Heart disease is the number one cause of death in the US and in most countries around the world. Statistics show that one in four people in the US will die of heart disease.
We often have a picture in our heads of someone at risk for a heart attack: an obese, older man who looks unhealthy, probably with a stressful job. It is often tempting to think that people who exercise, are thin, and look healthy are at low risk for heart disease. But beneath all the healthiness can lurk a genetically driven risk factor for a heart attack: elevated lipoprotein(a).
Just looking at the statistics, being obese increases the relative risk of heart disease by 28%.[ref] Compare this to the healthy-looking person who has no signs or symptoms but yet has a 300% increase in the risk of a heart attack due to a genetically elevated lipoprotein(a) — Lp(a) — level.
This article digs into research on lipoprotein(a) and the genetic variants that cause it to be elevated. I’ll explain how to check your genetic data to see if you carry the variants, and then the next steps to take with getting blood tests done.
What is Lp(a)?
Lipoprotein(a) or LP(a) — said “L- P- little 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 atherosclerosis.[ref]
We all know that fats and water don’t mix. This is true in the body when it comes to moving around fats in the bloodstream. The term lipoprotein is kind of a general term for a glob of fatty acid plus protein that is packaged in a way so it can easily be transported throughout the body. Lipoproteins include low-density and high-density cholesterol.
Lipoprotein (a) includes an LDL particle bound to an apolipoprotein (a) – known as apo(a) – and apoB100. The apo(a) part is what increases atherosclerosis. It also promotes clotting by interfering with the way that the body dissolves clots. [ref] So, you have a double-whammy of increasing atherosclerosis via increased inflammation plus oxidized LDL. The LDL tends to oxidize once inside a vessel wall adding more inflammation responses because their structure has changed. This all adds to a mechanism that increases the risk of blood clots.[ref]
The Lp(a) molecule can vary a lot in size, and you can inherit two different sizes of Lp(a) – one from mom, one from dad.[ref]
Lp(a) and risk of a sudden heart attack:
The Biggest Loser host and fitness trainer, Bob Harper, has been open about his recovery from a very serious heart attack that he had in 2017. He was the epitome of healthiness – fitness trainer, nutritional guru, athlete, and only in his early fifties. But he also had genetically elevated levels of Lp(a). Here is a Today Show interview where he explains some of his recovery and what he is doing to prevent a second heart attack.
A recent study in India showed that high Lp(a) levels – defined as >50mg/dl) increased the risk of coronary artery disease in younger people by 2 to 3-fold.[ref]
Is Lp(a) 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. A significant way that researchers have found family history playing a role is through the inheritance of a genetic variant that increases lipoprotein(a).
Lp(a) levels are estimated to be 90% hereditary. (That’s really high!)[ref]
Is Lp(a) a big deal – or just another scare tactic?
There are questions and controversy on the role that cholesterol plays in heart disease, and that may lead some people to dismiss Lp(a) as just the latest number to talk about. I think it would be a big mistake to dismiss the research on Lp(a).
- sudden heart attack
- narrowing of the arteries
- aortic stenosis.
Additionally, low Lp(a) levels are linked with a lower risk of heart failure, stroke, vascular disease, and aortic stenosis.[ref]
The kicker: Genetic studies show that variants linked to high Lp(a) correlate to 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]
How high is high?
When you get your Lp(a) test results, how do you know if it is just slightly high or seriously scary?
- One study shows a 3x risk of aortic valve stenosis for those with Lp(a) levels greater than 90 mg/dl.[ref]
- Another source says normal Lp(a) levels are less than 30 mg/dl (or 75 nmol/L).[ref]
- Some researchers consider normal to be less than 50 mg/dl.[ref][ref]
This is something to talk to a doctor about and keep up with the research as it comes out.
Not all studies agree…
A 2012 study in people with diabetes found that higher Lp(a) levels did not correlate with an increased risk of heart disease – above the already increased risk from having diabetes.[ref]
A study on women found that Lp(a) levels were only important in cardiovascular disease if the women also had high cholesterol (>220 mg/dl).[ref]
The 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.
Genetic variants that cause elevated Lp(a):
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The LPA gene controls the formation of the lipoprotein(a) molecule. Variants in the gene cause the body to create more Lp(a).
