Coronary Artery Disease as the Cause of Sudden

Cardiac Death Among Victims < 50 Years of Age

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 prev-
alence 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 vic-
tims. 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. © 2021 The Authors. Pub-
lished by Elsevier Inc. This is an open access article under the CC BY-NC-ND license
(http://creativecommons.org/licenses/by-nc-nd/4.0/) (Am J Cardiol 2021;147:33−38)

Coronary artery disease (CAD) is the leading cause of information is needed in order to develop effective risk pre-
sudden cardiac death (SCD),1 resulting from either acute diction strategies and prevent unexpected CAD related
coronary syndrome or fatal arrhythmias due to myocardial SCD. In this autopsy-based, observational study, our aim
fibrosis and/or scarring. Among young, nonischemic struc- was to determine the characteristics of ischemic SCD
tural diseases and arrhythmia disorders are more prevalent.2 among young and middle-aged victims under the age of
While CAD is prevalent in older population, the magnitude 50 years. Furthermore, we evaluated the proportion of CAD
of CAD as cause for SCD in younger subjects has also been related SCD in different age groups, as well as studied the
acknowledged.3,4 Nevertheless, there are very little data on different prevalence of CAD-related SCD during the last
CAD in young populations since it is uncommon in these 20 years. In Finland, all unexpected deaths undergo medi-
age groups. Compared with other causes of SCD in young colegal autopsy based on Finnish law, which has made it
population, CAD offers opportunities for effective preven- possible to gather the unique and large Fingesture SCD
tion strategies. Since the burden of CAD related SCDs cohort.
among young adults has remained unchanged, more

a
Research Unit of Internal Medicine, Medical Research Center Oulu, Methods
University of Oulu and Oulu University Hospital, Oulu, Finland; bForensic
Medicine Unit, Finnish Institute for Health and Welfare, Oulu, Finland; The study population was obtained from the Fingesture
c
Department of Forensic Medicine, Research Unit of Internal Medicine, study (The Finnish Genetic Study of Arrhythmic Events),
Medical Research Center Oulu, University of Oulu, Oulu, Finland; and which consists of 5,869 autopsy-verified SCD victims from
d
Biocenter Oulu, University of Oulu, Oulu, Finland. Manuscript received Northern Finland. Medico-legal autopsies were performed
November 25, 2020; revised manuscript received and accepted February 2, between the years 1998 and 2017 at the Department of
2021. Forensic Medicine of the National Institute of Health and
Sources of Funding: Aarne Koskelo Foundation, Finnish Foundation for
Cardiovascular Research, the Finnish Medical Foundation, Instrumentarium
Welfare and University of Oulu by experienced forensic
Science Foundation, The Maud Kuistila Memorial Foundation, The Ida Mon- pathologists, each performing more than 100 autopsies a
tin Foundation, The University of Oulu Scholarship Foundation, Sigrid Juse- year, using contemporary guidelines for the diagnosis of
lius Foundation cause of death. Medico-legal autopsies are mandatory in
*Corresponding author: Tel: (35) 840-653-7530. Finland, when the death is not due to known disease, when
E-mail address: [email protected] (J. V€ah€atalo). the victim was not treated by a physician during his and/or

0002-9149/© 2021 The Authors. Published by Elsevier Inc. This is an open access article under the CC BY-NC-ND www.ajconline.org
license (http://creativecommons.org/licenses/by-nc-nd/4.0/)
https://doi.org/10.1016/j.amjcard.2021.02.012
34 The American Journal of Cardiology (www.ajconline.org)

