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Millions of Americans are born genetically predisposed to extremely high levels of a type of cholesterol that causes fatal heart attacks and strokes in middle age, but they are almost always unaware of their risk.
Cholesterol is called lipoprotein(a) or Lp(a). Like low-density lipoproteins (LDL or “bad” cholesterol), it causes plaque to build up in the arteries. But Lp(a) has a second nasty trick that makes it even more dangerous: it causes blood clots. And unlike LDL, it is completely genetic, meaning that diet and exercise have no effect on Lp(a) levels.
The result is a high probability of suffering from life-threatening heart diseases that run in families and kill parents, aunts, uncles and siblings in their 40s and 50s.
“Every member of your family has had a heart attack, stroke, bypass surgery or stent by the time they were 40 years old,” said Dr. Steven Nissen, academic director of the Clinic’s Heart, Vascular and Thoracic Institute. Cleveland, about his patients with Lp(a). “They’re scared to death.”
Up to 64 million Americans have elevated Lp(a) levels. Anyone can get it, although it is more common among people of African and South Asian descent.
Routine blood cholesterol tests could look for Lp(a), but they don’t, largely because there is no effective treatment for it. Like other forms of high cholesterol, high Lp(a) has no symptoms.
But with several promising drugs undergoing clinical trials, doctors say people should be aware of their risk.
Dr. Erin Michos said Lp(a) screening 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 narrow down the number,” said Michos, an associate professor of medicine and director of Women’s Cardiovascular Health Research at Johns Hopkins. University of Baltimore School of Medicine. “I measure it in all my patients at least once to know who is on drugs because we can do things to reduce their risk.”
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Cardiologist Dr. Sahil Parikh believes that broader Lp(a) testing should be performed.
“The challenge has been: If you test for something and you 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 I couldn’t treat. But now I do, because I know that on the horizon we will have good treatments. This gives patients hope.”
One of those experimental drugs is called pelacarsen, from the pharmaceutical company Novartis. Previous studies showed it significantly reduced Lp(a) levels in 98% of people taking it. The question for researchers now is whether lower Lp(a) actually reduces early, life-threatening heart attacks and strokes. It is already well established that drugs such as statins can protect against heart disease by lowering LDL.
Lori Welsh, 51, of Dublin, Ohio, relies on pelacarsen for work. High levels of Lp(a) have been inherited in her family for years, with devastating effects.
“If you go back five generations in my mother’s family, everyone died of a heart attack or a stroke. No one was older than 54,” Welsh said.
Welsh was only 47 years old when he suffered a heart attack.
“I was driving on a six-lane highway in Columbus, Ohio, and I felt pressure in my chest. My hands went numb.”
He had a 90% blockage in the largest artery in his heart: the inferior anterior descending artery. He condition is known as “widow”–maker.”
“You go from being a perfectly healthy person on Monday, having a heart attack on Tuesday, and on Wednesday you have a heart history that you didn’t have before,” Welsh said. “Then you find out there’s no easy solution to this.”
Welsh is participating in a clinical trial of pelacarsen at Ohio University Wexner Medical Center, one of hundreds of study sites across the country. Neither she nor her doctors know if she is receiving the real drug or a placebo. She said that she has not felt any side effects since she enrolled in the trial.
Four other drugs targeting Lp(a) are in various stages of investigation. Early results for Eli Lilly’s drug lepodisiran show that the drug can reduce Lp(a) by more than 94%. Amgen said that his drug, they will smellhas shown similar results. AND Therapeutics of silence is studying a drug called zerlasiran. All of them, including pelacarsen, are given as an injection. Eli Lilly is also testing an oral drug called muvalaplin.
The first real results of 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 control and statins to lower other forms of cholesterol.
Dr. Wesley Milks, a cardiologist and assistant clinical professor of internal medicine at The Ohio State University College of Medicine, said he sees patients “who know their family history and are really trying to prevent a first heart attack or stroke.” cerebral”.
In those cases, he said doctors could start patients on “statins at a younger age than we would otherwise.”
“The hope is that we can keep them safe until we can get one of these drugs to market,” said Nissen, a lepodisiran clinical trial investigator. He and other cardiologists are calling for widespread Lp(a) screening.
The test should only be done once during a person’s lifetime because the level never changes.
“Why wait for those new medications?” said Michos of Johns Hopkins. Measuring Lp(a) now “identifies a high-risk patient. We can be proactive in prevention. We can take action.”
That is, maintaining a normal weight, exercising regularly, quitting smoking, and eating a diet rich in fruits, vegetables, and whole grains are effective ways to control heart risks in general, even for people with elevated Lp(a), Michos said.
Lori Welsh is convinced that knowing your own Lp(a) can save lives, even if there are no medications yet to treat it. Welsh’s mother suffered the first of three heart attacks when she was around 40 years old. The doctors examined her Lp(a) levels and explained how they significantly raised her heart risks.
“I saw her be more intentional with her diet and exercise,” Welsh said, adding that her mother paid close attention to any cardiac symptoms from that point on. In the end she lived well into her 70s, decades older than his ancestors.
“The only difference between her and the five generations was the knowledge that she had lipoprotein (a),” Welsh said. “That made a difference.”