Is Lp(a) Contributing to Unexplained Heart Attacks?

Are physicians overlooking a key risk factor for heart disease? Is Lp(a) contributing to unexplained heart attacks? For decades, doctors have focused primarily on LDL cholesterol as a determinant of cardiovascular risk. Scientists knew that lipoprotein (a), also known as L-p-little a, was an important risk factor but physicians rarely ordered laboratory tests for it. Unlike familial hypercholesterolemia, which is uncommon, elevated Lp(a) levels may affect up to 25% of the population.

A study published in JAMA Cardiology (October 11, 2023) confirms that people with high amounts of lipoprotein a in their bloodstreams have parents, siblings and children who are also likely to have elevated Lp(a) levels. As a result, the authors recommend testing close relatives whenever someone discovers they have worrisome quantities of Lp(a).

Is Lp(a) Contributing to This Family’s Heart Attacks?

Q. I am a woman who had a heart attack at age 54. My only risk factor was that some people in my father’s family had early heart attacks.

I started taking a statin and baby aspirin. Ten years later, my cardiologist tested my Lp(a), and it was 123. That’s very high, and he’s convinced that it is the culprit for my heart attack.

He prescribed Repatha injections to get my LDL below 70. My Lp(a) has fluctuated between 123 and 145 since starting the Repatha, and I’m still taking a statin.

My two daughters are in their early 30s, and one of them inherited high Lp(a). I do hope they come out with a drug to treat this soon. I feel like a ticking time bomb, despite my healthy diet and lifestyle.

A. As you have learned, lipoprotein (a) [Lp(a)] is an important risk factor for heart disease. In fact, some researchers believe it may be even more harmful than “bad” LDL cholesterol.

Drug companies are developing new medications to lower Lp(a) levels (Current Vascular Pharmacology, Dec. 20, 2023). Alarmingly, a meta-analysis published in the European Heart Journal (June 21, 2020) concluded that statin-type cholesterol-lowering drugs actually raise Lp(a).

You can learn more about Lp(a) and what to do about it in our eGuide to Cholesterol Control and Heart Health. This online resource may be found under the Health eGuides tab.

What’s Your Lp(a) Level?

Have you been tested for Lp(a)? Do you know what your number is? Many people know what their total cholesterol and their LDL cholesterol levels are. We think Lp(a) is at least as important! Drug companies have been developing new compounds that will be able to lower elevated levels of the lipoprotein. Consequently, testing now seems more relevant.

One physician recently wrote to tell us how he is addressing some heart disease risk factors that cardiologists sometimes overlook.

Taking Niacin to Keep Lp(a) from Contributing to Heart Disease:

Q. I am a physician with low levels of HDL cholesterol and high levels of Lp(a). To address these serious risk factors for heart disease, I started taking niacin 30 years ago. I don’t want them, especially Lp(a), contributing to a heart attack.

Niacin can cause flushing and quite a few people do not tolerate this reaction. I have found, however, that if the dose is raised very slowly starting with 50 mg twice a day, most people are able to adjust. Taking niacin after meals also minimizes the flush. This regimen raises my good HDL cholesterol and lowers Lp(a).

A. Thank you for sharing your experience. It is estimated that one out of five people inherits a high level of lipoprotein a, also known as Lp(a). This sticky cholesterol-protein particle contributes to blood clots that can clog arteries. It can also lead to calcification of heart valves.

Diet and exercise do not change Lp(a) levels dramatically. Statins may actually increase Lp(a). (Keep reading for more details on this unexpected effect.) On the other hand, niacin raises good HDL levels and lowers Lp(a), LDL cholesterol and triglycerides.

Readers can learn more about niacin and other approaches to lipid management in our eGuide to Cholesterol Control & Heart Health.

Why Heart Disease Prevention Matters:

Despite a concerted effort by the American Heart Association and over 30,000 cardiologists, heart disease is still our number one killer. According to the CDC:

“Every year, about 805,000 people in the United States have a heart attack.”

Put another way:

“One person dies every 36 seconds in the United States from cardiovascular disease.”

Why Did This Man Have A Heart Attack?

Q. You’ve written about the dangers of Lp(a). Doctors should absolutely test for this cardiac risk factor. Patients should insist on it.

My husband was a thin runner with low lipids and triglycerides; yet he had a heart attack. We learned that his Lp(a) level was high.

Three different cardiologists said that wasn’t important. One even said statins lower it. My husband consulted a fourth cardiologist, took niacin and lowered his level.

