Clinicians have long suspected that depression worsens cardiac symptoms, but recent research suggests this combination is even more dangerous than previously believed. A study published in the journal Heart found that on any given day participants with both depression and heart disease were nearly five times more likely to die than their healthy peers. Depression alone doubled mortality risk, and heart disease increased risk by only two thirds.

The study authors evaluated about 6,000 subjects, employing statistical models to see if other factors, such as age and medication use, affected the results. Surprisingly, heart disease became a relatively insignificant mortality risk once these other factors were accounted for, but the combination of depression and heart disease remained lethal. “It shows the pervasiveness of depression,” says Martica Hall, a psychologist at the University of Pittsburgh and a study co-author. Indeed, studies indicate at least 20 percent of the 17 million Americans with heart disease also suffer from depression. The mechanism behind depression’s lethality is unclear, but researchers surmise that inflammatory factors associated with the brain’s stress response play a role.