Discussion
We have developed an ongoing, population-based case registry of SUD in the adult <65 population over 12 months in a single North Carolina county. At 1 year of assessment of such victims, we find that the majority of such deaths were unwitnessed and occurred in white, unmarried, hypertensive men with an average age of 53 years. In comparison with the general population, women were significantly under-represented, and incidence in African-Americans was higher than expected. Younger women with coronary disease were more likely to die of SUD than men.
Demographics
Our estimate of the incidence of sudden death is 42.4/100 000 among male residents and 22.4/100 000 among female residents between the ages of 18 and 64 years. Only 1.5% of participants were both married and had a witnessed death, and there were significantly fewer married participants compared to all Wake County residents deceased in 2013 (33% vs 44%, p<0.01). This supports the observation that marriage is a protective factor from sudden death.
The association between marriage and sudden death has been described previously, specifically that marriage had beneficial health effects for unemployed women by providing an alternative source of financial resources and social support.13 Within our cohort, African-Americans, especially males, accounted for a higher proportion of the study population over the age of 55 years; whites, especially women, accounted for a higher proportion of the population aged 55 years and under. Different racial make-up of older and younger age groups within our sample suggests that older age as a predictor for sudden death may be modified by race. African-Americans were over-represented in the cohort compared to the living population in Wake County (35% vs 21%), which is partially accounted for by a significant excess of African-American women compared to living Wake County residents (43% vs 23%, p<0.001). Most participants had hypertension, with dyslipidaemia, smoking and BMI >30 kg/m2, and diabetes was also present in more than 30% of the cohort. Cardiomyopathy and CAD were less prevalent than expected.
There was a significant difference in estimated sudden death incidence between men and women in the cohort, but there was no difference in age at death or comorbidities such as hypertension or CAD. The cardioprotective effects of oestrogen may lead to less plaque and coronary disease.14 ,15 However, the average age of men and women was 53, despite the presumed protective effect of oestrogen. The similarity of average age between men and women may be explained by the age of the cohort. The average age at menopause is 51 years, when women lose a substantial amount of oestrogen,11 and the average age of the women in our cohort is 53.
Strength of no timing criteria
Our understanding of the aetiology and risk factors for sudden death is limited compared with other acute cardiovascular events such as myocardial infarction and stroke. Overlapping definitions of sudden death have contributed to variability in reported incidence rates and have impeded the study of sudden death aetiology and risk factors.16 ,17 The WHO's definition of sudden death focuses on sudden cardiac death, sudden cardiac arrest and SUD. Their definition describes sudden death as a witnessed sudden, unexpected death within 1 h of symptom onset or within 24 h of having been observed alive and symptom free.18 Although this definition is broad in defining the circumstances of death, studies that use the full definition, including the time restrictions, are prone to systematic exclusion of many victims. It may be ‘more meaningful to define the specific characteristics surrounding cardiac arrest, and register and collect data in a standardised way, than to try to define the word ‘sudden’ in the context of death’.6 ,18
Previous studies may have underestimated the incidence of SUD by systematic exclusion of people likely to die an unwitnessed death at an unknown time at home. They have also tended to study racially homogeneous cohorts and so have missed, for example, the excess mortality in African-American women we have identified. We found more women dying of sudden death compared to previous studies. This might be explained by differences in case ascertainment and selection methods.19 ,20
Death certificate data inconsistent with medical records
We found frequent and important discrepancies in the death certificates compared to medical records. For example, there were no cases of substance abuse listed on the death certificate. However, toxicology screens were positive in 31% of medical examiner cases. CAD seemed over-represented in older particiapants. Coding inconsistencies are important issues as they can significantly impact estimates of disease incidence and resource allocation.21
In the Framingham Heart Study, 26-year follow-up of men and women aged 35–84 years indicated that CAD morbidity was twice as high in men as in women, and 60% of coronary events occurred in men.22 The onset of symptomatic CAD is typically about 10 years earlier in men, but CAD incidence in women increases rapidly at menopause.22 Analysis by age and coronary disease using medical records and medical examiner data in our cohort shows that women under age 55 years have more coronary disease than men of the same age. Most men with coronary disease were over the age of 55 years. This finding is inconsistent with previous research showing a growing risk of cardiovascular disease in older women.23 This suggests that coronary disease is a risk factor for SUD in younger women. However, the opposite result is seen when using death certificate data. As previously discussed, this may suggest inaccuracy in documentation on death certificates. Sudden death is not just a disease of men but may have great impact on younger women.
Limitations
The overall limitations of SUDDEN have been outlined previously.6 Our methodology created a comprehensive medical database, exemplified by acquisition of hospital or physician medical records on 68% of participants and death certificates for all 190 participants.
We do not include all out-of-hospital victims. We do not include individuals who survived to the hospital or who died in the hospital, institutionalised patients, non-residents of North Carolina, minors and anyone over the age of 65 years. However, survival from sudden death is low and the number of these sudden death cases should be low.
SUDDEN subjects are restricted to under age 65 years, which limits the study of sudden death in postmenopausal women. Given that the focus of our project is to assess preventable SUD, the age restriction may be understandable.