Lp(a) are sticky lipids, so when there is turbulence in your arteries, for whatever reason, they glue things together and cause blood clots that can block arteries.

A. There is strong evidence that Lp(a), which is also referred to as lipoprotein a, can increase the risk for heart attacks and strokes (Biomedicines, July, 2021). In addition, high levels of Lp(a) are linked to aortic valve calcification (European Heart Journal, July 23, 2022).

The cardiologist who suggested that statins lower Lp(a) was mistaken. In fact, statins raise this risk factor for heart disease (European Heart Journal, Jan. 1, 2020).  This may explain why some people who eat right, exercise and even take statins could still have heart attacks.

Why Is This Reader’s Calcium Score Going Up?

Whenever we hear from a reader of our syndicated newspaper column that there is a family history of heart disease and plaque in the coronary arteries, we wonder: is Lp(a) contributing to atherosclerosis? This person could be vulnerable to this genetic risk factor:

Q. I have a family history of heart problems and have been on statins for 15 years. My cholesterol level was in the normal range. Nonetheless, I had a blockage in a coronary artery 14 years ago, though I did not suffer a heart attack.

Since then, my physician has increased my statin medication to the maximum dosage. I have always exercised and watched my diet and weight. My cholesterol at last check was 109 (HDL of 41 and LDL of 49). Triglycerides are 107.

For the past several years I’ve had coronary calcium scans. While my cholesterol has remained very low, every year the calcium score has increased. With lipid levels as low as mine, where is the cholesterol coming from to make these plaques? I have asked a cardiac specialist and it was clear that he did not know the answer. Do you have any thoughts on this?

A. A review of this phenomenon noted that statins have an undesirable effect on coronary calcium scores (Arteriosclerosis, Thrombosis, and Vascular Biology, Jan. 21, 2021).

The investigators wrote:

“Statins lower cardiovascular event risk, yet, they paradoxically increase coronary artery calcification, a marker consistently associated with increased cardiovascular risks”

It may take several years for this calcification to become apparent.

With a family history of heart disease and a clogged coronary artery, you should ask your cardiologist to check your blood level of Lp(a). This independent risk factor for heart disease can also cause calcification of arteries and heart valves. High levels run in families.

To learn more about Lp(a) and ways to lower this serious risk factor, you may wish to read our eGuide to Cholesterol Control and Heart Health. This online resource may be found under the Health eGuides tab. In addition to increasing calcification, statins also raise levels of Lp(a) (European Heart Journal, Jan. 1, 2020).

The Cardiologist’s Formula for Preventing Heart Disease:

Doctors have guidelines that are supposed to provide a roadmap for successful treatment of many serious health conditions. These protocols guide cardiologists and other physicians as they attempt to prevent or treat heart disease.

Ask most health professionals how to prevent heart attacks and you will likely be told that people should:

1) Never smoke
2) Eat a healthful diet, preferably low in fat
3) Keep blood pressure below 120/80
4) Exercise regularly
5) Lose weight if you are over the recommended range
6) Keep blood sugar under control
7) Take a statin daily to lower cholesterol.

The Statin Statistics:

Many people do their best to follow these recommendations. Just take statins, as one example.

At last count, nearly 50 million Americans received 219 million prescriptions for statin-type cholesterol-lowering drugs such as atorvastatin, simvastatin, pravastatin, rosuvastatin, lovastatin or pitavastatin. If each prescription has only 30 pills, that would equal 6.6 billion pills annually. Over a decade that represents tens of billions of statins swallowed.

And yet the CDC states that:

“About 659,000 people in the United States die from heart disease each year—that’s 1 in every 4 deaths.”

So, after hundreds of millions of statin prescriptions and decades of following dietary recommendations, a lot of people continue to die from heart disease. How could people who follow the rules for heart health still end up with heart disease?

The theory goes that if you manage all these risk factors, you might be able to escape heart disease. For many people, that is probably true. What is going wrong? Up to one-fifth of heart attacks happen to people who do a lot of things right.

How Do Cardiologists Explain This Sad Story?

We read about a doctor who specialized in heart attack prevention. He was a dedicated athlete and in fabulous shape. Because there was heart disease in his family, this middle-aged physician was taking a statin.

Despite his superb physical condition, his heart suddenly stopped beating. Quick action by friends trained in CPR saved his life. At the hospital, the cath lab found one artery that was almost completely blocked. Interventional cardiologists opened the blockage and inserted a stent to keep the artery open.

