A Tale of Two Lipid Panels

Awhile ago, TheFatNurse noticed something strange while reviewing some Lipid panels. Normally, when you receive a lab result, a reference range is given and any numbers above or below the reference range is flagged. What was strange about some of these lipid panels was the lack of flags for patient numbers that were clearly in the high risk range. For example, Let’s take a hypothetical patient:

Total Cholesterol: 165
HDL: 35
LDL: 105
Triglycerides: 244

If you’ve read through the critique of LDL Cholesterol as an indicator of risk you’ll know that LDL cholesterol can sometimes be inaccurate in gauging heart disease risk. However, that is a different problem all together (addressed later in the post) and for the purposes of this post let’s just use the standard numbers provided by the ATP-III clinical guidelines:

So according to the clinical guidelines, this patient’s total cholesterol would be classified as “desirable,” his HDL cholesterol would be “low,” his LDL cholesterol  is pretty much at “optimal,” and his triglycerides are “High.” Therefore, on a lipid panel  you may assume that his Triglycerides and HDL will be flagged. However, depending on what reference ranges a lab uses, this can differ. Here are two example:

ReferenceRange1

This patient is within “range” according to this reference

ReferenceRange2

This patient is not within “range” according to this reference

Before going on, it should be made clear that one should never make the mistake of thinking a reference range is the same thing as target goals (which change according to an individual’s risk category) for a patient. A reference range is simply the distribution of values that are seen in the folks of a given population. However, patients can make the mistake of comparing their numbers to the reference range (and sadly sometimes even clinicians make this mistake) and therefore think they are at low risk when the opposite is really true.

In the first panel, the numbers from our hypothetical patient would not be flagged and a person may think they are at low risk. In the second panel, the numbers from HDL and Triglyceride would be flagged as abnormal. Therefore, it’s more important to go by target goals rather than what a lab supplies as a reference range. As a side note, the advance lipid panels such as the NMR, VAP, and Ion Mobility advance lipoprotein tests, suggest a reference range for triglycerides at <150 mg/dL. The reference range supplied by the first lab at <250 is obviously way too high to be viewed as a target goal and should never be viewed as such.

However, as mentioned in a previous post, even reaching the target goals of LDL cholesterol can be inaccurate to risk. This is even mentioned in the ATP-III where it is suggested to use Non-HDL cholesterol as a target goal if triglycerides are above 200 like our hypothetical patient. However,  Non-HDL isn’t always supplied in a lipid panel and many clinicians do not understand its purpose nor do they know how to calculate it even if they wanted to use it. The same dilemma holds true for looking at the TG/HDL ratio as well. In this scenario, our hypothetical patient’s TG/HDL ratio of 6.97 indicates a high likely hood of increased small and total LDL particles which means he’s at risk for atherosclerosis despite being at target for his LDL cholesterol. If we could advance test everyone with LDL particle testing that could solve a lot of confusion but that would be very expensive  and it’s not always an appropriate test if the regular lipid panel is concordant. With this in mind and everything else we’ve discussed so far on reference ranges and target goals, it’s not hard to imagine a situation where the interpretation of risk between the patient and the clinician and another clinician is vastly different between each party.

TL:DR; Different labs provide different reference ranges which are not the same as target goals. Some of the supplied reference ranges can be vastly outside what would typically be considered a target goal. This can lead to different interpretations of a lipid panel where risk may be judged inaccurately.

HDL for all ages!

HDL cholesterol is often touted as a super stud in heart disease prevention. As a result, common knowledge has continually stressed increasing one’s HDL cholesterol without really moving beyond the “HDL Good LDL Bad” message. This belief can target researchers as well, but some recent studies, as covered by Peter Attia, reveal HDL cholesterol and heart disease not being as clear cut as one might believe.

As a result, TheFatNurse thought it would be a good idea to go over some simple basics about what exactly HDL is and does in your body through a comic. This comic is based on a series of lectures by Dr. Thomas Dayspring and is only a simplified version of his more detailed analysis. See below if you’re itching to read Dr. Daysprings more detailed lectures!

