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Can Good HDL Cholesterol Go Too High?

We have been told to get our LDL cholesterol down and our HDL choleserol up. Is there evidence that good HDL is bad if it gets too high?
Can Good HDL Cholesterol Go Too High?
Blood sample for HDL (High-Density Lipoprotein cholesterol) test

We have been told for decades that if we want to avoid clogged coronary arteries and a heart attack we must keep “bad” LDL cholesterol down and increase “good” HDL cholesterol. If we do those two things many cardiologists will pat us on the back and assure us we can delay the Grim Reaper’s grasp on our heart. But not all cardiologists agree. This one thinks HDL cholesterol can go too high.

Q. My HDL has always been high. The latest test showed HDL at 101, LDL of 123 and total cholesterol 229. My primary care doctor has always thought my numbers were OK.

I saw a cardiologist for palpitations. She thinks high HDL could be dangerous and wants me to take Lipitor. The drug sheet from the pharmacy says Lipitor can raise HDL. In that case, does it make sense for me to take the drug?

A. The cholesterol story gets more complicated by the day. Physicians have been telling patients to lower total cholesterol (TC), triglycerides (TG) and low-density lipoprotein cholesterol (LDL-C) for a very long time. These are all considered huge risk factors for heart disease, which is why doctors prescribe statins to tens of millions of Americans. Drugs like atorvastatin (Lipitor) are very good at reducing LDL-C.

Raising Good HDL cholesterol:

At the same time cardiologists tell patients to lower LDL-C, they encourage them to raise good high-density lipoprotein cholesterol (HDL-C). This dates back a long way to the Framingham Heart Study. 

In 1948 Framingham, Massachusetts was the location for a huge study of heart disease. Over 5,000 residents were recruited and followed for decades. Researchers are now studying the fourth generation of these participants. Here is what they discovered about HDL cholesterol (Drugs of the Future, Jan. 2010):  

“HDL-C modulates lipid metabolism and the process of atherosclerosis through a variety of pathways. These include reverse cholesterol transport, anti-inflammatory and antioxidant effects. HDL-C has been found to be a more important risk predictor for CVD [cardiovascular disease] than LDL-C, total cholesterol, or triglycerides in the Framingham Heart Study.”

Other research has also confirmed that higher levels of HDL cholesterol are linked to a lower risk of cardiovascular disease (Journal of Lipid Research, Feb. 2014). HDL-C appears to have beneficial anti-inflammatory, anti-oxidant and vasodilating effects (Journal of Atherosclerosis and Thrombosis, Oct. 1, 2018). 

The CDC (Jan. 31, 2020) describes the Yin-Yang of HDL and LDL cholesterol this way:

  • “LDL (low-density lipoprotein), sometimes called “bad” cholesterol, makes up most of your body’s cholesterol. High levels of LDL cholesterol raise your risk for heart disease and stroke.
  • HDL (high-density lipoprotein), or “good” cholesterol, absorbs cholesterol and carries it back to the liver. The liver then flushes it from the body. High levels of HDL cholesterol can lower your risk for heart disease and stroke.”

The Study That Backfired

Most of the drugs that doctors rely to prevent heart disease do not raise HDL cholesterol appreciably. That is why we suspect they have focused on lowering LDL cholesterol.

Then something strange happened. Along came a drug that does exactly that (lower LDL and raise HDL cholesterol). Eli Lilly’s experimental drug evacetrapib was the star in a very large and expensive clinical trial called ACCELERATE. Hopes were high.

The drug was shown to lower LDL cholesterol up to 40 percent and raise HDL cholesterol up to 129 percent. Those are spectacular results and no other medication has been able to accomplish such impressive changes in lipid levels. 

Over 12,000 patients were enrolled in this clinical trial at 540 sites in 37 countries. Hundreds of millions of dollars were invested and the expectations were that the drug would revolutionize the treatment of heart disease. Wall Street analysts anticipated that the drug would become a billion dollar blockbuster for Eli Lilly.

All that came to a screeching halt on October 15, 2015 when the clinical trial was stopped prematurely and the company abandoned further development of evacetrapib. Although the drug actually did what it was supposed to do in modifying blood lipids in all the right ways, it did not work to prevent heart attacks and strokes. 

