Postmortem examination in the morbidly obese

Eve Fryer,
1
Ian S D Roberts,
1
Mary N Sheppard
2
& Clare Verrill
1,3
1
Department of Cellular Pathology, John Radcliffe Hospital, Oxford,
2
Department of Cellular Histopathology, Royal
Brompton Hospital, London, and
3
Oxford Biomedical Research Centre, John Radcliffe Hospital, Oxford, UK
Date of submission 10 May 2013
Accepted for publication 4 July 2013
Published online Article Accepted 8 July 2013
Fryer E, Roberts I S D, Sheppard M N & Verrill C
(2014) Histopathology 64, 200210
Postmortem examination in the morbidly obese
Aims: The incidence of obesity is rising, and morbid
obesity is associated with increased mortality rates.
Pathologists will therefore encounter increasing
numbers of postmortems in the morbidly obese. It is
essential that pathologists recognize morbid obesity
and can identify its consequences at postmortem. The
aims of this study were to assess how often obesity is
included in the cause of death of morbidly obese
individuals, and whether obesity-related causes of
death are being missed.
Methods and results: The postmortem database of the
John Radcliffe Hospital was searched to identify all
medicolegal postmortems performed on morbidly
obese individuals between January 2007 and Septem-
ber 2012. Of 4742 coronial postmortems performed,
3911 (82%) reports contained a record of height and
weight, allowing body mass index calculation. Two
hundred and two (5.2%) were performed on morbidly
obese individuals. Death resulted from natural causes
in 189 (93.6%), of which obesity was included in the
medical certicate of cause of death in 41 (22%).
Conclusions: Postmortems in the morbidly obese rep-
resent a signicant percentage of the total performed,
but recognition of the contribution of obesity to death
and of obesity-associated conditions is poor. Postmor-
tems performed on the morbidly obese represent a
distinct group with specic causes of death, and
should be approached as such.
Keywords: body mass index, obesity, postmortems
Introduction
In 2010, over one-quarter of the population in Eng-
land was classed as obese; 26.2% of the male popula-
tion and 26.1% of the female population.
1
Obesity is
dened by the WHO as a body mass index (BMI) of
30 kg/m
2
,
2
and morbid obesity refers to a BMI of
40 kg/m
2
. The prevalence of morbid obesity in Eng-
land increased from 0.8% in 1993 to 2.0% in 2008,
3
and is predicted to rise further.
4
In 2004, a House of
Commons select committee estimated that 34 100
deaths were attributable to obesity (6.8% of all deaths
in England) and ~9000 of these were premature
deaths (occurring before state retirement age).
1
Mortality increases with BMI,
5
and increased num-
bers of postmortems are being performed on the mor-
bidly obese.
6,7
In view of the clear association of
obesity with many medical conditions, one would
predict that obesity would frequently feature in the
cause of death issued by pathologists following post-
mortem. This, however, is not the case. In the 2006
National Condential Enquiry into Patient Outcome
and Death (NCEPOD) report into the quality of coro-
nial postmortems, of 15 cases where postmortems
were carried out on morbidly obese individuals, only
four included obesity in the cause of death,
8
and in
only 52% of all reports were both body height and
weight recorded, enabling BMI to be calculated.
9
The
reason for this lack of inclusion is uncertain; it may
reect a lack of knowledge among pathologists
regarding obesity-related causes of death, but also
pathologists may feel reluctant to include obesity on
the death certicate for fear of offending or upsetting
the family of the deceased.
Postmortem examination of the morbidly obese pre-
sents a challenge to pathologists, and not just in terms
Address for correspondence: Dr E Fryer, Department of Cellular
Pathology, Level One, John Radcliffe Hospital, Headley Way,
Headington, Oxford OX3 9DU, UK. e-mail: evefryer@doctors.org.uk
2013 John Wiley & Sons Ltd.
Histopathology 2014, 64, 200210. DOI: 10.1111/his.12224
of the practicalities of handling and dissecting larger
bodies. There are a number of potentially fatal condi-
tions that almost exclusively occur in the obese, such
as obstructive sleep apnoea (OSA), obesityhypoventi-
lation syndrome (OHS; Pickwickian Syndrome),
10
and
obesity cardiomyopathy (OCM). These conditions are
generally poorly understood by pathologists, with
deaths potentially being misattributed to other causes.
