for me.
    I had a VAP test done after 6 weeks strict primal.
    LDL 183, Pattern A, HDL 47, VLDL 16, TG 60, LP(a) 4, ApoB 126, Apo AI 129, Apo Ratio is .98.
    As mentioned above, every single LDL particle has a single ApoB particle, but this doesn’t state which marker is the one to look at – if my ApoB is the right measurement my LDL is lower that expected which means my TC is lower and therefore TC:HD is better. If the LDL is the right measurement, then, well, I’m in trouble…
    Seems the desirable for ApoB is 109, so I’m a little elevated, but the ratios are ok.
    Seems from this Danish study ratio over 1.2 of Apo seems to be a higher risk factor
    It seems that (not surprisingly) vitamin E and exercise helps reduce ApoB.

    Andy wrote on December 28th, 2011
    • Andy, I was so glad to hear vitamin E helps lower ApoB!!! I looked at the article you linked but did not see that good information. Do you know if its been shown that plain alpha tocopherol (vit. E) or one with mixed tocopherols, and/or mixed tocotrienols is most useful for lowering ApoB?

      mm wrote on March 11th, 2013
  7. Your timing of both these posts was amazing. That day we had just got our results back. since going primal our results went from perfect CW results to not so perfect CW results. I am in the health field and used to interpret results for people in a wellness program and any LDL over 140 I suggested they get it down closer to 100 or else the doc might put them on meds. Now my LDL is 143. I decided from reading these posts and investigating on the web that I am not going to worry, if I am eatting primally and living a healthy lifestyle and my TC/HDL ratio is 2.5 with HDL 91, no need. These labs are not real tests they are just a screening tool. If the results are considered “abnormal” then you investigate further to see if there is reason to be concerned, are there areas in my lifestyle that would support the LDL’s in a bad way leading to heart diease. My investigation was to look at my lifestyle and to see if there is any area I can improve on that might give cause to be at risk. I came up with maybe being more concerned with how much omega 6’s I might be taking in from nuts etc. I used to be a chronic cardio type, still am somewhat so pay attention to that area. Thought about doing the VAP test but after this post why spend the money. Live healthy, watch your P’s and Q’s and don’t worry (stress, a risk) Thanks Mark

    Colleen wrote on December 28th, 2011
    • Hi Colleen,

      You are wise! Btw, I just watched a Danish special based on a new study that argued none of these numbers mean much for women who still have their periods. This study suggested that the better association was your Omega balance. Women with better Omega balances were thinner and had lower rates of heart issues, but the study only looked at 180 women.

      moreporkplease wrote on December 28th, 2011
      • I am old and wise, no longer have those messy ol periods, yay!!!! but traded those in for those damn night sweats and sleepless nites hmmmmmm
        Yes, will watch my omega balances, thanks

        Colleen wrote on December 29th, 2011
        • Those periods become quite tolerant when on a primal diet.
          I used to be in pain to the point of passing out and had my period for 5 days +.

          Now I don’t even feel when it starts and they’re gone by the 3rd day evening.

          I used to have irregular menstruation, but since primal it’s right on time every 28th day between 8 am-10 am it starts and leaves by the 3rd day around 6-8 pm.
          I love it.

          Issabeau wrote on February 14th, 2014
  8. I’m so happy you retracted your initial support of these tests. As a physician who sees a ton of these results, especially since I take care of a highly insulin resistant population, I can tell you that discordant results have left both my patients and myself confused. Most importantly they have not added value to using the more standard lipid profile test which as you know can be more refined through the use of non-HDL scores, TC/HDL ratios and TG/HDL ratios as well to evaluate the effects of a primal or low carb diet. When I have patients go primal or low carb, sometimes I only monitor the triglycerides initially since the other values vary so much over the first few months. Especially a common drop in the HDL with initial body composition changes can be discouraging. I agree that this technology will get better and then we can more reliably monitor our diet and exercise changes. Currently I find the VAP or NMR tests to mostly be useful in my intermediate risk patients. In these patients who have failed lifestyle changes and their numbers are on the edge of requiring medications (which I do my best not to overprescribe!), a positive test will push me further in favor of prescribing medications or hopefully providing additional motivation to get these patients to be more aggressive with lifestyle changes. I use coronary calcium testing in these situations also, but that’s a whole other topic.

