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

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) or had it measured. It is also referred to as “Lp little a.”

This cholesterol-protein particle is rarely monitored by physicians, but it is a key player in heart disease. It could be contributing to many preventable heart attacks. A new study to be published on March 5, 2024 in the Journal of the American College of Cardiology reveals that even relatively small increases in Lp(a) levels can lead to clogged coronary arteries, heart attacks, strokes and premature cardiovascular death. Such heart problems are abbreviated MACE (major adverse cardiovascular events).

Some People Get Heart Attacks Who Shouldn’t:

When you read about an unlikely candidate for heart disease–someone who is very fit, eats healthy food, has low cholesterol levels and doesn’t smoke–but ends up with a heart attack at age 54, consider lipoprotein(a) as a potential culprit. That’s especially true if there is a history of heart disease in the family.

We continue to get messages from people who did everything right, took statins for many years and still suffered a heart attack. Here is a link to just such a situation. Statins probably won’t prevent this kind of cardiovascular “accident.” In fact, statins might make matters worse if people have elevated Lp(a) levels.

Many healthcare professionals are unfamiliar with lipoprotein(a). They rarely test for it. And yet this independent risk factor was identified six decades ago as a key player in coronary heart disease (Clinical Biochemist Reviews, Feb. 2004).

Fast Forward to 2024:

The study in the Journal of the American College of Cardiology (March 5, 2024) reveals that levels of Lp(a) greater than 53 mg/dL or 112 nmol/L pose a risk for clogged coronary arteries and heart attacks. OK…I can hear you complaining already. Why two different metrics?

Cardiologists have been told that lipoprotein(a) is an independent risk factor for heart disease. But they have also been told that there is “no generalized consensus on Lp(a) risk thresholds.” The American College of Cardiology/American Heart Association suggests thresholds below 50 mg/dL or 125 nmol/L. The reason for these two different numbers is because of separate measurement techniques. We have read expert opinions that recommend the immunoassays that rely upon nmol/L is the desired metric.

Another study published in JAMA Cardiology, Feb. 14, 2024 also confirmed that elevated Lp(a) levels are linked to peripheral artery disease (PAD), heart attacks and major adverse cardiovascular events (MACE).

As if that weren’t enough evidence, there was a systematic review and meta-analysis published in Clinical Research in Cardiology (Feb. 26, 2024) that demonstrated a causal association between Lp(a) levels and coronary artery disease.

When readers learn about this risk factor, they naturally have concerns.

What Can You Do About High Levels of Lp(a)?

Q. I inherited very high Lp(a) levels. Despite a healthy lifestyle, I had a heart attack and stroke. Although it is a significant cardiac risk factor, I had to convince my doctors to test for Lp(a). They don’t do so routinely.

I’ve done my own research to learn how to lower Lp(a). It involves vitamin C, the amino acids lysine and proline and prescription-dose niacin. My doctor monitors my progress. So far, I am doing well with this regimen.

A. Lipoprotein a, also known as Lp(a), is a serious risk factor for heart attacks and strokes. One fourth to one fifth of the population has elevated levels due to genetic factors. Statins may raise levels of Lp(a) (European Heart Journal, June 21, 2020).

Here’s a similar story about heart disease and a “bad family history”:

Q. I have a bad family history of cardiovascular disease. My brother died at age 45 of a heart attack. Consequently, I have tried to lower my own risk.

A preventive cardiologist I consulted prescribed statins, which gave me terrible leg cramps and brain fog. After a few years of that, I gave up on those drugs. I was still struggling with the low-fat high-carb diet the dietician recommended. On it, I gained weight and felt tired. Eventually, I quit that too.

A diet with good-quality fats helped me lose 15 pounds. Even better, my Lp(a) levels dropped significantly and are no longer too high. I get my fats from grass-fed meats, free range eggs, avocados, olive and avocado oil, though I sometimes cheat with a little peanut butter or chocolate. Reading actual medical research on Lp(a) has been enlightening.

A. High levels of lipoprotein(a) or Lp(a) are now considered a major risk factor for atherosclerosis, heart attacks, strokes and heart valve calcification. Statins lower LDL cholesterol, but there is growing evidence that these medications may increase Lp(a) levels.

A study involving over 42,000 patients found that:

“The use of statins was associated with an increased risk of Lp(a) elevation compared with non-statin use counterparts” (European Journal of Medical Research, July 1, 2023).

Diet is not supposed to lower Lp(a) levels, but a study in the American Journal of Clinical Nutrition (Jan. 2022) suggests that a low-carb diet can be helpful. You can learn much more about Lp(a) and other strategies to lower this often-ignored risk factor for heart disease in our eGuide to Cholesterol Control and Heart Health. This online resource may be found under the Health eGuides tab.

