First, a little background: I'm a 45-year-old woman, fairly active, not overweight, no health problems except joint issues (currently, shoulder tendonosis). For the past 3 years I've been eating 80-20 primal. I've had my non-fasting cholesterol (just total and HDL) checked at work for the past 3 years:
2010: total 257, HDL 95
2011: total 262, HDL 95
2012: total 312, HDL 91
Despite my awesome HDL, the TC over 300 made me nervous and I got a full lipid panel drawn last week (my doctor wouldn't go for the VAP or NMR test). Results:
Total: 324 (yikes?)
Trigs: 23 (super low, woot)
HDL 95 (yay)
LDL 209 (yikes!)
The LDL must have been calculated, but I'm not sure how. When I calculated it myself I got 224 using the Friedwald formula and 160 using the Iranian formula (probably more accurate with my very low trigs).
My ratios are all fabulous, pretty much all in the "ideal" range:
Also, my low trigs suggest that while my LDL is high, it's probably the light 'n' fluffy kind.
All in all, after researching everything I was feeling quite reassured, but I came across this post on Chris Kresser's site. Chris Masterjohn makes a comment and states "Having a cholesterol level around 300 mg/dL is clearly indicative of a metabolic abnormality that should be addressed" and Chris Kresser replies "I agree that very high total cholesterol is often an indicator of an underlying metabolic abnormality or inflammatory process, I’m not convinced that a TC of 300 is problematic if the TG:HDL ratio is low and the person is in Pattern A and has no other evidence of disease." Kresser also states "HDL >85 is often indicative of an inflammatory process. Inflammation activates the peroxinase enzyme system, which in turn activates HDL. This can cause unusually high HDL levels in active inflammation" and "Very low triglycerides are sometimes seen in cases of immune dysregulation or autoimmunity".
Incidentally, my mom has a similar pattern of high TC and high HDL. Also, my vitamin D level was 46 (I take 5000 IU daily).
Other than off-and-on bouts of tendonitis/tendonosis issues in various parts of my body, I have no inflammation issues that I am aware of. I'm a bit concerned about this talk of metabolic abnormalities and immune dysregulation! Can anyone shed some light on this?
"you could possibly be a candidate for one of those "out of the blue, drop dead in the street" events."
You shouldn't panic based on comments here and your risk of "dropping dead in the street" is likely very small. First of all "discordance" is not "good ratios but high particle count." Rather its a discrepancy between LDL-C and LDL-P. I would guess that given your numbers, your discordance is likely an LDL-P that it lower than LDL-C since the other way round is mostly typical of people with Metabolic Syndrome (assuming your BP and BG are ok.) In fact, in one study, controlling for HDL and triglycerides negated the predictive value of LDL-P and your HDL and triglycerides are more than fine. See:
You may also want to look at the original Framingham risk numbers to see that at very high levels of HDL, the general risk for CVD changes in minuscule amounts for any level of LDL-C:
That said, you still have relatively a lot of cholesterol but "high cholesterol" is always only a risk marker as opposed to a disease in an of itself which is what Kresser and Masterjohn were saying. Yes, it needs to be addressed and they provide a means for checking it out, but if you don't find any other abnormalities it may just be reflective of what you are eating and no more. At the end of the day, health is much, much more than lab numbers.
Don't let the "War on Insulin" make you lose sleep. As the nomenclature suggests, this seems to be yet another way to push the Taubsian low-carb agenda (not to mention possible conflicts of interest involved with NMR testing.) Insulin is not the enemy any more than cholesterol and "discordance" appears to be no more than MetSyn redux.
It seems that the idea that “LDL-P is everything” is in danger of becoming a new paleo meme so it may be worth examining that idea and its relationship to the “War on Insulin.” Rather than being a consequence of too much insulin, large numbers of LDL particles is largely a result of insulin not being able to do its job property; I.E. insulin resistance. Through mechanisms I won’t detail here, insulin resistance results in elevated triglycerides generating large numbers of small, LDL particles and a corresponding decrease in large particles. The net result is an increase in particle number (LDL-P) without necessarily an increase in cholesterol concentration (LDL-C). (For more detail see http://clinical.diabetesjournals.org/content/26/1/8.full)
Since insulin resistance is a feature of Metabolic Syndrome, it therefore makes sense that people with MetSyn would be characterized by high LDL-P without necessarily high LDL-C and that is what is being called “discordance.” However, MetSyn is also associated with high triglycerides and low HDL and, as already noted, when those factors were controlled for, the predictive power of LDL-P for CVD was eliminated (see http://www.theheart.org/article/767865.do). In other words, when you take MetSyn out of the picture, LDL-P doesn’t seem so important and if it is picking up risk, it is through the same mechanisms as MetSyn.
That still leaves the question as to whether or not the increase in small LDL-P, essentially the reason for the increase in LDL-P, is causing CVD and a number of hypothesizes have been suggested. For example, some think that small particles are more easily oxidized and others that they can more easily penetrate the arterial wall. However, when researchers stratified subjects with MetSyn by small LDL-P, they found no association with CVD suggesting that other mechanisms part of MetSyn are the culprits (inflammation, glycation, ???). (See http://circ.ahajournals.org/content/113/1/20.full.pdf for more detail.)