In addition, there are a number of medical conditions
for which obesity is a strong risk factor, such as venous
thromboembolic disease (VTED).
11
It is becoming increasingly recognized that being
obese does not just mean being bigger than normal,
but rather that obesity is a condition that has specic
pathophysiological effects. Adipose tissue has an
endocrine role, and secretes adipocytokines that cre-
ate a proinammatory state, which has implications
for the development of conditions including cancer,
atherosclerosis, and thrombosis.
Postmortem studies have shown that missed diagno-
ses are more common in the obese, suggesting that a
larger body habitus impedes the clinical diagnostic pro-
cess.
12
Postmortems in the obese need specic consider-
ation, and guidelines akin to those published by the
Royal College of Pathologists on, for example, deaths in
anaphylaxis are required, but are conspicuously absent.
In this study, we retrospectively audited postmor-
tem reports in the morbidly obese over a 5-year,
9-month period in a UK teaching hospital to determine
postmortem ndings, the frequency of obesity-specic
conditions, and the accuracy of cause of death, with
the aim of providing guidance on how to approach
these challenging deaths.
Materials and methods
The postmortem database of the John Radcliffe Hospi-
tal, Oxford was searched to identify medicolegal post-
mortems performed on the morbidly obese in the
period January 2007 to September 2012. Morbid
obesity was dened by a BMI of 40 kg/m
2
. BMI was
calculated as weight (kilogrammes) divided by the
square of height (metres). Cases in which BMI could
not be calculated were excluded. Data including the
circumstances of death, position of the body, cause of
death and heart weight were recorded.
The Davies category for each cardiac death was
determined. The Davies categories constitute a well-
recognized system for estimating the likelihood of car-
diac pathology present at postmortem causing death
(Table 1).
13
Davies category 3, 4 and 5 deaths, i.e.
those where a cardiac cause is less certain, were
reviewed to assess the evidence for the stated causes
of death, with the aim of identifying deaths that were
likely to have been caused by OSA, OHS or OCM but
were mistakenly attributed to another cause. The his-
tology sections from cases that were suspected to
have been caused by OCM were reviewed by a spe-
cialist cardiac pathologist (M.S.), if there was consent
to use of the tissue for research.
In Oxford, it is standard practice to include the entire
clinical history provided by the Coroners Ofcer in the
autopsy report. In most cases, if pathologists obtain
additional information from the medical notes, this is
also included in the report, and therefore all of the
information should be available in the report for any-
one undertaking a retrospective review.
Table 1. A description of the Davies criteria, which assess the probability of the cardiac pathology present at postmortem
having caused death
13
Davies criteria Description
1 Coronary atheroma and clear evidence of coronary thrombosis and/or acute myocardial infarction
very high probability of causing sudden death
2 Coronary atheroma with at least one coronary artery <1 mm in diameter and evidence of healed
myocardial infarction moderate to high probability of causing sudden death
3 Coronary atheroma with at least one coronary artery <1 mm in diameter, but no evidence of healed
myocardial infarction questionable probability of causing sudden death: depends on the number
of stenoses and circumstances of death
4 No evidence of ischaemic heart disease, but evidence of congestive heart failure or signicant left or
right ventricular hypertrophy and/or dilatation moderate probability of causing sudden death;
cardiomyopathies should be excluded
5 No signicant cardiac pathology/unexplained sudden cardiac death (Sudden Adult Death Syndrome,
SADS) histology and toxicology essential if SADS is to be considered seriously
2013 John Wiley & Sons Ltd, Histopathology, 64, 200210.
Postmortems in the obese 201
Results
During the period January 2007 to September 2012,
4742 coronial postmortems were performed, of which
3911 (82%) contained a record of height and weight,
allowing BMI to be calculated. Of these, 202 (5.2%)
were performed on morbidly obese individuals. Death
resulted from natural causes in 189 (93.6%). The
breakdown of cases by year is shown in Table 2.
Of the 202 morbidly obese individuals, 120 were
female and 82 were male. The mean age was
63 years (range 1888 years). The median BMI was
44.1 kg/m
2
(range 4094.1 kg/m
2
). The heart
weights for cases where death was due to natural
causes were as follows: female, range 142892 g
(mean 527 g, median 510 g); and male, range 352
1699 g (mean 640 g, median 609 g). The heart
weights for the six female unnatural deaths were
260, 312, 386, 438, 485, and 500 g (mean 397 g,
median 412 g). The heart weights for the seven male
unnatural deaths were 333, 405, 573, 624, 627,
648, and 652 g (mean 552 g, median 624 g).
