Will Aspirin Prevent Heart Disease for You?

Many people take low-dose aspirin daily to prevent heart disease. But — does everyone benefit? The 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. This article explains some of the genetic research linking specific variants to benefiting from aspirin therapy.  Members will see their genotype report below, plus additional solutions in the Lifehacks section. Join today 

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 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. 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]


Aspirin and Heart Disease Genotype Report

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GUCY1A3 gene:

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 .

COMT gene:

Check your genetic data for rs4680 (23andMe v4, v5, AncestryDNA):

  • 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 .

IGTB3 Gene:

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 .

 


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References:

Bendall, Jennifer K., et al. “Tetrahydrobiopterin in Cardiovascular Health and Disease.” Antioxidants & Redox Signaling, vol. 20, no. 18, June 2014, pp. 3040–77. PubMed Central, https://doi.org/10.1089/ars.2013.5566.
Hall, Kathryn T, et al. “Genetic Variation at the Coronary Artery Disease Risk Locus GUCY1A3 Modifies Cardiovascular Disease Prevention Effects of Aspirin.” European Heart Journal, vol. 40, no. 41, Nov. 2019, pp. 3385–92. PubMed Central, https://doi.org/10.1093/eurheartj/ehz384.
—. “Genetic Variation at the Coronary Artery Disease Risk Locus GUCY1A3 Modifies Cardiovascular Disease Prevention Effects of Aspirin.” European Heart Journal, vol. 40, no. 41, Nov. 2019, pp. 3385–92. PubMed Central, https://doi.org/10.1093/eurheartj/ehz384.
Hall, Kathryn T., et al. “Polymorphisms in Catechol-O-Methyltransferase Modify Treatment Effects of Aspirin on Risk of Cardiovascular Disease.” Arteriosclerosis, Thrombosis, and Vascular Biology, vol. 34, no. 9, Sept. 2014, pp. 2160–67. ahajournals.org (Atypon), https://doi.org/10.1161/ATVBAHA.114.303845.
—. “Polymorphisms in Catechol-O-Methyltransferase Modify Treatment Effects of Aspirin on Risk of Cardiovascular Disease.” Arteriosclerosis, Thrombosis, and Vascular Biology, vol. 34, no. 9, Sept. 2014, pp. 2160–67. PubMed Central, https://doi.org/10.1161/ATVBAHA.114.303845.
Khatami, Mehri, et al. “Common Rs5918 (PlA1/A2) Polymorphism in the ITGB3 Gene and Risk of Coronary Artery Disease.” Archives of Medical Sciences. Atherosclerotic Diseases, vol. 1, no. 1, Apr. 2016, pp. e9–15. PubMed Central, https://doi.org/10.5114/amsad.2016.59587.
—. “Common Rs5918 (PlA1/A2) Polymorphism in the ITGB3 Gene and Risk of Coronary Artery Disease.” Archives of Medical Sciences. Atherosclerotic Diseases, vol. 1, no. 1, Apr. 2016, pp. e9–15. PubMed Central, https://doi.org/10.5114/amsad.2016.59587.
Oliver, Kendra H., et al. “Pro32Pro33 Mutations in the Integrin Β3 PSI Domain Result in ΑIIbβ3 Priming and Enhanced Adhesion: Reversal of the Hypercoagulability Phenotype by the Src Inhibitor SKI-606.” Molecular Pharmacology, vol. 85, no. 6, June 2014, pp. 921–31. PubMed, https://doi.org/10.1124/mol.114.091736.
—. “Pro32Pro33 Mutations in the Integrin Β3 PSI Domain Result in ΑIIbβ3 Priming and Enhanced Adhesion: Reversal of the Hypercoagulability Phenotype by the Src Inhibitor SKI-606.” Molecular Pharmacology, vol. 85, no. 6, June 2014, pp. 921–31. PubMed, https://doi.org/10.1124/mol.114.091736.
Porcelli, Stefano, et al. “Pharmacogenetics of Antidepressant Response.” Journal of Psychiatry & Neuroscience : JPN, vol. 36, no. 2, Mar. 2011, pp. 87–113. PubMed Central, https://doi.org/10.1503/jpn.100059.
Ridker, P. M., et al. “PIA1/A2 Polymorphism of Platelet Glycoprotein IIIa and Risks of Myocardial Infarction, Stroke, and Venous Thrombosis.” Lancet (London, England), vol. 349, no. 9049, Feb. 1997, pp. 385–88. PubMed, https://doi.org/10.1016/S0140-6736(97)80010-4.
Stanhewicz, Anna E., et al. “Folic Acid Supplementation Improves Microvascular Function in Older Adults through Nitric Oxide-Dependent Mechanisms.” Clinical Science (London, England: 1979), vol. 129, no. 2, July 2015, pp. 159–67. PubMed, https://doi.org/10.1042/CS20140821.
Stanhewicz, Anna E., and W. Larry Kenney. “Role of Folic Acid in Nitric Oxide Bioavailability and Vascular Endothelial Function.” Nutrition Reviews, vol. 75, no. 1, Jan. 2017, pp. 61–70. Silverchair, https://doi.org/10.1093/nutrit/nuw053.
Undas, A., et al. “Pl(A2) Polymorphism of Beta(3) Integrins Is Associated with Enhanced Thrombin Generation and Impaired Antithrombotic Action of Aspirin at the Site of Microvascular Injury.” Circulation, vol. 104, no. 22, Nov. 2001, pp. 2666–72. PubMed, https://doi.org/10.1161/hc4701.099787.
—. “Pl(A2) Polymorphism of Beta(3) Integrins Is Associated with Enhanced Thrombin Generation and Impaired Antithrombotic Action of Aspirin at the Site of Microvascular Injury.” Circulation, vol. 104, no. 22, Nov. 2001, pp. 2666–72. PubMed, https://doi.org/10.1161/hc4701.099787.
—. “Pl(A2) Polymorphism of Beta(3) Integrins Is Associated with Enhanced Thrombin Generation and Impaired Antithrombotic Action of Aspirin at the Site of Microvascular Injury.” Circulation, vol. 104, no. 22, Nov. 2001, pp. 2666–72. PubMed, https://doi.org/10.1161/hc4701.099787.
Wilmink, H. W., et al. “Influence of Folic Acid on Postprandial Endothelial Dysfunction.” Arteriosclerosis, Thrombosis, and Vascular Biology, vol. 20, no. 1, Jan. 2000, pp. 185–88. PubMed, https://doi.org/10.1161/01.atv.20.1.185.


About the Author:
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 also 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.