Highlights
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Sudden cardiac death is often caused by coronary artery disease among young adults.
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Among young, sudden death is typically the first manifestation of the heart disease.
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Advanced underlying heart disease is a common finding at autopsy in young victims.
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Special attention needs be paid to cardiovascular risk factors among young people.
Coronary artery disease (CAD) is the most common cause of sudden cardiac death (SCD). Atherosclerosis increases with age, but also many victims of SCD in young and middle-aged population have CAD at autopsy. The purpose of this study was to determine the characteristics and autopsy findings of SCD due to CAD among victims of SCD under the age of 50. Fingesture is a population-based study consisting of consecutive series of victims of autopsy verified SCD in Northern Finland between the years 1998 to 2017 (n = 5,869). Histological examinations were part of all autopsies and a toxicology investigation was performed if needed. Analyses included information accumulated from death certificates, medical records, autopsy data, standardized questionnaire to the closest family members of the victims of SCD and police reports of the conditions of the death. Overall, 10.4% of all SCDs occurred among victims under the age of 50 years (610 victims). Most common underlying cause of SCD among these younger SCD victims was CAD (43.6%). The prevalence of CAD as the cause of SCD became more common in young SCD victims after the age of 35 years. The mean age of ischemic SCD victims was 44±5 years and most were men (89.5%). Most victims (90.2%) had no clinical diagnosis of CAD, however 33.8% had an autopsy evidence of silent myocardial infarction. SCD occurred during physical activity in 24.1%. Three-vessel disease was detected in 44.4% of the study victims. Cardiac hypertrophy (58.3%) and myocardial fibrosis (82.6%) were also common. At least 1 cardiovascular risk factor was present in 64.7% of SCD victims. In conclusion, most SCDs among victims < 50 years of age are due to CAD.
Coronary artery disease (CAD) is the leading cause of sudden cardiac death (SCD), resulting from either acute coronary syndrome or fatal arrhythmias due to myocardial fibrosis and/or scarring. Among young, nonischemic structural diseases and arrhythmia disorders are more prevalent. While CAD is prevalent in older population, the magnitude of CAD as cause for SCD in younger subjects has also been acknowledged. , Nevertheless, there are very little data on CAD in young populations since it is uncommon in these age groups. Compared with other causes of SCD in young population, CAD offers opportunities for effective prevention strategies. Since the burden of CAD related SCDs among young adults has remained unchanged, more information is needed in order to develop effective risk prediction strategies and prevent unexpected CAD related SCD. In this autopsy-based, observational study, our aim was to determine the characteristics of ischemic SCD among young and middle-aged victims under the age of 50 years. Furthermore, we evaluated the proportion of CAD related SCD in different age groups, as well as studied the different prevalence of CAD-related SCD during the last 20 years. In Finland, all unexpected deaths undergo medicolegal autopsy based on Finnish law, which has made it possible to gather the unique and large Fingesture SCD cohort.
Methods
The study population was obtained from the Fingesture study (The Finnish Genetic Study of Arrhythmic Events), which consists of 5,869 autopsy-verified SCD victims from Northern Finland. Medico-legal autopsies were performed between the years 1998 and 2017 at the Department of Forensic Medicine of the National Institute of Health and Welfare and University of Oulu by experienced forensic pathologists, each performing more than 100 autopsies a year, using contemporary guidelines for the diagnosis of cause of death. Medico-legal autopsies are mandatory in Finland, when the death is not due to known disease, when the victim was not treated by a physician during his and/or her last illness, or when death has been otherwise unexpected (Act on the Inquest into the Cause of Death, 459 of 1973, 7th paragraph: Finnish Law). The autopsy rates in Finland are the highest in Western societies. , Sudden death was defined as witnessed death within 6 hours of the onset of symptoms or an unwitnessed death within 24 hours when the victim was last seen in a stable state of health. The Fingesture study included only sudden deaths determined to be caused by a cardiac disease. Victims with evidence of noncardiac cause, such as cerebral hemorrhage, pulmonary embolism as well as intoxications and other nonnatural causes were excluded from the study. The information on the SCD victims was gathered from autopsy reports, available medical reports, police reports and specific questionnaires for the relatives of the victim.
The study complies with the Declaration of Helsinki and was approved by the Ethics Committee of the University of Oulu and Finland’s Ministry of Social Affairs and Health. National Supervisory Authority for Welfare and Health (Valvira) and National Institute for Health and Welfare approved the review of autopsy data by the investigators.