This doctor survived his prolonged cardiac arrest because of excellent cardiopulmonary resuscitation. Paramedics arrived on the scene promptly and shocked his heart to get it beating again. At a nearby hospital, the emergency cardiac team was able to get blood flowing to the heart muscle within a relatively short period of time. Most people are not so fortunate.

But the key question is: why did this heart attack happen in the first place? A physician who was doing everything right should not have experienced such a life-threatening event.

The James Fixx Heart Attack:

There are other examples. James Fixx was a renowned runner. He had lost 60 pounds, stopped smoking and written a bestseller titled The Complete Book of Running.

Nonetheless, James Fixx died of a heart attack at age 52 during his daily run. Like the physician above, he too had a coronary artery that was almost completely blocked.

Is Lp(a) Contributing to Mysterious Heart Attacks?

If a middle-aged overweight man who smokes, doesn’t exercise and eats a lot of burgers and fries for lunch has a heart attack, most doctors nod knowingly. If there was a history of heart disease in the family, they chalk it up to bad genes and bad lifestyle…a deadly combination.

But how do cardiologists explain heart attacks in seemingly healthy people with “normal” cholesterol levels, no smoking history, a “good” diet and a regular exercise program? When a cardiac event occurs in a person who is taking statins, people often shrug is astonishment.

We don’t know the details of the personal medical history of either case we described above. All we know are the facts that have been publicly reported. But there is growing evidence that one risk factor might help explain these and many other mysterious cardiac deaths.

Relatively few people have heard of lipoprotein (a), abbreviated Lp(a). This lipid fraction is often described as “Lp little a.”

Why Don’t Doctors Consider Lp(a) Contributing to Heart Disease?

Doctors rarely test for Lp(a), even when they are trying to determine a patient’s risks for heart disease. Perhaps that is because they have been told that there isn’t much, if anything, they can do to lower Lp(a).

Exercise doesn’t appear to change it significantly, and neither does a conventional heart-healthy low-fat diet. Statin-type drugs are good at reducing so-called bad LDL cholesterol (LDL-C) and total cholesterol (TC), but a study published in the European Heart Journal (June 21, 2020) suggests that statins actually raise levels of Lp(a). And by the way, statins can also raise blood sugar levels and trigger diabetes. You can read about it here.

Lp(a) and Saturated Fat:

A new study of diet and Lp(a) will drive most cardiologists crazy (American Journal of Clinical Nutrition, September, 2024). Many physicians believe that diet has no impact on Lp(a). The above research reveals that eating more saturated fat lowers Lp(a) levels modestly.

Carbohydrates on the other hand, raise Lp(a) levels. Of course this research completely contradicts the usual dietary advice for controlling heart disease risk. Diet can also lower C-reactive protein, which is a measure of inflammation. Anti-inflammatory foods include dark green leafy vegetables, blueberries, flaxseed and cocoa.

Is Lp(a) Contributing to Heart Attacks?

Even though most health professionals ignore Lp(a), scientists have known for more than half a century that lipoprotein(a) is an important independent risk factor for cardiovascular complications. Approximately 20% of Americans inherit high levels of Lp(a). It is estimated that 30% of the world’s population has elevated levels of  Lp(a). When those climb above 50 mg/dL, the chance of a heart attack soars.

Here is a relatively recent “insight” from JAMA about “Lipoprotein(a) and Cardiovascular Diseases” (JAMA, July 8, 2021):

“Lp(a) is a risk factor for atherosclerotic cardiovascular disease (ASCVD), including myocardial infarction [heart attack] and ischemic stroke, in both primary and secondary prevention populations, as well as for incident calcific aortic stenosis.”

In other words, in answer to the question is Lp(a) contributing to heart attacks, strokes and calcification of the aorta, these health professionals said hell yes!

The authors recommend statins for patients with high Lp(a) levels even though they admit that statins:

“…may modestly increase Lp(a)…”

How much is “modest”? According to the authors of the article titled “Statin therapy increases lipoprotein(a) levels” published in the European Heart Journal (June 21, 2020):

“The mean percent change from baseline ranged from 8.5% to 19.6% in the statin groups and -0.4% to -2.3% in the placebo groups…The mean percent change from baseline ranged from 11.6% to 20.4% in the pravastatin group and 18.7% to 24.2% in the atorvastatin group.”

Is that modest? We leave it to you to decide.

