Ask the Doctors: High lipoprotein(a) may indicate heart disease

Q: My blood test results always include levels of HDL and LDL cholesterol, but what about lipoprotein(a)? Don't high levels triple the risk of a heart attack or stroke at an early age? If so, shouldn't doctors test for it?

A: The short answer is: for some people, yes.

The longer answer starts with some background: Lipoprotein(a) is a type of blood protein similar to the low-density lipoprotein (LDL) commonly measured in a cholesterol test. Because its structure resembles that of the proteins plasminogen and tissue plasminogen activator (TPA), which are involved in the breakdown of blood clots, lipoprotein(a) competes with those proteins and decreases their ability to break down clots. In other words, lipoprotein(a) boosts the blood's clotting ability. This could potentially aid wound healing and repair of tissues, but no specific need for lipoprotein(a) has been found.

The big concern with lipoprotein(a) is its potential to encourage clot formation within the arteries, raising the risk of heart attacks and strokes. A 2009 study in the Journal of the American Medical Association reviewed the results of 36 studies assessing the role of lipoprotein(a) and vascular disease in a total of 126,634 people. The authors found that, with every 3.5-fold increase in the level of lipoprotein(a), there was a 13 percent relative increase in coronary heart events and a 10 percent increase in stroke rate. The authors concluded that the high lipoprotein(a) levels were an independent risk factor for heart attacks and strokes, but not as strong a risk factor as other cholesterol markers.

However, very high levels of lipoprotein(a) are a significant risk factor for coronary heart disease, as illustrated in an Italian population study. The 2014 study measured lipoprotein(a) in 826 people and then followed them for 15 years. Those with lipoprotein(a) levels greater than 45 mg/dl — totaling 20 percent of the study group — had 2.3 times greater odds of stroke or coronary heart disease compared to those with lower levels.

As for why some people have higher lipoprotein(a) levels than others, the answer is in our genes. Variations of lipoprotein(a) levels appear to be related to a part of a gene called apo(a). Two different variations in this gene can cause elevation of lipoprotein(a). A grouped analysis found that people with one of the variations had 50 percent greater odds of coronary heart disease, while those who had both variations had 2.5 times greater odds.

So, to answer your question: If you have a family history of early heart disease, your doctor should consider checking your lipoprotein(a) level, especially if you have no other risk factors. People who have had a heart attack without any other risk factors also should have their levels checked.

As for lowering the lipoprotein(a) level, niacin can do this at high doses (2 to 4 grams per day), as can cholesterol-lowering PCSK9 inhibitors. Note, however, that no studies thus far have assessed the benefits of doing so.

Instead, people with very high levels of lipoprotein(a) may find greater benefit in significantly lowering their overall cholesterol with statins. Statins won't lower the lipoprotein(a) level itself, but they provide greater health-related bang for the buck. Lastly, because elevated lipoprotein(a) levels increase the risk of clot formation in the arteries, people at high risk may also find it prudent to take aspirin as a blood thinner.

In summary, for most people, overall cardiovascular health should be the focus in reducing the risk of heart attack and stroke, not lipoprotein(a).

Robert Ashley, M.D., is an internist and assistant professor of medicine at the University of California, Los Angeles. Send your questions to, or write: Ask the Doctors, c/o Media Relations, UCLA Health, 924 Westwood Blvd., Suite 350, Los Angeles, CA, 90095. Owing to the volume of mail, personal replies cannot be provided.


If you'd like to leave a comment (or a tip or a question) about this story with the editors, please email us. We also welcome letters to the editor for publication; you can do that by filling out our letters form and submitting it to the newsroom.

Powered by Creative Circle Media Solutions