These first two genetic variants cover about 40% of the variation in Lp(a) levels — there are other, less common variants that also raise Lp(a) levels.
Check your genetic data for rs3798220 (23andMe v4, v5, AncestryDNA):
- C/C: risk of elevated Lp(a), increased risk for heart disease – 3.7x risk of aortic stenosis[ref][ref][ref]
- C/T: risk of elevated Lp(a), increased risk for heart disease, increased risk of aortic stenosis
- T/T: typical
Members: Your genotype for rs3798220 is —.
Check your genetic data for rs10455872 (23andMe v4, v5; AncestryDNA):
- G/G: likely elevated Lp(a), increased risk for heart disease – 2x risk of aortic stenosis[ref][ref][ref]
- A/G: likely elevated Lp(a), increased risk for heart disease
- A/A: typical
Members: Your genotype for rs10455872 is —.
Studies also showed that carrying one risk allele for both of the above — compound heterozygous — also doubled the risk of aortic stenosis.[ref]
Genetic variants that increase LDL cholesterol levels are also linked with higher Lp(a) levels. This makes sense that there could be more Lp(a) if your cholesterol levels are really high.
If you have full genome testing, check for these other LPA gene variants as well:
- rs9457951 – this may be a better marker for African-Americans[ref]
- rs6415085 – T allele linked to higher Lp(a)[ref]
Variants that lower Lp(a):
Check your genetic data for rs6919346 (23andMe v5; AncestryDNA):
Members: Your genotype for rs6919346 is —
Check your genetic data for rs41272114 (23andMe v4, v5):
Members: Your genotype for rs41272114 is —.
Check your genetic data for rs143431368 (23andMe v5 only):
Members: Your genotype for rs143431368 is —.
So what do you do if you carry the risk alleles for high Lp(a)? Knowledge is power here!
Keep in mind that this is a fairly common genetic risk factor, so it isn’t a reason to stress out or be anxious. It is an excellent reason to make lifestyle changes to lower your risk of a heart attack: stop smoking, don’t drink too much, be active, eat healthily, reduce stress.
You know all of those healthy things…
… and now you know that healthy lifestyle stuff actually applies to you.
Lp(a) blood tests:
Talk to your doctor about getting an Lp(a) blood test done. This may be covered by insurance in your annual well-check, especially if you have a family history of early heart attacks.
I know a portion of my readers will ignore that advice and tend not to like to talk to their doctors. You can go and get a test done for Lp(a) in the US without going through your doctor. You can order the test online through Ulta Lab Tests (affiliate link) or through other online lab companies. UltaLab Tests is often the cheapest, and the Lp(a) test currently costs $29. (Shop around since other online lab test companies often run specials or may have more convenient locations for the lab draw.)
Seriously, the only way to know your Lp(a) level is to get it tested.
Therapies to talk with your doctor about:
In fact, there are a couple of therapies for high Lp(a) that have been well studied — as well as new drugs in trials to target it.[ref]
- Apheresis, where they run your blood through a machine to remove the LDL particles, is considered effective, but expensive and inconvenient.[ref]
- Statins have been shown to elevate Lp(a) levels a little bit. The newer cholesterol-lowering medications, PCSK9 inhibitors, have been shown to lower Lp(a) levels.[ref]
- A study of over 20,000 women looked at the effects of aspirin on heart disease. The study results showed that those women who carried one or two copies of the LPA risk allele cut their heart attack risk with aspirin therapy. (Women without elevated Lp(a) did not have a statistical benefit from aspirin.) The whole study is available here.
Keep up with new research: Phase III clinical trials are underway for a new medication that targets Lp(a) with an antisense oligonucleotide.[ref]
Natural options for lowering Lp(a):
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Article originally published July 2018. Updated Apr. 2021
Debbie Moon is the founder of Genetic Lifehacks. Fascinated by the connections between genes, diet, and health, her goal is to help you understand how to apply genetics to your diet and lifestyle decisions. Debbie has a BS in engineering and an MSc in biological sciences from Clemson University. Debbie combines an engineering mindset with a biological systems approach to help you understand how genetic differences impact your optimal health.