An Inconvenient Truth: Lp(a) Contributing…?

These same authors wrote an article titled “Statins and Increases in Lp(a): An Inconvenient Truth That Needs Attention” (European Heart Journal, Jan. 1, 2020):

“We feel that the importance of our study is that it points out a unique limitation of statin therapy, primarily in patients with elevated Lp(a), that must be understood pathophysiologically and studied for impact on residual risk. It may come across as an inconvenient truth that statins lower LDL-C but can raise levels of Lp(a). Our duty is to report these data to allow the clinical community to replicate them and allow clinicians to obtain experience in their practice for better-informed decision making and risk evaluation in their patients with elevated Lp(a).”

We interviewed the lead author of this article, Dr. Sotirios (Sam) Tsimikas on our nationally syndicated public radio show, The People’s Pharmacy. Dr. Sam is one of the world’s foremost authorities on Lp(a). We think you will find this podcast well worth your time. You can listen by clicking on the arrow inside the green circle under Dr. Sam’s photo or scroll to the bottom of the page and downloading the mp3 file. He discusses way to lower Lp(a).

Can Doctors Lower Lp(a)?

As we have pointed out, researchers have known for decades that Lp(a) is an independent risk factor for heart disease. Doctors have been told that they 1) do not have to measure Lp(a) and 2) they can’t do anything about it even if it is elevated. We’re not so sure that is correct.

Health professionals should not write off diet. A study in the American Journal of Clinical Nutrition (Jan. 2022) reports that a low-carb diet lowered Lp(a). If you don’t want to wade through that article (and we do not blame you if you don’t), why not listen to our interview with David Ludwig, MD, PhD? He is an endocrinologist and researcher.

Dr. Ludwig is a Professor of Pediatrics at Harvard Medical School and Professor of Nutrition at the Harvard T.H. Chan School of Public Health. He is also a primary author of the article above and discusses the impact of a low-carb diet on Lp(a) during our interview. Here is a link to the podcast. You can listen to the streaming audio by clicking on the arrow inside the green circle under Dr. Ludwig’s photo or download the free mp3 file.

Aspirin and niacin have been mostly abandoned for cardiac prevention, but they too can help against high Lp(a). Another off-label option is a PCSK9 inhibitors. These are drugs such as alirocumab (Praluent) or evolocumab (Repatha). Here is a review that explains why these are worth discussing with a physician (Atherosclerosis, May, 2022).

Perhaps it’s time doctors made this risk factor a priority. If there is a history of heart disease in your family, you may want to ask your doctor to consider a blood test for Lp(a). If your level is elevated, inquire about strategies to lower it.

Low Level of Lp(a) Contributing to Low Risk of Heart Attack:

Not everyone needs to worry that their Lp(a) is too high. We heard from a reader with an interesting perspective.

Q. You wrote about Lp(a) demonstrating that someone might be developing heart disease. I found the blood test useful for the opposite reason – showing that I have a low risk for heart attack.

I have had high LDL and high cholesterol measures for over a decade (since menopause). Every primary care doctor has wanted to put me on statins, despite the fact that I have a very low BMI, low bp and blood sugar, exercise regularly, eat a low-carb diet high in healthy fats and never smoked.

I have resisted their statin prescriptions, but finally I saw a cardiologist just to make sure I wasn’t in danger of dropping dead from a sudden heart attack. He tested my Lp(a) and ordered a coronary calcium scan. The latter showed a score of zero. The Lp(a) measured less than 6. Unless other things change, he doesn’t recommend a statin.

How Can You Prevent Lp(a) Contributing to Heart Disease?

A. It sounds like you are following a heart-healthy lifestyle. How smart of you to check in with a cardiologist to make sure you are on the right track!

Lp(a) is a long-recognized independent risk factor for heart disease. Because doctors believe there is no treatment to lower this lipid fraction, they rarely measure it.

Research now shows, however, that it may be responsible for otherwise unexplained heart attacks. As we mentioned above, a low-carb diet appears to lower Lp(a) levels (American Journal of Clinical Nutrition, Jan. 2022).

Learn More:

To learn more about Lp(a) and other underappreciated risk factors for heart disease, you may wish to read our eGuide to Cholesterol Control and Heart Health. It also describes many non-drug options for lowering blood fats as well as other risk factors for heart disease that may be overlooked. Anger and stress are emotional factors that cardiologists rarely deal with. Inflammation is also critical.

If you would like to read more about Lp(a), here is a link.

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