Sudden cardiac death: a nationwide cohort study among the young

Sudden cardiac death (SCD) is a tragic event affecting millions of individuals worldwide. Although several studies have investigated the epidemiology of SCD, these studies may have been affected by reporting and referral biases, which are reflected in the very different incidence rates and causes of deaths that have previously been reported. Among SCD victims aged < 36 years, inherited cardiac diseases are well known to play an important role. However, the extent to which inherited cardiac diseases also play a role in SCD victims aged < 50 years has not been completely described. Additionally, SCD in children is of particular interest. These deaths are often described as a part of the deaths of young adolescents up to 40 years of age, and the focus has recently shifted towards the prevention of these deaths. The SCD incidence rate among patients with psychiatric disease has also gained significant attention. Finally, the incidence rate of sports-related sudden cardiac death (SrSCD) has been thoroughly investigated in young competitive athletes. However, whether competitive athletes are at increased risk for SrSCD compared with non-competitive athletes remains unknown. These data should be available prior to discussing optimal screening strategies for (competitive) athletes. In this thesis, we investigated the SCD burden in Danes aged 1-49 years between 2007 and 2009. By using the unique Danish death certificates, autopsy reports, discharge summaries, and registries, we included all deaths in a nationwide setting. We described the incidence rates and causes of death, and we performed a sub-group analysis of SCD in children (1-18 years, 2000-2006). Furthermore, we described the SCD burden in competitive and non-competitive athletes and investigated how often SCD occurred in patients with previous psychiatric disease. SCD has an incidence rate of 8.6 (95% confidence interval (CI) 8.0-9.2) per 100,000 person-years in persons aged 1-49 years. We found a steep increase in the incidence rate with increasing age, reaching 38.5 (95% CI 32.9-44.7) per 100,000 person-years in persons aged 48-49 years. The most common causes of death were coronary artery disease (CAD) (n = 158) and sudden unexplained death (SUD) (n = 136). In the 1-35-year age group, SUD was significantly more common than CAD. In contrast, CAD was significantly more common than SUD in the 36-49-year age group. In children 1-18 years of age, SCD is a seemingly rare occurrence with an incidence rate of only 1.1 (95% CI 0.9-1.3) deaths per 100,000 person-years. Similarly to the 1-35-year age group, SUD is often the cause of death in children. Overall, 49% of all SCDs in children are caused by a potentially inherited cardiac disease, emphasizing the need for autopsy as well as for follow-up and genetic testing of the affected family members. In Denmark, SrSCD is a very rare occurrence. The SrSCD incidence rate increases with increasing age but remains much lower than the SCD incidence rate in the general population. Importantly, we found no differences in the incidence rate between competitive and non-competitive athletes aged 12-35 years (incidence rate ratio 1.1; 95% CI 0.2-5.1, p = 0.88) and 36-49 years (incidence rate ratio 2.2; 95% CI 0.9-5.1, p = 0.06). These results add important knowledge to the ongoing debate regarding whether mandatory screening programs with electrocardiograms should be recommended for young competitive athletes, as suggested by the European Society of Cardiology. The current results suggest that screening only competitive athletes would be ethically questionable because non-competitive athletes are at the same risk for SrSCD. Patients with psychiatric disease are known to have an increased cardiovascular risk. For the first time, we describe the nationwide SCD incidence rates of SCD as well as the causes of death in patients with previous psychiatric disease. We reported an SCD incidence rate ratio of 4.3 (95% CI 3.3-5.5: p < 0.01) in patients with previous psychiatric disease compared with patients without psychiatric disease. The higher incidence rate is largely driven by schizophrenia-spectrum and substance-related disorders. Interestingly, SUD is more common among patients with psychiatric diseases, suggesting that many of these deaths are triggered by medications that caused a primary arrhythmic event. Future research should investigate the extent to which CAD among individuals younger than 50 years of age is caused by inherited cardiac conditions such as familial hypercholesterolemia. The extent to which medication use prior to death may contribute to SCD and SUD should also be evaluated. Finally, with the availability of dried blood spot samples from all infants in Denmark, future research should also investigate the genetic substrate of SCD and SUD.