An Addition to the Cardiac Alphabet: “a” Novel Risk Factor

 

Lipoprotein (a) or Lp(a), pronounced “El Pee Little a”, is a lipid particle that is associated with plaque in the heart arteries, heart attack and cardiac death. What is Lp(a), what is its link to heart disease and how is it treated?

 

Lp(a) was discovered in 1963, but has been largely forgotten since then due to the lack of good treatment options.  Newer medications have shown some efficacy in lowering Lp(a) sparking a resurgence in research.  Plaque or blockage in the heart arteries mostly consists of low density lipoprotein (LDL, the “bad” cholesterol). In fact, plaque is more than 90% LDL cholesterol. Lp(a) however is also needed initiate and propagate plaque formation in the heart arteries. In addition, Lp(a) promotes blood clotting and inflammation, two properties contributing to heart disease. Abnormal elevation in Lp(a) is a common genetic entity. Lp(a) elevation above 50 mg/dl affects one in five people in the US or approximately 60 million Americans. Studies have linked Lp(a) to a higher risk for heart attack, stroke, aortic stenosis (thickening and blockage of  the aortic valve, limiting blood flow from the heart), heart failure, kidney disease and heart deaths.

 

Who should be tested for an abnormal Lp(a) level? Lp(a) may be measured in the blood and levels over 50 mg/dl are abnormal. However, the risk for heart disease increases as Lp(a) levels increase. Therefore, slight elevations may not be as clinically relevant as high levels of Lp(a).  There are a couple of scenarios where measuring Lp(a) may be beneficial. One consideration is in a patient with a strong family history for coronary artery disease (first degree relative with heart disease at age 60 or younger). Another possibility is a patient who has had recurrent heart events (heart attack or repeated cardiac stents) despite adequate treatment with a statin. In these cases knowing that there is an elevated Lp(a) level may change therapy. 

 

How should elevated Lp(a) be treated?  Ideally a medication should be chosen that reduces both LDL and Lp(a). Statins are the treatment of choice for patients with heart disease and high LDL levels. Statins lower LDL and reduce the risk for heart attack and cardiac death. Unfortunately, statins do not reduce Lp(a) levels. In fact, statins can increase Lp(a) by 10% to 20%.  Niacin reduces Lp(a) levels by 15-25%. Unfortunately, niacin has not been shown to reduce the risk for cardiac outcomes and has significant side effects (flushing of the skin after ingestion). For these reasons, niacin has not been used for heart patients for some time. PCSK9 inhibitors are new monoclonal antibodies that have very good data in heart disease. PCSK9 agents reduce LDL nearly 50% on their own and by 60% when used with a statin.  They have been shown to reduce the risk for heart attack and cardiac death. They are injected under the skin every two weeks and, since they are not a statin, do not have muscle pain as a side effect. In addition, PCSK9 agents reduce Lp(a) levels by 25%.  Another new medication is currently undergoing trials. Inclisiran reduces LDL by 50% and Lp(a) by 20%. It is also given by injection and is administered twice yearly. 

 

While the data associating Lp(a) with a higher risk for heart artery plaque, heart attack and cardiac death is well established, it is not known whether lowering Lp(a) will improve cardiac outcomes.  This is important because many treatments in cardiology that initially seemed promising (examples include vitamin E, hormone replacement therapy and folic acid) did not reduce the risk for heart attack or cardiac death when tested in large scale clinical trials and have thus fallen out of favor.  Trials are currently underway testing the Lp(a) hypothesis of heart artery disease and cardiac outcomes and the answer should be available very soon. Until then, we should try to identify patients who have significant elevations in Lp(a) and treat them as best we can.