Sudden cardiac death: recognising hidden risk among women versus men

Despite improvements in prevention and therapy of coronary artery disease, the burden of sudden cardiac death (SCD) remains high, as SCD accounts for up to 20% of all natural deaths in Europe. Hence, there is a continued need for improved strategies to identify those individuals at risk of sudden cardiac arrest (SCA) and SCD. Sudden death is defined as a nontraumatic, unexpected fatal event occurring within 1 hour of onset of symptoms in an apparently healthy subject (or, if unwitnessed, when the victim was in good health 24 hours before the event). According to the 2015 European Society of Cardiology guidelines, the term SCD is used either when a potentially fatal cardiac condition was known to be present during life, autopsy revealed a cardiac or vascular anomaly as the probable cause of the event, or no obvious extracardiac causes were identified by postmortem examination. Based on various prospective studies, the incidence of SCD is estimated to be around 50–150 per 100 000 personyears, but variability between cohorts exists due to differences in available (clinical) information and criteria used. To accommodate these variations, the SCD definition may be refined by subcategorising it into definite, probable or possible SCD depending on a number of criteria, as indicated in figure 1. Hence, accurate assessment of SCD incidence not only relies on the availability of autopsy findings and clinical information, but also on the presence of an immediate witness to the SCD event or a ‘remote witness’ (who witnessed the victim <24 hours before the SCD was discovered). Significant differences exist between men and women in SCD incidence, underlying cardiac pathology, as well as rhythm disturbances and symptoms preceding SCD, indicating a potential need for sexdependent risk stratification and prevention strategies. Skjelbred et al investigated this issue in more detail by examining incidence rates, clinical characteristics, comorbidities and autopsy findings between male and female SCD victims across all ages in a nationwide Danish study. The results show that, overall, SCD was especially more frequent in men in young and middleaged age groups, whereas the difference between sex was less apparent in older age groups. Using information from the Danish National Patient Registry, which contains International Classification of Diseases codes from all inpatient and outpatient hospital admissions, emergency departments and consults, the authors established that male SCD victims more often had a history of cardiovascular disease and diabetes compared with female SCD victims. Another strength of the study lies within the requirement of death certificates (containing information on circumstances preceding SCD and medical history) and a forensic autopsy in cases with an unknown or uncertain manner of death. Interestingly, the distribution between definite, probable and possible SCD (defined as indicated in figure 1) was significantly different between men and women. To meet the criteria for definite SCD, victims were either autopsied or had a documented ventricular arrhythmia preceding death. A significantly greater number of men were autopsied or externally examined by a public health officer, which is explained by the fact that male SCD victims were younger and therefore more likely to be thoroughly examined postmortem. Clearly, biological differences exist between men and women which significantly impact on cardiac pathologies and consequently arrhythmia mechanism and SCD risk. Overall, the majority of men suffering SCD are found to have underlying coronary artery disease; in contrast, autopsies on female SCD victims more often identify underlying nonischaemic heart disease, including dilated cardiomyopathy and valvular heart disease. Moreover, most men present with ventricular fibrillation in the setting of SCA, while women are more likely to have pulseless electrical activity or asystole as the first rhythm during resuscitation. Similarly, Skjelbred et al reported a lower rate of coronary artery disease but a higher frequency of hypertrophy, aortic dissection and myocarditis in women as compared with men (as identified on autopsy). In addition to biological differences, social and environmental factors contribute to sex differences in SCD occurrence and outcome. The definition of probable versus possible SCD is highly dependent on the delay between the actual occurrence of the arrest and the moment when the victim was found. Overall, SCA is less commonly witnessed in women than in men, because women suffer SCA less often in public places and they live alone more often, having outlived their spouses as a result of their longer life expectancy. Indeed, Skjelbred and colleagues reported that female SCD victims died more often at home compared with men, while male SCD victims died at the hospital more often than women. Nevertheless, even if SCA is witnessed in women, they are less likely to be resuscitated by bystanders than men and the delay to resuscitation is longer than in men. This may be partly explained by the fact that women more frequently experience ‘nonclassical’ symptoms of, for example, coronary artery disease. As a result, neither she nor her immediate surroundings (family, friends and colleagues, but also her general practitioner) may be aware of the fact that she may have an underlying cardiac condition, and hence an SCA may not be immediately recognised in the event of a collapse. Even if resuscitation attempts are made, women have lower survival rates, partly due to the fact that they present less often with a shockable initial rhythm, either due to differences in underlying aetiology (see above) or consequent to a longer delay before resuscitation was initiated. Hence, increasing awareness of these issues among healthcare professionals, patients and the general public