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Is Lp(a) the Best Kept Secret in Heart Disease?

Doctors worry about LDL cholesterol but rarely test for Lp(a). Statins can raise this risk factor for heart disease you've never heard about.
Is Lp(a) the Best Kept Secret in Heart Disease?
Red mark check on Cholesterol Triglyceride and HDL-Con request form with blood sample in blood tube for test.

Ask most people about their risk factors for heart disease and they will likely mention total cholesterol (TC), LDL-C (“bad”) cholesterol and HDL-C (“good”) cholesterol. Sometimes people even include triglycerides (TG). Chances are very good they have never heard about lipoprotein(a) aka Lp(a). It is also referred to as “Lp little a.” This cholesterol-protein particle is rarely measured, but it is a key player in heart disease. It could be contributing to many preventable heart attacks.

Lp(a) Is a Serious Risk Factor for Heart Disease!

It has been estimated that at least one fifth of the population has inherited high levels of lipoprotein a (Scientific American, Nov. 4, 2019).  Elevated levels of this lipoprotein can increase the risk of plaque buildup and blood clots.

This may sound cynical, but the reason we suspect that Lp little a has flown below the radar is because there is no pricey pharmaceutical to lower this risk factor for heart disease. There has been no motivation for drug companies to encourage doctors to measure Lp(a) because there was no money in it.

Diet doesn’t have much impact on this cholesterol-transport protein either. So, encouraging people to cut back on eggs, butter and red meat won’t make much of a difference.

We suspect that many cases of hereditary heart attacks may be linked to Lp(a). And because many physicians have not been educated about this risk factor it goes unmeasured and under-treated.

This reader describes just such a situation:

“I forget where I first heard of Lp(a) but it worried me, so I had mine tested. I had to cajole my family doctor, who didn’t know about it. To get it covered by insurance, she referred me to a heart doctor for high-risk patients. He required an EKG before he would even speak with me, but then he was great.

“As it turns out, my Lp(a) is very high, despite years of good diet and lots of exercise. My LDL is borderline high, my HDL is high (good) and my triglycerides are low (also good). The cardiologist and I sat together at his computer researching Lp(a).

“I won’t take statins. He did recommend baby aspirin. He still evaluated my risk of heart disease at 3 percent over ten years. What else can I do?”

A. Lipoprotein(a) has been a recognized risk factor for heart disease for decades (European Heart Journal, Dec. 2010). It is associated with clogged coronary arteries and blood clots.

People who inherit high levels of Lp(a) are at significant risk for heart attacks and strokes. Statins that lower LDL cholesterol may actually raise Lp(a) levels (European Heart Journal, June 21, 2020). 

Statins Raise Levels of Lipoprotein(a)

Did you pay attention to that last sentence? 

“Statins that lower LDL cholesterol may actually raise Lp(a) levels.”

This is not welcome news. That’s because many physicians believe that statins are one-stop-shopping when it comes to heart health. The idea that drugs such as atorvastatin, pravastatin, rosuvastatin or simvastatin could actually raise a cardiac risk factor like lipoprotein(a) comes as a total shock. It’s a little like driving with your foot on the brake as well as the accelerator.

Please do not take our word for this. A review in the European Heart Journal, (June 21, 2020) notes that: 

“This meta-analysis reveals that statins significantly increase plasma Lp(a) levels.”

Drugs to Lower Lp(a)?

Many cardiologists discount the clinical importance of this effect. They are absolutely convinced that if they just lower LDL cholesterol with a statin that patients are home free. But even after LDL is lowered significantly, high levels of lipoprotein(a) contribute to persistent risk for cardiovascular events (Current Cardiology Reports, July 1, 2021). What’s more, these researchers report that this forgotten risk factor is implicated in “atherosclerotic and calcific aortic valve disease.”

Some people have heart attacks despite taking statins. When that happens, health care providers may not have an explanation. But elevated Lp(a) levels could be to blame.

Earlier this year, we heard from a reader:

“You probably saved my life with your article on Lp(a). All four grandparents and both my parents had heart attacks or strokes.

