Understanding the Genetic Cholesterol That Affects Heart Health

TC, HDL, LDL: There are many types of cholesterol to be aware of. One of the newer ones is Lp(a), or lipoprotein(a). Even though it was , this specific type of “bad” cholesterol wasn’t well-known until recently. Now, it’s being discussed more and measured in people’s blood tests more often.

“Over the last ten years, new scientific knowledge has helped us better understand the role of Lp(a) in the risk of heart disease,” explains Dr. Ahmet Afsin Oktay, a cardiologist at Rush University System for Health in Chicago. “Because of this, doctors are now more aware of how measuring Lp(a) levels can help create a more personalized assessment of heart disease risk.”

Here’s what you should know about Lp(a) and the latest medical advancements that are bringing us closer to treating high levels.

What is Lp(a), and why is it important?

It has a similar structure to low-density lipoprotein (LDL) cholesterol, which is often referred to as “bad” cholesterol. Like LDL cholesterol, “Lp(a) is involved in the creation of plaque in our arteries, which contributes to atherosclerosis, and it also has inflammatory properties,” says Dr. Tamara Horwich, a clinical professor of cardiology and the medical director of cardiac rehabilitation at UCLA.

has demonstrated a strong connection between high Lp(a) levels and a greater risk of cardiovascular disease, including heart attacks, strokes, heart failure, blood clots, and peripheral arterial disease. Measuring Lp(a) “can help identify individuals who need to pay closer attention to their cardiovascular risks,” Horwich states.

What factors affect Lp(a) levels?

Unlike most types of cholesterol, “Lp(a) is not really affected by diet, exercise, or even statin therapy,” says Dr. Wesley Milks, a cardiologist and clinical associate professor of internal medicine at The Ohio State University College of Medicine. “The levels are about 90% determined by your genes, so we often see high levels that run in families and often correlate with a risk of early heart and vascular disease.”

This is particularly important because “some people have heart disease in their family, but their other cholesterol numbers don’t seem too bad—Lp(a) might be the risk factor for these individuals,” says Dr. Janet O’Mahony, an internal medicine doctor at Mercy Medical Center in Baltimore.

It’s estimated that have high Lp(a) levels. Women typically have than men, and this difference becomes even more pronounced after menopause, according to Horvath. has discovered that lipoprotein(a) concentrations are about 17% higher in postmenopausal women compared to men of the same age.

How can you measure it?

Your Lp(a) level can be determined through a specific blood test that isn’t part of routine cholesterol tests and doesn’t require fasting, according to Oktay. It is now that all adults have their Lp(a) checked at least once in their lifetime. Currently, measuring it once is considered enough because Lp(a) levels don’t respond to changes in lifestyle, and there isn’t a widely used drug to treat high levels.

Generally, Lp(a) levels range from 0.1 mg/dL to over 300 mg/dL. A normal level is below 30 mg/dL, and a level of 50 mg/dL or higher is considered high, according to the .

How do you treat abnormal levels?

For most people, the aim isn’t to lower the Lp(a) itself but to consider it as part of their overall cardiovascular risk profile. Since there isn’t a specific medication used to lower high Lp(a) levels yet, the focus is on making a strong effort to reduce other heart disease risk factors, such as high blood pressure, diabetes, and high LDL cholesterol. How? By not smoking, being more active, managing your weight, and maintaining a healthy diet (such as the Mediterranean diet), according to experts. Each of these steps can independently reduce the risk of heart disease, O’Mahony says.

In some cases, a person’s Lp(a) level might help guide decisions about medication. “If I have a middle-aged patient who has hypertension but doesn’t smoke and doesn’t have diabetes, their estimated 10-year risk of heart disease will probably be below the standard threshold for starting a statin,” says Milks. “However, if their Lp(a) is high, the presence of high Lp(a) might be enough to push the decision towards starting statin therapy sooner.”

Statins won’t lower Lp(a), but they can lower LDL cholesterol, which reduces the risk of heart attack and stroke, Horvath says. For individuals with high LDL who don’t respond well enough to statins and are at very high risk for cardiovascular disease, strong cholesterol medications called PCSK9 inhibitors have been found to .

Meanwhile, whether specially designed medications—including RNA-based drugs in development like pelacarsen, olpasiran, SLN360, and lepodisiran—can lower Lp(a) levels. Even though they aren’t available yet, these promising advancements are helping to encourage more widespread Lp(a) testing.

If these medications prove to be effective, they would directly address the source of the Lp(a) problem. “There is excitement about measuring Lp(a), especially now that we are so close to having approved therapies that directly inhibit the production of Lp(a) in the body,” says Milks.

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