Hey everyone, this is kind of a weird topic for today’s Medicine Mondays, but there has always been some confusion surrounding “cholesterol”, so I wanted to talk about it here. Today, we’re going to talk about Cholesterol, HDL, and LDL.

Stock Photo from: Pexels

Cholesterol, HDL, and LDL

So, here’s the deal. I’m not a young gun anymore. I’m an old man now, at the ripe old age of 36.

At my yearly checkup, my primary care doctor (who is great by the way), ordered a lipid panel since I haven’t had one for awhile. My total cholesterol is baseline high, with low HDL, and so-so LDL. I haven’t looked at the guidelines for cholesterol management in a long time, probably since I was an intern back in 2008. However, I do recall hearing that the guidelines for starting a statin kept changing on an almost yearly basis.

I’m not exactly sure when I learned this stuff, perhaps it was during USMLE or even the first two years of medical school. For this who need a quick refresher, HDL is “High Density Lipoprotein” and LDL is “Low Density Lipoprotein”.  My fuzzy recollection was the HDL is the “good cholesterol” and LDL is the “bad cholesterol”. Total cholesterol is the sum total of HDL, LDL, and Triglycerides.

If I recall correctly, back then, the guidelines for starting a statin were based primarily on the total cholesterol, although I do remember it changing to focusing on LDL at one point.

So where are we now?

So, long story short, I had no idea what the current guidelines were or what current research was saying. So, like most times in life, I did some research.

Here are my findings:

First of all, there are variations in the guidelines currently available. This depends on which organization’s guidelines you want to follow.

For example:

American College of Cardiology and the American Heart Association (ACC/AHA) have guidelines from 2013. *New guidelines are slated to be available in 2018.

However, newer guidelines have come out from:

2016 European Society of Cardiology/European Atherosclerotic Society (ESC/EAS)

2017 American Association of Clinical Endocrinologists and American College of Endocrinology (AACE)

So, what did they say?

ACA/AHA Guidelines (2013)

The ACA/AHA guidelines are the oldest (from 2013) and the full pdf can be found here.

The four groups they found to benefit are:

• Clinical ASCVD* (Atherosclerotic Cardiovascular Disease)
• LDL-C ≥190 mg/dL, Age ≥21 years
• Primary prevention – Diabetes: Age 40-75 years, LDL-C 70-189 mg/dL
• Primary prevention – No Diabetes†: ≥7.5%‡ 10-year ASCVD risk, Age 40-75 years, LDL-C 70-189 mg/dL

So, as you can see, there is a focus on LDL-C with stratification by age, diabetes, and 10 year risk.

I don’t really fit into any of these guidelines, since I’m between 21 and 40 years of age. However, if you read the whole article, in this age group, treatment can be discussed if you there is an LDL-C > 160. Therefore, by these guidelines, a statin is not indicated for me.

*New guidelines are slated to be available in 2018.

More Recent Guidelines

ESC/EAS Guidelines (2016)

The ESC/EAS guidelines are from 2016, and the full pdf can be found here.

AACE Guidelines (2017)

The ESC/EAS guidelines are from 2017, and the full pdf can be found here.

I’m going to talk about these two together since they are actually pretty similar.

Both of these newer guidelines place heavy emphasis on LDL-C with more narrow treatment goals, which are risk-stratified by other factors (Diabetes, Family History, etc.)

“Extreme Risk”

• AACE Recommendations are LDL-C < 55, non HDL-C < 80, apoB < 70
• ESC/EAS doesn’t have this category

“Very High Risk”

• ESC/EAS and AACE Recommendations are LDL-C < 70, non HDL-C < 100, apoB < 80

“High Risk”

• AACE Recommendations are LDL-C < 100, non HDL-C < 130, apoB < 100
• ESC/EAS Recommendations are LDL-C < 100, non HDL-C < 130, apoB < 90

“Moderate Risk”

• AACE Recommendations are LDL-C < 100, non HDL-C < 130, apoB < 90
• ESC/EAS Recommendations are LDL-C < 115

“Low Risk”

• AACE Recommendations are LDL-C < 130, non HDL-C < 160
• ESC/EAS Recommendations are LDL-C < 115

For the most part, these recommendations are pretty similar. However, since this is so much information, I’m going to distill it down into just the LDL-C treatment goals.

Extreme Risk = LDL-C < 55
Very High Risk = LDL-C < 70
High Risk = LDL-C < 100
Moderate Risk = LDL-C < 100 versus LDL-C < 115
Low Risk = LDL-C < 130 versus LDL-C < 115

However, the addition of the “non-HDL-C” (LDL + Triglyercide Total) guidelines are helpful to guide treatment in patients who have high triglyercides, while having somewhat low LDL-C. This is important in patients who have triglycerides above 200, as their risk seems to be different and more concordant with the non-HDL-C total and apoB rather than the LDL-C treatment goal.

