Lipoprotein(a) - the cholesterol test everyone should have checked

Have you ever heard of lipoprotein(a)? Pronounced lipoprotein "little a,” we are increasingly realizing that this particle is a very important, genetically determined cholesterol particle that increases risk for cardiovascular disease.

It’s a type of cholesterol test that I think should be measured at least once in everyone.

Here’s what is it and why I think I think it’s very important you should know if it’s elevated

What is lipoprotein(a)?

First of all, let’s back up and make sure we’re clear on some definitions.

Lipoprotein (a), or Lp(a) for short, is a type of lipoprotein - which is just a fancy name to describe a particle that is responsible for packaging and transporting cholesterol through our bloodstream (basically, the transport vehicle). You are probably most familiar with LDL lipoproteins, these are the lipoproteins that transport cholesterol throughout our body - often called the “bad cholesterol” since it can deposit in the arteries of our body causing atherosclerosis (heart disease).

Lipoprotein (a) is a type of LDL particle with a special protein attached to it (apolipoprotein A).

While what constitutes an elevated level of Lp(a) somewhat differs from expert to expert, normal is probably < 30 mg/dL (<75 nmol/L) and “elevated Lp(a)” is defined as >50 mg/dL (>125 nmol/L).

It is shockingly common, with an estimated 1 in 5 people possessing an elevated Lp(a), which translates to 1.4 BILLION people worldwide.

Most are unaware they have it.

Why is elevated lipoprotein(a) bad?

Over the last several years, it has increasingly been studied, and we now know it is strongly associated with (and data overwhelmingly indicates causal) to several types of cardiovascular diseases. 

First, we know that it is highly atherogenic - meaning it can build up in our arteries and cause heart disease and other types of vascular disease (ie stroke, peripheral arterial disease). Not only does it carry cholesterol similar to a regular LDL particle, but it is also an important delivery vehicle of oxidized phospholipids, which are highly pro-inflammatory substances. 

Secondly, the apolipoprotein A portion structurally resembles another molecule called plasminogen (a clotting factor) and so can result in increased formation of blood clots (like deep vein thrombosis and pulmonary embolism). 

And, lastly, it is also strongly associated with increased risk for aortic stenosis (a type of valvular heart disease in which the valve leaflets progressively thicken and impair the exit of blood from the heart). 

Elevated Lp(a) is associated with about a 2 fold increased risk for premature coronary artery disease, 2 to 4 fold increased risk of aortic stenosis, and a 3 fold increased risk of blood clots.

Who should have lipoprotein (a) checked?

Given it’s remarkably high prevalence in the general population, I believe it’s important to measure Lp(a) in everyone at least once in order to have a comprehensive understanding of both short and long-term cardiovascular risk. Given that it is genetically determined, the levels are quite stable in individuals throughout their lifetime (with the exception that in women, it may go up a bit after menopause). So, measuring it once is typically sufficient. 

Individuals who should absolutely have it measured include those with

• a personal or family history of premature (early) coronary artery disease

• familial hyperlipidemia (another genetic cause of high cholesterol)

• recurrent heart attacks or other cardiovascular events despite good medical and lifestyle treatment.

Others who should consider getting tested include those with high LDL cholesterol that does not seem to respond to statin treatment, those with valvular aortic stenosis, and a first degree relative with known elevated Lp(a).

What can we do about elevated lipoprotein (a)?

Before we can discuss what we do about Lp(a), it’s important to understand one key thing:

While we know that elevated levels of Lp(a) increases the risk for heart disease, we do not yet know that decreasing Lp(a) results in decreased risk for cardiovascular disease. While post hoc (after the fact) analysis of several large trials do demonstrate that some drugs like PCSK9 inhibitors reduce risk of cardiovascular disease when Lp(a) is lowered (beyond what would be expected due to their LDL-lowering properties alone), we do not yet have definitive outcome data. Meaning, can we lower Lp(a) and as a result, lower the associated risk of heart disease? This is important because there have been plenty of prior drugs that seemed promising based on their mechanism of action that ultimately failed to lower risk of heart attack and other bad outcomes (which is ultimately all that matters).

While we wait for this outcome data, what can and should we do about it?

Does diet lower lipoprotein (a)?

Because elevated Lp(a) is genetically determined, it is not typically very responsive to diet or other lifestyle measures. Study results have been inconsistent, with some showing modest changes in Lp(a) with diet, with many showing a mild increase in lipoprotein (a) with dietary changes aimed to lower LDL. One study of a plant based diet, seemed to lower Lp(a), but more data is needed. In my clinical experience, Lp(a) remains remarkably unchanged despite dietary modifications.

Do medications lower lipoprotein (a)?

Statins, the first line medications for lowering LDL cholesterol, statins, do not lower Lp(a) and, in some cases may increase it for reasons not yet fully understood. A very old drug, niacin, lowers Lp(a) but is typically poorly tolerated and didn’t result in improved cardiovascular outcomes in  a large randomized controlled trial, even in those with elevated Lp(a). The newest class of cholesterol lowering therapies mentioned above, PCSK9 inhibitors, do lower Lp(a) typically around 20-30%. However, they are not yet approved solely for the reduction of Lp(a) due to the lack of aforementioned outcome data. Trials evaluating a new class of drugs that specifically target Lp(a) - and dramatically lowering it - are ongoing, and will provide the answer to many of the above questions.

So what do we do with lipoprotein (a) right now?

In the meantime, managing elevated lipoprotein (a) levels remains a clinical challenge.

Although we may not have a specific treatment yet, it is an important risk factor that can help patients and physicians make informed decisions about the management of other cardiovascular risk factors. This is where personalized medicine becomes critically important - the patient with borderline cardiovascular risk with elevated Lp(a) becomes very different than the same patient but but without elevated Lp(a). Working with your doctor to lower your LDL-c, whether by lifestyle and/or medications is paramount.

Lastly, it’s also important to realize that while it increases your risk of cardiovascular disease, elevated Lp(a) should, at the moment, be viewed as a risk-enhancing feature. Meaning, there are plenty of people who have elevated Lp(a) who live their whole lives without a clinical event like a heart attack - it’s just one informational piece to the cardiovascular risk puzzle.