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:
- LDL Segmented Gradient Gel Electrophoresis – separates LDL particles into 7 subfractions by size and shape
- Vertical Auto Profile-11, or VAP – separates LDL particles into 6 subfractions by size, LDL-1 (most buoyant) through LDL-6 (least buoyant)
- NMR Lipoprofile – separates LDL particles into A (large, fluffy, buoyant) or B (small, dense)
- 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?).