Lowering LDL Cholesterol Isn’t Enough: The Hidden Risk of Lp(a)

Most cardiologists believe that elevated levels of “bad” LDL are the number one cause of heart disease. The solution: lower the LDL cholesterol, prevent heart attacks! For many decades this idea drove public health messages, clinical guidelines and billions of prescriptions. And yet after successfully lowering LDL cholesterol with a variety of medications, heart disease still ranks as America’s leading cause of death. Would it be fair to ask this critical question?

Why hasn’t lowering LDL cholesterol saved more lives?

So, what went wrong?

Perhaps a more relevant question might be:

What Did We Miss?

Lowering LDL Cholesterol but Ignoring Lp(a):

Modern medicine has focused intensely on LDL cholesterol for the last 50 years. Over that time we have seen drugs like clofibrate, cholestyramine, colestipol and niacin take center stage and then gradually fade away. Then came the statins! Lovastatin (Mevacor) hit the market in 1987 and rapidly became cardiologists’ favorite cholesterol-lowering medication. Guidelines virtually require physicians to prescribe a statin to most older Americans.

Five years ago we calculated that roughly 100 million statin prescriptions were dispensed to more than 21 million Americans. Our most recent assessment suggests that 200 million statin prescriptions were dispensed to over 50 million Americans.  That includes atorvastatin, rosuvastatin, simvastatin, pravastatin, and lovastatin.

Statins did make a difference: heart disease mortality dropped from 1970 to 2022 (JAHA, June 25, 2025). Other factors also played a critical role, including stop-smoking campaigns, rapid diagnosis, defibrillators, balloon angioplasty plus stents, and anticoagulants. Despite everything, though, heart disease is still the leading cause of death in this country, as it has been since 1921.

And that is after other LDL cholesterol-lowering drugs such as ezetimibe (Zetia) and PCSK9 inhibitors like alirocumab (Praluent) and evolocumab (Repatha) entered the marketplace. Many cardiologists are now able to get “bad” LDL cholesterol below 70 mg/dL. And if they really want to be aggressive, they can push LDL-C below 50 mg/dL or 30 mg/dL. That could not occur naturally.

Jump in our time machine and dial back to the 1980s to look at the National Cholesterol Education Program’s (NCEP) guidelines. In those days, if you were at “low risk” for a heart attack your cardiologist would strive to get your LDL cholesterol below 160 mg/dL. If you were at “intermediate risk” the goal was less than 130 mg/dL and if you were at “high risk,” say after a heart attack, the goal would be an LDL-C level less than 100 mg/dL.

Times have changed! The current thinking is that the lower the LDL-C the better! One might have expected that with so many powerful tools to reduce LDL cholesterol, heart disease would have dropped dramatically and no longer be the number one killer in America.

Cardiologists Ask a Hard Question: Is Lowering LDL Cholesterol the Answer?

In 2020, three cardiologists challenged their colleagues in BMJ Evidence-Based Medicine (online, Aug. 3, 2020) by reviewing randomized controlled trials of three classes of cholesterol-lowering drugs:

1. Statins
2. Cholesterol absorption inhibitors (ezetimibe)
3. PCSK9 inhibitors

Their argument was blunt: if lowering LDL cholesterol reliably saves lives, the relationship between LDL reduction and mortality should be clear and consistent. Yet across many trials, it wasn’t.

They highlighted an uncomfortable pattern: many cholesterol-lowering studies showed limited impact on cardiovascular events, and the overall mortality signal was often smaller than people assume.

Whether you agree with their interpretation or not, the paper captured something many patients have quietly wondered:

If we’ve lowered cholesterol for decades, why is heart disease still winning?

Lowering LDL Cholesterol vs. Living Longer: What Do Statins Really Deliver?

Most patients taking statins believe the benefit is dramatic. But some researchers have tried to quantify the effect in a more concrete way: not just “percent risk reduction,” but actual time gained.

A study in BMJ Open Sept. (24, 2015) asked how much statins postpone death in randomized trials. Their conclusion was sobering: for many trials, the median postponement of death was measured not in years, but in days. This analysis was confirmed in another review published in the Journal of General Internal Medicine, Aug, 2019. The most recent analysis we could find looked at “Time Gained to Cardiovascular Disease by Intensive Lipid-Lowering Therapy” published in the American Journal of Cardiovascular Drugs, (Nov. 2024).

Conclusion:

“Intensive lipid-lowering therapy during 2 or 5 years did not lead to fewer deaths or lifetime gained, and the effects on MI [heart attack] and stroke were negligible. The largest effect was that MACE [major adverse cardiovascular events] did not occur in two of 100 patients and was postponed 3-4 weeks after 5 years of intensive treatment. Given the small effect, patients should receive this information as part of shared decision making.”

This does not mean statins or other cholesterol-lowering treatments are useless. It does mean that the real-world payoff may not match the cultural mythology surrounding cholesterol medication — especially for people without diagnosed cardiovascular disease.

No one should stop any prescription medicine without careful medical supervision. But it’s worth being honest: lowering LDL cholesterol is not a magic wand that makes cardiovascular risk disappear.

Lowering LDL Cholesterol Didn’t End Heart Disease, So What Else Is Going On?

One reason heart disease persists is that it has never been caused by a single factor.

Cardiovascular disease is influenced by blood pressure, smoking, insulin resistance, inflammation, genetics, stress, sleep, diet quality, physical activity, air pollution, and more.