What does this all mean?

Well basically, LDL-C levels are still the mainstay the treatment goals. However, the ranges for treatment goals and initiating treatment are more narrow. However, this can become confusing if you throw high triglycerides into the mix (> 200), at which point looking at the non-HDL-C total and apoB amount are probably more important.

However, for me, this doesn’t really change anything for me. Since I’m less than 40 years without any risks, I’m basically in the “low risk” category and my LDL-C is < 115. However, if it was between 115 and 130, then a statin would be a consideration for the AACE recommendations by not for the ESC/EAS recommendations.

Wait… what about HDL-C?

Ahh yess.. the “good cholesterol”. While this has long been praised as being “cardioprotective”, the new research has demonstrated that “high HDL” may not be necessarily good.

There are some patients with high HDL who still have heart attacks and some with low HDL who never have heart attacks. It may depend on a difference which aren’t able to measure yet. Currently we can only measure “HDL” but not certain types, mutations, or which versions are “better” than others. By “better” I mean “more efficient”. Let me illustrate with an example.

Take two different types of HDL, we’ll call them HDL X and HDL Y.

HDL X is found in high amounts in the blood stream and felt to be cardioprotective.

HDL Y is found in low amounts in the blood stream and felt to place the patient at higher risk.

However, HDL X and HDL Y may not be the same. HDL X may be like a bicycle which only carries very small amounts of cholesterol, whereas HDL Y may be like a bus carrying large amounts of cholesterol. HDL X is slower and carries less cholesterol and even though it “measures high”, it doesn’t do much. However, HDL Y is fast and carries a lot of cholesterol and even though it “measures low”, it does a lot of work.

Currently, we don’t have any way to differentiate the two.

But maybe someday we will…

There is a small town between Milan and Venice called Limone sul Garda – from US News and World Report:

“The region is well-known for its many centenarians who make it into old age with plaque-free, healthy arteries despite HDL levels that hover around 10 to 15 milligrams per deciliter. We now know that these people carry a particular genetic mutation, dubbed Apo A1-Milano, marked by very low HDL levels and high triglycerides – another fatty substance known to fuel cardiovascular damage – but no heart disease. Why?” (emphasis mine)

Perhaps this town has the super version of my HDL Y example, something akin to an airplane which can really pack in the cholesterol and move it quickly to be metabolized.

It would be nice to know which version we have.

It’s good to note that Niacin has been shown to increase HDL levels in patients, but hasn’t be shown to be preventive by the Heart Protection Study 2–Treatment of HDL to Reduce the Incidence of Vascular Events – HPS2-THRIVE from July 16, 2014.

“Interpretation:

Among high-risk patients who went through two run-in phases to demonstrate tolerability to study medication, extended-release niacin/laropiprant did not reduce the frequency of major adverse events. Moreover, 25% of participants still terminated niacin therapy during the treatment period for a variety of side-effects, mostly due to skin, gastrointestinal, musculoskeletal, and diabetes-related reasons. Myopathy was more common among Chinese participants compared with European participants.

Unexpected findings were an increase in serious infections and bleeding events among niacin-treated patients. This large study with long-term follow-up complements the AIM-HIGH trial, which also failed to demonstrate benefit from niacin therapy.” (emphasis mine)

Anything else?

It’s important to note that medicine is constantly evolving and changing, as do its recommendations.

Sometimes it may feel like this:

However, I think it’s important to stay aware of what’s going on.

Also, for those who care, my repeat lipid panel showed that my total cholesterol went down as did my LDL. However, my HDL is still low. I made a few changes to diet and went from exercising zero to exercising some, and that seemed to help. Now I just need to try to stick to it so that I won’t need a statin.

TL;DR

Cholesterol management and treatment is still evolving.

LDL-C still appears to drive treatment goals. (see above)

However, in patients with Triglycerides > 200, non-HDL-C totals and apoB totals may be more important to monitor/treat.

HDL-C, long hailed as “cardioprotective”, may not be what we once thought. There are likely variations of HDL-C which are more or less efficient.

Finding these differences may help drive treatment in the future.

This is underscored by Niacin (which increases HDL in patients) not helping prevent major adverse events.

*** Note that the new ACA/AHA Guidelines will come out in 2018, and I will try to update when they do.

-Sensei

Agree? Disagree? Questions, Comments and Suggestions are welcome.

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