Female heart disease risk may have more to do with genetic factors interacting with sex hormones than previously thought, according to a new study by UBC Faculty of Medicine researchers.
Dr. Tara Sedlak
Led by UBC clinical associate professor Dr. Tara Sedlak, the study found evidence of under-explored genetic risk of cardiovascular disease connected to the hormone estrogen. Dr. Sedlak is one of the only certified women’s heart health cardiologists in Canada and director of the Leslie Diamond Women’s Heart Health Clinic.
The study findings, published recently in Frontiers in Cardiovascular Medicine, could help inform tailored prevention and treatment strategies for female heart health based on the person’s unique genetic and hormonal profile, while highlighting the urgent need for more sex-stratified research.
“As estrogen levels change, so too does the risk of cardiovascular disease,” said Emilie Théberge, a UBC PhD student in medical genetics and co-first author alongside UBC medical student Ava Aminbakhsh. “Our findings are a call to action for researchers in the field of cardiovascular disease to include hormone data in their studies, such as through sex stratification and female-specific variables in study design.”
Estrogen and heart health
Estrogen has been known to play an important protective role in female cardiovascular health, reducing inflammation in the body and helping to maintain blood vessel dilation, among other effects.
Emilie Théberge
However, estrogen levels change across a person’s lifespan, and are typically highest and most protective during a person’s reproductive years before gradually declining with the onset of perimenopause and menopause. Estrogen levels can also vary during pregnancy, with certain conditions affecting hormones such as polycystic ovarian syndrome, or with medications such as birth control, fertility treatments or menopausal hormone therapy.
These changes in hormone levels can affect many aspects of a person’s health from cholesterol to body fat distribution, but the overall impact on heart health remains understudied.
“As females age, their metabolism changes,” said Théberge. “Their bodies are more prone to holding onto fat. Muscle mass is more important to retain bone strength. They are also more prone to higher cholesterol and osteoporosis.”
Gene-hormone connection may unlock precision treatments
For the study, Dr. Sedlak and Théberge examined prior research on genetic variants linked to coronary artery disease in females, and mapped them to identify which are influenced by estrogen.
“Estrogen affects over 2,000 genes in the body—everything from how certain proteins are expressed, to the functioning of cells,” said Théberge.
Their review focused on small changes in the genetic code that are known as single nucleotide polymorphisms (SNPs), which can be present at birth or arise over time due to aging and other environmental factors.
“If your complete genome is a recipe book, and each gene is a recipe, SNPs are changes akin to spelling errors in one of the recipes,” said Théberge. “Many of these changes are small and have little impact in isolation. However, as a whole, an accumulation of these changes can increase the risk of heart disease.”
We need more research in this space to offer science-backed recommendations for the effective treatment of female patients with heart disease at all stages of life.
Emilie Théberge
Overall, the research identified 61 genes linked to coronary artery disease, of which, 26 genes were found to be modulated by estrogen. The estrogen-modulated genes were identified as playing a role in key heart disease markers, such as lipid synthesis, metabolism, lipoprotein mechanisms, vascular integrity and thrombosis—blood clots in the blood vessels or heart.
“This demonstrates a direct link between how estrogen levels can impact heart disease risk at the genetic level, and is an area that has been historically understudied in scientific research and not always factored in for treatment development in clinical trials,” said Théberge.
With a growing body of sex-specific evidence, Théberge believes that new tailored heart treatment avenues, including personalized precision medicine approaches and lifestyle changes, could be pursued for women whose estrogen levels are in a state of flux.
“Drug companies, researchers and doctors need to be aware of how estrogen levels may change the side effects and efficacy of the medications presently indicated for female heart patients, including gold-standard medications that affect blood pressure or cholesterol levels,” said Théberge. “We need more research in this space to offer science-backed recommendations for the effective treatment of female patients with heart disease at all stages of life.”
A version of this story was originally published on the VCHRI website.