Can My HDL Be Too High?

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HDL cholesterol is widely accepted as “good” cholesterol. However, in this conversation with Dr. Cynthia Shelby-Lane, we explore why high HDL cholesterols may not always be heart healthy.

Lisa Nelson: Are you concerned by unusually high HDL levels, such as greater than 100 mg/dl?

Dr. Shelby-Lane:

The main function of HDL is to help soak up excess cholesterol from the walls of blood vessels and carry it to the liver, where it breaks down and is removed from the body in the bile.

Measuring for particle size and particle number is the best way to tell if HDL cholesterol levels are safe/healthy. This involves testing and it is usually measured under the guidelines of an "expanded lipid profile." The usual and optimal range for HDL is (above 40 for men and 50 for women). Expanded lipid profiles are necessary to look at particle size. The laboratory test for HDL actually measures how much cholesterol is in the HDL, not the actual amount of HDL in the blood.

Normal results and general guidelines

In general, your risk for heart disease, including a heart attack, increases if your HDL cholesterol level is less than 40 mg/dL. An HDL 60 mg/dL or above helps protect against heart disease. Women tend to have higher HDL cholesterol than men.

Note: Normal value ranges may vary slightly among different laboratories. Talk to your doctor about the meaning of your specific test results.

Low HDL levels may indicate an increased risk of atherosclerotic heart disease. Abnormally high tests may be associated with:

HDL has been labeled "good" cholesterol because it helps remove damaged LDL cholesterol from your arteries and has generally been associated with having less cardiovascular disease. HDL is small in comparison to LDL, and it is higher in protein. It functions as a tow truck, latching on to spent or damaged LDL and returning it to your liver for recycling and/or clearance. The two main proteins that make up HDL are called apoA-I (75 percent) and apoA-II (25 percent). ApoA-I is the good guy, and its integrity of structure is vital for HDL's ability to clear damaged LDL from your circulation and the walls of your arteries.

ApoA-I vs. ApoA-II

ApoA-I is also vital for HDL's enzyme functions that give it anti-inflammatory and antioxidant activity. The role of apoA-II is much less understood, other than to say it is implicated as part of problems with fat metabolism and too much of it causes poor HDL function.

One aspect of HDL fitness is that, as it does its work, its supply of apoA-I is temporarily diminished and replaced by apoA-II. If HDL then fails to replenish apoA-I, it loses its ability to function in a helpful cardiovascular way and actually becomes a problem to cardiovascular health. One key sign that a person lacks apoA-I and has too much apoA-II is elevating triglycerides.

Other research has more accurately defined the nature of the fatty substances that make up the HDL cell membrane. These are rich in phospholipids (phosphatidylcholine, phosphatidylserine, phosphatidylethanolamine, and phosphatidylinositol). These phospholipids are linked to a unique cell membrane fat called sphingomyelin, which is used to make a major signaling molecule (Sphingosine-1-phosphate).

Other cholesterol factors

Triglycerides should never be more than twice your HDL, a relationship that in my opinion is far more important than your LDL/HDL ratio. The new science helps clarify why this is the case, explaining that as triglycerides go up then HDL quality goes down. In this handicapped condition HDL loses its ability to remove LDL, quench inflammation, and perform antioxidant functions.

HDL also signals molecules in your circulation, acting as a communication platform to help instruct other cells around it what to do. Researchers have proven direct communication from HDL to the endothelial cells that line your arteries, the smooth muscle that comprises your arterial walls, the macrophages that are involved with LDL-related plaque formation, and T-cells of your immune system.

Damaged HDL cholesterol

HDL can become damaged or "spent" at which point it no longer does any of these good things and instead actually contributes to cardiovascular disease, even winding up with LDL in plaque. There are three main reasons this happens.

  1. The failure to provide adequate nutrition to re-energize HDL after it has been out working. This leads to a lack of apoA-I and an HDL cell membrane that has lost functionality.

  2. Oxidative damage to apoA-I, caused by inflamed and overheated immune cells. This means individuals with inflammatory health issues will have poor quality HDL. The greater the inflammation, the worse the HDL quality.

  3. Sugar glycation of HDL, rendering it "cemented" so that it can't work. The more uncontrolled the blood sugar, the worse the HDL problem.

Lab tests that help to evaluate your heart are C-reactive protein, homocysteine, lipoprotein/(Lp(a), fibrinogen, ferritin, Total cholesterol (elevated), LDL cholesterol (elevated small-dense ldl particles), HDL cholesterol (reduced), Triglycerides (elevated), LDL and HDL particle size (pattern A and B) -VLDL, LDL particle number (increased number of particles), Apolipoproteins A and B, TG/HDL ratio of > 3.5 simple sign of insulin resistance.

Even if your test results are normal, you may still have a risk of heart disease. Kidney disease must also be ruled out as a cause. The gold standard for the diagnosis of coronary artery disease is a cardiac catheterization, but this is a fairly invasive test, and is not usually done without a history of severe and/or persistent symptoms or an actual heart attack. Other tests may include studies such as an ultrafast CT scan of the heart (if available, lots of radiation and soon to be taken off the market), a CT Angiogram, a nuclear stress test, an echocardiogram, a lipid profile for very low density lipids (with a complete cholesterol panel to look at subparticles), homocysteine level, HS-C-reactive protein, and an ankle-brachial index, just to name a few.

To summarize

HDL is generally thought to be protective and the levels for routine testing of HDL is as follows: greater than 50 for women and greater than 40 for men. The range for norms depends upon the lab reference ranges which can go from 40 to 90. More specific testing uses the measurements for particle size/number and particle density. Therefore, once you look at particle size for HDL cholesterol, you can determine if you are dealing with an abnormal HDL molecule (particle size, density, and particle numbers) as well. The only way to know the type you have is by completing an "expanded lipid profile" lab test which must be ordered by your doctor. Additional testing is also performed in the expanded lipid profile such as Lp(a), HS - C-reactive protein, homocysteine, VLDL, ferritin, etc.

See more helpful articles:

When Good Goes Bad: The Mystery of HDL

Tips on How to Raise Your HDL

Making Sense of Cholesterol Ratios, Lipid Profiles and Your Heart Disease Risk Scores