Asprin, Heart Disease Prevention, and Genetics

Key takeaways:
~ Low-dose aspirin may help prevent heart disease in some people.
~ Genetic variants influence whether aspirin is likely to be beneficial in heart disease prevention.
~ Understand your genes and then talk with your doctor to see what is right for you.
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Aspirin Therapy

Low-dose aspirin has long been recommended for heart disease prevention in middle-aged and older adults who aren’t at risk for bleeding problems. Recent trials, though, show that it may not have a clear benefit for the primary prevention of cardiovascular disease. Instead, the studies show that it is more likely to be beneficial in people who already have cardiovascular disease.[ref][ref]

Note: This article is only for informational purposes. Talk with your healthcare provider for medical advice on whether aspirin is right for you.

Aspirin is a COX enzyme inhibitor. The COX enzymes are essential for the synthesis of prostaglandins, which are inflammatory lipids that affect the blood vessels and platelets. By inhibiting the COX enzymes, aspirin reduces platelet adhesion and thus decreases the risk of a blood clot that could cause a heart attack. [ref]

Genetics and Aspirin for Heart Disease Prevention:

The recommendations about aspirin by doctors and medical authorities have gone back and forth over the past couple of decades, changing with every new study that comes out.

For example, a study published in 2009 with more than 95,000 patients involved found that aspirin reduced myocardial infarctions by 12% and didn’t affect stroke rates. However, another study a few years later showed the opposite.[ref]

Genetic variants play a role in whether someone is more likely to benefit from aspirin therapy.  When looking at the big population-wide studies, you see the average across all genotypes.

However, when you look at studies that segregate by different genetic variants, the results show that some people likely benefit from aspirin, while for others it may be a negative factor.

Here are three studies that have tackled the topic from different points of view.

GUCY1A3 gene and aspirin:

The GUCY1A3 gene codes for an enzyme that inhibits platelets from sticking together in the presence of nitric oxide.

Previous research showed that carriers of the more common GUCY1A3 variant (~63% of the European population) are less sensitive to platelet inhibition from nitric oxide. The body naturally produces nitric oxide, which is released by the inner layer of blood vessels and keeps them flexible. Nitric oxide also helps to prevent platelets from sticking and forming clots in the arteries — with the help of the GUCY1A3 enzyme.

A 2019 study with over 22,000 participants showed that carriers of the more common GUCY1A3 variant were likely to benefit from aspirin therapy with a reduction in the risk of cardiovascular disease (21% decrease in relative risk). On the other hand, individuals who carried one or two copies of the less common allele had a slight increase in the risk of cardiovascular disease with aspirin therapy.[ref]

COMT gene: Aspirin helps lower cardiovascular disease risk for some women

Catechol-O-methyltransferase (COMT) is the gene that codes for an enzyme that breaks down dopamine, epinephrine, and norepinephrine, as well as other substances. There are many studies on the common genetic polymorphisms of the COMT gene, and most of the studies focus on the neurological aspects of the enzyme.

A study published in the Journal of the American Heart Association looked at the effect of a common COMT polymorphism on cardiovascular disease.  The study also looked at the combined effect of the variant along with either aspirin or vitamin E and cardiovascular disease.[ref]

The study included 23,000 women and analyzed the incidences of cardiovascular disease over a 10-year period. It looked at the COMT Val158Met polymorphism, rs4680, where Val is the same as the G allele and Met is the same as the A allele. Those with two copies of the Val/Val variant (G/G allele) have approximately a 4 times faster rate of dopamine metabolism than those with the Met/Met variant (A/A).[ref]

The findings of the cardiovascular disease study show that women with the COMT Val/Val (G/G) variant are naturally at a lower risk of cardiovascular disease than those with the Met/Met (A/A) allele.

The study also showed that taking low-dose aspirin (100mg every other day) or Vitamin E (600 IU alpha-tocopherol every other day) significantly reduced the risk of cardiovascular disease for those with the Met/Met (A/A) allele. The opposite was true for women with the Val/Val (G/G); they actually had a slightly higher risk of cardiovascular disease with aspirin supplementation and no protection from Vitamin E.

ITGB3 gene and aspirin:

The benefits of aspirin for heart disease are due, at least in part, to its ability to thin the blood. The gene codes for a protein called Human Platelet Antigen-1 that is involved in how platelets form clots. A genetic variant in the ITGB3 gene impacts aspirin’s ability to thin the blood.

Carriers of the rs5918 variant (also known as P1A1/A2) have shown in studies to be at a greater risk of heart attacks. Studies also show that people carrying the P1A2 variant are more resistant to the anticoagulant effects of aspirin.[ref] Note that some studies show no increase in the risk of cardiovascular disease, so other diet or lifestyle factors may be at play here.[ref]

Lipoprotein(a) and aspirin:

Carriers of LPA variants are more likely to have higher lipoprotein(a) levels, and Lp(a) levels are strongly linked to heart attack risk. A recent study looked at over 12,000 individual in regards to their LPA genotype. The study found that taking aspirin regularly greatly reduced the risk of major cardiovascular events.  Individuals in the placebo arm who carried the LPA risk genotype were at almost double risk of major cardiovascular events, but those who were taking the aspirin (100mg/day) had no increase in risk. [ref]

Lifehacks:

Talk with your doctor about this one, especially if you are already on aspirin therapy. There may be other health factors that you should consider, in addition to your genes.

Check the excipients in aspirin:

Aspirin is an inexpensive medication that is cheap and readily available. It has been used for centuries. Willowbark, which contains the active ingredient in aspirin, has been used since ancient Egyptian times as an anti-inflammatory and to treat fevers. Aspirin, as we know it today, has been available as a medication since the mid-1800s.

Some manufacturers now try to differentiate themselves with a lot of extra ingredients in the aspirin tablets. Try looking for an inexpensive aspirin without a lot of ingredients you don’t want to take on a daily basis.

Additional ways of decreasing heart disease risk:

Related Articles and Genes:

Lipoprotein(a): Genetics and Lp(a) Levels

Elevated Fibrinogen: Risk factor for blood clots

Nitric Oxide Synthase (NOS3): Heart Health, Blood Pressure, and Healthy Aging