Stress Gene Linked To Higher Risk Of Heart Attack And Death

Rebekah Eliason for – Your Universe Online

A new study from Duke reveals that the genetic trait responsible for predisposing some people to strong stress reactions may also cause the risk of heart attack or death to rise by 38 percent.

This discovery provides a new biological explanation for why some people are inclined towards cardiovascular disease. Since in these cases the disease is linked to stress, the findings suggest that behavior modification and drug therapies targeting stress reduction may lower heart attack related disability and deaths.

Redford B. Williams Jr., M.D., director of the Behavioral Medicine Research Center at Duke University School of Medicine and senior author of the paper, said, “We’ve heard a lot about personalized medicine in cancer, but in cardiovascular disease we are not nearly as far along in finding the genetic variants that identify people at higher risk. Here we have a paradigm for the move toward personalized medicine in cardiovascular disease.”

Building on previous work at Duke and elsewhere, Williams and his colleagues were able to identify a variation in a DNA sequence known as single nucleotide polymorphism (SNP). In this sequence variation, one letter from the genetic code is swapped with another causing a change in the gene’s function. Specifically the team focused on the SNP occurring on the gene responsible for making a serotonin receptor that causes a hyperactive reaction to stress.

Last year, a study was published reporting that men with the genetic variation were found to contain twice as much cortisol in their blood after exposure to stress than men without the variant. Commonly known as the “stress hormone,” cortisol is designed to support the body’s biological response to stressful situations that cause negative emotions. This vital hormone is produced in the adrenal glands.

Beverly H. Brummett, PhD, associate professor of Psychiatry and Behavioral Sciences at Duke and lead author of the paper, said, “It is known that cortisol has effects on the body’s metabolism, on inflammation and various other biological functions, that could play a role in increasing the risk of cardiovascular disease. It has been shown that high cortisol levels are predictive of increased heart disease risk. So we wanted to examine this more closely.”

Several years of data from heart catheterization patients at Duke was formed into a large database used by researchers to run a genetic analysis of over 6,100 white participants. Of those studied, two-thirds were men and one-third was women. Approximately 13 percent of the group was found to possess the genetic variation for the overactive stress response.

Those found to carry the genetic variation corresponded with patients who had the highest rates of heart attacks and deaths when evaluating the median follow-up time of six years. Even when taking into account age, obesity, smoking history, other illnesses and the severity of their heart disease, the studied genetic trait was found to be associated with a 38 percent increased risk of heart attack and death.

“This finding requires independent replication and evaluation in a more diverse population,” said Peter Kaufmann, Ph.D., deputy branch chief of the Clinical Applications and Prevention Branch at the NIH’s National, Heart, Lung, and Blood Institute (NHLBI). “This research may one day help to identify patients who should be candidates for more intensive disease prevention and treatment strategies.”

Both Williams and Brummett said the researchers are developing a hypothesis about why this genetic trait can lead to heart disease problems. Specifically, they are focusing on an enzyme, known as MMP9, found in blood that becomes elevated as cortisol levels rise. MMP9 softens the hard plaque that builds up on blood vessel walls which causes the risk of rapture to be more likely and produces clots that can cause heart attack or death.

“We plan to study this further,” Williams said. “But what this work suggests already is that we have a found genetic variant that can be easily identified, so we can begin to develop and test early interventions for those heart patients who are at high risk of dying or having a heart attack.”

“The exciting part to me this is that this genetic trait occurs in a significant proportion of people with heart disease,” Brummett said. “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.”

The team’s study was published in the December 18, 2013 issued of the journal PLOS ONE.

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