her last illness, or when death has been otherwise unex- autopsies, thorough cardiac investigations were performed
pected (Act on the Inquest into the Cause of Death, 459 of in all victims including macroscopic investigation and dis-
1973, 7th paragraph: Finnish Law). The autopsy rates in section of myocardium and coronary arteries, heart weight
Finland are the highest in Western societies.5,6 Sudden measurement, and several histological samples were
death was defined as witnessed death within 6 hours of the obtained and analyzed. Classification of SCD as ischemic
onset of symptoms or an unwitnessed death within 24 hours was based on evidence of an acute coronary complication,
when the victim was last seen in a stable state of health. defined as an acute intracoronary thrombus, plaque rupture
The Fingesture study included only sudden deaths deter- or erosion, intraplaque hemorrhage or critical stenosis
mined to be caused by a cardiac disease. Victims with evi- (>75%) in major coronary artery or chronic atherosclerotic
dence of noncardiac cause, such as cerebral hemorrhage, lesions with healed scar or fibrosis. Left ventricular hyper-
pulmonary embolism as well as intoxications and other trophy (LVH) was defined at autopsy by a heart weight >
nonnatural causes were excluded from the study. The infor- the predicted value based on body surface area (at least 420
mation on the SCD victims was gathered from autopsy g) with hypertrophic myocytes. More detailed methods for
reports, available medical reports, police reports and spe- the classification of cause of death and diagnostic criteria
cific questionnaires for the relatives of the victim. have been reported earlier.7
The study complies with the Declaration of Helsinki and
was approved by the Ethics Committee of the University of
Results
Oulu and Finland’s Ministry of Social Affairs and Health.
National Supervisory Authority for Welfare and Health Among all SCD victims, a total of 610 victims (10.4%)
(Valvira) and National Institute for Health and Welfare were aged < 50 years in the Fingesture study. Of these vic-
approved the review of autopsy data by the investigators. tims 86.4% (n = 527) were male. CAD was the most com-
Causes of sudden death were determined by forensic mon cause of SCD among the victims under 50 years of age
pathologists in medicolegal investigations, which were (266 victims, 43.6%), followed by cardiomyopathy related
based on police reports, available medical records, autopsy to obesity (102 victims, 16.7%), alcoholic cardiomyopathy
findings, and complementary analyses. Medicolegal autop- (67 victims, 11.0%) and primary myocardial fibrosis (63
sies were performed according to standard protocols and a victims, 10.3%). Distribution of the causes of SCD among
specialized pathologist was consulted if necessary. Causes victims under 50 years of age are presented in Figure 1.
of death were reported according to the International Classi- Most ischemic SCDs occurred among victims
fication of Diseases, Tenth Revision code classifications between 45-50 years of age (n = 151, 56.8%) and fewer
(ICD-10). Histologic examination was part of all autopsies. number among victims under 30 years of age (n = 2, 0.8%)
Toxicology investigation, including ethanol, drugs and (Figure 2). Starting from the age of 35 years, CAD was the
medications, such as psychotropics, for example, was per- most common single cause of SCD and after the age 40,
formed if autopsy findings were insufficient to define a CAD accounted for nearly half (47.1% to 49.8%) of all
cause of death or if a toxic exposure was suspected. At SCDs. The proportion of CAD-related SCDs among the

Figure 1. Distribution of the causes of sudden cardiac death in victims aged under 50 years between years 1998-2017 in Northern Finland. SCD = sudden car-
diac death; CM = cardiomyopathy; DCM = dilated cardiomyopathy; HCM = hypertrophic cardiomyopathy; ARVC; arrhythmogenic right ventricular cardio-
myopathy.
 Coronary Artery Disease/Coronary Artery Disease & Sudden Death 35

Figure 2. The proportions of ischemic sudden cardiac deaths (SCDs) to other cause of SCDs among victims under 50 years old.