But one risk factor has been quietly rising in importance. For decades it was mostly ignored in routine care:

Lipoprotein(a), or Lp(a).

It’s pronounced “ell-pee-little-a” (rhymes with “hay”), and it may help explain why lowering LDL cholesterol didn’t eliminate heart attacks the way many expected.

Lp(a) is largely genetic. Lifestyle changes don’t reliably lower it. And about one-fifth of the population may have elevated levels.

For years, most doctors chose not to test for Lp(a). The standard “lipid panel” or “lipid profile” tests for total cholesterol, LDL cholesterol (LDL-C), HDL cholesterol and triglycerides. Because there have been no FDA-approved medications to lower Lp(a), many cardiologists may have figured, if you can’t fix it, why look for it?

That era may be ending.

Lowering LDL Cholesterol vs. Lp(a): The Risk Factor Most People Never Hear About

A major long-term study published in JAMA Cardiology (Jan. 7, 2026) followed more than 27,000 healthy women for three decades. Researchers measured Lp(a) levels at the start, long before any heart disease appeared.

Women with higher Lp(a) levels had increased cardiovascular risk in the years that followed. Those with very high Lp(a) — around 120 mg/dL or above — were at greater risk for stroke and fatal heart disease.

The authors emphasized that only a fraction of people with elevated Lp(a) fall into the highest-risk category. But for those who do, the threat can be comparable to familial hypercholesterolemia, the inherited condition that can drive early and dangerous heart disease.

In other words: some people may have been doing “everything right,” lowering LDL cholesterol, yet still carrying serious hidden risk.

Something most cardiologists would prefer not to talk about is the effect of statins upon Lp(a). Years ago we stumbled upon a fascinating study in the European Heart Journal (June 21, 2020) titled:

“Statin Therapy Increases Lipoprotein(a) Levels”

The conclusion:

“This meta-analysis reveals that statins significantly increase plasma Lp(a) levels. Elevations of Lp(a) post-statin therapy should be studied for effects on residual cardiovascular risk.”

Not surprisingly, this bombshell caught a lot of healthcare professionals off guard. It created quite a controversy. The authors followed up with this response to some of the criticism.

“Statins and increases in Lp(a): an inconvenient truth that needs attention”

You can read their commentary (European Heart Journal, Jan. 2020) in part at this link.

Lowering LDL Cholesterol When Lp(a) Is High: What Can People Do?

Some people have tried high-dose niacin (not slow-release niacin and not niacinamide) in an attempt to address high Lp(a).

One physician wrote to us that he has taken it for decades, slowly increasing the dose over time and taking it after meals to reduce flushing:

“I have been taking high-dose niacin (not slow-release or niacinamide) for about 30 years because of low HDL-C and high Lp(a). Although people have different tolerance levels to niacin, most do okay if the dose is raised slowly, beginning at 50 mg twice a day and increasing at intervals of a week or two and always taking the niacin after meals.

“If flushing is a problem at a given dose, it is then easy to either maintain the dose for a longer period or drop back slightly until symptoms are gone. I have never taken aspirin before my niacin and have taken a gram (1000 mg) two or three times a day with only occasional mild flushing–perhaps once or twice a month.”

Niacin is not a casual supplement. It can cause side effects and must be handled thoughtfully with medical supervision. Doctors used to prescribe it to lower total and LDL cholesterol before statins.

More intriguingly, one of the country’s leading experts on Lp(a), Dr. Sotirios Tsimikas, has suggested that people with elevated Lp(a) may be more likely to benefit from regular aspirin use than those with normal levels (American Journal of Preventive Cardiology, April 27, 2024). We suspect this will come as a surprise to many physicians, especially since preventive aspirin treatment has been discouraged in recent years. If you have high Lp(a) levels, you should discuss this research with your health care team. No one should ever undertake regular aspirin use without medical supervision!

You may find our interview with Dr. Tsimikas helpful for that conversation. Here is a link to Show 1421:

Is Lp(a) the Heart Risk No One Talks About?
A lack of medications to lower it may have made Lp(a) the heart risk factor no one talks about. What should you know about it?

Dr. Tsimikas discusses his research and the role of aspirin in people with high Lp(a) levels.

• If early heart disease or stroke runs in your family…
• If you have cardiovascular trouble that seems out of proportion to your LDL results…
• Or if you simply want a clearer picture of risk…

Ask your clinician this direct question:

“Have I ever had my Lp(a) measured?”

You can’t address a risk factor that you have not been tested for. And in the long war against heart disease, it may be time to look beyond LDL — without abandoning what we’ve learned from lowering it. Remember, roughly one in five people is believed to have elevated Lp(a), making it far more common than most patients, or physicians, realize.

Lowering LDL Cholesterol with Other Strategies:

There are many lifestyle interventions that are important whether or not a person is taking medicine to lower cholesterol. Physical activity, stress reduction and a diet that focuses on plants and minimizes processed foods are crucial.

We cannot say that lowering LDL cholesterol with dietary interventions will reduce the risk of heart attacks and strokes or prolong life. There are data, however, that pomegranate juice, grapefruit, cinnamon, psyllium and red yeast rice can all lower LDL cholesterol.

So can a “portfolio” vegetarian diet. It includes foods such as almonds, barley, eggplant, oats, okra and soy. You can learn more about these nondrug approaches in our eGuide to Cholesterol Control and Heart. It is available in the Health eGuides section of PeoplesPharmacy.com.

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