“I had never heard of Lp(a) and now I know how to lower it. I read Robert Kowalski’s book, The New 8-Week Cholesterol Cure. He quotes numerous reputable studies where sustained-release niacin lowers Lp(a) as much as 33 to 50 percent. I have begun taking it.

“My husband has taken this supplement for years to control his cholesterol. He told a cholesterol statin researcher about it, and that guy started taking it instead of a statin.”

Niacin and Aspirin:

Scientists have known for decades that niacin can lower this cholesterol-protein particle (Atherosclerosis, June, 2010). But many doctors discourage its use (Progress in Cardiovascular Diseases, May-June 2020). They worry that niacin has been associated with adverse effects such as flushing, itching, dizziness, headache, nausea or vomiting. It can raise blood sugar and liver enzymes, though so can statins. Some doctors may also prescribe aspirin for people with high levels of Lp(a) (Drugs in Context, Sept. 4, 2019).

Niacin and aspirin may be two of the cheapest drugs in the pharmacy. We won’t say that is the reason there is little excitement about them, but no drug company is promoting their use to lower lipoprotein(a). There are no commercials on television describing the pros and cons of medicines to reduce this risk factor for heart disease. 

ASOs to Lower Lipoprotein(a):

That will soon change. Drug companies are developing medicines to lower Lp(a). Clinical trials are currently underway to test an entirely new class of medication for lowering Lp(a). The HORIZON trial is testing the safety and effectiveness of “antisense oligonucleotides” (ASO). Results are expected in 2024.

We suspect that the new ASO drugs will be quite pricey. Once they hit the market, you will be hearing a lot more about the dangers of high levels of lipoprotein(a). As soon as the ASOs are on drugstore shelves, we are willing to bet a month’s salary that doctors will be inundated with ads for these meds and you will see commercials on TV. 

In the meantime, some cardiologists prescribe alirocumab (Praluent) or evolocumab (Repatha) for ultra-high-risk patients. Although these PCSK9 inhibitors were designed to lower LDL cholesterol, they also modestly lower Lp(a). Perhaps this risk factor will soon get the attention and respect it deserves.

As we have already pointed out, eating a very healthy diet doesn’t seem to make much of a difference in controlling levels of lipoprotein(a). Neither does exercise. Even though both niacin and aspirin seem to lower Lp(a) levels, it is not clear if doing so prevents heart attacks or strokes.

Do Statins Really Raise Lp(a)?

Does this question seem heretical? Shortly after statins were introduced in the U.S. in the late 1980s, a drug company researcher contacted us. He had been involved in statin research and was concerned that these drugs might raise a little-known lipid fraction called lipoprotein(a).

He was in favor of lowering LDL cholesterol with a statin. But he thought that also raising Lp(a) with a statin might be a little like pushing a boulder up a steep mountain. Remember the Myth of Sisyphus?

Here is a question about this issue from a reader of our syndicated newspaper column.

Q. I inherited very high levels of Lp(a), and I have known for years there is little I can do to reduce it. Although I tried niacin, I can’t tolerate it.

In Germany where I grew up, doctors test for this routinely. In the US, I have had difficulty getting it tested.

My cholesterol is around 220, with HDL over 60. Since my LDL is high (around 140), I am now on Crestor.

My doctor said lowering my LDL is vital, because it will also lower the Lp(a). Is that true? I have read a lot about this problem over the years to educate myself. Everything I read says there are no medications to date that lower lipoprotein(a).

I am 69 years old and worked hard for years following a healthy diet so as NOT to take a statin. (I ate tons of oat bran.) The more I read about high lipoprotein(a), the more scared I got. My mother had a stroke. Can a statin drug like the Crestor I now take really lower Lp(a)?

LDL vs Lp(a):

A. Lipoprotein(a) is a particle in the blood that contains fat, protein and cholesterol. In the US, cardiologists have focused primarily on LDL cholesterol as the bad actor in the development of heart disease. Statins are very effective at lowering LDL.