victims under 50 years of age decreased during past 20 years 44.4% of the victims (118 victims). In total, 71 victims
from about 50 % to 35 % (Figure3). (28.2%) had a single-vessel disease, determined by occlu-
The demographics and clinical characteristics of the sion of a single epicardial coronary artery. The most
ischemic SCD victims aged under 50 years are presented in commonly affected major coronary artery was left ante-
Table 1. The mean age of the study victims was 44.2 § rior descending artery in 90.1% of the victims. The coro-
4.5 years and 89.5% (238 victims) of the victims were nary artery status between different age groups is
males. In 90.2% (n = 231), CAD had not been diagnosed presented in Figure 4. More than 75% stenosis measured
prior to SCD. Over a half of the victims (64.7%, 172 vic- in the cross-sectional area was detected in 56.8% of the
tims) had ≥ 1 cardiovascular risk factor (diabetes mellitus, study victims (151 victims). Myocardial scar was
hypertension, dyslipidemia, smoking, or obesity [consid- detected in 38.7% of all victims and in 33.8% of victims
ered as body mass index ≥ 30 kg/m2]). One fourth (26.8%) without history of CAD indicating a prior silent myocar-
of victims (71 victims) were known to a have history of dial infarction (MI). Fibrosis of the myocardium was
abundant use of alcohol and 84 out of 110 victims (76.4%) present in 82.6% of the victims with varying magnitude.
had a history of smoking. Over a third (38 out of 110 vic- Alcohol in blood or urine was detected in 32.1% of the
tims, 34.5%) were known to have a family history of SCD. victims of whom toxicology investigation was performed
One-fourth of victims (24.1%, 64 victims) SCD occurred (212 victims, 79.7%).
during physical activity.
The autopsy findings of the study victims are shown in
Table 2. The mean body mass index of the study victims Discussion
was 27.5 § 5.4 kg/m2, 66 victims were obese (24.8%). The In the present study consisting of all autopsy-verified
mean total heart weight of the study victims (454 § 117 SCD victims in Northern Finland during the years 1998-
g) was beyond normal heart weight (<420 g) and over 2017, we investigated the burden of CAD-related SCDs
half of the victims had LVH (58.3%, 155 victims). CAD among victims aged under 50 years. Of the total of 5,869
affecting all 3 main coronary arteries was present in SCD victims from the Fingesture study, we found 610

Figure 3. Temporal trends in the prevalence of ischemic sudden cardiac deaths (SCDs) among victims under the age of 50 years during 1998 to 2017.
36 The American Journal of Cardiology (www.ajconline.org)

Table 1 Table 2
Clinical characteristics of ischemic sudden cardiac death in victims under Autopsy findings of ischemic SCD victims under 50 years old
50 years of age Characteristic n=266
Characteristic (n=266) BMI (kg/m2) 27.5 § 5.4
Age (years) 44 .2 § 4.5 ≥30 66 (24.8%)
Men 238 (89.5%) Heart weight (g) 453.5 g § 117.0
Prior LVH 155 (58.3%)
Coronary artery disease 25/256 (9.8%) Myocardial scar 103 (38.7%)
Acute myocardial infarction 16/258 (6.2%) Prior silent myocardial infarction 78/231 (33.8%)
Hypertension 60/254 (23.6%) Degree of myocardial fibrosis n=265
Diabetes mellitus 49/255 (19.2%) Substantial 24 (9.1%)
Dyslipidemia 31/255 (12.2%) Patchy, moderate 109 (41.1%)
Angina pectoris 25/255 (9.8%) Patchy, mild 86 (32.5%)
Dyspnea 9/255 (3.5%) None 46 (17.4%)
Heavy alcohol ingestion 71/265 (26.8%) Blood/urine ethanol concentration >0% 68/212 (32.1%)
Smoker 84/110 (76.4%) Significant occlusion of coronary artery 151 (56.8%)
≥1 CVD risk factor 172 (64.7%) (reduction in the cross-sectional area >75%)
(DM, hypertension, dyslipidemia, obesity, smoker) Number of coronary arteries narrowed
Family history of SCD 38/110 (34.5%) 3 118 (44.4%)
Conditions of death 2 73 (27.4%)
During physical activity 64 (24.1%) 1 71 (28.2%)
In hospital, health center, or ambulance 22 (8.3%) LAD 64 (90.1%)
Outdoors 49 (18.4%) CX 1 (1.4%)
Time of death n=186 RCA 6 (8.5%)
12 AM−6 AM 33 (17.7%)
Values are expressed as mean § SD or number of victims (percent).
6 AM−12 PM 49 (26.3%) BMI = body mass index; LVH = left ventricular hypertrophy; LAD = left
12 PM−6 PM 68 (36.6%) anterior descending; CX = Circumflex; RCA = right coronary artery.
6 PM−12 AM 36 (19.4%)
Values are expressed as mean § SD or number of victims (percent).
CVD = cardiovascular disease; DM = diabetes mellitus, SCD = sudden car- aged population. Similar trend has also previously been
diac death, obesity = body mass index ≥30 kg/m2. observed in overall SCD population.10 The decrease in the
SCD caused by CAD may be due to improved primary pre-
vention strategies, such as lifestyle changes and statin ther-
victims under the age of 50 years. As seen in previous stud- apy, during the past decades.
ies on SCDs among young victims,8,9 CAD was the most SCD is more often the first manifestation of the underly-
common cause of SCD in the present study (266 victims, ing heart disease, especially in CAD1,11 and among younger
44%) and at least to our knowledge, this study provides victims,12 which was also seen in our study. It is noteworthy
the largest autopsy population of young and middle-aged that most ischemic SCDs among young and middle-aged
ischemic SCD victims so far. victims occurred without a previously diagnosed CAD
The proportion of ischemic SCDs increased regularly (90.2%). As expected, ischemic SCD victims aged under
with increasing age-groups, being lowest in victims under 50 years were mostly men, even more commonly than in
30 years (7.1%) and highest among victims aged from 45 to the previous study among Danish CAD-SCD victims (90%
50 years (49.8%). Over a period of 20 years, the proportion vs76%).13 Among women, SCD and coronary heart disease
of ischemic SCDs compared with other causes has occur at significantly older age and SCD is more often
decreased in our SCD cohort among young and middle- caused by non-ischemic heart diseases.14

