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Burden of sudden death in young adults: A one-year observational study at a tertiary care centre in India
For correspondence: Dr Sudheer Arava, Department of Pathology, All India Institute of Medical Sciences, New Delhi 110 029, India e-mail: aravaaiims@gmail.com
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Received: ,
Accepted: ,
Abstract
Background & objectives
Sudden death, defined as death occurring within one hour of symptom onset in witnessed cases or within 24 h of last being seen alive in unwitnessed cases, remains a major public health concern. This study aimed to evaluate the incidence, causes, and risk factors associated with sudden death in young adults.
Methods
A cross-sectional study was conducted over one year at a tertiary care centre in New Delhi. Cases meeting the definition of sudden death were included, excluding trauma, suicide, homicide, and drug abuse. Each case underwent whole-body imaging, autopsy, and histopathological examination. A multidisciplinary team comprising forensic experts, pathologists, radiologists, and clinicians determined the cause of death. Comparative analysis was performed between sudden death in young adults (18–45 yr) and older adults (46–65 yr).
Results
Out of 2214 autopsies, 180 cases (8.1%) met the criteria for sudden death. Sudden death in young accounted for 103 (57.2%) cases. Mean age was 33.6 yr in sudden death in young (IQR=10) and 53.8 years in sudden death in old, with male predominance in both. Cardiovascular causes were most common in young (n=40, 42.6%), followed by respiratory causes (n=20, 21.3%) and sudden unexplained deaths (n=20, 21.3%), where no pathology was identified. Other causes included gastrointestinal, central nervous system, and genitourinary pathologies. Smoking and alcohol intake was equally prevalent in those who died young and at old age.
Interpretation & conclusions
Sudden death in young adults is a significant concern requiring targeted public health strategies. Coronary artery disease remains the leading cause. Respiratory and unexplained deaths warrant further investigation.
Keywords
Arrhythmic deaths
coronary artery disease
sudden cardiac death
sudden death in young
unexplained deaths/negative autopsy
Sudden death (SD) is defined as ‘a death that occurs within one hour of onset of symptoms in witnessed cases and/or within 24 h of last being seen alive in unwitnessed cases’1,2. It is one of the major public health concerns noted amongst all age groups, gender, socio-economic strata and ethnic categories. Despite major advancements in health care, sudden death remains a significant public health burden with substantial mortality. Commonly, sudden deaths are noted in the extremes of age groups- infants and elderly; however, sudden death is relatively rare among individuals under 45 years of age, with an estimated global incidence ranging from 0.8 to 6.2 per 100,000 persons per year3,4. It is often the first manifestation of the underlying disease in a previously asymptomatic and apparently healthy individual.
Presently, the incidence of sudden death in young appears to be increasingly seen as a public health concern with a broad spectrum of diseases involving cardiac (accounting for two thirds) and non-cardiac (accounting for one-third) causes3,4. The aetiology of sudden death in young adults differs substantially from that in the elderly, with a higher prevalence of arrhythmogenic disorders, structural cardiomyopathies and congenital anomalies. Hence, it is of paramount importance to identify the various causes and etiological factors leading to sudden death for future health programmes and prevention strategies.
Methodical examination, conventional autopsy, post-mortem imaging and histopathology, is mandatory to identify the probable cause of death. Despite thorough investigation, approximately one-third of cases remain unexplained and are classified as ‘sudden unexplained deaths (SUDs)’2,3. Incorporation of post-mortem genetic study (molecular autopsy) has proven to be an efficient diagnostic tool in these cases.
Recent studies indicate that many cases of sudden death in young are not autopsied due to administrative constraints and limited awareness among medical and legal authorities. Current knowledge regarding the actual incidence, various causes and risk factors in sudden death, is limited and uncertain in India. This study aims to investigate the spectrum of causes underlying sudden death in young adults.
Materials & Methods
This cross-sectional study was conducted at department of Pathology and Forensic medicine, All India Institute of Medical Sciences, New Delhi, India, from May 2023 to April 2024. All procedures followed were in accordance with the Helsinki Declaration of 1975, as revised in 2000 and carried out after the approval and guidelines of the Institute Ethics Committee.
All sudden death cases brought to the forensic mortuary, meeting the definition criteria of sudden death, were included in this study. Accidents, poisoning, history of drug abuse, homicide, suicide and cases with prior severe medical illness were excluded from this study. The cases were categorized according to their age group as sudden death in young (18-45 yr) and sudden death in old (46-65 yr).