Lowering Lipoprotein a:

It is not easy to lower Lp(a), but one approach that has been shown to be effective utilizes high-dose niacin (Metabolism, Nov. 2016).  It should only be taken under medical supervision, though. In addition to uncomfortable flushing, niacin can boost blood sugar and increase the risk for an attack of gout.

To learn more about Lp(a) and other cardiac risk factors, you may wish to read our eGuide to Cholesterol and Heart Health.

Lowering Lp(a) with Niacin:

Q. Long ago, a doctor friend sent me a scientific article showing that high Lp(a) levels contribute to cardiac problems. My physician was not aware of Lp(a) or its significance. But after reviewing the article and doing some additional research, he prescribed slow-release niacin.

I have been taking this for the last 20 years. A daily dose of 1500 mg brought Lp(a) below 50, but even 1000 mg seems to keep the level reasonable. A baby aspirin about half an hour before taking niacin helps keep the side effects of flushing and itchiness to tolerable levels.

A. Lipoprotein a, or Lp(a), is a recognized risk factor for heart disease. It runs in families and may be even more important than elevated cholesterol. Some cardiologists estimate that one fifth of the population has high levels of this cholesterol-protein particle. It can also increase the chance that heart valves will calcify.

Doctors have known about Lp(a) and its link to heart disease since the 1960s (Journal of Lipid Research, March 2016). There are relatively few drugs that lower this risk factor, but niacin is among them. Expect a couple of new pharmaceuticals to address this risk factor soon, though. Once doctors can prescribe a treatment, they may also start measuring Lp(a).

Could Dietary Supplements Help Lower Lp(a)?

Q. You’ve written that statins raise Lp(a). Do other drugs or supplements do the same? Hopefully, a research cardiologist is looking into this matter.

I am one of many who has stellar numbers (HDL=110, VLDL and triglycerides at the lower bound, 64.5 inches tall and 115 lb female runner). Despite proven heart disease among some older men in my family, I look and feel very healthy.

However, my Lp(a) is quite elevated at 142 nmol/L. I’ve set up an appointment with a local cardiologist, but I’m not sure what he will do.

You’ve had cutting edge researchers on your radio show. Perhaps a great investigator looking into Lp(a) will answer questions for the 20 percent of us with elevated Lp(a).

In checking PubMed, I found that elevated Lp(a) may be a risk factor for a worse case of COVID. Also, it seems that flaxseed might decrease the level of Lp(a). What can you tell us about this?

Could Flaxseed Make a Difference?

A. Thank you for the hint about flaxseed. When we checked PubMed for research articles, we found two recent meta-analyses on the effects of flaxseed supplementation (Alternative Therapies in Health and Medicine, May 2021; Phytotherapy Research, July 2020).
Both concluded that flaxseed supplementation may lower Lp(a) levels.

Lp(a) is short for lipoprotein a, an independent risk factor for heart disease. As you note, statins raise this lipid factor rather than controlling it.

Other Useful Supplements:

Drugs to lower Lp(a) are still under development; research suggests that nutraceuticals including l-carnitine, Coenzyme Q10 and an extract of red yeast rice called xuezhikang can reduce Lp(a) levels significantly (Journal of Cellular Physiology, Aug. 2019).  As we noted above, niacin in the form of nicotinic acid also lowers this risk factor. You may want to consider adding flaxseed or one of these other supplements to your regimen.

As you mentioned, we do speak with leading researchers on our radio show. Dr. Sorios Tsimikas is one of the country’s foremost experts on Lp(a). You can listen to our interview with him in the podcast, “The Best-Kept Secret in Heart Disease” (Show 1306).

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

Experts estimate that at least one fifth of the population has inherited high levels of lipoprotein( a) (Scientific American, Nov. 4, 2019). This independent risk factor is comprised of a lipid-protein compound. Part of it is like “bad” LDL-C and part of it is a combination of  apo B100 and apo(a). The combo known as Lp(a) can be deadly.

That’s because levels greater than 50 mg/dl [>100 nmol/L] increase the risk of heart attacks and strokes. What makes this lipid fraction so toxic is its ability to clog arteries and promote the formation of blood clots. Lp(a) can also lead to calcification of the aortic heart valve. That is not good, as it reduces blood flow into the aorta and impairs circulation. Symptoms may include angina, dizziness, fatigue, shortness of breath and heart palpitations.

Learning About Lp(a) Could Save Your Life:

Q. You probably saved my life with your article about lipoprotein a [Lp(a)]. All four grandparents and both parents had a heart attack or stroke. I had never heard of Lp(a) and now I know it is an important risk factor for clogged arteries.

