A stealthy cholesterol is killing people, and most don’t know they’re at risk

A stealthy cholesterol is killing people, and most don’t know they’re at risk
02.02.2024

Millions of Americans are born genetically predisposed to extremely high levels of a type of cholesterol that cause deadly heart attacks and strokes by middle age, yet they are almost always unaware of their risk.

The cholesterol is called lipoprotein(a), or Lp(a). Like low-density lipoprotein — LDL, or the “bad” cholesterol — it leads to plaque buildup in arteries. But Lp(a) has a second nasty trick that makes it even more dangerous: it causes blood clots. And unlike LDL, it’s entirely genetic, which means diet and exercise have no effect on Lp(a) levels.

The result is a high likelihood of life-threatening heart disease that runs in families, killing parents, aunts, uncles and siblings in their 40s and 50s.

“Everybody in their family has had a heart attack or stroke or bypass surgery or stent in their 40s,” Dr. Steven Nissen, chief academic officer of the Heart, Vascular & Thoracic Institute at Cleveland Clinic, said of his patients with high Lp(a). “They’re scared to death.”

As many as 64 million Americans have elevated Lp(a) levels. Anyone can have it, though it is most common among people of African and South Asian descent.

Routine blood cholesterol tests could look for Lp(a) but do not — largely because there is no effective treatment for it. Similar to other forms of high cholesterol, there are no symptoms with high Lp(a).

But with several promising drugs making their way through clinical trials, doctors say people should be aware of their risk.

Dr. Erin Michos said screening for Lp(a) is part of her preventive care for patients.

“To me, it doesn’t make any sense that I’m not going to measure it just because I can’t bring the number down,” said Michos, an associate professor of medicine and director of Women’s Cardiovascular Health Research at Johns Hopkins University School of Medicine in Baltimore. “I measure it in all my patients at least once to just find out who’s high because we can do things to lower their risk.” 

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Cardiologist Dr. Sahil Parikh believes there should be wider testing for Lp(a).

“The challenge has been, if you test for something and don’t have a treatment for it, are you doing the patient any favors?” said Parikh, director of endovascular services at Columbia University Irving Medical Center in New York. “I used to not test for things that I couldn’t treat. But now I do, because I know on the horizon, we’re going to have good treatments. It gives patients hope.”

One of those experimental drugs is called pelacarsen, from drugmaker Novartis. Earlier studies showed it significantly drove down Lp(a) levels in 98% of people taking it. The question for researchers now is whether a lower Lp(a) actually reduces early and potentially deadly heart attacks and stroke. It’s already well established that medications such as statins can protect against heart disease by lowering LDL.

Lori Welsh, 51, of Dublin, Ohio, is betting on pelacarsen to work. High Lp(a) levels have run in her family for years, with devastating effects.

“If you go back five generations in my mom’s family, everybody died of a heart attack or stroke. Nobody made it past the age of 54,” Welsh said.

Welsh was only 47 when she had a heart attack.

“I was driving down a six-lane highway in Columbus, Ohio, and I felt pressure in my chest. My hands went numb.”

She had a 90% blockage in her heart’s biggest artery: the lower anterior descending artery. The condition is known as a “widow-maker.”

“You go from a perfectly healthy person on a Monday, have a heart attack on a Tuesday, and on Wednesday, you have a heart history that you didn’t have before,” Welsh said. “Then you find out that there’s no easy fix for this.”

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Welsh is participating in a clinical trial of pelacarsen at the Ohio University Wexner Medical Center, one of hundreds of study sites nationwide. Neither she nor her doctors know whether she’s getting the real drug or a placebo. She said she has not felt any side effects since enrolling in the trial.

Four other drugs that target Lp(a) are in various stages of research. Early results for Eli Lilly’s drug, lepodisiran, show the drug can drive down Lp(a) by more than 94%. Amgen said its drug, olpasiran, has shown similar results. And Silence Therapeutics is studying a drug called zerlasiran. All of those, including pelacarsen, are given as an injection. Eli Lilly is also testing an oral drug called muvalaplin.

The first real-world results for pelacarsen are not expected until next year.

Until the drugs are proven to work, doctors can only treat patients’ other heart disease risk factors, such as blood pressure management and statins to bring down other forms of cholesterol.

Dr. Wesley Milks, a cardiologist and clinical assistant professor of internal medicine at The Ohio State University College of Medicine, said he sees patients “who are aware of their family history and are really trying to prevent a first heart attack or stroke.”

In those cases, he said that doctors might start patients on “statins earlier in life that we might otherwise.”

“The hope is that we can keep them safe until we can get one of these drugs on the market,” Nissen, who is an investigator for clinical trials of lepodisiran, said. He and other cardiologists are calling for widespread screening of Lp(a).

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The test only needs to be given once during a person’s life because the level never changes.

“Why wait for those new drugs?” said Michos of Johns Hopkins. Measuring Lp(a) now “identifies a high-risk patient. We can be proactive about prevention. We can take action.”

That is, maintaining a normal weight, getting regular exercise, stopping smoking and eating a diet rich in fruits, vegetables and whole grains are effective ways of managing heart risks overall, even for people with elevated Lp(a), Michos said.

Lori Welsh is convinced that knowing one’s own Lp(a) can be life-saving, even if drugs to treat it don’t yet exist. Welsh’s mother had the first of three heart attacks in her late 40s. Doctors tested her Lp(a) levels and explained how they greatly elevated her heart risks.

“I saw her be more intentional with her diet and with exercise,” Welsh said, adding that her mother paid close attention to any heart symptoms from then on. She ultimately lived well into her 70s, decades longer than her ancestors.

“The only difference between her and all five of those generations was the knowledge that she had lipoprotein(a),” Welsh said. “That made all the difference.”

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