Figure 4. The number of affected coronary arteries between different age groups among ischemic sudden cardiac death victims under 50 years of age.
 Coronary Artery Disease/Coronary Artery Disease & Sudden Death 37

At least one cardiovascular risk factor was present in an old myocardial scar was found in approximately one-
over half of the victims (64.7%), emphasizing the impor- third of the victims without a known CAD, indicating a
tance of early screening and cardiovascular preventive previous, unrecognized MI. In our previous study,26 silent
measures also in the young population. Similar observations MIs in SCD victims were associated with male gender,
have been made in sudden cardiac arrest (SCA) victims LVH and sudden death during exercise. Patients with
aged under 35 years.15 Since CAD comprises a great deal unrecognized MI may have even worse prognosis than
of SCDs among the young and is a preventable disease, pre- those with recognized MI27,28 and a prior MI has been
vention strategies should focus on lowering cardiovascular shown to predict a significantly higher mortality in young
risk factors also in the younger populations. Smoking is adults.29
one of the most important risk factors for both CAD and It is generally accepted that the disease process of CAD
SCD.16,17 Significant proportion, about 1/3 of the study begins already in adolescence at the latest. However, these
victims were known to been smokers. In addition to con- autopsy findings suggest that CAD may be highly advanced
tributing to the development of atherosclerosis in long- even at young age, a notion that enhances the need for early
term use, smoking has acute effects on endothelial func- recognition of coronary disease among young. Since CAD
tion and thrombosis formation.16 Along with established is primarily a disease of older population, it is not as well
cardiovascular risk factors, about one-third of the victims characterized in young subjects. The long-term mortality in
had a family history of SCD, which is a well-known risk young adults with CAD has been shown to be even higher
factor for dying suddenly during an acute coronary than in older population,4 which emphasizes the need for
event.18 better detection of CAD in the young to improve the prog-
Approximately one-fourth of study victims were known nosis. Along with previous studies,15 the present study
to have a history of abundant use of alcohol. While alcohol highlights the role of screening cardiovascular risk factors
consumption may have some beneficial influences like at earlier ages. Although the standard 12-lead electrocardio-
increase in blood HDL-cholesterol levels, the protective gram (ECG) is an inexpensive and practical study, its role
effect disappears in heavy drinkers due to increase in blood in detecting CAD is minor. However, ECG could be useful
pressure levels.19,20 Additionally, heavy use of alcohol in detecting prior MIs,26 which were common among our
increases probability of myocardial disease related to alco- study victims and would be crucial to find out because of
hol, which would undoubtedly have additive risk for life- the increased risk for fatal arrhythmias.
threatening arrhythmias during an ischemic event.21 Acute The present study does not prove any causal relation-
alcohol intake may also induce electrical instability in ship between clinical characteristics or autopsy findings
ischemic heart disease and increase the risk of arrhythmias and SCD, since the design of our study was descriptive.
