The genetic risk of depression is a stronger predictor of heart problems in women than men: new research

It accounts for one in three deaths for Australian women, yet women with heart disease remain under-studied, under-diagnosed and under-treated.

Meanwhile, depression affects about twice as many women as men. Our recent study indicates women are in double jeopardy, as those with a higher genetic predisposition to depression were also found to have increased heart disease risk. The same pattern is not observed for men.

Here’s what we’re learning and what we need need to investigate.

Previous studies have shown people with depression also have a higher risk of developing heart disease.

The cause of this relationship is complex.

For example, some psychiatric medications are known to have adverse effects that lead to weight gain and higher cholesterol levels.

At the same time, depression can lead to lifestyle behaviours such as smoking, poor diet and reduced exercise which can exacerbate the risk of developing heart disease.

Researchers haven’t looked in detail at the shared biological factors and whether they differ in men and women.

Our research, led by the University of Queensland’s Institute for Molecular Bioscience, used genomic and health data from about 345,000 people in the United Kingdom to investigate the brain-heart link in females and males separately.

Human genetic studies have previously identified many parts of our DNA that contribute to different diseases. These allow researchers to determine if a person’s genetic makeup puts them at a higher risk of developing a particular disease.

We used study data to calculate each person’s genetic risk of depression. Then we checked whether this risk was associated with a higher risk of developing heart disease in the future.

Our study found women with a higher genetic risk of depression are more likely to develop cardiovascular disease (specifically, coronary artery disease, atrial fibrillation and heart failure).

This link was observed even among women who had never had a diagnosis of depression or other psychiatric disorders, nor reported use of any psychiatric medication. This indicates the increased heart disease risk in women is not simply a result of behavioural changes or medication use following a depression diagnosis.

Interestingly, the same was not observed in men.

The results suggest the same genetic or biological factors that increase the risk of depression may also play a role in heart disease in women.

The study found this sex difference could not be explained by a difference in well-known heart disease risk factors, such as BMI, high blood pressure or smoking.

The risk of heart disease in women is also known to increase after menopause. However, we found a similar link between the genetic risk of depression and the future incidence of heart disease regardless of whether women had undergone menopause or not.

Heart disease risk calculators are used by doctors around the world to identify people at high risk of developing heart disease. In Australia, we use the AusCVDRisk calculator.

These risk calculators bring together information on well-known risk factors, such as blood pressure and blood cholesterol levels. Appropriate interventions (lifestyle changes and/or medication) are recommended in people with high risk to reduce the chances of having a heart attack or a stroke.

But studies have shown relying on these traditional risk factors alone tends to underestimate heart disease risk in women. Improving the risk prediction accuracy in women requires the consideration of female-specific risk factors.

Currently, only QRISK3 (used by doctors in the UK) directly incorporates a diagnosis of depression into its risk calculation. However, this calculator considers the effect of a depression diagnosis on heart disease risk to be similar in men and women. Our new paper suggests women’s genetic risk of depression can put them at greater risk.

Further research is needed to understand whether depression risk can help better predict heart disease risk in women. But this study highlights the importance of frequent heart health checks in women with a family history or diagnosis of depression. This is especially true for younger women, a group with a high depression prevalence but traditionally thought to have low heart disease risk.

When it comes to heart disease, women are not just “smaller men”. As such, research focused on understanding heart disease in women is essential for developing tailored approaches.

At the same time, increased awareness around sex differences in heart disease is crucial to encourage more women to prioritise getting their heart health checked.