C A U S E O F D E A T H
The stated causes of death for the 202 morbidly obese
individuals are shown in Table 3, and the respiratory
and cardiac deaths are further subdivided in Tables 4
and 5. Table 6 shows the subdivision of the cardiac
deaths into Davies categories.
Table 2. Coronial postmortems performed by year
2007 2008 2009 2010 2011 2012* Total
Total no. of cases 731 742 778 913 771 807 4742
Reports including height and weight 708 642 645 709 690 517 3911
Morbidly obese individuals 42 24 31 30 43 32 202
Death due to natural causes 40 23 29 28 40 29 189
*Nine months only assessed.
Table 3. Summary of stated causes of death, which are also further subdivided into BMI categories 40.044.9, 45.049.9,
and 50.0 kg/m
2
[no. (%)]
40.044.9 kg/m
2
45.049.9 kg/m
2
50.0 kg/m
2
Total
Cardiac disease (for subdivision, see Table 5) 41 (38.3) 29 (62) 16 (33.3) 86 (42.6)
Respiratory disease (for subdivision, see Table 4) 22 (20.6) 7 (14.9) 11 (22.9) 40 (19.8)
Pulmonary embolism 12 (11.2) 4 (8.5) 12 (25.0) 28 (13.9)
Diseases of blood vessels 6 (5.6) 2 (4.3) 2 (4.2) 10 (5.0)
Complications of surgery 6 (5.6) 2 (4.3) 1 (2.1) 9 (4.5)
Diseases of the gastrointestinal tract 3 (2.8) 1 (2.1) 3 (6.3) 7 (3.5)
Accident 4 (3.7) 1 (2.1) 1 (2.1) 6 (3.0)
Drug toxicity/hanging 4 (3.7) 1 (2.1) 1 (2.1) 6 (3.0)
Malignancy 3 (2.8) 0 0 3 (1.5)
Diseases of the liver, pancreas, and biliary tree 3 (2.8) 0 0 3 (1.5)
Intracranial pathology 3 (2.8) 0 0 3 (1.5)
Diseases of the kidneys 0 0 1 (2.1) 1 (0.5)
Total 107 47 48 202
2013 John Wiley & Sons Ltd, Histopathology, 64, 200210.
202 E Fryer et al.
O B E S I T Y I N T H E M E D I C A L C E R T I F I C A T E O F C A U S E
O F D E A T H
Of the 189 deaths resulting from natural causes,
obesity was included in the Medical Certicate of
Cause of Death (MCCD) in 41 (22%).
Obesity was most commonly included in the MCCD
in deaths resulting from ischaemic heart disease (9/
61), venous thromboembolic disease (14/28), respira-
tory disease (4/31), and other cardiac causes (7/21).
O B S T R U C T I V E S L E E P A P N O E A
There were two deaths recorded as resulting from
OSA. The position of the body was recorded in only
one of these cases, the deceased being found on their
back. There was a further death that had been
recorded as congestive cardiac failure resulting from
ischaemic heart disease, but, on review by the
authors, was felt to have been caused by OSA, as
there was a history of OSA and there had been a
problem with a continuous positive airway pressure
(CPAP) mask around the time of death. A summary
of the three OSA deaths is shown in Table 7.
The supine position of the body is pivotal to diag-
nosing OSA at postmortem. Forty of the 202 cases
were found dead in bed, and in only nine of 40 was
the position of the body provided to the pathologist.
O B E S I T Y H Y P O V E N T I L A T I O N S Y N D R O M E
Three cases of OHS were identied (Table 8). In two
cases, OHS was given explicitly as the cause of death
in the MCCD; in the other case, the cause of death
was given as hypertensive heart disease and obesity,
but the possibility of OHS was discussed in the com-
ments. In all three cases the deceased had a history
of shortness of breath; one had a history of obesity-
related hypoventilation and one had a history of
OSA. One patient died during exertion, one was
found dead in bed, and one was found dead on the
bedroom oor. In all three cases, obesity was included
in the MCCD.