Verbal autopsy, which involved interaction with the close relatives and friends of the deceased regarding the circumstances of the death, previous medical history including COVID disease and vaccination, drug abuse, smoking and alcohol habits, were noted in a standard proforma with proper informed consent. All the autopsies were conducted within 48 h of death.
A virtual autopsy was done using a whole-body 16-slice multislice spiral computed tomography (MSCT) scanner (Toshiba America Medical Systems, IncAquilion Lightning TSX-035A CT). CT scan was cross-verified by a radiologist trained in post-mortem CT. The conventional autopsy was subsequently carried out by standard ‘I’ shaped incision. Gross examination and dissection of all the internal organs, including the brain was carried out according to the standard prescribed protocol. The cardiac dissection included dissection of the coronary arteries, heart valves and all the chambers.
Histopathology
Representative tissue sections from all the internal organs, and from the grossly abnormal areas were taken and processed overnight in the automated histokinetic processor. 4-5-micron thin sections were cut from the paraffin blocks and stained with routine haematoxylin and eosin stain (H&E) for the microscopic evaluation. Relevant special histochemical and immunohistochemical stains were performed wherever necessary for the final diagnosis.
Finally, all these cases were collectively evaluated by a multidisciplinary team, including clinicians, for the conclusion of the final diagnosis.
Statistics
Statistical analysis was performed using STATA 64 (StataCorp LP, Texas, USA). The tests included chi- square and Fishers exact test for categorical variables and independent t-test for continuous variables. P<0.05 was considered as significant.
Results
A total of 2214 cases were received at forensic mortuary during the study period, in which cases meeting the criteria of sudden death were 180 (8.1%). Among the total sudden deaths, sudden death in young (18-45 yr) accounted for 57.2 per cent (n=103) and sudden death in old (46-65 yr) accounted for 42.8 per cent (n=77). The incidence of sudden death in young people among the total autopsied cases accounted for 4.7 per cent. The study cohort included 94 cases of sudden death in young and 68 cases of sudden death in old; the rest (n=18) were excluded due to extensive autolytic changes.
The mean age of young cases was 33.6 yr (IQR=10) with a male-to-female ratio of 4.5:1. Most common age group observed was in the fourth decade (46.8%, n=44), followed by the third decade (31.9%, n=30) and the early fifth (17%, n=16). The mean age in older individuals was 53.8 yr (IQR=8), with a male-to-female ratio of 16:1 (Table I).
| Parameter | Sudden death in young (19-45 y) (n=94); n (%) | Sudden death in old (46-65 yr) (n=68); n (%) | P value |
|---|---|---|---|
| Age (Mean±SD) yr | 33.6 (6.87) | 53.8 (5.06) | - |
| Sex (M:F) | 77:17 | 64:4 | 0.031 |
| Diabetes | 3 (3.2) | 8 (11.8) | 0.035 |
| Hypertension | 5 (5.3) | 13 (19.1) | 0.006 |
| Family history of sudden death | 14 (14.9) | 14 (20.6) | 0.344 |
| History of COVID illness | 4 (4.3) | 6 (8.8) | 0.323 |
| History of vaccination against COVID | 77/ 93 (82.8) | 56/ 64 (87.5) | 0.421 |
| Smoking | 54 (57.4) | 45 (66.2) | 0.261 |
| Alcohol intake | 49 (52.1) | 44 (64.7) | 0.110 |
About 71.6 per cent of the total sudden death cases (n=116) were residents of Delhi and NCR region, while others belonged to neighbouring States of Haryana and Punjab. About 80.2 per cent (n=130) belonged to the lower and middle socioeconomic class according to the modified Kuppuswamy scale5. The population practiced varied jobs constituted by skilled (n=48, 29.6%), unskilled (n=48, 29.6%), semi- or professional jobs (n=33, 20.4%) and 20.4 per cent (n=33) were unemployed. 38.9 per cent of the informants (n=63) for verbal autopsy were siblings, followed by the children of the deceased (n=36, 22.2%).
Among the 54 (57.4%) smokers in sudden death in young, 75.9 per cent (n=41) were regular smokers, while 24.1 per cent (n=13) were occasional smokers having less than three cigarettes a week. In the older cohort, 66.2 per cent (n=45) were smokers, of which 84.4 per cent (n=38) were regular smokers and rest 15.6 per cent (n=7) were occasional smokers. Among those who consumed alcohol (n=49, 52.1% of young and n=44, 64.7% of old), 71.4 per cent (n=35) and 59.1 per cent (n=26) were regular alcoholics in young and old cases, respectively; the rest were occasional alcohol drinkers.
