By Mattis Ranthe
Most people regard cardiovascular disease as results of poor lifestyle, and the majority of patients are thought of as older persons. However, over recent decades an increasing pool of genetic findings has implicated that some cardiovascular diseases have a genetic component. The most common, coronary artery diseases, and some less common cardiac conditions, including disturbances in heart rhythm and diseases of the cardiac muscle itself (cardiomyopathies) have a lot of genetic traits associated with them. These genetic cardiac diseases often tend to present at young age and some can lead to early and often sudden death; a worst case scenario is when they present with sudden cardiac death as a first sign. Sudden cardiac death is internationally defined as sudden, unexpected death due to natural unknown or cardiac causes, with an acute change in cardiovascular status within one hour of death or, in unwitnessed cases, in a person last seen functioning normally within 24 hours of being found dead. In young people it is most often caused by undiagnosed heart problems that may be hereditary, indicating that there may be genetic mutations causing the condition. Such an unexpected sudden cardiac death is a dreadful and devastating event, leaving families torn. A question to the family physician is often, “What about the rest of family?”
One cardiovascular condition which can lead to sudden cardiac death is the long QT syndrome, the first genes associated with this syndrome was discovered in the mid 1990s. Several other inherited cardiac conditions can lead to sudden death and in a landmark article in the Lancet in 2003, Elijah Behr and colleagues presented results that indicated a burden of cardiovascular disease in families of victims of sudden unexplained death. In 2013, both cardiologists and pathologists have increasingly focused on the problem, which has led to the discovery of a vast number of genes associated with cardiovascular disease. Today, several US and European cardiac centres have set up units especially focusing on inherited cardiovascular disease. These units focus on early prevention and treatment of the conditions in question to prevent sudden cardiac deaths. But these noble initiatives have, until recently, been based primarily on studies in selected groups of patients, and population bases studies have lacked.
We recently published a significant contribution to this question of risk in those left behind. In nationwide Danish health registers we examined more than 3,000 first- and second-degree relatives of victims of sudden cardiac death. We followed them from 2000 to 2011 and overall we identified 292 cases of cardiovascular disease. The expected number based on rates in the background population was 219, and so we saw a relatively modest relative risk increase of 33%. The study was made possible by combining a previous study were researchers identified 470 victims of sudden cardiac death, aged between 1-35, in Denmark between 2000 and 2006. We identified relatives of these 470 victims and this gave us the first nationwide cohort of relatives of victims of sudden cardiac death ever described in the literature.
An increase in risk of 33% may sound alarming, but as a comparison, cigarette smoking doubles your risk of clotted coronaries, that is 100%, or a 2-fold relative increase in risk. But due to the size of our cohort we were able to examine subgroups in a greater level of detail, and extreme difference in risk revealed itself. If “bad genes” lead to a disease, one should expect that a closer kinship with someone potentially having a genetic disease, should lead to higher risks, and in fact we found that first-degree relatives had an increase in risk of up to 20-fold. What was even more alarming was that the risk was very much dependent on age, such that in relatives of victims of sudden cardiac death aged 60 year or more there were no increase in risk, whereas in the youngest persons under 35 years the risk was increased 6-fold or more. We witnessed a three-fold increased risk of any cardiovascular disease (CVD), a six-fold increased risk of ischaemic heart disease (reduced blood supply to the heart), and a more than 10-fold increased risk of cardiomyopathies (damaged or weakened heart muscle) and ventricular arrhythmias (potentially fatal disturbances in the rhythm of the heartbeat).
From this we can see that sudden cardiac death, or the underlying heart problems, has a large hereditary component. Relatives, particularly young, first-degree relatives, are at much greater risk of developing heart conditions compared with the general population. Family members of young sudden cardiac death victims should be offered comprehensive and systematic screening, with the focus on the youngest and nearest relatives.
Most of the cardiovascular diseases leading to sudden cardiac death are treatable, if diagnosed in time. Our findings reinforce the concept of screening as a rational ‘tool’ to identify such cardiovascular diseases in family members at risk, and thereby possibly prevent future sudden cardiac deaths.
Mattis Flyvholm Ranthe is a medical doctor from Copenhagen, Denmark. He graduated from medical school in 2006 and has a clinical experience from both general practice and clinical cardiology, but has since 2010 undertaken various studies within cardiovascular epidemiology at Department of Epidemiology Research at Statens Serum Institut, Copenhagen. Mattis is handing in his Ph.d. thesis on familial aspects of cardiovascular disease and early cardiovascular death later in 2013, and expects to resume a clinical career along with continued research in cardiovascular epidemiology. The study was presented by Mattis at the European Society of Cardiology Congress 2012 in Münich, where he won the Young Investigator Award in population sciences. His paper, ‘Risk of cardiovascular disease in family members of young sudden cardiac death victims’ was published in the European Heart Journal.
The European Heart Journal is an international, English language, peer-reviewed journal dealing with Cardiovascular Medicine. It is an official Journal of the European Society of Cardiology and is published weekly. The journal aims to publish the highest quality material, both clinical and scientific, on all aspects of Cardiovascular Medicine. It includes articles related to research findings, technical evaluations, and reviews. In addition it provides a forum for the exchange of information on all aspects of Cardiovascular Medicine, including education issues.
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Image credit: The anatomy of the heart. By Tvanbr (Own work) [Public domain], via Wikimedia Commons.