Coronary Artery Disease as the Cause of Sudden Cardiac Death Among Victims < 50 Years of Age

Abstract

•Sudden cardiac death is often caused by coronary artery disease among young adults.•Among young, sudden death is typically the first manifestation of the heart disease.•Advanced underlying heart disease is a common finding at autopsy in young victims.•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 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),1Myerburg RJ Junttila MJ Sudden cardiac death caused by coronary heart disease.Circulation. 2012; 125: 1043-1052Crossref PubMed Scopus (283) Google Scholar 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.2Bagnall RD Weintraub RG Ingles J Duflou J Yeates L Lam L Davis AM Thompson T Connell V Wallace J Naylor C Crawford J Love DR Hallam L White J Lawrence C Lynch M Morgan N James P du Sart D Puranik R Langlois N Vohra J Winship I Atherton J McGaughran J Skinner JR Semsarian C A prospective study of sudden cardiac death among children and young adults.N Engl J Med. 2016; 374: 2441-2452Crossref PubMed Scopus (421) Google Scholar While CAD is prevalent in older population, the magnitude of CAD as cause for SCD in younger subjects has also been acknowledged.3Corrado D Thiene G Pennelli N Sudden death as the first manifestation of coronary artery disease in young people (less than or equal to 35 years).Eur Heart J. 1988; 9: 139-144Crossref PubMed Google Scholar,4Rubin JB Borden WB Coronary heart disease in young adults.Curr Atheroscler Rep. 2012; 14: 140-149Crossref PubMed Scopus (67) Google Scholar 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. 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.5Saukko P Medicolegal investigative system and sudden death in Scandinavia.Nihon Hoigaku Zasshi. 1995; 49: 458-465PubMed Google Scholar,6Lahti RA From findings to statistics: An assessment of finnish medical cause-of-death information in relation to underlying-cause coding.2005Google Scholar 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.7Hookana E Junttila MJ Puurunen VP Tikkanen JT Kaikkonen KS Kortelainen ML Myerburg RJ Huikuri HV Causes of nonischemic sudden cardiac death in the current era.Heart Rhythm. 2011; 8: 1570-1575Abstract Full Text Full Text PDF PubMed Scopus (93) Google Scholar 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).Figure 3Temporal trends in the prevalence of ischemic sudden cardiac deaths (SCDs) among victims under the age of 50 years during 1998 to 2017.View Large Image Figure ViewerDownload Hi-res image Download (PPT) 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/m2]). 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.Table 1Clinical characteristics of ischemic sudden cardiac death in victims under 50 years of ageCharacteristic(n=266)Age (years)44 .2 ± 4.5Men238 (89.5%)Prior Coronary artery disease25/256 (9.8%) Acute myocardial infarction16/258 (6.2%) Hypertension60/254 (23.6%) Diabetes mellitus49/255 (19.2%) Dyslipidemia31/255 (12.2%) Angina pectoris25/255 (9.8%) Dyspnea9/255 (3.5%) Heavy alcohol ingestion71/265 (26.8%) Smoker84/110 (76.4%) ≥1 CVD risk factor(DM, hypertension, dyslipidemia, obesity, smoker)172 (64.7%)Family history of SCD38/110 (34.5%)Conditions of death During physical activity64 (24.1%) In hospital, health center, or ambulance22 (8.3%) Outdoors49 (18.4%)Time of deathn=186 12 AM–6 AM33 (17.7%) 6 AM–12 PM49 (26.3%) 12 PM–6 PM68 (36.6%) 6 PM–12 AM36 (19.4%)Values are expressed as mean ± SD or number of victims (percent). CVD = cardiovascular disease; DM = diabetes mellitus, SCD = sudden cardiac death, obesity = body mass index ≥30 kg/m2. Open table in a new tab Values are expressed as mean ± SD or number of victims (percent). CVD = cardiovascular disease; DM = diabetes mellitus, SCD = sudden cardiac death, obesity = body mass index ≥30 kg/m2. The autopsy findings of the study victims are shown in Table 2. The mean body mass index of the study victims was 27.5 ± 5.4 kg/m2, 66 victims were obese (24.8%). The mean total heart weight of the study victims (454 ± 117 g) was beyond normal heart weight (<420 g) and over half of the victims had LVH (58.3%, 155 victims). CAD affecting all 3 main coronary arteries was present in 44.4% of the victims (118 victims). In total, 71 victims (28.2%) had a single-vessel disease, determined by occlusion of a single epicardial coronary artery. The most commonly affected major coronary artery was left anterior descending artery in 90.1% of the victims. The coronary artery status between different age groups is presented in Figure 4. More than 