TheFatNurse also wants to extend a personal thank you to Dr. Dayspring. TheFatNurse is still beginning his journey in exploring all things lipid and Dr. Dayspring your encouragement, feedback and information have made exploration exciting.

Before reading, TheFatNurse recommends you read the first two comics on cholesterol as it builds upon some knowledge needed for this third comic. Click here to read the HDL comic (semi-long read!) or the picture below.

***For the first two comics see: #1 Cholesterol For All Ages and #2 Cardiovascular Markers For All Ages. Interested in more? TheFatNurse highly recommends you look up Dr. Dayspring’s lectures on HDL which you can start with here and here.

What is LP(a) and How Does Diet Potentially Play a Role?

There is some evidence that having a large amount of Lp(a) might be associated with heart disease. What is this Lp(a) thing you might ask? Well it is a protein that attaches onto ApoB which is an apoprotein found in LDL. It’s theorized that it can cause disease since it resembles plasminogen which is a precursor for plasmin that reduces fibrin clotting. Since LP(a) looks like plasminogen, it’s believed to increase the risk of heart disease by competing with plasminogen and therefore limiting conversion of plasminogen to plasmin. Additionally, LP(a) may also be the preferred carrier for oxidized phospholipids (OxPls) which may be associated with inflammation and the progression of arterial disease. Need more details? Here just watch this video instead:

One study decided to investigate how diet may play a role in Lp(a) and OxPls. They mention some previous studies that have found associations of Lp(a) and heart disease:

“Elevated plasma Lp(a) concentrations are associated with increased risk of cardiovascular disease (CVD) (1314), and there is increasingly strong data that they may be causal in the etiology of myocardial infarction.”

Alright so Lp(a) is bad, but what really shocked TheFatNurse was what elevated Lp(a). A large part of it is genetics and TheFatNurse recalls last year’s National Lipid Association panel stating that it was mostly genetic. However, there have been some recent studies suggesting there might be a dietary factor at play. Must be a high fat diet right?

“Low-fat diets have been shown to increase plasma concentrations of lipoprotein(a) [Lp(a)], a preferential lipoprotein carrier of oxidized phospholipids (OxPLs) in plasma, as well as small dense LDL particles.”

“Diets low in total and saturated fat have been shown to increase plasma Lp(a) levels (252641) and there is evidence that this effect may be specific for saturated fat (41).”

This is ironic since many people still advocate a low fat diet as pointed out:

“Low-fat diets are recommended to reduce risk of coronary heart disease, but LFHC diets have been shown to induce a more atherogenic lipoprotein profile in healthy individuals by increasing small dense LDL particles (Table 3), reducing HDL cholesterol, and increasing plasma triglyceride levels (Table 4) (27). LFHC diets result in increased concentrations of triglyceride-rich lipoproteins (TRLs) (46) and a reciprocal shift from medium-size LDL particles to very small LDL.”

Anyways, back to the original study that was trying to find associations between diet Lp(a), OxPls and LDL particles. What they discovered was an association between all these variables on subjects with a low fat high carb diet:

“These results demonstrate that induction of increased levels of Lp(a) by an LFHC diet is associated with increases in OxPLs and with changes in LDL subclass distribution that may reflect altered metabolism of Lp(a) particles.”

However, to be fair the difference in Lp(a) mg/dl was 2.17 +/- 4.5 (p value = <0.01). Is this increase enough to do serious cardiovascular risk? Certainly is worth exploring more and adds more interest for future studies between low fat and high fat diets.

LDL Cholesterol = Bad? Not Quite That Simple

Continuing with this week’s HDL mainstream news, TheFatNurse thought you should be aware of a man named Dr. Ronald Krauss and his work on LDL cholesterol (you know, the “bad” one). In the 1980’s, Dr. Krauss was one of the prominent researchers to point out that many studies showed those with heart disease and those without had almost the same LDL levels.

