Researchers examined data on 950 people in Australia and New Zealand with stable coronary artery disease, which happens when plaque accumulates in the arteries supplying the heart and causes them to harden and narrow. Also called atherosclerosis, this process can weaken the heart muscle, cause an irregular heartbeat and lead to heart attacks.

About 4 percent of participants reported regularly suffering from moderate or severe psychological distress over the first four years of the study, and they were roughly four times more likely to die of heart disease and almost three times more likely to die from any cause during the next 12 years compared to people with no distress.

The heart patients who reported only occasional or mild distress, however, didn’t appear to have an increased risk of premature death, researchers report in the journal Heart.

“This really indicates that over the longer term it is the amount of distress that matters,” said lead author Dr. Ralph Stewart, a cardiologist at Auckland City Hospital and the University of Auckland.

“We do not yet know whether treatments for anxiety and distress reduce mortality, but there is enough evidence to recommend that people should look for ways to reduce high levels of persistent distress,” Stewart said by email.

At the start of the study, all of the participants had experienced a heart attack or hospitalization for unstable angina, when the heart doesn’t get enough blood flow or receive enough oxygen, in the previous 3 to 36 months.

They completed a psychological questionnaire when they joined the study, and again after six months and at one year, two years and four years.

Questions to assess depression and anxiety asked, among other things, if participants felt constantly under strain, found life a struggle all the time, got scared or panicky for no good reason, or thought they played a useful part in things.

Overall, 587 people, or 62 percent, were not distressed at any of the psychological assessments. Another 255 individuals, or 27 percent, reported at least mild distress during two or more assessments and 35 people, or about 4 percent, regularly suffered from moderate or severe psychological distress.

Researchers followed half of the participants for at least 12 years. During this monitoring period, 398 people died from all causes and 199 died from cardiovascular disease.

The study wasn’t a controlled experiment designed to prove that depression or anxiety causes premature death for people with heart disease.

Another limitation of the study is that the psychological assessments stopped after four years, so it’s possible the findings might underestimate the impact of persistent distress, the authors note.

The psychological assessment used in the study also doesn’t do a good job of pinpointing the exact nature of stress and is no longer used for assessing it, Dr. Gjin Ndrepepa, a researcher with the German Heart Center Munich at the Technical University of Munich, writes in an accompanying editorial.

But mental distress can activate the body’s so-called flight or fight response, the sympathetic nervous system, and boost levels of stress hormones, Ndrepepa told Reuters Health by email. This might contribute to elevated blood pressure, high cholesterol or diabetes and prompt unhealthy behaviors like smoking or drinking or being inactive.

“These stress-related internal and external adverse reactions aggravate the progression of the disease and predispose people to poor outcomes including increased odds of death,” Ndrepepa said. “My belief is that depressed patients with coronary heart disease, particularly severely depressed ones, should be treated for depression.”