Key takeaways:
~ Lipoprotein(a) – Lp(a) – is a cholesterol carrier.
~ High Lp(a) levels are strongly linked to an increased risk of heart attacks and aortic stenosis.
~ Genetic variants in the LPA gene drive Lpa(a) levels. It is highly genetic.
~ Knowledge is power here: If you likely have genetically higher Lp(a), you can know to talk with your doctor and get your Lp(a) levels tested.
What is lipoprotein(a)?
Lipoprotein(a), or Lp(a), is a blood particle that carries LDL cholesterol and proteins. Elevated levels of Lp(a) are a strong risk factor for having a heart attack due to atherosclerotic plaque buildup.[ref]
Lipoproteins are fat-protein packages that transport cholesterol through the bloodstream, including LDL, HDL, and lipoprotein(a).
Atherosclerosis:
Lipoprotein(a) consists of an LDL particle bound to apolipoprotein(a) [apo(a)] and apoB100. The apo(a) component increases atherosclerosis and promotes clotting by interfering with the body’s clot-dissolving mechanisms. LDL oxidizes within vessel walls, which triggers inflammation. This creates a double-whammy: increased atherosclerotic plaque formation and elevated blood clot risk.[ref][ref]
Prothrombotic effect:
In addition to increasing atherosclerosis, higher Lp(a) levels also have a prothrombotic – clot-forming – effect during inflammation. Lp(a) can bind to fibrin and defensins that are released by neutrophils during infections or inflammation. [ref]
Lp(a) molecule size:
The Lp(a) molecule can vary a lot in size and have different risk levels. You inherit one variant from each parent, and these size differences affect your risk of heart attacks and strokes.[ref]
Lipoprotein(a) levels are hereditary:
“Family history” is always mentioned by the doctor as an important indicator of your risk of heart disease, especially if a family member had a heart attack at a young age. Lp(a) is often the reason that this question is asked.
A significant way that researchers have found family history plays a role in early heart attacks is by the genetic variants that increase lipoprotein(a).
Lp(a) levels are estimated to be 90% hereditary.[ref] (That’s really high when it comes to hereditary estimates!)
High Lp(a) increases the risk of cardiovascular events:
There is abundant research that high Lp(a) significantly increases the risk for:[ref][ref][ref][ref][ref]
- sudden heart attack
- narrowing of the arteries
- stroke
- aortic stenosis
- peripheral artery disease
- heart failure
For example, moderate to high levels of Lp(a) increase the risk of coronary stenosis (narrowing of the arteries) by 67%.[ref]
Additionally, the opposite is true –> low Lp(a) levels are linked with a lower risk of heart failure, stroke, vascular disease, and aortic stenosis.[ref]
A 2024 study showed that high Lp(a) levels increase the risk of heart attacks more than standard modifiable risk factors (SMuRFs), which include diabetes, dyslipidemia, hypertension, and smoking.
The kicker: Shorter lifespan
Genetic studies show that variants linked to high Lp(a) correlate with a shorter lifespan. When averaging together information from more than 100,000 people, the presence of an Lp(a) genetic variant caused an average decrease in lifespan of 1.5 years.[ref]
What is a high level of Lp(a)?
When you get your Lp(a) test results, how do you know if it is just slightly high or seriously scary?
Some researchers consider normal to be less than 50 mg/dl.[ref][ref] Another source says normal Lp(a) levels are less than 30 mg/dl (or 75 nmol/L).[ref]
Risk increases with Lp(a) levels:
A study involving over 58,000 individuals in Denmark showed that major cardiovascular event rates (e.g. heart attacks) increased as Lp(a) levels increased. Lp(a) levels less than 10 mg/dL (18 nmol/L) had the lowest risk.[ref]
- 28% increased relative risk of major cardiac event with Lp(a) 10 to 49 mg/dL (18 – 105 nmol/L)
- 44% increased relative risk of major cardiac event with Lp(a) between 50 to 99 mg/dL (105–213 nmol/L)
- 114% increased relative risk of major cardiac event with Lp(a) ≥100 mg/dL (214 nmol/L)
For aortic valve stenosis, there is a 3-fold increase in relative risk for those with Lp(a) levels greater than 90 mg/dl.[ref]
Higher Lp(a) expression is a risk factor for calcific aortic valve disease. [ref]
A recent study in India showed that Lp(a) levels >50mg/dl (105 nmol/L) increased the risk of coronary artery disease in younger people by 2 to 3-fold.[ref]
Not all studies agree: Gender and lipid level interactions
An epidemiological study involving women found that Lp(a) levels were only important in cardiovascular disease if the women also had high cholesterol (>220 mg/dl).[ref]
A 2012 study in people with diabetes found that higher Lp(a) levels did not correlate with an increased risk of heart disease. There was no additional risk above and beyond the high risk from diabetes.[ref] One problem with the epidemiological studies on Lp(a) is that most of them only last for 5 to 10 years, which may not be enough time to really determine causality.
Modifying factors:
A study looking at hsCRP levels along with Lp(a) levels showed that inflammation may be a modifying factor in increasing the risk of cardiovascular disease with Lp(a) levels between 50-100 mg/dL. In individuals with hsCRP <2mg/L there was no statistically significant cardiovascular disease risk observed. However, with hsCRP ≥2 mg/L, a significant CVD risk was seen >50mg/dL and even more so at >100mg/dL of Lp(a).[ref]
Lipoprotein (a) Genotype Report
LPA gene: encodes lipoprotein(a). These first two genetic variants cover about 40% of the variation in Lp(a) levels — other, less common variants also raise Lp(a) levels.
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Lifehacks: Reducing high lipoprotein(a)
So what do you do if you carry the risk alleles for high Lp(a)? First, let’s look at testing options, and then I’ll explain multiple research-backed ways of lowering Lp(a) either with diet, natural supplements, or medications.
Knowledge is power here! You aren’t doomed to have a heart attack from your high Lp(a) levels, but you may need to take some action.
Test your Lp(a) levels:
Talk to your doctor or do it yourself:
The only way to know your current Lp(a) level is to get it tested. It may be covered by insurance in your annual well-check, especially if you have a family history of early heart attacks.
You can also get a test done for Lp(a) in the US without going through your doctor. For example, on UltaLabTests, the Lp(a) test currently costs $29. There are other places online to order the Lp(a) test, and there’s also a new, at-home Lp(a) test for $99. (I haven’t used it, so check for reviews on it).
Increased Risk with high CRP:
One study showed that hsCRP >2 mg/L combined with Lp(a) in increasing risk of cardiovascular disease.[ref] hsCRP is also a readily available and inexpensive test. Again, talk with your doctor or get the test done yourself so that you have a baseline to know if the interventions are working for you.
Now let’s take a look at ways you can lower your Lp(a) levels. Keep in mind that you can stack multiple interventions together – consider a dietary change plus supplements, along with talking to your doctor about aspirin therapy or other medications.
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Related Articles and Topics:
PCSK9 Gene: Understanding the variants that cause high or low LDL cholesterol
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