Lipoprotein(a): A big genetic risk for heart disease

lipoprotein(a) gene check your 23andMe

By reading this information, you could possibly save your life today. This isn’t a scare tactic or overblown health-alert type of article – just statistics and solid genetics research on the increased risk of cardiovascular disease.

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 risk of heart disease by 28%, and when combined with other risk factors such as high blood pressure, obesity can increase the risk almost 2-fold.[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.

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. [refTrusted Source: Peer Reviewed Paper]

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 a 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. [refTrusted Source: Peer Reviewed Paper]  So, you have a double-whammy of increasing atherosclerosis via increased inflammation plus oxidized LDL. The LDL has a tendency to oxidize once inside a vessel wall adding more inflammation responses because their structure has changed. All added to a mechanism that increases the risk of blood clots.[refTrusted Source: Peer Reviewed Paper]

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. [refTrusted Source: Peer Reviewed Paper]

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. [refTrusted Source: Peer Reviewed Paper]

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).[refTrusted Source: Peer Reviewed Paper]

Another study that included only women found that Lp(a) levels were only important in cardiovascular disease if the women also had total cholesterol levels over 220 mg/dl. [refTrusted Source: Peer Reviewed Paper]

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.

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 fairly young. 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).  There is abundant research on the increased risk for heart attack, narrowing of the arteries, and stroke  (i.e. cardiovascular disease) being caused by elevated lipoprotein (a).[refTrusted Source: Peer Reviewed Paper][refTrusted Source: Peer Reviewed Paper][refTrusted Source: Peer Reviewed Paper][refTrusted Source: Peer Reviewed Paper]

Conversely, there are also studies showing that low Lp(a) levels are linked with a lower risk of heart failure, stroke, vascular disease, and aortic stenosis.[refTrusted Source: Peer Reviewed Paper]

How high is high?

One study shows a 3x risk of aortic valve stenosis for those with Lp(a) levels greater than 90 mg/dl.[refTrusted Source: Peer Reviewed Paper]  Another source says normal Lp(a) levels are less than 30 mg/dl (or 75 nmol/L)[refTrusted Source: Peer Reviewed Paper]  while others put normal as less than 50 mg/dl.[refTrusted Source: Peer Reviewed Paper] Again – this is something to talk to a doctor about and keep up with the research as it comes out.

 


Genetic variants that cause elevated Lp(a):

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 [refTrusted Source: Peer Reviewed Paper][refTrusted Source: Peer Reviewed Paper][refTrusted Source: Peer Reviewed Paper]
  • C/T: risk of  elevated Lp(a), increased risk for heart disease, increased risk of aortic stenosis
  • T/T: typical

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 [refTrusted Source: Peer Reviewed Paper][refTrusted Source: Peer Reviewed Paper][refTrusted Source: Peer Reviewed Paper]
  • A/G: likely elevated Lp(a), increased risk for heart disease
  • A/A: typical

Studies also showed that carrying one risk allele for both of the above — compound heterozygous — also doubled the risk of aortic stenosis.[refTrusted Source: Peer Reviewed Paper]

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 [refTrusted Source: Peer Reviewed Paper]
  • rs6415085 – T allele linked to higher Lp(a) [refTrusted Source: Peer Reviewed Paper]

Variants that lower Lp(a):

Check your genetic data for rs6919346 (23andMe v5; AncestryDNA):

  • C/C: typical
  • C/T: possibly decreased Lp(a)
  • T/T:  decreased Lp(a)[refTrusted Source: Peer Reviewed Paper][refTrusted Source: Peer Reviewed Paper][refTrusted Source: Peer Reviewed Paper]

Check your genetic data for rs41272114 (23andMe v4, v5):

  • C/C: typcial
  • C/T: lower Lp(a)
  • T/T: lower Lp(a)[refTrusted Source: Peer Reviewed Paper] 5.25mg/dl lower Lp(a)[refTrusted Source: Peer Reviewed Paper]

Check your genetic data for rs143431368 (23andMe v5 only):

  • T/T: typcial
  • C/T: lower Lp(a)[refTrusted Source: Peer Reviewed Paper]
  • C/C: lower Lp(a)[refTrusted Source: Peer Reviewed Paper]

 


Lifehacks:

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.[refTrusted Source: Peer Reviewed Paper]

  • Apheresis, where they run your blood through a machine to remove the LDL particles,  is considered effective, but expensive and inconvenient.[refTrusted Source: Peer Reviewed Paper]
  • 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.[refTrusted Source: Peer Reviewed Paper]
  • 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.

Natural options for lowering Lp(a):

  • Niacin (vitamin B3) has been used for decades to lower the risk of heart disease. Studies show that 1 -3 g/day lowers Lp(a) levels by an average of 30-40%.[refTrusted Source: Peer Reviewed Paper][refTrusted Source: Peer Reviewed Paper][refTrusted Source: Peer Reviewed Paper]  Most studies use the type of niacin that causes flushing.
  • Overall, lowering your LDL cholesterol numbers can help lower Lp(a) some since Lp(a) is the carrier for LDL. Here is a good article on it from the Cleveland Clinic.  How do you lower your cholesterol with diet? That seems to be the million-dollar question.  A more whole-food, plant-based diet, in comparison with a higher meat/fat-based diet, works to lower cholesterol for some people. It may be that you need to try out several diets – Mediterranean, DASH, etc – and test to see what works for your body.
  • One study showed Gingko Biloba reduced Lp(a) levels. The study used 120mg, twice a day and showed a 23% decrease in Lp(a). [refTrusted Source: Peer Reviewed Paper]
  • Berberine has been shown to decrease cholesterol levels as well as Lp(a) levels. [refTrusted Source: Peer Reviewed Paper] Read through my article on berberine for more info as well as ways to increase absorption.
  • A clinical trial showed a ‘defined plant-based diet’ for 4 weeks lowered Lp(a) by an average of 16% (along with reducing total cholesterol by 16%) The diet seemed to consist of fruits, vegetables, nuts, seeds, and whole grains – with 1oz of meat per day. The study notes that the amount of decrease in Lp(a) is similar to that of using niacin or a PCSK9 inhibitor. [refTrusted Source: Peer Reviewed Paper]

More to read/watch:


Related Genes and Topics:

LDL Cholesterol: Genetic variants that increase cholesterol levels
Your genes combine with your diet to influence your LDL cholesterol level. Learn more about why LDL cholesterol levels may matter in heart disease – and find out how your genes are important here.

Triglyceride Levels:
High triglycerides are linked with an increased risk of cardiovascular disease. Both genetics and diet combine to elevate triglyceride levels. Learn how your genes interact with what you eat to lower your triglycerides.

 

Article originally published July 2018. Updated Dec. 2019.

 



Author Information:   Debbie Moon
Debbie Moon is the founder of Genetic Lifehacks. She holds a Master of Science in Biological Sciences from Clemson University. Debbie is a science communicator who is passionate about explaining evidence-based health information. Her goal with Genetic Lifehacks is to bridge the gap between scientific research and the lay person's ability to utilize that information. To contact Debbie, visit the contact page.