O B E S I T Y C A R D I O M Y O P A T H Y
Six possible cases of OCM were identied by reviewing
the Davies criteria 3, 4 and 5 deaths, and these are
summarized in Table 9. One case had been recorded
as OCM, three as dilated cardiomyopathy, and one
as biventricular hypertrophy; a sixth case had the
Table 4. The 40 stated respiratory causes of death in mor-
bidly obese patients
Cause of death Number of cases
Pneumonia 20
Asthma 5
Mechanical airway obstruction 3
Obesityhypoventilation syndrome 2
Obstructive sleep apnoea 2
Pulmonary brosis 2
Mesothelioma 2
Adult respiratory distress syndrome 2
Chronic obstructive pulmonary disease 1
Pneumothorax 1
Table 5. The 86 stated cardiac causes of death in morbidly
obese patients
Cause of death Number of cases
Ischaemic heart disease (no evidence of
acute myocardial infarction)
28
Myocardial infarction 18
Ischaemic and hypertensive heart disease 13
Hypertensive heart disease 8
Dilated cardiomyopathy 3
Valvular disease 3
Congestive cardiac failure, not
otherwise specied (NOS)
2
Ischaemic heart disease and
valvular disease
2
Left ventricular hypertrophy, NOS 2
Biventricular hypertrophy, NOS 1
Cor pulmonale 1
Hypertensive heart disease
and cor pulmonale
1
Cardiac amyloidosis 1
Obesity cardiomyopathy 1
Pericarditis 1
Infective endocarditis 1
Sudden adult death syndrome 0
2013 John Wiley & Sons Ltd, Histopathology, 64, 200210.
Postmortems in the obese 203
immediate cause of death recorded as aortic dissec-
tion, but with dilated cardiomyopathy as a contribu-
tory factor (in part 2 of the MCCD). Two of the six
cases (cases 2 and 4) had no histology for review; all
four cases available for review were felt to represent
OCM after specialist cardiac pathology review.
Case 1
This was a case of sudden death at home after gastric
bypass surgery. The cause of death had been recorded
as OCM, and this was conrmed on review. The heart
weighed 497 g, but it was difcult to be certain
about hypertrophy because of decomposition. There
was extensive fat inltration in the right ventricle on
histology.
Case 3
This patient collapsed and died in the street. The
cause of death had been originally recorded as dilated
cardiomyopathy. There was a slightly heavy heart, at
520 g (the normal adult male heart weighs up to
500 g), with left ventricular concentric hypertrophy
Table 6. The numbers of cardiac deaths in each Davies category
Davies category 2007 2008 2009 2010 2011 2012 Total %
1 7 1 2 1 0 4 15 18
2 3 5 4 4 7 2 25 30
3 2 2 2 4 4 4 18 21
4 4 3 6 4 3 5 25 30
5 0 0 0 0 0 0 0 0
Uncategorizable 0 0 0 1 0 0 1 1
Table 7. A summary of the three deaths resulting from obstructive sleep apnoea (OSA)
BMI Toxicology
Heart
weight (g)
Right ventricular
hypertrophy
History of sleep
apnoea prior
to death Position of body
Cause of death
given as OSA
45.8 Not done 555 Yes Yes In bed, exact
position not given
No
40.3 Negative 635 Yes No In bed on back Yes
42.3 Ethanol level unknown,
morphine 124 lg/l,
nordiazepam
600 Not stated in
postmortem
report
Yes Not given Yes
Table 8. A summary of the main features of the three deaths in which obesityhypoventilation syndrome (OHS) was diag-
nosed
BMI Toxicology
Heart
weight (g)
Right ventricular
hypertrophy
History of OHS
prior to death Position of body Stated COD
51.7 Not done 684 Yes No Collapse in street Acute bronchitis, and OHS and
pulmonary hypertension
43.8 Not done 628 Not known No Dead in bed Hypertensive heart disease and
obesity
43.9 Not done 568 Yes No Floor of bedroom OHS with pulmonary hypertension
and cor pulmonale
2013 John Wiley & Sons Ltd, Histopathology, 64, 200210.
204 E Fryer et al.
with biventricular dilatation. There was only mild ath-
eroma (<50% stenosis). On histological review, there
was extensive fatty inltration involving almost the full
thickness of the right ventricular wall, but just sparing
the trabeculae. There was an increase in collagen
around the trabeculae (normal in the right ventricle),
but no brosis to indicate arrythmogenic right ventric-
ular cardiomyopathy. The left ventricle showed some
subtle trabecular brosis, but was otherwise normal.