Causes of sudden death were determined by forensic pathologists in medicolegal investigations, which were based on police reports, available medical records, autopsy findings, and complementary analyses. Medicolegal autopsies were performed according to standard protocols and a specialized pathologist was consulted if necessary. Causes of death were reported according to the International Classification of Diseases, Tenth Revision code classifications (ICD-10). Histologic examination was part of all autopsies. Toxicology investigation, including ethanol, drugs and medications, such as psychotropics, for example, was performed if autopsy findings were insufficient to define a cause of death or if a toxic exposure was suspected. At autopsies, thorough cardiac investigations were performed in all victims including macroscopic investigation and dissection of myocardium and coronary arteries, heart weight measurement, and several histological samples were obtained and analyzed. Classification of SCD as ischemic was based on evidence of an acute coronary complication, defined as an acute intracoronary thrombus, plaque rupture or erosion, intraplaque hemorrhage or critical stenosis (>75%) in major coronary artery or chronic atherosclerotic lesions with healed scar or fibrosis. Left ventricular hypertrophy (LVH) was defined at autopsy by a heart weight > the predicted value based on body surface area (at least 420 g) with hypertrophic myocytes. More detailed methods for the classification of cause of death and diagnostic criteria have been reported earlier.
Results
Among all SCD victims, a total of 610 victims (10.4%) were aged < 50 years in the Fingesture study. Of these victims 86.4% (n = 527) were male. CAD was the most common cause of SCD among the victims under 50 years of age (266 victims, 43.6%), followed by cardiomyopathy related to obesity (102 victims, 16.7%), alcoholic cardiomyopathy (67 victims, 11.0%) and primary myocardial fibrosis (63 victims, 10.3%). Distribution of the causes of SCD among victims under 50 years of age are presented in Figure 1 .
Most ischemic SCDs occurred among victims between 45-50 years of age (n = 151, 56.8%) and fewer number among victims under 30 years of age (n = 2, 0.8%) ( Figure 2 ). Starting from the age of 35 years, CAD was the most common single cause of SCD and after the age 40, CAD accounted for nearly half (47.1% to 49.8%) of all SCDs. The proportion of CAD-related SCDs among the victims under 50 years of age decreased during past 20 years from about 50 % to 35 % ( Figure3 ).
The demographics and clinical characteristics of the ischemic SCD victims aged under 50 years are presented in Table 1 . The mean age of the study victims was 44.2 ± 4.5 years and 89.5% (238 victims) of the victims were males. In 90.2% (n = 231), CAD had not been diagnosed prior to SCD. Over a half of the victims (64.7%, 172 victims) had ≥ 1 cardiovascular risk factor (diabetes mellitus, hypertension, dyslipidemia, smoking, or obesity [considered as body mass index ≥ 30 kg/m 2 ]). One fourth (26.8%) of victims (71 victims) were known to a have history of abundant use of alcohol and 84 out of 110 victims (76.4%) had a history of smoking. Over a third (38 out of 110 victims, 34.5%) were known to have a family history of SCD. One-fourth of victims (24.1%, 64 victims) SCD occurred during physical activity.
| Characteristic | (n=266) |
| Age (years) | 44 .2 ± 4.5 |
| Men | 238 (89.5%) |
| Prior | |
| Coronary artery disease | 25/256 (9.8%) |
| Acute myocardial infarction | 16/258 (6.2%) |
| Hypertension | 60/254 (23.6%) |
| Diabetes mellitus | 49/255 (19.2%) |
| Dyslipidemia | 31/255 (12.2%) |
| Angina pectoris | 25/255 (9.8%) |
| Dyspnea | 9/255 (3.5%) |
| Heavy alcohol ingestion | 71/265 (26.8%) |
| Smoker | 84/110 (76.4%) |
| ≥1 CVD risk factor (DM, hypertension, dyslipidemia, obesity, smoker) | 172 (64.7%) |
| Family history of SCD | 38/110 (34.5%) |
| Conditions of death | |
| During physical activity | 64 (24.1%) |
| In hospital, health center, or ambulance | 22 (8.3%) |
| Outdoors | 49 (18.4%) |
| Time of death | n=186 |
| 12 AM–6 AM | 33 (17.7%) |
| 6 AM–12 PM | 49 (26.3%) |
| 12 PM–6 PM | 68 (36.6%) |
| 6 PM–12 AM | 36 (19.4%) |
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