When celebrity fitness trainer Bob Harper woke up in the hospital in 2017, he was shocked to learn that he had suffered a heart attack two days prior while exercising. It led him on a journey to discovering that, despite his healthy lifestyle, he was genetically at a higher risk for a heart attack due to his body having high levels of lipoprotein(a), also called Lp(a).
Approximately one in five people worldwide have a high Lp(a), making it a common risk factor for cardiovascular disease, according to the American Heart Association. That’s why cardiologist Gregory Schwartz, MD, PhD, a professor in the University of Colorado Department of Medicine and chief of cardiology at the Rocky Mountain Regional Veterans Affairs Medical Center, is encouraging all adults to get their Lp(a) levels measured to determine their risk, consistent with recent guidelines from several national and international scientific organizations.
“Because Lp(a) is not part of a standard ‘lipid profile’ lab test, only about 1% of the Americans have had their Lp(a) measured,” Schwartz said during a recent Department of Medicine Grand Rounds presentation. “If you don’t look, you won’t know; and if you don’t know, you can't act.”
Lipoproteins are particles that travel in the body’s bloodstream and carry cholesterol and triglyceride (fat) to and from cells. Lp(a) is a type of lipoprotein, and its levels are genetically determined; therefore, lifestyle choices have little impact on Lp(a) levels.
“By and large, a person with high Lp(a) will have high levels throughout life,” Schwartz said.
Lp(a) is found in only a few species — including humans and non-human primates — but not other animals, he explained. The reason humans evolved to have Lp(a) is uncertain. Some experts believe that in prehistoric times, Lp(a) may have enhanced wound healing or prevented serious bleeding, Schwartz noted.
On the other side of the coin, in modern society, a high Lp(a) level increases the risk of cardiovascular problems. Lp(a) promotes buildup of cholesterol deposits (plaques) in artery walls, inflammation in those plaques, and thickening and narrowing of the aortic heart valve. Because of those effects, Schwartz noted that “higher Lp(a) increases the risk of coronary artery disease, stroke, peripheral artery disease, and aortic valve stenosis.”
Research has found that Lp(a) levels differ in humans based on sex and race. For instance, data have shown that Lp(a) levels rise in women as they experience menopause. Studies suggest that estrogen suppresses Lp(a), which is presumably why levels go up in women around the age of 50 as estrogen declines.
Studies have also found that Lp(a) levels are higher in Black people than in white, Asian, or Hispanic people, he explained. While the clinical significance of these population differences remains uncertain, within each racial and ethnic group, higher Lp(a) is associated with higher cardiovascular risk.
“The main message here is that the higher your levels, the higher the risk, no matter who you are,” he said.
Lp(a) levels can be measured through a blood test. A level of 50 milligrams per deciliter or more (or approximately 125 nanomoles per liter, depending on the units of measurement) is considered elevated and associated with increased risk of heart attack or stroke, according to the American Heart Association.
“My recommendation, which is consistent with several recent guidelines, is to measure it once in every person’s lifetime,” Schwartz said.
After a person asks their doctor to get their Lp(a) measured and they find out they have a high Lp(a), what should they do next?
First, because Lp(a) levels are genetically determined, close family members may share the same risk factor. Discussing this with first-degree relatives (parents, siblings, children) may be important so that they can also get screened, Schwartz explained.
Second, because there are no currently approved specific treatments to lower Lp(a), it’s important to implement aggressive measures to control other risk factors and reduce overall cardiovascular risk. These steps should include the best possible treatment with medications for high blood pressure, diabetes, and elevated low-density lipoprotein (LDL) cholesterol, as well as adopting lifestyle changes such as a healthier diet and more exercise.
“Will doing this change your Lp(a)? No, but we should encourage it because lowering overall cardiovascular risk is what counts in the end,” he said.
Two interventions have been shown to lower Lp(a) levels. The first is lipoprotein apheresis, which is a nonsurgical procedure to remove excess lipoproteins from the blood with an external machine, usually once or twice a month. This is the only treatment for elevated Lp(a) that has been approved by the U.S. Food and Drug Administration, and it is only approved under specific conditions.
The second intervention is a class of cholesterol-lowering medicines called PCSK9 inhibitors. Although these medications were developed to lower LDL cholesterol and have only modest effects to lower Lp(a), some research suggests that PCSK9 inhibitors may be particularly effective in reducing cardiovascular risk in people who have both elevated LDL cholesterol and elevated Lp(a).
“In the future, we may have very effective approaches to lower Lp(a) levels. New drugs are in development that specifically suppress Lp(a) production in the liver and lower Lp(a) levels in the bloodstream by 70% to more than 90%,” Schwartz said. “These drugs are currently being evaluated in clinical trials to determine whether they reduce the risk of cardiovascular events like heart attack and stroke, and whether the treatment is safe.”