There was a history during life of atrial brillation. In
summary, the heart was slightly heavy as a result of
left ventricular hypertrophy, with dilatation and mild
coronary artery disease. In view of the history of atrial
brillation, the most likely mode of death was sudden
cardiac arrhythmia due to an underlying OCM.
Case 5
This patient collapsed in the community and then
suffered in-hospital cardiac arrest. The immediate
cause of death was retroperitoneal haemorrhage sec-
ondary to aortic dissection. The heart weighed 905 g,
and dilated cardiomyopathy had been given in part 2
of the MCCD. Histologically, the right ventricle
showed extensive fatty inltration, extending through
the full thickness of the wall to the trabeculae and
surrounding blood vessels. On review, this case was
felt to be one of OCM rather than dilated cardiomyop-
athy (DCM), because, although the left ventricle wall
was dilated, it had a thickness of 18 mm (thickness
in DCM usually <10 mm). There was a single focus
of signicant coronary artery atherosclerosis, and the
heart disease present was felt to be due to a combina-
tion of ischaemia, hypertension, and OCM.
Case 6
This patient was found deceased at home in bed. The
heart weighed 938 g, and the cause of death was
issued as biventricular hypertrophy. On histology
review, there was fatty inltration in the outer third
of the right ventricle around blood vessels, but no
brosis. The left ventricle showed myocyte hypertro-
phy and subtle areas of brosis, particularly in the
epicardial aspect, and the features were felt to be
those of OCM.
V E N O U S T H R O M B O E M B O L I C D I S E A S E
There were 28 cases of VTED (14.8% of natural
deaths). In 10 cases, the cause of death was given as
VTED alone. Of the 18 cases in which additional fac-
tors were included, obesity was one of those addi-
tional factors in 14. Pulmonary embolism was
proportionately more common in the higher BMI cat-
egory (50.0 kg/m
2
; Table 3).
Discussion
This is the largest published series of postmortem
ndings in the morbidly obese, with 202 deaths being
examined. Despite its undoubted importance in sev-
eral causes of death, obesity is not being consistently
recorded in the MCCD, being included for only 22%
of deaths in this study. The reasons for this may
include a wish to avoid offending or upsetting the
family of the deceased, as well as a lack of knowledge
regarding obesity-related causes of death. Lack of
Table 9. Possible cases of obesity cardiomyopathy (OCM) showing both recorded heart weight, and heart weight (50th
centile) predicted from body weight using recently described tables.
30
Case
Age
(years) Sex BMI
Heart
weight (g)
Predicted heart
weight (g)
(50th centile) Toxicology
Original stated
cause of death
Cause of death following
histology review
1 40 F 54.5 497 450 Negative OCM OCM
2 61 M 44.6 951 490 Not done DCM Histology not performed
3 62 M 41.9 520 480 Negative DCM OCM
4 74 F 41.1 575 440 Not done DCM Slides disposed of
5 62 M 42.6 905 520 Not done DCM (in part
2 of MCCD)
OCM (in part 2 of MCCD)
6 56 M 62.6 938 Off scale Not done Biventricular
hypertrophy
OCM
DCM, dilated cardiomyopathy; MCCD, medical certicate of cause of death.
2013 John Wiley & Sons Ltd, Histopathology, 64, 200210.
Postmortems in the obese 205
awareness of the role of obesity in the cause of death
in many of these cases needs to be addressed with
education, perhaps best achieved by a Royal College
of Pathologists dataset and a national audit of these
deaths. There is a balance to be struck when consid-
ering inclusion of obesity in the MCCD, as it is impor-
tant to remember that many deaths in the morbidly
obese will be unrelated to obesity, and not to over-
state the issue. Obesity should be included in the
cause of death when it has a strong association;
either it directly causes the condition (part 1 of the
MCCD) or it is a well-recognized risk factor for the
condition (part 2 of the MCCD). It should be included
in cases of OSA where it is a direct cause of this con-
dition, and placed in part 1 of the death certicate. In
this study, in the three cases of OSA, obesity was
included in the cause of death (in part 2) in one case
only. In OCM and OHS, obesity is present in the
name of the condition, and is therefore automatically
included in part 1 of the MCCD. Obesity should be
included in part 2 of the MCCD in cases such as pul-
monary embolism where obesity is a risk factor. Obes-
ity is an independent risk factor for coronary heart
disease, and therefore should be included in part 2,
along with conditions such as hypertension and dia-
betes mellitus, although, in actual practice, this may
not happen in every case.
