As many as one in five people — an estimated 64 million in the United States — have elevated levels of a tiny particle in their blood. It can greatly increase the risk of heart attacks and strokes.
But few know about it, and almost no doctors test for it, because there was not much to be done. Diet does not help. Neither does exercise. There have been no drugs.
But in the near future, that may change.
On Sunday, cardiologists announced that an experimental drug made by Eli Lilly, lepodisiran, could lower levels of the particle, Lp(a), by 94 percent with a single injection. The effects lasted for six months and there were no significant side effects.
But it is not yet confirmed that reducing Lp(a) levels also reduces the risk of heart attacks and strokes. That awaits large clinical trials that are now underway.
The Lilly research was presented Sunday at the annual meeting of the American College of Cardiology and simultaneously published in the New England Journal of Medicine. At least four other companies are also testing innovative drugs that block the body’s production of Lp(a), a mix of lipids and a protein.
Dr. David Maron, a preventive cardiologist at Stanford not involved in the Lilly research, said the evidence of profound and long-lasting reduction in lipoprotein levels with lepodisiran was “thrilling.”
Dr. Martha Gulati, a preventive cardiologist at Cedars-Sinai Medical Center also not involved in the trial, said the study was “really elegant.”
Eli Lilly is now conducting a large clinical trial asking if its drug can prevent heart attacks or strokes or cardiovascular deaths. It will conclude in 2029. Clinical trials of other drugs targeting Lp(a) will conclude sooner. The first will be a study of a Novartis drug, injected monthly, with results expected in 2026.
Cardiologists caution, though, that there is no guarantee the drugs will protect people. They remember too well a lesson learned from assuming that altering a risk factor can alter risk. Cardiologists once were enthusiastic about drugs that raised levels of HDL, known as the “good cholesterol.” People with naturally high HDL levels had lower rates of heart disease. Those HDL-raising drugs did not help.
Lp(a)-lowering “is a huge new frontier in cardiovascular medicine,” said Dr. Daniel Rader, a preventive cardiologist at the University of Pennsylvania’s Perelman School of Medicine. Dr. Rader is a member of the scientific advisory board for Novartis and wrote an editorial to accompany the new paper.
Treatments targeting Lp(a) have been a long time coming.
The lipoprotein was identified in 1974 as a risk factor for heart disease that is controlled by genes rather than lifestyle or environment.
People with Lp(a) levels that are slightly higher than normal have about a 25 percent increased risk of a heart attack or a stroke. And very high levels — as seen in 10 percent of the population — can double the risk.
Cardiologists say that often in patients with no obvious reason for having a heart attack or a stroke — whose cholesterol levels and blood pressure are normal and who do not smoke — they learn that the patients have high levels of Lp(a). Usually it turns out they also have family histories of unexplained heart disease.
The same goes for people having heart attacks at a young age, said Dr. Steven Nissen, a preventive cardiologist at the Cleveland Clinic who is the academic leader for the Lilly drug trial and for clinical trials of three other new drugs.
“If you go into the coronary care unit and see someone who is 40 years old with an acute myocardial infarction, you need to know the level of their Lp(a),” he said, referring to a heart attack. All too often, he said, their levels are 250 nanomoles per liter or even higher. The upper limit of normal is 75.
Dr. Maron said his clinic was full of people who had no idea why they developed heart disease, until they found out they had high levels of Lp(a).
One is Monte Wooden, a 71-year-old retired firefighter who lives in Redding, Calif. His LDL cholesterol levels were moderately elevated. His blood pressure was normal. He did not smoke. Yet he had his first heart attack in 2006 while taking a cholesterol-lowering statin.
It seemed as if almost everyone in Mr. Wooden’s family died from heart disease.
His paternal grandmother had her first heart attack when she was in her 40s. She died from a heart attack at age 63. His father and his father’s brother died from heart disease. Mr. Wooden’s brother died from a heart attack.
When Dr. Maron tested Mr. Wooden’s Lp(a) level, it was greater than 400.
Dr. Maron and other preventive cardiologists, like Dr. Gulati, Dr. Nissen and Dr. Rader, say they routinely test all their patients’ Lp(a) levels. Because Lp(a) levels are controlled by genes, they add, patients have to be tested only once.
Dr. Nissen is blunt with his Lp(a) patients.
“We say: You have a disorder with serious implications. I want to take every risk factor you have off the table,” he said.
Yet, Dr. Gulati said, one study found that just 0.3 percent of the U.S. population has had an Lp(a) test — which is paid for by insurance — and just 3 percent of those with heart disease have been tested.
She and other preventive cardiologists say all adults should have an Lp(a) test. If levels are high, doctors should aggressively treat every other risk factor.
For Mr. Wooden, that meant taking a powerful cholesterol-lowering drug, Repatha, that got his LDL cholesterol level down to 30.
Mr. Wooden’s case, though, didn’t end there. Dr. Maron got him into a clinical trial testing one of the new drugs that lower Lp(a) levels.
During the trial, Mr. Wooden had no symptoms of heart disease — no chest pain, no breathlessness. When the trial ended, his symptoms came back, leading to a quadruple bypass operation.
“It’s anecdotal,” Dr. Maron said, “but it speaks to the likelihood that these drugs prevent heart attacks.”
