Many people take low-dose aspirin daily to prevent heart disease. But — does everyone benefit? This ‘daily aspirin’ advice is based on large-scale group studies that show that aspirin reduces heart attacks.
We are all unique, and newer research shows that not everyone benefits the same way from aspirin therapy.
There may be multiple ways that aspirin helps to protect some people from heart disease — and it may be different for women than for men.
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, in the presence of nitric oxide, inhibits platelets from sticking together.
Previous research had shown 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 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 an increase in the risk of cardiovascular disease with aspirin therapy.[ref]
COMT gene and aspirin study in 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 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 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. A genetic variant in the ITGB3 gene impacts aspirins’ ability to thin the blood. The gene codes for a protein called Human Platelet Antigen-1 that is involved in how platelets form clots.
Carriers of the rs5918 variant (known also 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]
Genetic Variants that Impacts Aspirin and Heart Disease:
Check your genetic data for rs7692387 (AncestryDNA):
- G/G: decreased risk of heart disease with aspirin therapy[ref]
- A/G: increased risk of heart disease with aspirin therapy
- A/A: increased risk of heart disease with aspirin therapy
Members: Your genotype for rs7692387 is —.
- G/G: (women) naturally at a slightly lower risk of heart disease; aspirin supplementation increased the risk for heart disease[ref]
- A/G: in the middle for heart disease risk, no significant effect on heart disease from aspirin
- A/A: (women) generally higher risk for heart disease; both aspirin and vitamin E significantly decreased the risk for heart disease
Members: Your genotype for rs4680 is —.
Check your genetic data for rs5918 (23andMe v4, v5; AncestryDNA):
- C/C: increased risk of heart disease, may not benefit from aspirin for heart attack prevention[ref][ref][ref]
- C/T: somewhat increased risk of heart disease, may not benefit as much from aspirin for heart attack prevention[ref][ref][ref]
- T/T: typical
Members: Your genotype for rs5918 is —.
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.
Other ways of decreasing heart disease risk
- As an antioxidant, folate (vitamin B9) or methylfolate (an active version of folate) can improve endothelial function (a little) through decreasing oxidative stress.[ref][ref][ref]
- For people with the MTHFR C677T variant, riboflavin (vitamin B2) may also help. Check your MTHFR gene here.
- DHFR, an important enzyme in the folate cycle, also acts to regenerate BH4 when it has been lost due to high oxidative stress.[ref] You can check your genetic variants for DHFR and read more about this enzyme.
- Foods high in folate include dark leafy green veggies, legumes, and beef liver.
Related Genes and Topics:
Lipoprotein(A): a big genetic risk factor for heart attacks
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.
Nitric Oxide Synthase: Heart health, blood pressure, and aging
Nitric oxide acts as a signaling molecule in the endothelium, impacting blood pressure, cardiovascular disease, brain health, and more. Lifestyle factors and genetic variants in nitric oxide related genes are important here. Everyone needs a healthy heart!