This study evaluated the MCCD only in cases
where there had been a postmortem examination.
Further studies could be undertaken, comparing these
data with those held by the Ofce for National Statis-
tics (ONS) on MCCD in deaths in the morbidly obese
which are based on clinical grounds, with no post-
mortem taking place.
In addition to the conditions described below, obes-
ity is a risk factor for the metabolic syndrome, cere-
brovascular accidents, type 2 diabetes mellitus,
osteoarthritis, hypertension, some malignancies, sur-
gical site infections, nosocomial infections, and skin
infections.
14
O B S T R U C T I V E S L E E P A P N O E A
In this study, OSA was under-recognized, being stated
as the cause of death in two of three cases that were
determined on review to represent OSA. OSA is a
condition characterized by episodes of obstruction of
the upper airway during sleep, interrupting the ow
of air, followed by transient awakening.
15
This results
in chronic alveolar hypoxia, pulmonary artery con-
striction, and pulmonary hypertension, and can
result in cor pulmonale.
16
It is caused by accumula-
tion of fat in the neck region. The condition is sug-
gested by a history including snoring and observed
apnoeas, but denitive diagnosis is made by polysom-
nography during life, and treatment is by CPAP ven-
tilation.
Deaths caused by OSA are a challenge at postmor-
tem, because ndings are often limited and may be
restricted to obesity alone. A history of this condition
during life is therefore of key importance. An unwary
pathologist may mistakenly attribute death to
another condition, such as non-signicant ischaemic
heart disease. Cases without a history of OSA during
life present even more of a problem, although the
diagnosis may be suggested by the circumstances of
the death. These deaths will always occur in bed,
usually in the supine position,
17
and details of the
exact position of the body are vital (this was provided
for only nine of 40 cases found dead in bed in this
study). OSA should also only be given as a cause of
death when all other causes have been excluded,
including by histology and toxicology. Toxicology is
important, because consumption of alcohol or other
sedatives exacerbates the condition. Criteria for giving
the cause of death at postmortem as OSA are given
in Table 10 (modied from Robinson et al.
17
).
O B E S I T Y H Y P O V E N T I L A T I O N S Y N D R O M E
Obesityhypoventilation syndrome is a condition
involving obesity, hypoventilation and sleep-disor-
dered breathing (usually OSA) with daytime hyper-
capnia (which distinguishes it from OSA), in the
absence of other causes of hypoventilation such as
chronic obstructive pulmonary disease.
18
Like OSA, it
requires a test performed during life for diagnosis
(daytime arterial blood gas), making it a difcult diag-
nosis to make at postmortem. The chronic hypercap-
nia means that OHS is more likely to progress to cor
pulmonale than is OSA. In OHS, unlike in OSA, death
does not typically occur in bed because of respiratory
failure or ventricular arrhythmia triggered by
hypoxia; rather, the mode of death is a fatal cardiac
arrhythmia secondary to cor pulmonale. In this
study, of the three deceased persons, one was found
dead in bed, one was found on the oor of the bed-
room, and one collapsed in the street.
In the absence of a known history of OHS (one of the
three cases in this study had a history of OHS during
life, and one had a history of OSA), clues to the diagno-
sis from the clinical history include symptoms of sleep
apnoea and shortness of breath, and symptoms and
signs of cor pulmonale. As in OSA, deaths that are sus-
pected to be secondary to OHS usually require a full
postmortem with histology and toxicology.
2013 John Wiley & Sons Ltd, Histopathology, 64, 200210.
206 E Fryer et al.
Criteria for giving a cause of death as being second-
ary to OHS are given in Table 10. Right ventricular
hypertrophy is dened by the Fulton technique as an
isolated right ventricular weight of greater than 65 g
or a reduced left to right ventricular weight ratio (the
normal left: right ventricular weight ratio is 2.3
3.3).
19
OHS is illustrated in Figure 1.
