Lipoprotein(a), often abbreviated as Lp(a), is a fatty particle that circulates in the bloodstream and resembles LDL cholesterol in structure but poses a significantly higher risk to cardiovascular health. Elevated levels of Lp(a) can double or even triple the likelihood of heart attacks and are increasingly recognized as a key contributor to heart disease, particularly in younger individuals. Despite its dangers, public awareness of Lp(a) remains surprisingly low. This is largely because, until recently, medical guidelines did not recommend routine testing for Lp(a) levels, mainly due to the genetic nature of the condition and the historical absence of effective treatment options.
The value of Lp(a) in a person’s bloodstream is determined almost entirely by genetics, making lifestyle factors such as diet and exercise largely irrelevant in its management. This limited the clinical utility of testing since interventions to reduce the particle’s concentration were not available. However, this is beginning to change, thanks to new therapies currently in development that specifically target Lp(a). These advances have brought renewed attention to the importance of testing and have shifted medical perspectives on managing Lp(a)-related cardiovascular risk.
In the United States, formal recommendations for Lp(a) testing only appeared in 2024 when the National Lipid Association endorsed it. This followed years of low testing rates; data between 2012 and 2019 revealed that only 0.3% of individuals had undergone Lp(a) screening, with half of those tests ordered by a small pool of healthcare providers. In contrast, European countries have adopted more routine testing protocols. The call for one-time Lp(a) screening for everyone has gained momentum globally, especially as insurance coverage for the test becomes more widespread across various regions.
While specific therapies to reduce Lp(a) levels are not yet available on the market, individuals with high levels can still benefit from more aggressive cardiovascular risk management. This may include initiating statin therapy even if LDL cholesterol levels are within normal ranges, as well as exploring low-dose aspirin for heart attack prevention. Lp(a) is measured using two units: nanomoles per liter (nmol/L), the preferred metric, and milligrams per deciliter (mg/dL). There is no universally agreed-upon threshold for elevated levels, but values above 125 nmol/L or 50 mg/dL are typically considered high.
Unlike LDL cholesterol, which can fluctuate over a lifetime and is influenced by lifestyle, Lp(a) tends to remain stable, making a single test generally sufficient. Exceptions may exist for individuals undergoing hormonal changes or suffering from specific medical conditions. Groups recommended for Lp(a) testing include those with a family history of early cardiovascular disease, individuals with very high LDL cholesterol, and close relatives of people with known elevated Lp(a) levels.
The most exciting development in the field is the emergence of therapies that significantly lower Lp(a) concentrations by targeting RNA molecules responsible for its production. Four such drugs—lepodisiran, olpasiran, pelacarsen, and zerlasiran—are currently being tested and have shown the ability to reduce Lp(a) levels by up to 100%. These drugs are administered via injections given every one to six months, with mild injection site pain being the most common side effect. Longer clinical trials are ongoing to determine whether these treatments can reduce the incidence of heart attacks and other cardiovascular events.
Another promising therapy, muvalapin, works differently by preventing the formation of the Lp(a) particle altogether. It is taken as a daily pill and has also shown a significant reduction in Lp(a) levels. However, side effects like headaches, back pain, and fatigue have been noted. While some may prefer oral medications, injectable drugs may be favored for their less frequent dosing schedules.
As research continues, the future for Lp(a) management appears brighter than ever, offering hope for individuals at risk of premature heart disease due to this previously untreatable condition.
