April 25, 2024 – Getting a standard cholesterol screening may soon involve one more blood test that has been around for decades but is rarely used. Evidence continues to mount showing that the additional analysis can flag otherwise unknown risks of dangerous heart problems resulting from plaque buildup in arteries.
The test looks for a particle called lipoprotein(a), and it’s widely available for less than $100. Often referred to as Lp(a), an estimated 1 in 5 people have dangerously high levels of it, usually due to a genetic predisposition.
“It is not uncommon for someone to have elevations in Lp(a) despite a normal total or LDL cholesterol reading,” said Nathan D. Wong, PhD, lead author of a new study on Lp(a) in the Journal of the American College of Cardiology.
The latest study from Wong and colleagues is the largest and most ethnically diverse examination to date of Lp(a) in the U.S. and showed that people with very high levels may have up to twice the risk of serious heart problems. Also this month, for the first time a professional medical group in the U.S. has called for every adult to have their Lp(a) levels checked at least once in their lifetime.
“Up to now, Lp(a) has been something mainly discussed among specialists but hasn’t filtered out much to non-specialists and primary care providers. But that is likely to change,” said Gregory G. Schwartz, MD, PhD, chief of the cardiology section at Rocky Mountain Regional VA Medical Center and professor of medicine at the University of Colorado in Aurora, CO.
Schwartz said it’s his profession’s responsibility to help educate the wider health care community and general public about Lp(a).
“I don’t think we’re quite at the finish line of that, but we’re getting closer and we’re learning more about this particle that was discovered and first identified in 1963,” he said.
Potentially groundbreaking treatments for high Lp(a) may be just a year or two away. In the meantime, experts are urging their colleagues to help patients learn if they need to address a heightened risk and, since high levels run in families, it’s important for those with high levels to alert their children and relatives who may also be at risk.
The evidence is so strong that people don’t need to wait for their doctor to suggest the testing, said P. Barton Duell, MD, a professor of medicine and Lp(a) expert at Oregon Health & Science University.
“They should insist on having their Lp(a) level measured,” said Duell, who sits on the board of directors of the National Lipid Association, which this month recommended that everyone get tested.
Without Testing, Lp(a) Is Hidden Threat
This latest Lp(a) study from Wong and his colleagues examined the relationship between Lp(a) levels and the likelihood of having a major heart event for 27,000 people who didn’t previously have a diagnosis of what medical professionals call atherosclerotic cardiovascular disease, or ASCVD. Types of ASCVD range from heart attack and stroke to chest pain and include the most common and deadly types of heart disease in the U.S. and worldwide.
Conditions like heart attack and stroke usually arise from the buildup of plaque in arteries, which is known to be related to high levels of LDL cholesterol, also called “bad” cholesterol. Other factors that can contribute include high blood pressure, tobacco smoking, and diabetes. Lp(a) is another cholesterol-containing particle in the blood that can be a hidden risk factor since it’s not widely included in standard lab workups.
A study earlier this year by European researchers found that Lp(a) is as much as six times as atherogenic as LDL cholesterol, meaning it can be a very potent factor in plaque building up in arteries.
Other studies have shown that some people may be more likely to have elevated levels of Lp(a), such as Black people, whose levels may be 30% higher on average compared to White people, whereas people of East Asian ancestry often have levels lower than in White people, Schwartz said. Women in menopause also tend to have elevated levels.
But for all the research about lipoprotein(a) over the decades, there had been a lack of knowledge about whether elevated levels affected cardiovascular risks -- or risks to the heart and blood vessels -- differently in people of different genders or racial groups. The people in Wong’s study included 55% who were women and 36% who were Black and suggests that the risk of developing ASCVD is similarly high in any person who has elevated Lp(a) levels.
“I think this study by Wong, which puts together several prior studies that included data on liproprotein(a) and cardiovascular events, shows that -- as I titled my editorial -- this may be for the most part an equal opportunity risk factor if their level of lipoprotein(a) is high. That’s important,” said Schwartz, who authored a commentary published alongside Wong’s study in JACC.
Overall, the study showed that those who had extremely high Lp(a) levels (in the 90th percentile) were 46% more likely to be diagnosed with ASCVD over a period of about 20 years, compared to people with average Lp(a) levels.
People in the study with type 2 diabetes who also had extremely elevated Lp(a) levels were at the highest risk of ASCVD, the study showed, nearly doubling their chance of ASCVD problems, compared to people with mid-range levels.
“This further emphasizes the importance that people seeing patients with diabetes, especially, include this in their assessments in addition to the standard lipid profile,” Wong said.
A Sign to Reduce Other Risk Factors
A specialist in preventive cardiology and lipid metabolism, Duell said it’s not uncommon for him to see patients with a long list of heart problems who have never had an Lp(a) test.
“I see patients who come in and they’ve had two heart attacks, maybe they’ve even had stents or bypass surgery, and nobody understands what’s going on. We measure Lp(a), and it’s super high,” said Duell, noting that a normal level is up to 30 mg/dL.
“I have one patient whose level is 450 mg/dL, for example. That’s astronomically elevated,” Duell continued. “That is a very potent explanation for why this patient has such severe heart disease and has had bypass surgery.”
The patient was in his late 50s, and Duell suggested that the man’s children have their levels tested, too, since elevated levels tend to run in families. Half of his children had high levels, too, and Duell suggested they take medicines and work to lower their LDL cholesterol to reduce their overall risk.
“These patients are also very motivated to do other things” after seeing their father face life-threatening heart problems, Duell said.
Universal Lp(a) testing is now recommended by major professional medical groups in Canada and Europe, but testing remains extremely uncommon in the U.S. One estimate using data from the University of California health care system showed that just 0.3% of all adults seen from 2012 to 2021 had Lp(a) testing. Among people who had lipid panels done (which look at cholesterol and triglycerides), less than 2% got Lp(a) testing, and between 2% and 6% of people with heart problems had their Lp(a) levels evaluated.
Along with its recommendation for universal testing in U.S. adults, the National Lipid Association is publishing a paper in its Journal of Clinical Lipidology detailing how clinicians can evaluate test results and consider treatments.
One challenge in addressing Lp(a)’s impact on ASCVD risk is that, despite having been identified since the 1960s, scientists haven’t yet determined if lowering Lp(a) levels will also reduce someone’s risk of cardiovascular problems.
Lp(a) levels tend to hold relatively steady throughout life, which is why recommendations are for only testing once in a person’s lifetime.
“The levels don’t fluctuate that much,” Schwartz said. “If you’re undeniably high, you’re high, and if you’re undeniably low, you’re low and that’s not going to change.”
Experts say knowing someone has high Lp(a) allows them to address their overall cardiovascular risk, such as lowering LDL cholesterol and perhaps starting medications to address other related problems.
“If you have high LDL and high Lp(a), it’s worse than having one alone,” Duell explained.
One complex factor is that statin drugs may increase Lp(a) slightly. But statins offer a proven benefit to reduce overall cardiovascular risk by lowering LDL cholesterol, Schwartz said.
Duell said options that have been shown to lower Lp(a) include aspirin and, for older women, postmenopausal estrogen replacement therapy.
A number of treatments already shown to dramatically reduce Lp(a) are in development. A drug called pelacarsen is currently in its final study phase to see if people with high Lp(a) experience a reduced risk of heart problems over 4 years. Results are expected in the middle of 2025.
“The unanswered question is whether lowering Lp(a) with these drugs will reduce cardiovascular risk as much as genetically elevated Lp(a) increases risk, and whether any benefits will come with safety concerns. So stay tuned,” Schwartz said.