Other Drugs to Raise HDL Cholesterol Have Not Prevented Heart Attacks:

Evacetrapib is the third drug in this class (CETP inhibitors) to flame out despite promising results on blood cholesterol biomarkers. Prior to the Eli Lilly debacle with evacetrapib, both Roche and Pfizer abandoned similar compounds. Dalcetrapib was scrapped in 2012, while torcetrapib was dropped when it was found that it actually increased the death rate of subjects in the clinical trial. The study was stopped in 2006.

Too High HDL Cholesterol?

We have searched high and low for published studies that demonstrate naturally high HDL cholesterol levels are dangerous. They are few and far between, if they exist at all.

What we do know is that drugs designed to raise HDL cholesterol and lower LDL cholesterol have not worked to prolong life. That does not mean that people with high levels of HDL-C need to worry.

Raising HDL Cholesterol?

We do know is that low levels of HDL cholesterol may pose a risk for heart disease. That’s why cardiologists have been trying to figure out ways to raise this lipid fraction. Are there non-drug approaches that can raise HDL and improve heart health?

Olive Oil to Raise Good HDL Cholesterol: 

Q. My HDL cholesterol has always been low (in the mid to upper 30s). Recently I read your article about someone who took two tablespoons of good olive oil a day to lower blood pressure.

I began taking two tablespoons every day (one in the morning in my cereal and one in my salad with dinner or used with cooking). On my most recent blood test, my good HDL went up to 50. I was pleasantly surprised, since I had made no other changes. Is there any correlation?

Spanish Scientists Cheer for Virgin Olive Oil:

A. Spanish scientists have examined this question. They found that virgin olive oil consumption boosts good HDL cholesterol (Molecular Nutrition & Food Research, March 2019). In addition, people at high risk of cardiovascular problems also have better HDL function when their diets contain plenty of legumes, whole grains, fish and nuts.

A review of the research on HDL cholesterol finds that virgin olive oil consumption improves the antioxidant and anti-inflammatory activity of this natural blood fat (Nutrients, Feb. 26, 2020). The phenols in virgin olive oil improve HDL function; thyme phenols also contribute (Nutrients, July 26, 2019). People with high levels of good HDL cholesterol activity are less likely to develop atherosclerosis.

Answering Our Reader’s Question About High HDL-C:

Perhaps your cardiologist wants to lower your LDL-C and total cholesterol with atorvastatin (Lipitor). It might raise your HDL-C levels, but it’s not clear whether that would be problematic.

To learn more about these and many other risk factors for heart disease along with non-drug approaches for optimizing cardiovascular health, you may want to consult our eGuide to Cholesterol Control & Heart Health. This online resource is available in the Health eGuides section of this website. 

Our radio show/podcast for this week (Show 1232) was with a preventive cardiologist and a lipidologist (an MD who specializes in lipids like cholesterol, LDL-C and HDL-C). You may find this conversation particularly relevant to the ongoing questions about statins and cholesterol. Just click on the arrow inside the green circle below the photo of Dr. Michael Blaha, Director of Clinical Research for the Johns Hopkins Ciccarone Center for the Prevention of Cardiovascular Disease. 

It seems that there may be more to staving off heart attacks than simply lowering LDL cholesterol and raising HDL cholesterol with a drug. One other lipid fraction that rarely gets mentioned is worth your consideration. That happens to be Lp(a). Here is an article that you may find intriguing. It might explain why some people who take statins still get heart attacks:

Is Lp(a) the Best Kept Secret in Heart Disease?
Most people have had their LDL cholesterol measured. Have you ever had your Lp(a) tested? Did you know that statins may actually raise this key risk factor?

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About the Author
Joe Graedon is a pharmacologist who has dedicated his career to making drug information understandable to consumers. His best-selling book, The People’s Pharmacy, was published in 1976 and led to a syndicated newspaper column, syndicated public radio show and web site. In 2006, Long Island University awarded him an honorary doctorate as “one of the country's leading drug experts for the consumer.” .
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Citations
  • Rye, K-A and Barter, P.J., "Cardioprotective functions of HDLs," Journal of Lipid Research, Feb. 2014, doi: 10.1194/jlr.R039297
  • Nagao, M, et al, "Cardioprotective Effects of High-Density Lipoprotein Beyond its Anti-Atherogenic Action," Journal of Atherosclerosis and Thrombosis, Oct. 1, 2018, doi: 10.5551/jat.RV17025
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