and SCD.19 About one-third of the victims also had alcohol The history of previously diagnosed CAD, cardiovascular
detected in their blood or urine sample in post-mortem risk factors and symptoms like angina and dyspnea were
examinations. As noted in the earlier study,19 further studies based on available medical records at the time of postmor-
are needed to investigate the actual role of acute alcohol tem examinations and therefore, the accurate occurrence
intake on SCDs. rate of diagnosed conditions and symptoms may remain
SCDs among athletes, especially among young, have unclear. Also, the information about the family history of
attracted a lot of public attention, even though the incidence SCD and smoking were gathered afterwards via letters for
of SCD in young athletes is very low.22 In this study, we the closest family members of the victims. Unfortunately,
observed a higher proportion of ischemic SCDs during we did not receive response letters from all relatives, and,
physical activity, compared with the previous study for example, the length of the past smoking status was not
(24% vs 12%).13 However, this is not surprising consider- specified.
ing the characteristics and autopsy findings of our study vic- In conclusion, CAD was the most common underlying
tims. Young and middle-aged ischemic SCD victims were cause of SCD among victims under 50 years of age in our
mostly men and autopsy findings like LVH and myocardial autopsy population. Substantial amount of ischemic SCDs
scarring were common, all of which have been associated among young and middle-aged victims occurred without
with SCD during physical activity.23 previously diagnosed CAD and still, many victims had
Despite the young age of our study victims, substantial advanced underlying heart disease and a previously unde-
amount of young and middle-aged ischemic SCD victims tected MI at autopsy.
had significant CAD at autopsy. Three-vessel CAD was
detected in nearly half of the victims and myocardial fibro-
Authors Contributions
sis (82.6% of the victims) and hypertrophied hearts (58.3%
of the victims) were common findings among the study vic- Study design and conception: Juhani Junttila, Heikki
tims. The prevalence of three-vessel disease was surpris- Huikuri, Juha Perki€om€aki. Acquisition, analysis or inter-
ingly high in comparison with the previous observations pretation of data: Juha V€ah€atalo, Lauri Holmstr€om, Lasse
(44% vs 21%), as well as the prevalence of cardiac hyper- Pakanen, Kari Kaikkonen, Juha Perki€om€aki, Heikki Hui-
trophy (58% vs 40%).13 Both three-vessel CAD and cardiac kuri, Juhani Junttila. Drafting of the manuscript: Juha
hypertrophy independently increase the risk of fatal V€ah€atalo & Juhani Junttila. Statistical analysis: Juha
arrhythmias.24 Myocardial fibrosis is a common finding in V€ah€atalo & Lauri Holmstr€om. Critical revision of the
most myocardial diseases, affecting both the contractibility manuscript for important intellectual content: Lauri
of cardiac muscle and electrical conductive system and is Holmstr€om, Lasse Pakanen, Kari Kaikkonen, Juha Per-
associated with prior cardiovascular events.25 In addition, ki€om€aki, Heikki Huikuri, Juhani Junttila. Obtained
38 The American Journal of Cardiology (www.ajconline.org)

funding: Juha V€ah€atalo & Juhani Junttila. Supervision: 14. Haukilahti MAE, Holmstrom L, Vahatalo J, Kentta T, Tikkanen J,
Juhani Junttila & Heikki Huikuri Pakanen L, Kortelainen ML, Perkiomaki J, Huikuri H, Myerburg RJ,
Junttila MJ. Sudden cardiac death in women. Circulation
2019;139:1012–1021.
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