At the time of this writing, a typical VAP test report would provide direct measures of the cholesterol content of LDL, Lp(a), IDL, HDL, and VLDL particles. It would also provide additional measures referred to as secondary risk factors, notably particle density patterns and apolipoprotein concentrations. Finally, it would provide a customized risk summary and some basic recommendations for treatment. Below is the top part of a typical VAP test report (from the company Atherotech), showing measures of the cholesterol content of various particles. LDL cholesterol is combined for four particle subtypes, the small-dense subtypes 4 and 3, and the large-buoyant subtypes 2 and 1. A breakdown by LDL particle subtype is provided later in the VAP report.
In the table above, HDL cholesterol is categorized in two subtypes, the small-dense subtype 2, and the large-buoyant subtype 3. Interestingly, most of the HDL cholesterol in the table is supposedly of the least protective subtype, which seems to be a common finding in the general population. VLDL cholesterol is categorized in a similar way. IDL stands for intermediate-density lipoprotein; this is essentially a VLDL particle that has given off some of its content, particularly its triglyceride (or fat) cargo, but still remains in circulation.
Lp(a) is a special subtype of the LDL particle that is purported to be associated with markedly atherogenic factors. Mainstream medicine generally considers Lp(a) particles themselves to be atherogenic, which is highly debatable. Among other things, cardiovascular disease (CVD) risk and Lp(a) concentration follow a J-curve pattern, and Lp(a)’s range of variation in humans is very large. A blog post by Peter (Hyperlipid) has a figure right at the top that illustrates the former J-curve assertion (). The latter fact, related to range of variation, generally leads to a rather wide normal distribution of Lp(a) concentrations in most populations; meaning that a large number of individuals tend to fall outside Lp(a)’s optimal range and still have a low risk of developing CVD.
Below is the middle part of a typical VAP report, showing secondary risk factors, such as particle density patterns and apolipoprotein concentrations. LDL particle pattern A is considered to be the most protective, supposedly because large-buoyant LDL particles are less likely to penetrate the endothelial gaps, which are about 25 nm in diameter. Apolipoproteins are proteins that bind to fats for their transport in lipoproteins, to be used by various tissues for energy; free fatty acids also need to bind to proteins, notably albumin, to be transported to tissues for use as energy. Redundant particles and processes are everywhere in the human body!
Below is the bottom part of a typical VAP report, providing a risk summary and some basic recommendations. One of the recommendations is “to lower” the LDL target from 130mg/dL to 100mg/dL due to the presence of the checked emerging risk factors on the right, under “Considerations”. What that usually means in practice is a recommendation to take drugs, especially statins, to reduce LDL cholesterol levels. A recent post here and the discussion under it suggest that this would be a highly questionable recommendation in the vast majority of cases ().
What do I think about VAP tests? I think that they are useful in that they provide a lot more information about one’s lipids than standard lipid profiles, and more information is better than less. On the other hand, I think that people should be very careful about what they do with that information. There are even more direct tests that I would recommend before a decision to take drugs is made (, ), if that decision is ever made at all.
12 comments:
Ned,
what's your take on NMR testing? Chris Kresser talked about on the Paleo Solution recently.
It seems that knowing one's LDL particle NUMBER (not just its size) seems to be a much more predictable marker for assessing one's risk of CVD.
Hi Stephan. The nuclear magnetic resonance (NMR) spectroscopy seems to make sense because it is reasonable to assume that, if LDL particles are causing problems, their number is more important than their cargo.
The still open issue is whether LDL particles cause problems in the absence of other factors, such as inflammation – which is a vascular response that seems to be at the source of CVD.
Also, LDL particle number can be estimated based on LDL-C and LDL particle pattern – e.g., it should be high for those with high LDL-C and pattern B.
It's nice that such a test exists for research purposes. I'm extremely dubious about its prescriptive value--especially all the "good" and "bad" numbers taken in isolation.
The history of cholesterol and CVD seems to consist of lurching from one hypothesis to the next.
Nothing wrong with that from a science point of view. But making health recommendations on vague correlations that are likely to be abandoned within a couple of years strikes me as irresponsible.
Thank god engineering doesn't work like this. We'd have building collapsing on us every day--and the newer the building, the less faith you could have that the materials would perform!
Ned, here is my take:
The VAP test provides a “derived” figure for Apo B100 which approximates the number of LDL particles as determined by NMR.
A great deal of evidence indicates that the primary cause of coronary heart disease is not native LDL but inflammation which leads to oxidation of LDL which in turn increases expression of the lectin-like oxidized LDL receptor (LOX-1). Therefore neither the number of LDL particles or the level of LDL cholesterol are very good indicators of CHD risk. Lowering cholesterol with statins drugs therefore does not significantly reduce CHD risk. Lowering inflammation will significantly reduce CHD risk. (Unrelated to lowering of cholesterol, statins do lower inflammation somewhat by blocking the mevalonate pathway, but that causes many other problems.)