75% stenosis measured in the cross-sectional area was detected in 56.8% of the study victims (151 victims). Myocardial scar was detected in 38.7% of all victims and in 33.8% of victims without history of CAD indicating a prior silent myocardial infarction (MI). Fibrosis of the myocardium was present in 82.6% of the victims with varying magnitude. Alcohol in blood or urine was detected in 32.1% of the victims of whom toxicology investigation was performed (212 victims, 79.7%).Table 2Autopsy findings of ischemic SCD victims under 50 years oldCharacteristicn=266BMI (kg/m2)27.5 ± 5.4 ≥3066 (24.8%)Heart weight (g)453.5 ± silent myocardial of myocardial occlusion of coronary artery in the cross-sectional area of coronary arteries (28.2%) are expressed as mean ± SD or number of victims (percent). = body mass LVH = left ventricular = left anterior = = coronary artery. Open table in a new tab Values are expressed as mean ± SD or number of victims (percent). = body mass LVH = left ventricular = left anterior = = coronary artery. In the present study consisting of all autopsy-verified SCD victims in Northern Finland during the years we the burden of CAD-related SCDs among victims aged under 50 years. Of the total of 5,869 SCD victims from the Fingesture study, we 610 victims under the age of 50 years. seen in on SCDs among young R J of sudden cardiac death in aged 1 to study in PubMed Scopus Google D J L A M R in sudden death from coronary artery disease in young Heart J. 2011; PubMed Scopus Google Scholar CAD was the most common cause of SCD in the present study (266 victims, and at least to our this study the autopsy population of young and middle-aged ischemic SCD victims The proportion of ischemic SCDs with in victims under 30 years and highest among victims aged from to 50 years Over a of 20 years, the proportion of ischemic SCDs with other causes has decreased in our SCD among young and middle-aged has also been in SCD MJ E Kaikkonen KS Kortelainen ML Myerburg RJ Huikuri HV trends in the clinical and characteristics of victims of sudden cardiac death in the of heart 2016; PubMed Scopus Google Scholar The in the SCD caused by CAD be due to primary prevention such as and during the past SCD is more often the first manifestation of the underlying heart disease, in RJ Junttila MJ Sudden cardiac death caused by coronary heart disease.Circulation. 2012; 125: 1043-1052Crossref PubMed Scopus (283) Google Huikuri HV M Myerburg RJ ML J for sudden cardiac current status and for the Heart J. PubMed Scopus Google Scholar and among younger of sudden cardiac death in children and young PubMed Scopus Google Scholar which was also seen in our study. is most ischemic SCDs among young and middle-aged victims occurred without a diagnosed CAD ischemic SCD victims aged under 50 years were more commonly than in the study among victims R C J J Sudden cardiac death and coronary disease in the a study in J Full Text Full Text PDF PubMed Scopus Google Scholar Among SCD and coronary heart disease at older age and SCD is more often caused by heart L J T Tikkanen J L Kortelainen ML J Huikuri Myerburg RJ Junttila MJ Sudden cardiac death in PubMed Scopus Google Scholar At least cardiovascular risk factor was present in over half of the victims the of and cardiovascular also in the young have been made in sudden cardiac victims aged under 35 R A C J factors of sudden cardiac death in the PubMed Scopus Google Scholar Since CAD a of SCDs among the young and is a disease, prevention strategies on cardiovascular risk factors also in the younger is of the most risk factors for CAD and N J MJ MJ M G E J smoking, and risk of 3 major atherosclerotic PubMed Scopus Google D T E and the risk of sudden cardiac a review and of prospective J PubMed Scopus Google Scholar about of the study victims were known to been In to to the of in has acute on and N J MJ MJ M G E J smoking, and risk of 3 major atherosclerotic PubMed Scopus Google Scholar with cardiovascular risk about of the victims had a family history of which is a risk factor for during an acute coronary KS Kortelainen M E Huikuri HV and the risk of sudden cardiac death as a manifestation of an acute coronary PubMed Scopus Google Scholar of study victims were known to have a history of abundant use of While alcohol have in blood the in due to in blood J E Kaikkonen Junttila J Kortelainen ML Huikuri alcohol in victims of sudden cardiac death in 2016; PubMed Scopus Google M P G JB J D A V G P N Alcohol and cardiovascular risk in a population with mean alcohol J Full Text Full Text PDF PubMed Scopus