New research finds that a gene change already linked to stress is also tied to a 38% higher risk of heart attack or death in people with heart disease.
Researchers from the Duke University Medical Center, Durham, NC, suggest the finding explains the biology behind why some people may be more susceptible to cardiovascular disease and death.
They report their findings in the online journal PLOS ONE.
The team hopes this means there is a good chance the discovery will lead to drugs and behavior change treatments that reduce disability and deaths from heart attack.
Senior author Redford B. Williams Jr., professor of medicine and director of the Behavioral Medicine Research Center at Duke, says:
"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."
Gene variant causes extreme reaction to stress
A genetic variant is a piece of DNA that varies from person to person, like different spellings of the same word or phrase. A single change in a DNA sequence, known as a single nucleotide polymorphism (SNP), is where one letter in the genetic code is swapped for another. This is enough to change how the gene functions, with big or small results.
The new study builds on previous work that found a variation in a DNA sequence in the gene that makes a serotonin receptor - and causes an extreme reaction to stress. The gene is called 5HTR2C.
In the earlier research, the investigators found that under stress, men with this single SNP change in their serotonin receptor gene had twice as much of the "stress hormone" cortisol in their bloodstream than men without the genetic variant.
Cortisol is a hormone secreted in the adrenal gland that helps the body produce a biological response to situations that trigger negative emotions, for example fear. Among other things, it increases blood sugar, changes immune response and suppresses systems that are not immediately required to deal with the perceived stressful event, such as those that deal with digestion, reproduction and growth.
Lead author Beverly H. Brummett, associate professor of Psychiatry and Behavioral Sciences at Duke, also explains:
"It has been shown that high cortisol levels are predictive of increased heart disease risk. So we wanted to examine this more closely."
Carriers at higher risk of heart attack and death
For the study, the team analyzed data gathered from more than 6,100 white heart patients followed for 6 years, one-third of whom were women. About 13% of the patients had the gene variant that produced an extreme stress response.
They found that the highest rates of heart attacks and deaths over the follow-up occurred in patients who carried the gene variant.
Even after they corrected for other possible influencing factors like age, overweight, smoking, other diseases and heart disease severity, the analysis showed that being a carrier of the gene variant was linked to a 38% higher risk of heart attack and death.
Dr. Peter Kaufmann is deputy branch chief of the Clinical Applications and Prevention Branch at the body that funded the study, the National Heart, Lung, and Blood Institute (NHLBI), which is part of the National Institutes of Health (NIH). He says:
"This research may one day help to identify patients who should be candidates for more intensive disease prevention and treatment strategies."
He says further studies should now corroborate the findings in a more diverse population.
Speculating on how the gene variant causes the raised cardiovascular risk, the researchers say it may be something to do with a blood compound called MMP9, an enzyme that rises in line with cortisol levels.
They suggest MMP9 softens the hard plaques that build up in the linings of arteries, making them more likely to burst and make clots that can lead to heart attack or death. The team plans to look further into this.
But in the meantime, Prof. Williams says:
"...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."
In 2011, scientists working on two large international studies, published in Nature Genetics, discovered 17 new gene variants tied to coronary heart disease, more than doubling the number of known genetic links to the disease.