Sudden death cases spanned across all seasons –20.9 per cent (n=34) in summer (May to July), 32.1 per cent (n=52) in autumn (August to October), 27.8 per cent (n=45) in winter (November to January) and 19.1 per cent (n=31) in spring (February to April). About 40.1 per cent of the patients (n=65) had died at night or early morning, 30.2 per cent in the morning (n=49) and rest during the afternoon. Thursday and Wednesday (mid-week) accounted for the maximum number of deaths. About 55 per cent (n=89) had died at their home, 30.2 per cent (n=49) during travelling and 14.8 per cent (n=24) at their workplace/outside. The common history reported by the informants was a sudden loss of consciousness in both cohorts (n=58, 35.8%). Rest complained of uneasiness (n=13, 8%), shortness of breath (n=17, 10.5%), chest pain (n=33, 20.4%), gastrointestinal symptoms like abdominal pain and vomiting (n=31, 19.1%) and fever (n=10, 6.2%). In the young, few had prior history of comorbidities- diabetes mellitus (n=3, 3.2%), hypertension (n=5, 5.3%), tuberculosis (n=1, 1.1%) and epilepsy (n=1, 1.1.%). Among the older group, a higher proportion had history of comorbidities including diabetes mellitus (n=8, 11.8%), hypertension (n=13, 19.1%), tuberculosis (n=1, 1.5%) and asthma (n=1, 1.5%). Three older individuals had history of joint replacement/ cataract surgery.
Documented history of prior COVID illness was present in four and six cases in young and old, respectively. Most of the patients had received COVID vaccination- 82.8 per cent (n=77 of 93) and 87.5 per cent (n=56 of 64).
Sudden death in young
Cardiovascular system-related causes constituted the most common cause of death in young, followed by respiratory-related causes. Sudden unexplained deaths (negative autopsy) in which detailed gross and microscopic examination of all the organs did not reveal any significant pathology was observed in 21.3 per cent (n=20). Gastrointestinal, central nervous system and genitourinary-related causes constituted the remaining (Table II, Figure).
| Major system involved | Cause based on histopathology evaluation, n (%) | Mean age (yr) | M:F |
|---|---|---|---|
| Cardiovascular system | 40 (42.6) | 35.6 | 7:1 |
| Myocardial infarction/CAD | 34 (85) | 36.3 | 5.8:1 |
|
Structural causes – Hypertrophic cardiomyopathy |
2 (5) | 28.5 | Both males |
|
Congenital – Deep myocardial bridging with tiny microscopic infarcts (1), & – Severe calcific bicuspid aortic valve with left ventricular hypertrophy (1) |
2 (5) | 35.5 | Both males |
|
Infective/inflammatory – Infective endocarditis (large vegetations with multifocal septic emboli & bronchopneumonia) (1) – Myocarditis (multifocal, patchy) (1) |
2 (5) | 30 | Both males |
| Pulmonary system | 20 (21.3) | 33 | 5.66:1 |
| Asphyxia due to aspiration | 10 (50) | 32 | 9:1 |
| Pneumonia | 6 (30) | 34 | 5:1 |
| Disseminated TB | 3 (15) | 36.3 | All males |
| Pulmonary TB | 1 (5) | 26 | Female |
| Sudden unexplained death or negative autopsy | 20 (21.3) | 30.5 | 3:1 |
| Gastrointestinal system | 6 (6.4) | 34.7 | All males |
| Acute haemorrhagic pancreatitis (all chronic alcoholics) | 4 (66.7) | 31.3 | All males |
| Intestinal TB with perforation | 1 (16.7) | 38 | Male |
| Upper GI bleed due to varices leading to haemorrhagic shock | 1 (16.7) | 45 | Male |
| CNS causes | 3 (3.2) | 34.3 | All males |
| Intracranial haemorrhage & its complications | 2 (66.7) | 33 | Both males |
| Intracranial epidermal inclusion cyst at suprasellar location | 1 (33.3) | 37 | Male |
| Genito-urinary causes | 4 (4.3) | 31.0 | All females |
| Ruptured tubal ectopic leading to hemorrhagic shock | 2 (50) | 29.5 | Both females |
| Uterine rupture | 1 (25) | 30 | Female |
| Disseminated ovarian malignancy with peritoneal haemorrhage | 1(25) | 35 | Female |
| Miscellaneous | 1 (1.1) | 36 | Male |
| – Haemorrhagic shock due to splenic rupture |
- (A) Large friable tricuspid valve vegetation’s in a case of Infective endocarditis. (B) Case of HCM revealing asymmetrical hypertrophy of the interventricular septum (IVS) and left ventricular (LV) free wall. (C) Left ventricular wall showing features of chronic myocardial infarction with complete blockage of left coronary artery (inset). (D) A case of intestinal tuberculosis showing gangrenous bowel segment with perforation (arrow). (E) Cardiac section showing large area of replacement fibrosis in a case of chronic myocardial infarction (2X, HE). (F) Microscopic sections from HCM revealing myocyte disarray, hypertrophy and interstitial fibrosis (20X, HE). (G) Section of left coronary artery showing critical luminal occlusion (more than 75% blockage) due to atherosclerosis (2X, HE). (H) Sections from lung parenchyma showing large areas of caseous necrosis with epithelioid cell granulomas in a case of tuberculosis (4X, HE).