S U D D E N C A R D I A C D E A T H I N O B E S I T Y
Obese subjects have an increased risk of arrhythmias
and sudden death, even in the absence of cardiac dys-
function.
20
The sudden unexplained cardiac mortality
rate is 40 times higher in the obese than in a
matched non-obese population.
20
In this study, Davies category 4 deaths accounted
for 30% of cases; this is proportionately high when
compared with a previous study of 1292 postmor-
tems (616 of which were cardiac causes of death)
21
which showed 25% category 1, 27% category 2,
19% category 3, 22% category 4, 4% category 5 and
3% unclassied deaths.
A prolonged QT interval is seen in a relatively high
percentage of obese subjects,
20
but the clinical signi-
cance of this remains speculative. Although no de-
nite cases were found in this study, it seems plausible
that there is a scenario of sudden death related to
cardiac arrhythmia, in morbidly obese patients
without prominent cardiac hypertrophy or dilatation;
and that this is a diagnosis of exclusion, akin to sce-
narios such as sudden unexpected death in epilepsy
(SUDEP), dead in bed syndrome (type 1 diabetes mell-
itus), and sudden unexpected death in alcohol misuse
(SUDAM).
C O R O N A R Y H E A R T D I S E A S E
Ischaemic heart disease was the commonest cause of
death in this series. Meta-analysis has shown that
abdominal obesity is an independent risk factor for
coronary heart disease.
22
Interestingly, there is an
inverse relationship between body weight and mortal-
ity in patients with known cardiovascular disease
or post-acute myocardial infarction (the obesity
Table 10. Diagnostic criteria for obstructive sleep apnoea (OSA), obesityhypoventilation syndrome (OHS), and obesity car-
diomyopathy (OCM)
Diagnosis Diagnostic criteria
OSA A diagnosis during life of OSA, even in the absence of respiratory failure. Without an established
diagnosis, an appropriate history, e.g. snoring
The circumstances of the death, in particular death in bed, during sleep in the supine position,
often while not using CPAP
Absence of specic postmortem ndings such as an acute cardiac or cerebral event
Evidence of intoxication with alcohol or other sedatives
OHS A history during life of OHS. In the absence of this, a history of OSA or snoring during life. There may
be no prior history
Sudden death in the absence of a clear alternative cause of death such as an acute cardiac or cerebral event
Features of pulmonary hypertension and cor pulmonale such as right ventricular hypertrophy and
dilatation (Figure 1)
OCM Increased heart weight (see text)
Left ventricular or biventricular hypertrophy and dilatation of atria and ventricles. Small foci of interstitial
brosis may be present, but not extensive ischaemic brosis
There may be marked fat in the right ventricle, usually subepicardial and extending between blood vessels
(in the absence of brosis, which suggests arrhythmogenic right ventricular cardiomyopathy), often
up to the trabeculae. Usually, the anterior and lateral wall is affected to a greater extent than the
posterior wall (Figure 2)
Exclusion of signicant coronary artery disease, myocarditis, acute infarction, or other clear
alternative cause of death
2013 John Wiley & Sons Ltd, Histopathology, 64, 200210.
Postmortems in the obese 207
paradox), suggesting that excess body weight actually
confers a lower risk for adverse events (including
death) in patients with cardiovascular disease, includ-
ing those with heart failure.
23,24
O B E S I T Y C A R D I O M Y O P A T H Y
Obesity directly causes structural and functional
changes to the heart,
25
and it is difcult to separate
this from coexisting conditions such as hypertension
and OSA/OHS. Obesity produces an increase in total
blood volume and cardiac output, because of the high
metabolic activity of excessive adipose tissue,
26
result-
ing in biventricular hypertrophy and dilatation. If
systemic hypertension is also present, this further
promotes left ventricular dilatation and hypertrophy,
their effects being additive, not synergistic.
26
The
term obesity cardiomyopathy is used when the effects
of obesity on the heart have led to congestive cardiac
failure; this typically occurs in those with severe
and long-standing obesity, the mode of death being
progressive congestive cardiac failure or sudden
arrhythmia.
