Lipoprotein(a) [Lp(a)] was, until recently, an underrecognized cardiovascular risk factor. However, extensive research over the last 15 years (including vast genome-wide association studies) has confirmed an independent, causal link between elevated lipoprotein(a) levels and atherosclerotic cardiovascular disease (ASCVD). The science has shown that, despite their small size, Lp(a) particles can have a substantial health impact, and as many as one in every five individuals worldwide has elevated levels (defined as greater than 125 nmol/L).

Unfortunately, only a tiny fraction of the U.S. population has undergone Lp(a) testing, including those with existing cardiovascular disease. This is a missed opportunity that is now being corrected. Lp(a) screening is at the center of a major shift, with several clinical organizations now recommending all adults undergo testing at least once in their lifetime. For clinicians who are interested in learning more, below is an overview of the current science, the guidelines, and the nuances of Lp(a) assays.

Lp(a) and its impact on cardiovascular health

Lp(a) is a small LDL-like particle, comprising two major proteins that are covalently bound: apolipoprotein(a) and apolipoprotein B-100. Along with its inflammatory effects, Lp(a) has been shown to be “proatherogenic” or capable of driving the development of atherosclerotic plaques in arteries. As a result, lifelong exposure to elevated Lp(a) levels increases the risk of many forms of ASCVD, including coronary artery disease, aortic valve disease, heart failure, ischemic stroke, and peripheral arterial disease. A growing body of evidence has also linked elevated Lp(a) levels with an increased risk of secondary events in patients with existing cardiovascular disease.

Unlike LDL cholesterol and other known CVD risk factors, up to 90 percent of individual variation in plasma Lp(a) levels is genetically determined. Lp(a) cannot be directly mitigated through diet, exercise, or therapies like statins. Levels may increase slightly with conditions such as hypothyroidism or chronic kidney disease, or in stages of life such as post-menopause. However, for the most part, levels remain constant after five years of age and throughout adulthood.

New guidelines for testing

Medical guidelines around Lp(a) have undergone major changes during the last 15 years, as more research has shed a spotlight on the risks associated with elevated levels.

In 2018, the new American Heart Association/American College of Cardiology guidelines began recommending selective screening for high-risk individuals. This included men under the age of 55 and women under the age of 65 who had already experienced a major cardiovascular event, people who have a close relative with premature cardiovascular disease or elevated Lp(a) levels, and people with very high LDL cholesterol (190 mg/dL or higher).

While these guidelines were a good start, selective screening does not adequately capture everyone at risk. Individuals with high Lp(a) levels are typically asymptomatic prior to a serious event, such as a heart attack or stroke, which can progress quietly over many decades. It’s also hard to identify when family members have elevated Lp(a) levels, as so few individuals have been tested.

In 2024, the National Lipid Association (NLA) released a scientific statement on the use of lipoprotein(a) in clinical practice. The NLA now recommends that all adults be screened at least once in their lifetime. This mirrors guidance from the European Society of Cardiology (ESC), which also advocates for one-time Lp(a) testing for all adults to better understand their overall cardiovascular risk. As with other lipid tests, the bulk of these will likely be ordered by primary care physicians and cardiac specialists.

Prioritizing molarity-based Lp(a) assays

Along with broader recommendations for who gets screened, the NLA statement encourages Lp(a) to be measured in molar units (nmol/L) where possible, an important distinction that speaks to the nuances and limitations of traditional mass-based (mg/dL) assays. Apo(a) isoforms within Lp(a) can vary considerably in size, which, in turn, influences mass-based measurements and potentially confounds the results. Research has shown that the number of particles of Lp(a) per volume of blood (i.e., Lp(a) concentration) is more closely associated with ASCVD risk than the size of the particles.

In January 2025, the first IVD test reporting Lp(a) concentration in molar units was cleared for use, providing an accurate measure of Lp(a) concentration, mitigating the impact of apo(a) particle size. The test is conducted from a routine blood draw and measured on a fully automated analyzer, setting the stage for high-volume testing, akin to how lipids are currently measured.

Why screen the general population

In a study published in May 2025, a retrospective analysis of health records of 70 million adults in America found just 0.1 percent had taken a lipoprotein(a) test. Of the 70,000 individuals that had been tested, approximately one in five (21.4 percent) were found to have elevated levels, in line with previous estimates. Clearly, we have a long way to go. However, there is a silver lining: Given its genetic basis, testing for Lp(a) concentration is only required once in a person’s lifetime. This can then guide appropriate risk mitigation, potentially over many decades.

While lifestyle changes can’t lower someone’s Lp(a) level, it is still clinically relevant and actionable information. If Lp(a) levels are elevated, steps may be taken to lower the overall risk of cardiovascular disease. Recommendations support setting more aggressive targets for other ASCVD risk factors, such as high cholesterol, blood pressure, and blood glucose. Broader counsel around healthy diet, exercise, and rest may also be appropriate. There are also a number of therapies in late-stage clinical development that are specifically designed to target and lower Lp(a) levels.

Embarking on an era of lipoprotein(a) monitoring

The first step in risk mitigation is determining an individual’s Lp(a) level. This will require a concerted effort from clinicians and medical and scientific groups throughout the United States. Rolling out testing at this scale will also require nuance and customization, and initiatives are underway to understand what wide-scale testing might look like. For example, the American Heart Association (AHA) recently launched the Lp(a) CHC Discovery Project to identify barriers to Lp(a) testing within community health centers and what systems may be needed to make it feasible and routine.

For clinicians that are eager to learn more, the American Heart Association and other groups have a wealth of information. And when it comes to ordering tests, there is often an easy place for clinicians to start: understanding your own Lp(a) levels with an FDA-cleared molarity assay.

Alexander Fohl is a pharmacist and health care executive.