Cardiovascular system (CVS)
Atherosclerotic coronary artery disease (CAD) causing myocardial ischemia and infarction was the predominant finding, accounting for 85 per cent of the total CVS cases (n=34). In CAD, critical luminal occlusion of more than 70 per cent was considered as the cause of death. The left anterior descending (LAD) was the commonest artery involved, followed by the right coronary artery (RCA). Male preponderance was noted in all age groups, with the incidence of CAD increasing with an increase in age. The fourth and early fifth decades were the most commonly affected age group (n=25, 73.5%), followed by the third decade (n=9, 26.5%). The mean age for CAD was 36.3 yr. Histopathological examination from the affected areas showed evidence of acute ischemic change (n=16, 47.1%), chronic ischemic change with replacement fibrosis (n=7, 20.6%) and acute on chronic ischemia (n=9, 26.5%) in the myocardium. Ischemic damage was comparatively extensive and patchy, involving a larger myocardial area commonly observed in the left ventricular free wall and apex. Acute plaque changes, including plaque erosion with intraluminal thrombus, intra-plaque haemorrhage and plaque rupture, constituted few cases (5.9%, n=2). Amongst the young CAD individuals with myocardial infarction, chronic smokers constituted 58.8 per cent (n=20), chronic alcoholics constituted 44.1 per cent (n=15), and both alcoholics and smokers were 29.4 per cent (n=10).
The mean age of structural heart-related deaths like HCM was observed to be a decade lesser than that of CAD-related deaths in young.
Respiratory system (RS)
It is the second most common cause of death in young. All asphyxia-related deaths were found to be chronic alcoholics. Pneumonia constituted both severe multifocal and multilobar bronchopneumonia and lobar pneumonia. In miliary tuberculosis, multiple necrotising epithelioid cell granulomas were observed in all the internal organs. In pulmonary TB, extensive active necrotising granulomas were noted in the lung parenchyma.
Sudden unexplained deaths (SUDs-negative autopsy)
The fourth decade was the commonest (n=10, 50%) among SUDs, followed by 3rd decade (n=8, 40%) with a mean age of 30.5 yr. Nearly half of these cases on histopathological examination revealed non-specific findings like hypertrophy, uncomplicated atheromatous plaque, and tiny ischemic focus in the myocardium, which could not have been responsible as the direct cause of death.
Sudden death in older adults (n=68, 42.8%)
CAD is the single most common cause of sudden death in older individuals (46-65 yr), constituting 72.1 per cent (49), followed by SUDs (14.1%), gastrointestinal (7.4%) and pulmonary causes (4. 4%). In GIT, sub-massive hepatic necrosis due to heavy alcohol drinking was the most common, followed by necrotising pancreatitis and haemorrhagic shock due to oesophageal varices. In RS, two showed severe pneumonia, and one case was of disseminated TB. A single case of intracranial haemorrhage was observed in CNS (Table III).
| Major system involved % cause based on histopathology evaluation | Sudden death in young (n=94), % (n) | Sudden death in old (n=68), % (n) |
|---|---|---|
| Cardiovascular system | 42.6 (40) | 72.1 (49) |
| Pulmonary system | 21.3 (20) | 4.4 (3) |
| Sudden unexplained death or negative autopsy | 21.3 (20) | 14.1 (10) |
| Gastrointestinal system | 6.4 (6) | 7.4 (5) |
| CNS causes | 3.2 (3) | 1.5 (1) |
| Genito-urinary causes | 4.3 (4) | Nil |
| Miscellaneous | 1.1 (1) | Nil |
Sudden death in young cases had a significantly higher proportion of females (P=0.031). Comorbidities such as diabetes (P=0.035) and hypertension (P=0.006) were significantly more prevalent in the sudden death in old group. No significant differences were observed regarding COVID-related history or vaccination status.