    Dr.Ron wrote on December 28th, 2011
    • Ty, Dr. Ron. I also wish Mark would admit women exist. It’s important. Women are different – our numbers are different – these tests apply differently to us – they need to be interpreted differently – but alas in the Paleo world no one will admit that women exist.

      We are different! Vive la difference! When will a paleo person speak honestly about women’s health?

      moreporkplease wrote on December 28th, 2011
  9. This is so frustrating for me, I have been VLC for about 18 months, lost 40# and was on a statin prior to this. I have been off of the statin for 6 months before this test was performed. BTW my HDL increased when I went off of the statin. These are my latest numbers – My doctor can’t interpret these, I have to get an appt with a lipidologist just to find out what this result means.

    Cholesterol – 299 mg/dl
    Cholesterol/HDL – 3.4
    Crea .62 mg/dl
    Glucose 105 mg/dl
    HDL – 88 mg/dl
    HDL Particles – 42.5 (15332984) umol/L
    HDL Size – 9.8 nM
    INS Resistance Score – 4
    LDL – 199 mg/dl
    LDL Particle Numbers – 2202 nmol/L
    LDL Particle Size – 21.9 nM
    Large HDL Particles – 15.9 (15332984) umol/L
    Large VLDL Particles – < 0.7
    Non HDL Cholesterol 211
    Protein TOTA – 7.0 gm/dl
    Small LDL Particles – 179 nmol/L
    Trigs – 61
    VLDL Size – not applicable

    Mary Jo wrote on December 28th, 2011
    • Because your HDL is excellent over 60 is very good and your Trig are only 61(150 is considered normal) don’t be concerned, that’s the least of your problems.
      Your glucose is a little high if it’s at fasting. Non-Diabetic fasting blood glucose ranges from 70 to 90. Of course no one agrees with these numbers.
      For the real information (not ADA) on everything related to diabetes an more check Dr.Richard K Bernstein’s “Diabetes Solution” is worth reading.
      Good Health to You~

      Leo wrote on December 28th, 2011
      • I am one of those people whose fasting glucose is the highest if the day. My glucose actually goes down after I eat. My A1C number is 4.9

        Mary Jo wrote on December 28th, 2011
        • Mary Jo, I had that problem (reactive hypoglicemia) for about 5 years too. It can get to a debilitating condition, be aware. It is perfectly possible to see the blood glucose go all the way down (way below fasting levels) right after eating, especially when eating a higher glicemic load food like carbs, because your insulin response is disproportional.
          I don’t know about you, but in my case the problem was the wrong intestinal flora: I was cured after a full disbiosis (a week of diarrhoea) and recovering with probiotic supplements and foods. (It beats doing fecal transplant!!) 😉

          Vasco Névoa wrote on December 29th, 2011
    • Get off the statins period Mary Jo. Research shows they do nothing – zero, zip, zilch – for women. All these blood numbers have different meaning for women in different life stages – with period, peri-menopause, menopausal.

      But no matter what stage you’re in, statins don’t work for women. They just don’t. So get off them ASAP.

      moreporkplease wrote on December 28th, 2011
      • As I stated in my post, I have been off of the drugs for 6 months. Since then my numbers have gone astray, LDL rising alot.
        That is why I had the particle test done to determine what particle size I have.

        Mary Jo wrote on December 28th, 2011
    • Your TC and LDL-C could be high if you are one of those people in which long-term VLC diets depress the thyroid. The depressed thyroid down regulates the LDL receptor, keeps cholesterol in the blood for longer and then the liver synthesises more.

      Steven wrote on December 28th, 2011
  10. Interesting that the subfraction tests aren’t so accurate. I just got one done using the gel electrophoresis method, not surprisingly my LDL size was nearly all in the top 2 categories. Can’t wait for the next installment!

    Burn wrote on December 28th, 2011
  11. Wow, Mark!
    Just when I thought I knew “everything” you give a cause to stop and question … At my last doctor visit he brought up the subject of cholesterol (idiotic hoax). I asked him; how’s my triglycerides and HDL ? To which his reply was, very good.

    You think I’ll be taking that poison?
    For me, I strive to keep my triglycerides 75 or lower the better. HDL 60 of higher, higher the better and A1C under 5, between 4.6 to 4.9 is my goal. A very low carb diet works for me.

