The Obscure Genetic Cholesterol That Can Impact Your Heart Health
'Over the past decade, new scientific knowledge improved our understanding of the Lp(a) role in heart disease risk,' explains Dr. Ahmet Afsin Oktay, a cardiologist with the Rush University System for Health in Chicago. 'As a result, providers have become more aware of how measuring Lp(a) levels can help form a more personalized risk assessment for heart disease.'
Here's what you need to know about Lp(a) and the new medical advances bringing us closer to treating elevated levels.
What is Lp(a), and why is it important?
It's similar in structure to low-density lipoprotein (LDL) cholesterol, often called 'bad' cholesterol. And like LDL cholesterol, 'Lp(a) is involved in creating plaque in our arteries, [thus] contributing to atherosclerosis, and it has inflammatory properties,' says Dr. Tamara Horwich, a clinical professor of cardiology and medical director of cardiac rehabilitation at UCLA.
Research has shown a strong association between elevated Lp(a) levels and an increased risk of cardiovascular disease, including heart attacks, strokes, heart failure, blood clots and peripheral arterial disease. Measuring Lp(a) 'can help identify someone who should be paying more attention to their cardiovascular risks,' Horwich says.
What factors affect Lp(a) levels?
Unlike most forms of cholesterol, 'Lp(a) is not really impacted 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 genetics alone, so we can see elevations that run strongly in families and often correlate with risk of premature heart and vascular disease.'
This is especially important because 'there are some people who have heart disease in the family and the [other] cholesterol numbers do not look that bad—these people may have Lp(a) as the risk factor,' says Dr. Janet O'Mahony, an internal medicine doctor with Mercy Medical Center in Baltimore.
It's estimated that 20% of people around the world have high levels of Lp(a). Women generally have slightly higher Lp(a) levels than men, and the gender divide increases even more after menopause, Horvath says. Research has found that lipoprotein(a) concentrations are about 17% higher in postmenopausal women than in men of the same age.
How can you measure it?
Your Lp(a) level can be checked with a specific blood test that isn't a part of routine cholesterol tests and doesn't require fasting, says Oktay. It is now recommended that every adult have their Lp(a) checked at least once in their life. At this point, having it measured once is considered sufficient since Lp(a) levels don't respond to lifestyle modifications, and there isn't currently a drug that's widely used to treat elevated levels.
Generally, Lp(a) levels range from 0.1 mg/dL to >300 mg/dL. A normal level is less than 30 mg/dL, and a level of 50 mg/dL or greater is considered high, according to the U.S. Centers for Disease Control and Prevention.
How do you treat abnormal levels?
For most people, the goal isn't to reduce the Lp(a) itself but to consider it as part of their overall cardiovascular risk profile. Because there isn't yet a dedicated medication that's used to lower elevated Lp(a) levels, the focus shifts to making a concerted effort to reduce other heart disease risk factors such as high blood pressure, diabetes, and high LDL cholesterol. How? By not smoking, moving more, managing your weight, and sticking with a healthy diet (such as the Mediterranean diet), according to experts. Each of these measures can lower heart disease risk independently, O'Mahony says.
In some instances, someone's Lp(a) level might help guide medication decisions. 'If I have a patient who is middle-aged, has hypertension but is a non-smoker and without diabetes, the predicted 10-year heart disease risk estimate will likely be below the standard threshold of starting a statin,' says Milks. 'However, if Lp(a) is elevated, the presence of high Lp(a) may be enough to nudge the decision for earlier implementation of statin therapy.'
Statins won't lower Lp(a), but they can reduce LDL cholesterol, thereby lowering the risk of heart attack and stroke, Horvath says. For people with elevated LDL who don't respond sufficiently to statins and are at very high risk for cardiovascular disease, strong cholesterol drugs called PCSK9 inhibitors have been found to reduce elevated Lp(a) levels by 20 to 25%.
Meanwhile, clinical trials are investigating whether specially targeted medications—including in-development RNA-based drugs such as pelacarsen, olpasiran, SLN360, and lepodisiran—can lower Lp(a) levels. Even though they're not yet available, these promising advances are helping to drive more widespread Lp(a) testing.
If they're found to be effective, these would address the source of the Lp(a) problem directly. 'There is enthusiasm for Lp(a) measurement particularly now that we are so close to having approved therapeutics that directly inhibit production of Lp(a) in the body,' says Milks.
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