Bottom line is that insulin does not cause either high LDL-P nor does high LDL-P cause CVD. High LDL-P and discordance with LDL-C result from the insulin resistance that is a feature of Metabolic Syndrome and as such, discordance is a marker for MetSyn. It would seem that restoring insulin sensitivity rather than declaring a “War on Insulin” is the order of the day. If somebody suggests medication based on LDL-P in healthy people, please ask them to produce the randomly controlled trials which showed meaningful reduction in hard, clinical endpoints from such treatment (NNT- numbers need to treat). Otherwise, consider any cholesterol measurement to be a risk marker at best.
Calling for everybody to have an NMR and to be medicated for "high LDL-P" would seem to be another in the long line of attempt to enlarge the pool of statin customers, not to mention the market for NMR testing.
"what are Chris Masterjohn and Chris Kresser alluding to"
(I will answer here instead of as a reply due to space limitations.)
I am not sure exactly which post you are alluding to but I remember reading through the long posts which they did on the subject. What they were saying was that it might be wise to rule out metabolic issues as opposed to saying that this level of cholesterol necessarily implies such issues. There have been many theories discussed in this regard including thyroid problems, micronutrient deficiencies, etc, etc. One question which is never asked is if these people had metabolic issues, why did they only show up after a change in diet? Leaving out the issue of genetic variants, the only thing we know for sure is that for some people, eating a paleo diet results in an increased LDL level. Yes, try to rule out what you can but at the end of the day, what does it mean?
If you look at the most recent metastudy on statins, even pretty dramatic lowering of LDL in healthy people (although they actually threw in people with pre-existing CVD), was associated with only minuscule changes in general as opposed to relative risk (.5-2%) (even if you accept that it was the LDL change that was the agent and that the statistics and selection of studies were appropriate, big ifs). Are you willing to go back to your old way of eating to achieve a difference that small even if was real? Please remember that at your age and making some assumptions about BP and smoking, your Framingham Risk Score is already less than 1%.
I am not advising you to blithely ignore the situation but on the other hand, remember that first there was Total Cholesterol, and then HDL/LDL, and then LDL particle size. Now the parameter de jour is LDL-P. We even have "advanced lipodologists" as if medicine had not specialized enough to the point of insanity. If in all other ways you are healthy, then higher "out of range" LDL does not make you sick. All of these numbers are just risk markers based on epidemiological studies that can NEVER show cause. If you read through the Attia series you will come across a question from a reader who asks him if he can either demonstrate cause and effect or show some kind of evidence from randomly controlled trials per LDL-P. Of course he couldn't and he tried to wiggle out of the question. As I explained above, if you have "discordance" in LDL-P and LDL-C, its because of insulin resistance and insulin resistance would be the issue not the LDL-P number. In your case, there is an overwhelming probability that you are not insulin resistant and so you won't show "discordance." What an NMR will tell you is that you have have a lot of cholesterol and likely an LDL-P that is higher than what the "advanced lipodologists" say you should have. How is that different from being told your LDL is too high?
As some point you are going to have to deal with this anxiety and make a decision. Either you start eating and living governed by your cholesterol test or you put the issue to bed and go on with your life. As a means for making that decision, ask your advisors to produce a randomly controlled trial (NOT an epidemiological study) showing that lowering LDL levels, independent of any other changes, results in meaningful reductions in clinical endpoints. In other words, will lowering your LDL significantly (much more than 1%) change your risk of dying or becoming seriously ill?
If no such studies can be produced, then there is no reason to believe that changing your LDL level will make any difference at all.
You could look into if there might be an underlying cause to the high TC numbers, like thyroid:
You have an issue, absolutely. So go read Dr. Peter Attia's blog, which is now called Eating Academy, not War on Insulin any longer, and get through his mammoth 6-part cholesterol series. Then go to lecturepad.org and watch Dr. Tara Dall's lecture on advanced lipid testing.
You need advanced testing, a direct particle count. Large and fluffy or small doesn't matter. Total particle count is the marker of risk, and you need to know it. You could be what's called "discordant," good ratios but high particle count. This means you could possibly be a candidate for one of those "out of the blue, drop dead in the street" events. And you don't want that. :)
If you are in fact discordant, you'll want to double-down on the low-carb and possibly start very low-dose metformin, unless more testing can find the source of a hidden inflammation/autoimmune issue. Definitely take control now and if the doctor won't order an NMR, fire him. Get the tests you need NOW - only you are in charge of your own health, screw the doctor. :)
Doctors are often slow to aggressively investigate heart issues in women with periods because they mistakenly believe your estrogen protects you no matter what. Don't believe them or put up with second-tier treatment.
I guess my real question at this point is this: what are Chris Masterjohn and Chris Kresser alluding to when they say that number like mine indicate metabolic abnormality or immune dysregation (again, that post is HERE)? A couple of people asked this in the comment section, but the question went unanswered. I've spent quite a while at both their blogs but can't figure it out. I have a couple of podcasts queued up; I'm hoping to find the information there.
Skyrocketing LDL at 313 - concerns? 7 Answers