Google Scholar use of alcohol increases of myocardial disease related to which have risk for arrhythmias during an ischemic A C L M C A A G is known and is not J Med. Full Text Full Text PDF PubMed Scopus Google Scholar Acute alcohol also in ischemic heart disease and the risk of arrhythmias and J E Kaikkonen Junttila J Kortelainen ML Huikuri alcohol in victims of sudden cardiac death in 2016; PubMed Scopus Google Scholar of the victims also had alcohol detected in blood or urine in in the J E Kaikkonen Junttila J Kortelainen ML Huikuri alcohol in victims of sudden cardiac death in 2016; PubMed Scopus Google Scholar are needed to the of acute alcohol on SCDs. SCDs among among young, have a of the of SCD in young is very C M Sudden cardiac death in Med. PubMed Scopus Google Scholar In this study, we a proportion of ischemic SCDs during physical with the study R C J J Sudden cardiac death and coronary disease in the a study in J Full Text Full Text PDF PubMed Scopus Google Scholar this is not the characteristics and autopsy findings of our study victims. and middle-aged ischemic SCD victims were men and autopsy findings LVH and myocardial were all of which have been with SCD during physical T E Junttila J Kaikkonen Tikkanen J J Kortelainen ML Huikuri HV Sudden cardiac death during physical of victims and autopsy Med. PubMed Scopus Google Scholar the young age of our study victims, of young and middle-aged ischemic SCD victims had CAD at autopsy. Three-vessel CAD was detected in nearly half of the victims and myocardial fibrosis of the victims) and of the victims) were common findings among the study victims. The prevalence of disease was in with the as well as the prevalence of cardiac hypertrophy R C J J Sudden cardiac death and coronary disease in the a study in J Full Text Full Text PDF PubMed Scopus Google Scholar CAD and cardiac hypertrophy the risk of fatal KS Kortelainen ML Huikuri HV of risk between and victims of sudden cardiac death from an acute coronary Med. PubMed Scopus Google Scholar Myocardial fibrosis is a common finding in most myocardial affecting the of cardiac and system and is with prior cardiovascular of myocardial fibrosis and cardiovascular the study of Heart J PubMed Scopus Google Scholar In an myocardial scar was in of the victims without a known CAD, indicating a In our Huikuri HV L Kaikkonen KS Tikkanen J Myerburg RJ Junttila MJ of silent myocardial infarction and sudden cardiac PubMed Scopus Google Scholar silent in SCD victims were with LVH and sudden death during with have than with and for clinical of myocardial J Full Text Full Text PDF PubMed Scopus Google Davis of myocardial scar detected by cardiac on in with or symptoms of coronary artery disease.Circulation. PubMed Scopus Google Scholar and a prior has been shown to a in young Weintraub of coronary artery disease in young PubMed Scopus Google Scholar is the disease of CAD in at the these autopsy findings CAD be at young age, a the for of coronary disease among Since CAD is a disease of older population, it is not as well in young The in young adults with CAD has been shown to be than in older JB Borden WB Coronary heart disease in young adults.Curr Atheroscler Rep. 2012; 14: 140-149Crossref PubMed Scopus (67) Google Scholar which the for of CAD in the young to the with R A C J factors of sudden cardiac death in the PubMed Scopus Google Scholar the present study the of cardiovascular risk factors at the standard is an and study, in CAD is be in prior Huikuri HV L Kaikkonen KS Tikkanen J Myerburg RJ Junttila MJ of silent myocardial infarction and sudden cardiac PubMed Scopus Google Scholar which were common among our study victims and be to out of the risk for fatal The present study not between clinical characteristics or autopsy findings and since the of our study was The history of diagnosed CAD, cardiovascular risk factors and symptoms and were based on available medical at the of examinations and the of diagnosed conditions and symptoms the information about the family history of SCD and were gathered for the closest family members of the victims. we not from all for example, the of the past status was not In conclusion, CAD was the most common underlying cause of SCD among victims under 50 years of age in our autopsy of ischemic SCDs among young and middle-aged victims occurred without diagnosed CAD and many victims had underlying heart disease and a at autopsy. Study and or of of the of the for Junttila Huikuri The have no known or have to the reported in this

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