On the other hand, lipoprotein(a) is also an important risk factor for heart disease. High lipoprotein(a) levels can contribute to calcification of aortic valves (Biomolecules, Dec. 2019). 

Surprisingly, statins may actually raise levels of Lp little a (European Heart Journal, May 20, 2019).  A meta-analysis of statin trials found that even when LDL cholesterol levels are lowered, people run a substantially higher risk of heart disease if statins raise their Lp little a above 50 mg/dl (Lancet, Oct. 13, 2018). Some cardiologists are recommending levels below 30 mg/dl. 

Don’t give up on exercise and diet just because you are taking rosuvastatin (Crestor). You may also want to ask your doctor about an alternate treatment for lowering LDL cholesterol. Evolocumab (Repatha) reduces both LDL and Lp(a) and in your case may be helpful against heart disease (Circulation, March 19, 2019). 

You can learn about a wide variety of strategies to protect your heart by listening to our interview with preventive cardiologist Michael Blaha, MD, MPH. He is professor of cardiology and epidemiology at Johns Hopkins School of Medicine. He is the Director of Clinical Research for the Johns Hopkins Ciccarone Center for the Prevention of Cardiovascular Disease. Here is a link to our podcast:

Show 1232: What Should People Do to Protect Their Hearts?
People can use sensible approaches to protect their hearts, such as a Mediterranean diet and exercise. What risk factors matter?

Get Ready for Lipoprotein(a) and New Drugs:

We are reading a lot more in the medical literature about Lp little a. We strongly suspect that pharmaceutical companies are moving aggressively into this lipid-lowering arena. You will soon be reading about how important Lp(a) is once those drugs are marketed.

Why do we say this?

Here is a relatively recent article that suggests our crystal ball might be surprisingly clear (Annals of Medicine, May 26, 2020):

“Lipoprotein(a) (Lp(a)) was discovered more than 50 years ago, and a decade later, it was recognized as a risk factor for coronary artery disease. However, it has gained importance only in the past 10 years, with emergence of drugs that can effectively decrease its levels.

“Lipoprotein(a) is an important risk factor in patients with cardiovascular diseases. Lipoprotein(a) has many functions, which include proatherosclerotic, prothrombotic, and pro-inflammatory roles. Treatment options to lower lipoprotein(a) levels are currently scarce, but new drugs are on the horizon.”

We only hope that they will be compared head-to-head with niacin and aspirin to see if the pricey new pills are more effective at reducing heart attacks and strokes compared to the old and inexpensive drugs.

Don’t hold your breath, though. We suspect that drug companies will test the new Lp(a) drugs with statins. That’s because the drug companies and the researchers are convinced that statins are the foundation of heart health and the new drugs are just the icing on the cake, to mix metaphors. 

Readers Comment:

What do you think? Have you ever had your lipoprotein(a) levels measured? Is there a strong family history of heart disease? Has your doctor ever mentioned that statins might raise levels of this important risk factor? Will you ask about getting a blood test for this lipid next time you see your doctor? Share your thoughts in the comment section below.

Did you find this information helpful? If so, please share it with friends and family. We suspect that most people have never heard of Lp(a). It might account for heart attacks in people who have a family history of heart disease, even if they are taking statins. Of course no one should ever stop taking a medicine without consulting the prescribing physician!

You can send this article by clicking on the email, Twitter or Facebook icon at the top of the page and thank you for helping us keep readers up-to-date on new health information. You can learn more about many other risk factors for heart disease in our eGuide to Cholesterol Control and Heart Health at this link

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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.” .
Citations
  • Tsimikas, S., et al, "Statin therapy increases lipoprotein(a) levels," European Heart Journal, June 21, 2020, doi: 10.1093/eurheartj/ehz310
  • Nordestgaard, B.G., et al, "Lipoprotein(a) as a cardiovascular risk factor: current status," European Heart Journal, Dec. 2010, doi: 10.1093/eurheartj/ehq386
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