Lp(a) and Familial Hypercholesterolemia
What is Lp(a)?
Lipoprotein (a) (Lp(a)), also known as lipoprotein “little a,” is a particle that carries cholesterol in the blood just as LDL is a particle that carries cholesterol. Individuals with familial hypercholesterolemia (FH) are more likely to have high Lp(a) levels than the general population. High Lp(a) levels are associated with higher risk for heart attacks, aortic stenosis, and possibly stroke; this appears to be particularly true for people with FH and other causes of high cholesterol. What causes Lp(a) to be associated with this higher risk of heart attacks is not currently known. Lp(a) levels are inherited, similar to FH, and not associated with diet, exercise, or obesity.
Current prevention recommendations in the United States pay limited attention to Lp(a). This is because until recent genetic studies, the role of Lp(a) in risk was unclear. The mechanism of how Lp(a) increases risk is under study but not confirmed.
- If you have high Lp(a), the most important preventive treatment is to make sure your LDL cholesterol level is below goal.
- While new treatments are in development, there currently is no Lp(a) treatment that has been shown to prevent heart attacks.
Why should Lp(a) be checked in people with FH?
If you have FH, the most important reason to check an Lp(a) level is for overall risk assessment. The risk for a heart attack in those with high Lp(a) (> 50 mg/dl) is increased about 3 times compared to those with lower levels.
A second reason is that people with high Lp(a) may be very similar to those with FH. Because it is an inherited condition, people with high Lp(a) can have early heart attacks in their families. There can be enough cholesterol carried on the Lp(a) particles to cause high cholesterol to increase to levels of LDL cholesterol seen in FH. Some people who test negative for the FH gene have very high Lp(a) levels.
If my Lp(a) level is high, what should I do?
Treatment to lower Lp(a) is controversial. Today there are no clinical trials showing lowering Lp(a) reduces heart attack or stroke rates. Medications/treatments in current use that lower Lp(a) also lower cholesterol. There are apheresis and niacin. These both have substantial side effects. PCSK9 inhibitors lower Lp(a) while lowering LDL cholesterol. Statins have no effect on Lp(a). Genetic studies suggest the amount of clinical lowering of Lp(a) to lower risk would have to be substantial. Your physician may only consider treatments in those with the highest risk for recurrent events.
There are ongoing clinical trials with new drugs that lower Lp(a) without lowering LDL cholesterol. These studies should help clarify the role of treatment for Lp(a).
Treatments to consider with high Lp(a) include statins to lower LDL cholesterol and prevent heart attacks (this is particularly important if you have FH) and blood thinners if it is thought elevated Lp(a) is causing problems with blood clotting. Neither of these treatments lower Lp(a) but would help prevent the consequences of a high level.
Lp(a) and children
Children with FH should have Lp(a) tested. If the levels are high (> 50 mg/dl), making sure LDL cholesterol is below goal on treatment (130mg/dl) is even more important.
There is a statistical association between high Lp(a) in children and unexplained stroke. This association has not been reproduced in adults. Strokes in children are rare and have different causes than in adults where stroke is more common and typically related to high blood pressure, diabetes, and other long standing conditions. Thus, the association of stroke with Lp(a) may be harder to find.
It is unclear whether or not children with isolated high Lp(a) and stroke should be treated to lower Lp(a) because of medication side effects of niacin, apheresis, and blood thinners. The balance between risk of a recurrent stroke and side effects is not known. Therefore treatment decisions should be made by experienced clinicians.