1. Lp(a) is an important but underappreciated risk factor for heart disease.
While most people know that low-density lipoprotein (LDL)-C, or bad cholesterol, can cause heart disease, relatively few people know about the risk posed by lipoprotein(a), or Lp(a). Also referred to as “LP little a,” this type of lipoprotein is comprised of an LDL-like particle with a second protein, called apolipoprotein(a), or apo(a), coiled around it. Recent studies indicate that people born with elevated LP(a) may have a two-fold to four-fold increased risk of heart attacks and other serious events compared to people with low Lp(a) levels.
Despite this risk, awareness of Lp(a) is still very low among physicians, especially doctors who don’t specialize in heart disease. But even cardiologists may overlook Lp(a), in part because Lp(a) is not as well-understood as other risk factors and treatment options are still very limited (see below).
2. Lp(a) is an independent risk factor.
Previously, many cardiologists believed Lp(a) was only a risk in patients with other risk factors, such as high LDL. Now we know that Lp(a) is an independent risk factor that has been linked to heart disease in younger adults and otherwise healthy people with no other known cardiovascular risks. Tennis legend Arthur Ashe, who had his first heart attack at 36, was reported to have high Lp(a), as was Bob Harper, a celebrity fitness trainer who nearly died of a massive heart attack at age 52. Sandra Tremulis, founder of the Lipoprotein(a) Foundation, was diagnosed with a 95% blockage in one of her coronary arteries at age 39.
3. Your genes control how much Lp(a) your body makes.
Although healthy eating and exercise can help reduce LDL cholesterol, there’s no evidence that a healthier lifestyle can lower Lp(a). Your Lp(a) level is currently thought to be dictated almost entirely by the genes you inherit. There are many variants of the LPA gene (see below), and some variants are among the largest single-gene risk factors identified for heart disease. Even though diet and exercise can’t directly impact Lp(a), people with high levels should still pursue a healthy lifestyle, in consultation with their doctors, to address other heart risks and reduce their overall likelihood for disease.
4. Lp(a) comes in different sizes, and smaller particles are linked to higher Lp(a) levels.
Lp(a) can vary in size depending on the length of the apo(a) protein that is wrapped around the particle’s fatty core. The structure of apo(a) includes looped segments, known as kringles. One subtype of kringle can be repeated up to 40 times or more, depending on the genes that you inherited. People born with genes that produce fewer kringle repeats have smaller Lp(a) particles, but they also have much higher Lp(a) levels.
5. Lp(a) levels of 50 mg/dL (125 nmol/L) or higher carry added risks.
Most people have Lp(a) levels in the range of under 5 to 29 milligrams per deciliter (mg/dL), which roughly equals under 13 to 73 nanomoles per liter (nmol/L. See item 8 below). There is evidence that the risk of heart disease may start to rise at 30 mg/dl (about 75 nmol/L), and it rises more steeply at levels of 50 mg/dL (about 125 nmol/L) and higher. An estimated one in seven people are at or above this threshold. There are racial and ethnic variations in Lp(a) levels, with Black individuals more likely to have elevated Lp(a) than Whites, Hispanic, or Asian individuals. More research and improved testing methods are needed to better understand the influence of race and ethnicity on Lp(a), quantify the risks of elevated Lp(a) in different types of patients, and determine which types of patients would benefit most from Lp(a)-lowering therapies.
6. There are currently no approved medicines that directly target Lp(a).
Statins, the most widely used type of LDL-lowering drugs, do not reduce Lp(a) and may even cause a slight increase. Niacin (vitamin B3) can provide modest reductions in Lp(a), but it is not approved for the treatment of Lp(a). Moreover, large studies have failed to show that niacin reduces heart disease risk, and it may cause serious side effects in some patients.
The most effective therapy for high Lp(a) is apheresis, a blood filtering process similar to dialysis, in which a patient’s blood is circulated through a machine that removes Lp(a) particles. The procedure is normally reserved for very high-risk patients because it’s expensive, requires weekly visits to an apheresis center, and involves certain risks. Apheresis can initially lower Lp(a) by about 70 percent, but levels start to gradually rise again the day following apheresis.
7. People with low LDL may have high Lp(a).
Since the structure of Lp(a) includes a particle of LDL cholesterol, your Lp(a) level contributes to the level of LDL-C that is measured by blood tests. The cholesterol portion of Lp(a) is referred to as Lp(a)-C. On average, every 10 mg/dL of Lp(a) in the blood increases levels of LDL-C by 3 to 4 mg/dl. If your Lp(a) level is low, its impact on total LDL-C is minimal. But in patients with high or very high Lp(a), their LP(a)-C can account for much or most of their LDL-C test results.
For example, two people with relatively low LDL-C levels of 70 mg/dL could have very different heart disease risks. One person could have an Lp(a) level of 10 mg/dL, meaning that only about 3 percent of their LDL-C is derived from Lp(a)-C. The other person could have an Lp(a) level of 150 mg/dL, meaning that more than two-thirds of their measured LDL-C is actually Lp(a)-C. That’s why testing for Lp(a) is so important, especially in people who have recurrent heart disease despite LDL-lowering therapy.
8. More accurate and standardized tests for Lp(a) are needed.
Because Lp(a) particles vary in size, the most commonly used lab tests are not ideal. These tests measure the total mass of Lp(a) in the blood in milligrams per deciliter (mg/dL). A more accurate approach is to measure Lp(a) in nanomoles per liter (nmol/L), which tells you the number of particles in your blood, not just the mass.
Physicians and researchers specializing in this blood lipid have called for the development of more accurate, standardized tests that measure Lp(a) in nanomoles per liter. More precise testing methods will help physicians to better identify high-risk patients and support research into the link between Lp(a) and heart disease.
9. Lp(a) testing can help to identify high-risk patients.
Lp(a) testing should be considered in patients who are at high risk for cardiovascular disease, including people with:
- Premature heart disease or a family history of premature heart
- A familial history of high Lp(a).
- Familial hypercholesterolemia (FH).
- Recurrent heart disease despite optimal LDL-lowering
- A 5% or greater risk for a fatal cardiovascular event within 10 years.
Since Lp(a) levels are driven by your genes, you generally need only one test to learn your risk. Even though direct treatment options are limited for now, knowing your Lp(a) level can help you and your doctor devise a treatment plan that reduces your overall risk.
10. Amgen is working on a medicine to silence the LPA gene.
In collaboration with Arrowhead Pharmaceuticals, Amgen is exploring a new type of therapy called short interfering RNA (siRNA) to treat high Lp(a). This approach targets and disrupts the messenger RNA that is required to translate the LPA gene into particles of Lp(a). By silencing the gene, the goal is to achieve a large and durable reduction of Lp(a). An investigational therapy based on this new drug modality has entered Phase 2 clinical testing.
Any medicine designed to lower Lp(a) levels will require large outcome studies to show that it can actually reduce the risk for heart attacks, strokes, and other serious events. According to one study based on genetic data, a large reduction in Lp(a) may be needed to achieve a meaningful reduction in risk.