Discussion
In the present observation, sudden death in young individuals accounted for 4.7 per cent of all autopsies carried out during the study period, highlighting the significant unexpected fatalities in this group. A male preponderance and a mean age of 33.6 yr were consistent with the previous studies6,7. Cardiovascular-related causes, particularly atherosclerotic CAD with histopathological evidence of myocardial ischemia, emerged as the leading observation, affirming the growing burden of premature CAD in young individuals8-10. Structural and congenital-related CVS causes were the next most common in the CVS category, emphasising the need for early recognition of the underlying cardiac pathology in young patients. Interestingly, respiratory-related causes and negative autopsy constituted the second most common category in both young and old sudden deaths. Incidence of CAD-related causes was proportionately higher in old adults when compared to the young deaths. The present study did not find any significant correlation between COVID-related history or vaccination status11.
According to Jha et al12, more than 75 per cent of India’s 9.5 million annual deaths occur at home, the majority of which have no clearly defined cause-and-effect findings that parallel our observations. Individuals belonging to lower socioeconomic strata have been reported to have 30-80 per cent greater risk of sudden death and are more likely to have CAD risk factors, in addition to psychosocial issues, poverty and addictions, also observed in our case group13,14. Seasonal variation in mortality, though minimal in our cohort, may be attributed to geographical and environmental differences reported worldwide6,15.
The increasing burden of non-communicable diseases (NCDs) in young people emphasises the ongoing global epidemiological transition11,16,17. In the present study, cardiovascular abnormalities accounted for the majority of the deaths, with a significant rise in the incidence of CAD. The higher incidence of young CAD-related deaths observed in the present study is particularly concerning and remains under documented in the Indian context. A study from Kerala also reported a substantial burden of CAD-related mortality in the younger population, which may be attributed to changes in work-life, stress, and dietary habits18. In older individuals, CAD is still the single most common cause of sudden death all over the world. Pneumonia and disseminated tuberculosis were the leading respiratory related causes. Despite numerous advancements in diagnostics and therapeutics of tuberculosis, it still remains the common cause of mortality in developing countries, emphasising the persistent gap between disease control efforts and ground-level outcomes15,19.
Most published studies on sudden death have focused mainly on sudden cardiac death (SCD) and neglected the non-cardiac causes of death, which are equally significant and important in understanding the complete spectrum of sudden death7,20-22. This is a worrying but unrecognised public health concern which can be prevented with proper incorporation of health education and screening programmes. Furthermore, conduction of post-mortem genetic studies in unexplained cases of sudden death could help to uncover inherited cardiomyopathies and arrhythmogenic disorders, enabling cascade screening of close family relatives and implementation of preventive interventions to reduce premature mortality in at-risk families.
Our study highlighted a small amount of regional data on various etiological factors. Similar multicentric studies across different regions in India will provide the true incidence of etiological factors relating to sudden death in young. Though histopathology is still the gold standard, in the era of molecular diagnostics, it is imperative to understand the sudden deaths at the molecular level, especially in cases of negative autopsy.
A comprehensive multidisciplinary approach that integrates verbal autopsy, post-mortem radiology, histopathological examination, and genetic testing holds the potential to establish a definitive cause of death in the majority of cases23. Incorporation of such investigative modalities into routine forensic and clinical workflows would not only enhance diagnostic accuracy but also contribute valuable data toward national mortality surveillance and the prevention of avoidable deaths.
Acknowledgment
Authors acknowledge the following experts for evaluating all the cases in this study: Goel A (Directorate General of Health Services, New Delhi), Chauhan H (National Centre for Diseases, New Delhi), Agarwal A (Post Graduate Institute of Medical Education and Research, Chandigarh), Kakkar N (Post Graduate Institute of Medical Education and Research, Chandigarh), Chowdhury D (GB Pant Hospital, New Delhi), Pradhan G (Maulana Azad Medical college, New Delhi) and Sandhu MS (Post Graduate Institute of Medical Education and Research, Chandigarh). Authors also acknowledge all the technical staff for their cooperation and support for carrying out this project.
Financial support & sponsorship
The study received funding support by the Indian Council of Medical Research (project code I-1540; 55/4/1/TF-Sudden Deaths/203-NCD-II).
Conflicts of Interest
None.
Use of Artificial Intelligence (AI)-Assisted Technology for manuscript preparation
The authors confirm that there was no use of AI-assisted technology for assisting in the writing of the manuscript and no images were manipulated using AI.
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