"Stress gene" may increase heart attack risk by almost 40 percent

Heart disease and stroke killed more than 787,000 people in 2010 -- about one in three Americans. A new study suggests a “stress gene” may be to blame for some of these deaths.

While obesity, high blood pressure, smoking, physical inactivity and eating a high-sodium diet devoid of fruits and vegetables all can raise risk for cardiovascular problems, the study authors say they’ve found a biological explanation for why some people are predisposed to develop heart disease or die early from a stroke or heart attack.

"The exciting part to me this is that this genetic trait occurs in a significant proportion of people with heart disease," Dr. Beverly Brummett, an associate professor of psychiatry and behavioral sciences at Duke University School of Medicine in Durham, N.C., said in a statement.

The study builds on work scientists previously did to identify a genetic variant called a single nucleotide polymorphism, or SNP, in a DNA chain that makes a receptor for the neurotransmitter serotonin. Serotonin is a chemical messenger in the brain that is tied to emotion regulation. Essentially, an SNP is when one letter in a DNA sequence is swapped with another letter, which leads to a change in function. I this case, the function of the gene is changed to cause a hyperactive reaction to stress.

The researchers point out that a study last year found men with these gene variants had twice as much cortisol, a hormone related to stress, in their blood while under stress compared to men without the variant. 

"It has been shown that high cortisol levels are predictive of increased heart disease risk. So we wanted to examine this more closely," said Brummett.

They conducted a genetic analysis of more than 6,100 people who underwent cardiac catheterization procedures, two-thirds of whom were male. In that procedure, a long, flexible tube is threaded through a blood vessel in the arm so doctors can perform tests or treatments that directly target the bloodstream.

They found the overactive stress gene in 13 percent of the patients. After tracking them for six years, the researchers discovered the genetic trait raised risk for heart attack and early death by 40 percent. This was the case even after ruling out other factors like age, obesity, smoking history and severity of their heart disease.

The study didn’t look specifically at what is going on in the body to cause this increased risk, but the researchers have a theory that rising cortisol levels cause elevations in an ezyme called “MMP9.” This enzyme breaks down plaques in blood vessels, making them more likely to form cloths that could cause a blockage that leads to a heart attak. 

"If we can replicate this and build on it, we may be able to find ways to reduce the cortisol reaction to stress -- either through behavior modification or drug therapies -- and reduce deaths from heart attack," said Brummet.

The study was published Dec. 18 in PLoS One.

Previous research has linked stress and rising cortisol levels to Alzheimer’s disease risk.