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LDL-P: Best Predictor of Heart Disease

What is the best predictor of future heart disease? Is it blood pressure, LDL, HDL, cholesterol? It turns out that, while all of these are important, the number one predictor of heart disease hands down is something called LDL-P, or the LDL Particle Count. LDL-P is not the same as LDL-C, which is the standard LDL measurement that you get as part of your annual physicial. LDL-P is a little more expensive test and counts the total number of particles in your blood.

I have written a little about this before, but a Peak Testosterone Forum member asked the following, and I realized that I had not done enough to show the extreme importance of LDL-P in predicting arterial plaque and heart disease in general:

"Thanks for the response and the info, bud! I really appreciate it. Sorry that it took so long to respond, I have been traveling and also been swamped with work. With regards to LDL-P, I don't know if a specific study that states that LDL-P (regardless of composition of sizes) is the best indicator of CVD risk. I'm not saying that it doesn't exist, I just dont know if it does. That would be pretty compelling." [1]

To answer this poster's question, I would say that not only is there evidence LDL-P is the best predictor of future heart disease, but there is abundant evidence that it is so.  Here are Five Powerful Examples from the Research (and there are many more):

1. Every 100 nmol/l Counts!  I argue in this page on Target LDL-P Levels for Plaque Reversal that you want your LDL-P at least below 1000 nmol/l and, ideally, even lower. But I bring this up, because this paper stated that "the risk of a CHD event increased with approximately 4% for each 100 nmol/L increase in LDL-P." [5] Thus, if you compare a man with an LDL-P of 1500 versus one sitting at 1000 nmol/l, the risk of a heart attack, etc. is about 30% higher.  And most importantly to most men:  this means that the risk of plaque and erectile dysfunction will be that much higher as well

Therefore, it is prudent to work on every 100 points of LDL-P that you can.  Keep working on it and bring it down. CAUTION:  There is a small percentage of men with extremely low cholesterol and lipid numbers.  These men do not need to bring their numbers down and may even need to try to boost them.

This same study in the journal Atherosclerosis basically showed the LDL-P blew away LDL-C as far a predicting heart events: 

"Particularly in patients whose LDL-P and LDL-c levels are discordant, LDL-P seems to better predict cardiovascular (CV) events than LDL-C levels [6-8]. Several expert panels and guidelines already advocate the use of LDL-P as target of therapy in certain at-risk patients. This report aimed to provide real world evidence that confirms that clinical management aided by LDL-P." [3]

The reason that the above is so significant is that LDL-C is much cheaper to pull.  You can get LDL-C, total cholesterol and triglcyerides for $25 with one of the labs here:  Inexpensive Self-Testing Labs. LDL-P costs more and so doctors, in our overburdened, health insurance-based environment, are very reluctant to rely on anything that will cost more. However, LDL-P is the clear winner over the old test and so the medical community has to let go in this case.

BUT WHY?  Why is LDL-P so important and clearly so much more predictive than LDL-C?  Because LDL-P essentially measure the concentration of LDL particles in your plasma and it is the concentration of LDL that determines if it will be pushed into your artery walls.

2. Arterial Plaque (via IMT) in Healthy Men.  Many studies show that LDL-P is associated strongly with the buildup of arterial plaque, the Great Bedroom Killer.  One way to measure plaque is via an IMT, an ultrasound that measures the thickness of your carotid (neck) artery, i.e. plaque buildup.  Researchers in one study found that LDL-P was a powerful and independent predictor of IMT:

"In a community-based sample of Japanese men, free of clinical CVD, LDL-P was a robust marker for subclinical atherosclerosis, independent of LDL-C and other lipid measures. Associations of LDL-C and other lipid measures with either cIMT or CAC were generally not independent of LDL-P." [6]

Again, notice that they said that, while LDL-C cannot be entirely ignored, LDL-P was the more powerful and independent predictor.

3. Framingham Offspring Study.  Researchers examined this set of data and concluded that "in a large community-based sample, LDL-P was a more sensitive indicator of low CVD risk than either LDL-C or non-HDL-C, suggesting a potential clinical role for LDL-P as a goal of LDL management." [2] And the event rate was much improved over other CVD markers examined as well:

"Subjects with a low level of LDL-P (<25th percentile) had a lower CVD event rate (59 events per 1000 person-years) than those with an equivalently low level of LDL-C or non-HDL-C (81 and 74 events per 1000 person-years, respectively)."

4. PLAC-I Trial (Statin Treated Men).  In this study, the authors found that "within treatment groups, CAD progression was strongly associated with total LDL-P, after adjusting for other lipid levels, and a small LDL-P level of over 30 mg/dl was associated with a ninefold increased risk in CAD progression." [5] In other words, it doesn't matter whether you are on statins or off, LDL-P is the big gun. And notice that your heart disease risk goes up exponentially if you have a high small particle count number.

5. Quebec Cardiovascular Study.  Again, researchers emphasized the critical importance of apo B, which is an alternative and parallel lipid measurement:  "The results of this prospective study confirm the importance of both elevated plasma cholesterol and decreased high-density lipoprotein cholesterol levels as risk factors for ischemic heart disease. They also emphasize the high prevalence of an elevated apo B dyslipidemic state in ischemic heart disease." [4] NOTE:  ApoB is also less expensive to pull than LDL-P and gives the same information.  However, the only disadvantage is that thresholds for plaque control and reversal do not seem to be as well-researched.  See my pages on Penile Arterial Plaque Regression for more information.

CAUTION:  There are many other important predictors of heart disease and events, including CRP, Lp(a), fibrinogen, blood pressure, etc.  So do NOT monitor your heart disease risk with just one number.  That said, it's hard to beat LDL-P as the biggest cardiovascular market now and many notable high fat, Paleo and Low Carb bloggers have discussed this. 

REFERENCES:

1) http://www.peaktestosterone.com/forum/index.php?topic=9550.0

2) J Clin Lipidol, 2007 Dec 1, 1(6):583 592, "LDL Particle Number and Risk of Future Cardiovascular Disease in the Framingham Offspring Study Implications for LDL Management"

3) Atherosclerosis, 2014 Aug, 235(2):585-91, "Cardiovascular risk in patients achieving low-density lipoprotein cholesterol and particle targets"

4) Am J Cardiol, 1995 Jun 15, 75(17):1189-95, "Prevalence of dyslipidemic phenotypes in ischemic heart disease (prospective results from the Qu bec Cardiovascular Study)"

5) http://www.medscape.com/viewarticle/712122_3

6) J of Clin Lipidology, "Associations of serum LDL particle concentration with carotid intima-media thickness and coronary artery calcification"