Doctors know many lifestyle factors that increase the risk of sudden cardiac arrest. Nevertheless, many people at high risk live long without problems, whereas others die young. Researchers believe that genetic differences are the reason. Now a major research project with Danish participation has been the first to show a genetic link. The aim is to identify who are in acute danger based on their genes.
Sudden cardiac arrest is a brutal form of death because it suddenly takes people away from their family and friends. Sudden cardiac arrest accounts for 10% of all deaths among people 1–35 years old. Since lifestyle alone cannot explain these deaths among either young or old people, researchers have searched for a genetic link for decades. One of the largest genome-wide association studies so far on sudden cardiac arrest has now been published.
“The results show a genetic link between sudden cardiac arrest and such factors as blood pressure, height, body mass index, diabetes, atrial fibrillation and electrocardiographic changes. Not one but many gene variants combined with lifestyle factors make the difference. Now that we have shown the link, more focused genetic studies can clearly provide important answers that can help us to identify and treat people who are in danger of dying from sudden cardiac arrest,” explains one of the authors of the study, Jacob Tfelt-Hansen, Cardiologist and Professor at the Heart Centre of Rigshospitalet in Copenhagen.
Identifying the genetic fingerprint
The researchers examined the genomes of 3939 people who had died from a sudden heart attack in Europe and the United States. By comparing the genomes of these people with those of 26,000 other people, the researchers tried to find the most common gene variants – especially among the genes suspected of causing arrhythmia. In addition, the researchers tried to find genetic links between the genes associated with known risk factors.
“We had naturally hoped that one or two genes would be prominent among people who had died from a heart attack in relation to the others. However, we had not really expected the evidence we found: that complicated interaction between many gene variants makes the difference.”
The researchers confirmed the association between sudden cardiac arrest and a complicated genetic situation through a genome-wide association study in which they compared the genes associated with known physical risk factors among people who experienced sudden cardiac arrest.
A combination of high blood pressure, high cholesterol, high weight, diabetes, atrial fibrillation and arteriosclerosis significantly increases the risk, and the research therefore showed clear associations between sudden cardiac arrest and these factors, so there really is a genetic fingerprint. The task now is to make this even clearer so we can identify the most important genetic risk factors.
Reasons differ between young and old people
Although the new study is the largest genetic analysis of sudden cardiac arrest so far, the researchers say that there is still room for improvement and more knowledge to be obtained on the links between genes and sudden cardiac arrest.
“This study is actually a meta-analysis of nine existing sequencing studies, and the problem is that the people are from very different cohorts. The younger and older people are pooled together, and what causes sudden cardiac arrest among 80-year-olds naturally differs greatly versus 10-year-olds. We will also get much clearer results if we can carry out much more focused studies.”
The researchers believe that a serious genetic disorder often causes sudden cardiac arrest among young people, whereas many risk factors are involved for older people. Keeping the data separate is therefore important. Unfortunately, the researchers had to combine the data in the current study anyway to ensure enough data to obtain statistically significant results.
So many factors interact in assessing the risk of sudden cardiac arrest. Improving risk assessment and prevention therefore requires more knowledge on the most important factors. Major genetic studies of both young and old people are thus very important. Ultimately, this knowledge will not only provide a better roadmap for identifying the most vulnerable people but also will help us to discover new treatment pathways.
“A comprehensive evaluation of the genetic architecture of sudden cardiac arrest” has been published in European Heart Journal. In 2014, the Novo Nordisk Foundation awarded a grant to Jacob Tfelt-Hansen for the project Risk Factors for Sudden Cardiac Death During Acute Myocardial Infarction (MI-RISK).