“If you look in the literature and just look at the average coronary patients…their LDL-cholesterol levels are often barely discernibly elevated compared to patients who do not have coronary disease.” (1)

So how prominent a figure was he? He was once the chairman for the nutritional committee for the American Heart Association (AHA) – The same AHA that was recommending low fat intake resulting in more carbohydrate intake as a consequence in order to decrease heart disease. This is ironic, as mention by Gary Taubes in Good Calories Bad Calories, since Krauss had found associations between carbohydrate increase and the risk of Heart Disease.

Did Krauss’ research make him a socially awkward penguin in the AHA?

Additionally, Krauss also found substituting fat with carbohydrates increased small dense LDL particles which are associated with increased heart disease compared with the not as dense LDL particles from saturated fat which is not as bad. (2) In a NPR interview (2007):

“…recommendations are now pushing hard for lowering LDL cholesterol by reducing fat and saturated fat…based on the assumption that it would improve LDL related heart disease risk. Our evidence is it doesn’t effect the dense LDL at all. Substituting carbohydrate for fat, a natural consequence of those recommendations will actually increase levels of the small LDL”

“…processed and refined starches and sugars that are the most deleterious metabolically…food that contain a lot of fiber…have a lot of bulk but not as much carbohydrates…this recommendation [eating more carbs rich in fiber] is very difficult in practice…[agree with Taubes in] considering all carbohydrates as  potentially adverse.”

Dissecting Heart Disease Like a Boss

Much of Krauss’ work points to how much of the advice that is considered fact may instead be harmful to us. In an interview just last month (3):

“…we fed these low fat diets and reduced the fats by substituting carbohydrates, which was at that time and still remains the current paradigm, we really didn’t achieve what we had wanted to achieve…some improvement in the overall amount of cholesterol in the very small percentage of individuals who had very high amounts of small LDL particles in their blood already… the majority of people we studied, the high percentage of people who had the normal metabolic profile, with more of the safer, Pattern A, larger particle LDL, shifted into the riskier, pattern B mode when we reduced their saturated fat intake.”

Because of his work, Krauss is well known in the low carb community when they need supporting claims from a well established nationally recognized physician and researcher:

“…we were certainly concerned about increasing heart disease risk, so we turned our attention ultimately away from feeding higher carbohydrate, lower fat diets, to doing the reverse, to lowering carbohydrate and raising fats, and that’s where we intersected with the world of people very interested in very low carbohydrate diets.”

“[Interviewer] You’re saying that in people who ate more fat and less carbohydrate, and in fact, who ate more saturated fat, they had a little more total cholesterol fat in their blood, but it was mainly being transported in big, fluffy LDL particles, which are the kind that scientists who study heart disease consider pretty safe.

[Krauss] Yes. When people ate more fat and less carbohydrate, the number of small particle LDLs remained low, and switching from monounsaturated to saturated fat didn’t increase their number at all.  In fact, when people switched from mono- to saturated fat in this study, the large particle LDLs might have gone up a little bit…the small particles went down.  So by anybody’s current criteria about whats’s important for heart disease risk, saturated fat caused no increase in risk.”

What is interesting about the LDL particle theory is the debate on whether or not the size and density of the particles matter. Krauss seems to believe the smaller denser particles are more of a concern, whereas others believe it doesn’t matter such as Dr. Dayspring from last week’s post. As Krauss states:

“I and many of my colleagues would argue that the biggest concern is warranted when the number of smaller particles is high, not the larger ones.”

