We’ve long known that stress appears to put our hearts at risk, but researchers have still been puzzling as to why. A new study fills in an important piece, finding that the same genetic variant that makes some of us more responsive to mental and emotional stress also makes us more likely to have a heart attack, and die. The good news is that knowing whether a person carries this genetic trait may help heart medicine “catch up” to other fields, like cancer medicine, where determining risk and arriving at treatments is becoming highly personalized.
The team focused on a patch of DNA that controls the formation of the serotonin receptor - a particular variation of this gene seems to cause a person to have a more pronounced reaction to stress. Last year another study found that men with this genetic variant had double the level of cortisol - the famous stress hormone - circulating in their blood when they were stressed, compared to men without it. The new study set out to see whether the gene might also be linked to the risk of heart attack and death.
Indeed the results showed that people with the genetic variant were 38% more likely to have a heart attack, and 38% more likely to die, compared to those without it. About 13% of the people in the study had the variation.
Cortisol is responsible for our “fight of flight” response to stressors. And while it’s incredibly important during specific stressful events, over the long term high levels of cortisol can seriously compromise various body systems, like the immune system, the reproductive system, and our metabolism, raising blood sugar and affecting insulin function. So it’s not much of a stretch to think it might affect the cardiovascular system - and this is exactly what the study found.
“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,” said study author Beverly H. Brummett. “It has been shown that high cortisol levels are predictive of increased heart disease risk.”
Still, exactly why cortisol level raises heart attack risk is still not totally clear, but the authors have a pretty good hypothesis going. They suspect that along with cortisol, an enzyme called MMP-9 also rises, and it’s this one that’s actually the problem. The compound MMP-9 seems to make the plaques that build up along blood vessel walls more “vulnerable” and likely to break off and form clots, which can lead to a heart attack.
In other words, the new pathway they propose is: Genetic variant -> Cortisol -> MMP-9 -> Plaques “Burst” -> Heart Attack.
Knowing whether a person has the genetic variant would be very helpful in heart attack prevention. For this subgroup, it may one day be possible to predict risk even more accurately, and prescribe interventions (either drug- or lifestyle-based) earlier on.
“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. He also said that unlike in the cancer field, in which personalized medicine has been steadily growing, this kind of personalized risk analysis has been lacking in the cardiovascular realm - until now. “Here we have a paradigm for the move toward personalized medicine in cardiovascular disease.”
Managing one’s stress level is so important these days, as our lives get more and more harried. Some people may need pharmaceutical interventions, but for others, lifestyle methods work well, like meditation, yoga, eating well, and exercise. If your stress level feels out of control, it’s important to talk with a mental health care provider to figure out ways to manage it.