Heart patients with the genetic change had a 38% increased risk of heart attack or death, say US researchers.
Personalised medicine may lead to better targeting of psychological or drug treatment to those most at risk, they report in PLOS ONE.
The study adds to evidence stress may directly increase heart disease risk, says the British Heart Foundation.
A team at Duke University School of Medicine studied a single DNA letter change in the human genome, which has been linked to being more vulnerable to the effects of stress.
They found heart patients with the genetic change had a 38% increased risk of heart attack or death from heart disease after seven years of follow up compared with those without, even after taking into account factors like age, obesity and smoking.
This suggests that stress management techniques and drug therapies could reduce deaths and disability from heart attacks, they say.
Dr Redford Williams, director of the Behavioural Medicine Research Center at Duke University School of Medicine, said the work is the first step towards finding genetic variants that identify people at higher risk of cardiovascular disease.
“This is one step towards the day when we will be able to identify people on the basis of this genotype who are at higher risk of developing heart disease in the first place,” he told BBC News.
“That’s a step in the direction of personalised medicine for cardiovascular disease.”
Identifying people with the genetic change could lead to early interventions for heart patients who are at high risk of dying or having a heart attack, say the researchers.
About one in 10 of men and 3% of women in the group of 6,000 heart patients studied had the genetic change associated with handling emotional stress badly.
Commenting on the study, Prof Jeremy Pearson, associate medical director at the British Heart Foundation, said the results provided further evidence that stress may directly increase heart disease risk.
“By finding a possible mechanism behind this relationship, these researchers have suggested tackling the problem either by changing behaviour or, if needed, with existing medicines,” he said.
“There are positive lifestyle changes you can make to help you cope with stress. A balanced diet and regular physical activity will help you feel better able to cope with life’s demands.
“If you often feel anxious and you’re worried about your stress levels, make an appointment to talk it through with your doctor.”