Scientists have found that women with a high genetic risk of depression also have a higher risk of developing heart disease over the course of their lives. The same link wasn’t found in men, despite heart disease being much more common in men than in women.

“We found a significant association between genetic risk of depression and risk of developing cardiovascular disease even in women who had never had a depression diagnosis or been on any depression medication,” said Sonia Shah from the Institute of Molecular Bioscience at the University of Queensland, Australia.

Moreover, this difference between women and men couldn’t be explained by known risk factors for heart disease, such as smoking or high blood pressure.

“This suggests that genetic and biological factors that predispose to depression may also play a role in cardiovascular disease in women,” she added.

The study highlights the lack of research on how cardiovascular disease affects women differently than men — despite it being the leading cause of death for women worldwide — and the need to improve how doctors assess risk factors for heart disease in women. 

Looking for a brain-heart link

While previous studies have looked at potential links between depression and heart disease, results about differences between women and men have been inconsistent in the past.

“Though we know that people with depression have a higher risk of developing cardiovascular disease, sex differences do exist for both conditions,” said Shah. “For example, the prevalence of depression is much higher in women, while heart disease is more prevalent in men. This is why we wanted to look at the brain-heart link separately in men and women.”

The researchers looked for sex-specific links between the risk of psychiatric disorders and cardiovascular diseases using genetics data from over 345,000 people provided by the UK Biobank — a large-scale database that records genetic, lifestyle and health information of over half a million volunteers across the UK.

What they found was that women that carried genes linked to a higher risk for depression were more likely to develop cardiovascular diseases, including atrial fibrillation, coronary artery disease and heart failure.

“Previous studies of this link have been observational, which means they have simply looked at whether people who get depression are also more likely to get heart disease, or vice versa,” Shah explained. “Observational studies don’t tell you about whether there is a causal link and what direction that link goes in. Here, we used genetic risk of depression, which is fixed from birth, and therefore provides a clear direction of effect.”

The researchers then looked into whether these results could be explained by other risk factors of heart disease. “We know that having depression can lead to behaviours such as being less physically active, having a poor diet and smoking, while medications used to treat depression can have side-effects such as weight gain and raising cholesterol, which could explain the increased risk of heart disease,” said Shah.

However, after accounting for risk factors including age, body mass index and smoking, there was still a significant link between depression and cardiovascular disease in women that couldn’t be found in men. This link was also seen in women with a genetic risk of depression who had never been diagnosed with depression or been prescribed antidepressants.

Towards more inclusive research

While heart disease is the leading cause of death for women, they have been historically underrepresented in cardiovascular research, including in clinical trials. This can cause problems when results from studies focusing on men are extrapolated to women, which can lead to worse outcomes and more side effects for women being treated for the same conditions.

While the study led by Shah takes a step forward in our understanding of the differences between women and men when it comes to cardiovascular disease, more research will be needed to better understand the link between depression and heart disease in women. One limitation of the study was that, because depression is more prevalent in women, the number of men in the study was lower.

“Ideally we want a genetic study of depression done in men and women separately and with a similar number of participants,” Shah said. “This would allow us to understand whether the genetic factors that increase risk of depression in men are the same as those in women, and how these are associated with heart disease.”

Future research should also look at more diverse data, as participants in the UK Biobank project are mainly of European ancestry. This is unfortunately a common problem in genetics research due to a lack of large datasets in people of non-European ancestries.

“We hope to repeat this study in other ancestries in the future, as data becomes available, which will be important to further address the gaps in knowledge,” said Shah.

Meanwhile, there’s still a need to improve how doctors estimate a person’s risk of heart disease. Typically, risk calculators used by healthcare providers do not consider depression or predisposition to depression, nor any other risk factors that are unique to women. Recent studies have shown that some of the algorithms used today underestimate the risk of heart disease in women.

“The next step is to understand what is driving this risk, which may help us develop better risk calculators for women,” said Shah.

Reference: Jiayue-Clara Jiang et al., Sex-Specific Association Between Genetic Risk of Psychiatric Disorders and Cardiovascular Diseases, Circulation: Genomic and Precision Medicine (2024). DOI: 10.1161/CIRCGEN.124.004685

Feature image credit: Priscilla Du Preez 🇨🇦 on Unsplash