    BTW I really loved your last book…

    Leo wrote on December 28th, 2011
  12. Thank you for all of this information Mark! I’ve been trying to research VAP and NMR tests for a while and this post was extremely helpful.

    I’m a “hardgainer” and have been eating generally 18-24 eggs a day (the best quality eggs I can find). This scared the daylights out of my doctor who recommended that I get my cholesterol tested, but I’d prefer to analyze the results on my own rather than blindly follow someone else’s advice.

    Colin Gordon wrote on December 28th, 2011
    • Very few people looking at research take the ‘dietary cholesterol increases serum cholesterol’ idea seriously. Even the new dietary guidelines for Australians made no mention of it

      Steven wrote on December 28th, 2011
  13. Age 35, male, 185lbs, low bf%

    TC = 506
    HDL 30
    LDL 450
    Tri 131

    Paleo 1 year+

    Should I take statins?

    Bill wrote on December 28th, 2011
    • You work out like mad? Then refeed carbs for the muscles?
      You do this often?

      Arty wrote on December 29th, 2011
    • try lowering carbs

      DThalman wrote on December 31st, 2011
    • @Bill @Mary Jo,
      Paul Jaminet at did a blog series earlier this year about high LDL on Paleo diets. I highly recommend reading the series.
      Best of luck!

      Peter wrote on January 1st, 2012
  14. Apo B is a much better risk factor than LDL-C. LDL-C really plays no part in oxidation and atherosclerosis. Apo B can give you an idea of how many LDL particles you have and therefore the total surface area of the phopholipid membranes. Higher surface areas are exposed to more oxidants. The small, dense may have less cholesterol in more LDL, high surface area. The large, buoyant have more cholesterol in less LDL, low surface area.

    Steven wrote on December 28th, 2011
  15. excellent article and series…

    rik wrote on December 28th, 2011
  16. Great post Mark.

    Erik wrote on December 28th, 2011
  17. Great post Mark, I have nothing to say about the tests, but before I went off statins a couple of years ago I did a CAT scan of my heart arteries which revealed I had no plaque that would show up due to the calcium found in fat. The radiation was none too flash but if you need to be sure there is no risk of a heart attack this is the one.

    •Multidetector computed tomography (MDCT)
    is used to conduct this examination.

    There are other reasons than heart disease for a cardiac arrest but this does a good job of eliminating the question around blocked arteries.

    BT wrote on December 28th, 2011
    • Can we have more information on the reliability of CAT scans for arterial plaque?

      ellie wrote on December 29th, 2011
  18. Solid post – I need to get a cholesterol test done or something on general health, even a blood test.

    Bodybuilder Meal wrote on December 28th, 2011
  19. Great post. Thanks!

    Alex wrote on December 29th, 2011
  20. Mark,
    Have you looked into other ways to measure arterial health? For example, using a tool like the Bio-clip Plus to measure aortic pulse wave velocity? Or the EndoPAT test? Or CIMT ultrasound?
    Would love your take on those tests, especially given what you have discovered about the usefulness of the lipid tests.

    Alex wrote on December 29th, 2011
  21. Ughhh, how frustrating. I had a standard panel done last month, numbers came back “high”, so by myself, I went and got both the NMR and VAP profiles down. Just got the results, the interesting thing to note is that my total was 30 points lower, just two weeks after the first test.

    I need to dig into the results and figure out what they all mean, maybe I’ll post over on the forums to get some feedback.

    But it’s a bummer to hear that these results could now be meaningless, $195 later :-(

    I love primal living/eating, but do have nagging worries about the cholesterol numbers, and the advice to not be so concerned. I sure would hate to find out we are wrong about this.

    Peter wrote on December 31st, 2011
    • see my comment below

      Michele wrote on September 22nd, 2013
  22. symbiotic relationships are what makes life thrive here on the globe, earth. if any one species were permitted to expand, it would wipe itself out… everything is in check, life dies for life to live. i.e autotrophs and heterotrophs. isn’t it a great place?
    sure glad i’m at the top of the food chain.

    dasbutch wrote on January 1st, 2012
  23. woops, previous post should be on weekend love like

    dasbutch wrote on January 1st, 2012
  24. One reason to avoid the VAP test is that once you pay for and take the test, you are on your own to interpret the results. At least I found Atherotech Diagnostic Labs unwilling to discuss results to anyone other than a physician.