However, both viewpoints can be compatible based on numbers and the ability of the larger LDLs to carry more cholesterol:

“It’s definitely associated with lower heart disease risk if the cholesterol is carried in larger particles, and that’s because there are fewer of them”

Confused? Here’s a lecture from Dr. Tara Dall that might clarify things better:

So does Krauss’ work offers more support that you can eat all the saturated fat you want? After all in the same interview last month:

“…in our 2006 study, the blood work was better when feeding people higher fat diets, than…feeding them lower fat and more carbohydrates…keep in mind, this was in the setting of lower carb and a mixed protein diet, proteins from various sources from white meat and dark meat and chicken and fish and beef.”

However, you may recall TheFatNurse posting last month about another Krauss study that showed saturated fat could be associated with increased CHD risk if it came from high amount of red meat (all beef in that study). Krauss touches upon that study in this interview:

“…keep in mind, this was a very high beef diet.  People were eating beef breakfast lunch and dinner.  So this is really way outside of what we would ever consider to be a usual health practice.  Maybe some people do it.  But not many.”

Cause you’re in the low beef study group dude

Currently, Krauss is using these latest results to try and isolate the reason for excessive red meat being associated with heart disease. Whereas before someone might easily blame it on the saturated fat, Krauss believes it could be other dietary consumptions with the saturated fat in red meat. Is it the iron? That’s one idea from Krauss and TheFatNurse looks forward to seeing more from Dr. Krauss in the future.

Bottom Line: Dr. Ronald Krauss has been a pioneer in the field of dietary consumption and heart disease. His work throughout the years shows how science and nutrition are constantly evolving and we must never accept anything as fact until it’s been fully tested. When long held facts such as “HDL = good LDL = bad” or “saturated fats can cause heart disease” are no longer that clear cut, we as a society need to be open to reexamining these long held beliefs and begin research on new ones.

1) Taubes, Good Calories Bad Calories, page 170

2) http://www.npr.org/templates/story/story.php?storyId=15886898

3) http://www.meandmydiabetes.com/2012/04/17/ron-krauss-saturated-fat-red-meat-it-depends/

HDL Not Useful Anymore? Maybe the Whole Lipid Profile is Useless

So the New York Times dropped a stunner to the world this week with an article that called into question how useful HDL really is. Lots of TheFatNurse’s fellow peers were shocked by it. Is this really new tho? Or has the community just been looking at HDL cholesterol in the wrong manner? Indeed, just earlier in the month another study showed HDL being harmful depending on whether the HDL has a apoC-III protein on it. In a manner similar to the discovery of Dr. Krauss that not all LDLs are alike, not all HDLs are alike either.

Dr. Thomas Dayspring, a lipidologist, has been saying all along that the standard LipidProfile test that you get done at the doctor’s office is outdated and may not accurately predict atherogenic risk. I know I know this is probably your reaction:

Just hear TheFatNurse out!

However, with the exception of Non-HDL (Total cholesterol- HDL cholesterol) and triglyerides/HDL to get a “poor man’s insulin resistance” (ratio of 3 or above = likely insulin resistance)” the other values on the standard lipid profile may not be as useful. Yes even the LDL cholesterol (insert another GTFO pic!). Instead, getting a test to see the size and number of particles in LDL may be a better predictor of atherogenic risk.

What is this particle nonsense you say? It’s the view that risk is not dependent on total LDL cholesterol but the way LDL cholesterol is carried through the number and size of LDL particles (Some evidence is showing that the size is of lesser importance than previously believed and it’s the number of LDL particles themselves that are important). The more particles the higher the risk (driven by insulin resistance). Dayspring believes a number below 1000 nmol/L would be ideal and a number above 1600 nmol/L is the start of high risk. If you find this intriguing, the video below features Dr. Dayspring talking about all of this along with a case study to follow along with:

The Bottom Line: The New York Times article is a good starting point for people to reevaluate and redefine what cholesterol is. Much of the cholesterol knowledge that is taught in schools and to the public is outdated and there have been newer theories and tests developed that are much better than the traditional “HDL = good LDL = bad” advice. Are these newer theories right? Maybe, maybe not, but they should certainly be discussed more often than the same old archaic advice which is often treated as medical fact rather than theory.