Lipoprotein(a): An update on testing and treatment

A fatty particle that circulates in the bloodstream, lipoprotein(a) is similar to LDL cholesterol but more dangerous. High levels of Lp(a), as it is commonly called, can double or even triple a person's risk of a heart attack. It's considered a common culprit in heart disease that occurs at a young age. So why do so few people know about it?

Until recently, most guidelines didn't recommend testing for Lp(a) — but with good reason. Your genes determine your Lp(a) value. Eating and exercise habits have virtually no effect on the levels in your bloodstream. Plus, there were no effective treatments to lower Lp(a), which also elevates the risk of stroke and aortic stenosis (a thickened, stiff aortic valve).

Now, with five promising therapies to lower Lp(a) in development, the landscape is changing. Here's the latest advice and information about Lp(a).

Lp(a) testing trends

International consensus groups recommend one-time Lp(a) testing for everyone. In Europe, such testing is routine. But in the United States, the first official endorsement for Lp(a) testing didn't appear until 2024, from the National Lipid Association.

"Recent data show that only 0.3% of people received Lp(a) screening between 2012 and 2019," says Harvard Medical School associate professor Dr. Michelle O'Donoghue, a cardiologist at Brigham and Women's Hospital. Also, about half of those tests were ordered by a very small number of health care providers, she adds.

But Lp(a) testing should soon become more widespread, for several reasons. First, the tests are now covered by most insurers in most states. Second, even though targeted therapies to lower Lp(a) are not yet on the market, people with high levels (see "Lp(a) readings: Check the units") may benefit from more intensive treatment to manage their overall risk of heart disease, says Dr. O'Donoghue. "This may include taking cholesterol-lowering drugs like statins, even if your LDL cholesterol is normal," she says. Low-dose aspirin is also being investigated as a possible therapy for preventing heart attacks in people with high Lp(a).

A one-time test?

Unlike LDL, which rises with age and is influenced by diet and exercise, Lp(a) remains largely constant over a person's lifetime, so a one-time test suffices for screening. However, researchers are working to better understand changes that may occur in Lp(a) in women around the time of menopause and for men and women with certain medical conditions. The following groups of people are specifically recommended for testing:

• people with premature cardiovascular disease, defined as those who've had a heart attack, stroke, peripheral artery disease, or aortic stenosis before age 55 (for men) or 65 (for women)
• people who have a father, mother, sister, or brother with premature cardiovascular disease
• people with very high LDL cholesterol (190 mg/dL or higher)
• close relatives (siblings, children, and parents) of anyone with an elevated Lp(a) level.

Therapies to lower Lp(a)

Most of the drugs in development for lowering Lp(a) work by interfering with RNA, the molecule that copies and transfers genetic instructions from DNA, the cell's genetic blueprint. Currently, there are four RNA-based drugs that effectively silence the gene that makes Lp(a) in liver cells: lepodisiran, olpasiran, pelacarsen, and zerlasiran. All are administered by injection every one to six months and have been shown to lower Lp(a) levels 80% and 100%. The side effects appear to be limited to mild, short-lived pain at the injection site. Larger, longer trials looking at whether these drugs will help prevent heart-related problems are currently under way, with results expected within the next one to two years, says Dr. O'Donoghue, who is a lead investigator on the clinical trials of olpasiran.

Preliminary results also look promising for another experimental drug called muvalapin, which works by preventing the assembly of the Lp(a) particle. Like the RNA-based drugs, muvalapin also leads to dramatic drops in Lp(a), but it is taken as a daily pill. Side effects include headache, back pain, and fatigue. While some people prefer pills over shots, injectable drugs have the advantage of much less frequent dosing, Dr. O'Donoghue notes.

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