    Keith wrote on May 23rd, 2012
  25. I’ve been reading Dr. Peter Attia’s articles on cholesterol, parts 1-7,

    From his refresher points, “LDL-P (or apoB) is the best predictor of adverse cardiac events, which has been documented repeatedly in every major cardiovascular risk study.”

    It seems to be a very thorough discussion thus far.

    Steve wrote on June 26th, 2012
    • Not sure about his conclusion. I eat a VERY similar strict primal diet as Dr. Attia. Have been for 2 years.
      At 40 years old 5’9″ 170 sub 10% BF, my LDL-P is 2081. According to him I am high risk. So what changes should i make? Eat grains? Take drugs? My TC is 302, HDL 70, Trigs 44, LDL size 21.8 and Small LDL-P 160.

      Don’t buy into his “theory”. These guys don’t get it. There is no one “marker”. All of our bodies are different and we each have different “healthy numbers” My resting HR is also below 50 but i don’t think that makes me healthy.

      The proof is how you feel and look (naked).

      Jim wrote on July 2nd, 2012
  26. Hmm so is there a bottom line here? Should I even get one of the three tests? NMR, VAP or GGE?

    Mike C wrote on July 5th, 2012
  27. Well, FWIW, after one year of Wheat Belly, and I mean assiduously followed, along with x1 per week HIT with the addition of x1 per week Japanese Sword , every single one of my NMR parameters, save for triglycerides, was “worse” than the previous measurement. Same lab on each measurement occasion.

    anthony wrote on September 25th, 2012
  28. Had particle size test done, but I find it difficult to comprehend results. I need to know if I need to see a preventative medicine cardiologist. Thanks.

    LDL Particle Number (NMRLIP) 1674 nmol/L
    Low: 2000
    LDL Cholesterol (NMRLIP) 96 mg/dL
    Optimal: 190
    HDL Cholesterol (NMRLIP) 50 mg/dL
    Desirable: >= 40
    Triglycerides (NMRLIP) 96 mg/dL
    Desirable: <150
    Total Cholesterol (NMRLIP) 165 mg/dL
    Desirable: 34.9
    Intermediate: 34.9 – 26.7
    High Risk: <26.7
    Small LDL-P (NMRLIP) 951 nmol/L
    Low Risk: 839
    LDL Particle Size (NMRLIP) 20.7 nm
    Large (Pattern A):
    23.0 – 20.6
    Small (Pattern B):
    20.5 – 19.0

    Small LDL-P and LDL Size are associated with CVD risk, but
    not after LDL-P is taken into account.
    Large VLDL-P (NMRLIP) 2.7 nmol/L
    Insulin Sensitive: 6.9
    Small LDL Particle (NMRLIP) 951
    Unit: nmol/L
    Insulin Sensitive: 839
    Large HDL-P (NMRLIP) 1.8 umol/L
    Insulin Sensitive: >7.3
    Intermediate: 7.3 – 3.1
    Insulin Resistant: <3.1
    VLDL Size (NMRLIP) 53.7 nm
    Insulin Sensitive: 52.5
    LDL Size (NMRLIP) 20.7 nm
    Insulin Sensitive: >21.2
    Intermediate: 21.2 – 20.4
    Insulin Resistant: 9.6
    Intermediate: 9.6 – 8.9
    Insulin Resistant: <8.9
    LP/IR Score (NMRLIP) 74
    Insulin Sensitive: 63

    The LP-IR Score combines the information from the above
    6 markers to give improved assessment of insulin resistance
    and diabetes risk.
    These laboratory assays, validated by LipoScience, have not
    been cleared by the US Food and Drug Administration. The
    clinical utility of the laboratory values has not been
    fully established.
    Test performed by: Mayo Medical Laboratories, Rochester, MN, unless
    otherwise specified above.

    Sally wrote on January 8th, 2013
  29. What everyone should be most worried about are their homocysteine and/or hs-CRP levels, both of which measure the inflammation in your body – the main culprit of CVD. Without a high inflammatory process, your blood vessel lining is good to go and your cholesterol values don’t mean a thing. Most persons observing a Paleo lifestyle should have very good homocysteine and/or hs-CRP levels. If not, then you can investigate your LDL particle sizes.

    Michele wrote on September 22nd, 2013

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