In this study, OCM was present in four of 202
(2.0%) deaths after review, having originally been
reported in only one of 202 deaths, again suggesting
that this condition is under-recognized by patholo-
gists. Two per cent may be an underestimate, as
OCM potentially accounted for death in a further two
cases of dilated cardiomyopathy that had no tissue
available for review. In this study, OCM was misinter-
preted as dilated cardiomyopathy and biventricular
hypertrophy. In a previous small series of sudden car-
diac deaths in 22 morbidly obese patients, dilated car-
diomyopathy accounted for death in 10 patients, and
many of these may have had OCM.
27
Criteria for giving the cause of death as OCM (mod-
ied from Hookana et al.
28
) are given in Table 10.
One of the major difculties in the obese is determin-
ing what is a normal heart weight. Traditionally,
this would have been assessed by comparison with
an upper limit of normal of, for example, 500 g for
males and 400 g for females.
29
If this method is used,
those in the morbidly obese category will commonly
have apparent cardiomegaly (even if they have died
of other causes in the unnatural deaths in this
study, three of six females and ve of seven males
would have been described as having cardiomegaly).
New reference tables for human hearts have been
described in which heart weight increases with body
mass index,
30
owing to hypertrophy (not fat or bro-
sis). The heart weights of the four OCM cases in this
study were 497, 520, 905, and 938 g. The respective
predicted heart weights (calculated from body weight)
were 450, 480, 520 g, and unassessable. In two of
the assessable cases the heart weight was close to
that predicted for the body weight, but in the other it
was high, as assessed either by comparison with the
upper limit of normal or derivation from body weight.
The distinction of OCM from DCM is an important
one (a diagnosis of DCM having familial implications),
and is not entirely straightforward. One could make
the assumption that, if there is a clear cause for car-
diomyopathy, such as alcohol or obesity, this is actu-
ally the cause. Alternatively, one could attempt to
make the distinction by using the following features.
DCM shows ventricular dilatation with an inadequate
degree of left ventricular (LV) hypertrophy (LV wall
Figure 1. A midventricular slice from the rst case of OHS in
Table 8 (BMI 51.7), showing right and left ventricular
hypertrophy.
Figure 2. A case of obesity cardiomyopathy showing extensive fat
within the right ventricular myocardium. Note the absence of
brosis.
2013 John Wiley & Sons Ltd, Histopathology, 64, 200210.
208 E Fryer et al.
thickness <10 mm), whereas OCM shows LV hyper-
trophy and dilatation (wall thickness >10 mm)
(Figure 2). Microscopically, in DCM there is myocardial
brosis, but this is less often seen in OCM. Fat may be
present in the right ventricle, but is not essential for
diagnosis, and can be seen in the right ventricle of
the non-obese. Fat is not seen in the left ventricle unless
it surrounds blood vessels in the outer wall, which is
a normal feature. It is recommended that a sample
of heart and spleen be frozen for genetic studies,
to enable the investigation of a possible inherited
cardiomyopathy.
Hypertensive heart disease is differentiated from
OCM by the pattern of left ventricular hypertrophy
(concentric in hypertension, and eccentric with
OCM), and by the presence of little dilatation, non-
specic brosis, and changes in other organs related
to hypertension.
O B E S I T Y A N D V E N O U S T H R O M B O E M B O L I C D I S E A S E
In this cohort of morbidly obese patients, VTED
accounted for 14.8% of deaths attributable to natural
causes. Obesity is a signicant and well-established
risk factor for the development of VTED.
31,32
How-
ever, despite this, obesity was included in the cause
of death in only 14 of 28 cases, with a further four
cases having other risk factors recorded (postsurgery,
malignancy, and immobility) and 10 having no risk
factors recorded at all. The pathogenesis of increased
VTED risk in the obese is complex, and potentially
involves a number of hormones, cytokines and
growth factors secreted by adipose tissue.
33
Conclusions
In summary, postmortems performed on the morbidly
obese represent a distinct group with specic causes
of death, and histology and toxicology are required in
many cases. A history of conditions during life, such
as OSA and OHS, and precise details of the circum-
stances of the death and body position should be
sought. OSA, OHS and OCM are under-recognized,
with deaths being misattributed to other causes, and
the role of obesity in deaths resulting from VTED is
under-reported.
Contributions
C. Verrill conceived and planned the study. E. Fryer
performed the data collection. All authors contributed
to writing and revising the text.
Acknowledgements
We would like to thank HM Coroner, Oxfordshire, for
his support and helpful comments in the production
of the manuscript.
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