In Robert Kowalski’s book from 2002, The New 8-Week Cholesterol Cure, he quotes numerous studies where SR (sustained release) niacin lowers Lp(a). I have begun taking it. My husband has taken niacin for years under medical supervision.

A. Lp(a) is a serious genetic risk factor for heart disease and stroke. Cardiologists have known for almost 60 years that this blood lipid is probably as dangerous as LDL cholesterol.

Niacin is one of the few drugs that can lower Lp(a). Statins may actually raise this risk factor (European Heart Journal, June 21, 2020).

A traditional “heart healthy” low-fat diet does not change Lp(a) levels. New research shows, however, that a low-carb diet can reduce this worrisome risk factor (American Journal of Clinical Nutrition, Jan. 2022).

Why Have You Never Heard of Lp(a) Before?

This may sound cynical, but the reason we suspect that Lp little a has flown below the radar is because there is, as yet, 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. As a result, blood tests for this heart attack risk factor are rarely, if ever, performed.

The accepted dogma has been that diet and exercise have little to no impact on this risk factor. Perhaps that’s because cutting back on eggs, butter and red meat doesn’t reduce this cholesterol-transport protein.

That explains why some people who exercise regularly, follow a low-fat or vegan diet and take statin-type cholesterol-lowering drugs can still end up with heart disease. But there is one dietary intervention that might make a big difference! More about that shortly.

We suspect that many cases of hereditary heart attacks may be linked to Lp(a). Because many physicians have not been educated about this risk factor, it goes unmeasured, unreported and untreated.

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.

Bill also has elevated levels of lipoprotein(a):

“I inherited very high Lp(a) levels. Despite living a healthy lifestyle, I had a heart attack and stroke. (I think there is some correlation there.) My genetic predisposition led me to a PhD in Natural Health. I am now 78 years old and otherwise doing fine.

“My experience has been that most doctors do not have a clue about Lp(a). You have to educate them. Furthermore, despite it being a significant cardiac risk factor, they do not test for Lp(a) in lipid panels. They have to special order the test. One approach that has worked for me involves both niacin and vitamin C.”

Can You Control Lp(a)?

A. 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). More about this momentarily!

A new study suggests that diet might be more helpful than most health professionals realize. A low-carb approach lowered Lp(a) by about 15 percent (American Journal of Clinical Nutrition, Jan. 2022).

The authors of this randomized controlled feeding trial suggest that a low-carbohydrate diet:

“…promotes insulin sensitivity and protects against atherogenesis. In addition, we found a potentially novel dietary effect on Lp(a), a major independent and causal risk factor for atherosclerosis.”

Statins Raise Levels of Lipoprotein(a)

Many healthcare professionals are unaware that statins can raise levels of Lp(a). Here is what the authors of the article in the European Heart Journal wanted to know:

Aims:

“Lipoprotein(a) [Lp(a)] is elevated in 20–30% of people. This study aimed to assess the effect of statins on Lp(a) levels.”

Discussion:

“This individual-patient-data analysis demonstrates that Lp(a) levels increase significantly in patients started on statin therapy and that the findings were directionally consistent among most statins studied. Cell culture studies revealed a time and dose-dependent, statin-mediated increase in LPA mRNA expression and apolipoprotein(a) production, suggesting the mechanism is at least in part related to increased Lp(a) production. Whether statin-mediated increases in Lp(a) contribute to residual risk in patients treated with statin therapy should be evaluated in future studies.”

A review in the journal Biomedicines (Aug. 9, 2021) states:

“Statin treatment does not lower but may even increase the level of Lp(a) by 10-20%”

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. The review in the European Heart Journal, (June 21, 2020) notes that:

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

An article in in the European Heart Journal (Jan. 1, 2020) was titled:

“Statins and Increases in Lp(a): An Inconvenient Truth That Needs Attention” 

Just as many physicians find it hard to believe that statins could raise blood glucose levels and/or make it harder to control diabetes, so to it is hard from them to imagine that statins could raise the risk for MACE. And yet a study published in BMC Cardiovascular Disorders (Nov. 8, 2022) reported that statin therapy raised Lp(a) levels about 19.3% and that:

“Patients with a severe increase in Lp(a) after statin therapy have a higher risk of MACE [major adverse cardiovascular events] than those without an increase in Lp(a).”

We suspect that most cardiologists as well as other physicians don’t know what to make of the statin-Lp(a) problem.

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.

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, although statins can too. 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 an 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.

Until we have data proving that the new lipoprotein(a)-lowering drugs reduce the risk of blood clots, heart attacks, and calcification of the aortic heart valve, why not consider a balanced low-carb diet. It can also help people lose weight! You can read more about the latest research on this approach at this link.

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.