HDL cholesterol reduces CHD risk by many mechanisms in addition to reduce cholesterol transport. Serum HDL is inversely proportional to inflammation because inflammation stimulates an increase in expression of endothelial lipase which destroys (catabolizes) HDL. Higher serum triglycerides increases the TG content of HDL which impairs the protective capacity of HDL. Serum triglycerides are proportional to inflammation because inflammation decreases synthesis of lipoprotein lipase which is required for hydrolysis of TG. Accordingly, the ratio of triglycerides to HDL cholesterol (TG/HDL) is a very good indicator of inflammation and therefore a good indicator of CHD risk.
Studies have shown that a high fat diet (comprised of mainly high in saturated and monosaturated fats) will increase HDL cholesterol and decrease TG relative to a low fat diet but will not significantly change the number of LDL particles even though measured LDL cholesterol increases somewhat due to larger LDL particles. It is apparent therefore that the increased inflammation associated with a high carbohydrate diet, as indicated by an increase in the TG/HDL ratio, does not change the number of LDL particles. It must therefore be concluded that the number of LDL particles is not significantly associated inflammation or with CHD risk.
A high carbohydrate diet is but one of many factors that can increase inflammation that increases CHD risk. Another major dietary factor is excess intake of LA from modern vegetable oils which is promoted by USDA dietary guidelines. Deficiency of CoQ10, which is a potent anti-oxidant and which also regenerates vitamin C, can also result in increased inflammation. Deficiency of CoQ10 can result from deficiencies of the vitamins required for its synthesis or from increased utilization of CoQ10 due to inflammatory conditions such as asthma and arthritis.
The table at the top of this post shows various correlations that illustrate, through numbers, several of the connections mentioned by Jack C.:
http://bit.ly/ta9lPE
A study of 28,000 women followed for 11 years found; “ CONCLUSIONS:
In this prospective study of healthy women, cardiovascular disease risk prediction associated with lipoprotein profiles evaluated by NMR was comparable but not superior to that of standard lipids or apolipoproteins.”
http://www.ncbi.nlm.nih.gov/pubmed?term=19204302
There are vastly differing opinions about the benefits of the lipoprotein particle distribution provided by the VAP test. Many studies show a strong correlation between particles size distribution and CHD risk while other studies are contradictory.
It is of interest that a preponderance of mall dense LDL particles are associated with low levels of testosterone in healthy males (2), and that testosterone can regulate atherosclerosis progression (in rabbits) via nuclear factor kB (3). (NF-kB). So it may be assumed that a preponderance of small dense LDL particles may indicate low T that may lead to atherosclerosis. It is noted that increased vitamin K2 intake has been found to increase testosterone levels (4) which, it would seem, would result in lower risk of atherosclerosis.
(2) http://www.ncbi.nlm.nih.gov/pubmed?term=8855825
(3) http://www.ncbi.nlm.nih.gov/pubmed?term=23022624
(3) http://www.ncbi.nlm.nih.gov/pubmed?term=21914161
A preponderance of small dense LDL particles in men shown on a VAP test might therefore be an indication of low T that could increase CHD risk.
I note that ". . cardiovascular disease risk prediction associated with lipoprotein profiles evaluated by NMR was comparable but not superior to that of standard lipids or apolipoproteins."
Unless VAP, NMR and the usual lipo profiles indentify the SAME subpopulations for treatment, I place little weight on them for evaluating my own risk.
Slainte
Hi Jack. Not only in rats; see this figure relating free testosterone and IMT:
http://www.nature.com/ijo/journal/v27/n7/fig_tab/0802292f1.html
The full text from which the figure was taken is below; btw, they seem to have controlled for age.
http://www.nature.com/ijo/journal/v27/n7/full/0802292a.html
Here is an interesting observation based on data from HCE users who suffer from FH. Several of those users have pattern A and high HDL, and yet CVD progression is still accelerated compared with non-FH controls.
I should have said “… not only in rabbits …”
Hi LeonRover,
I fully agree the these measures do not accurately define risk of heart disease. I consider statin drugs to be toxic and believe they do more harm than good. My interest is in understanding the relationship between some of the lipid measures and diet. For the most part standard lipid measures are sufficient for this purpose but the determination of particle size may have some value.
Hi Ned Kock,
The article you cited on therelationship between low testosterone and progression of atherosclerosis as measured by intima media thickness is most interesting.
The correlation between small dense LDL and testosterone deficiency was of particular interest in relationship to the VAP test as it could inspire someone with low LDL to get his testosterone tested and perhaps increase intake of aged cheese, which is high in vitamin K2, to increase testosterone. (Or take K2 supplements)
I had the VAP test two years ago and then again a few months ago. Before getting the last VAP test I increased intake of fat from about 50% to about 65% of calories and cut out grains entirely just to see what effect it might have. I was also taking magnesium supplements which seem to be necessary when I am eating three or four ounces of cheese a day. Both VAP tests showed pattern A (non-atherogenic) LDL, but the percent of large particles increased from 50% to 73%.
HDL increased from 80 to 88 and TG stayed the same at 60. In my opinion thee most important lipid measure is the ratio of TG/HDL as it is an indicator of inflammation which most people can control by diet.
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