Q J Med 2007; 100:501–507

doi:10.1093/qjmed/hcm055

Laboratory risk factors for hospital mortality in acutely

admitted patients
K. ASADOLLAHI, I.M. HASTINGS, N.J. BEECHING and G.V. GILL
From the Liverpool School of Tropical Medicine, Liverpool, UK

Received 7 September 2006 and in revised form 5 February 2007

Summary
Background: Many factors affecting hospital 602 cases and 1073 controls. Hyperglycaemia

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mortality in acutely admitted patients are poorly
understood. Although scoring systems exist for
critically ill patients, usually in intensive care units
(ICUs), there are no specific mortality prediction
systems for general acute admissions.
Aim: To assess the relationship between simple
admission laboratory variables on the risk of
in-patient mortality.
Design: Retrospective analysis of hospital admis-
sions and laboratory databases.
Methods: Where possible, all deceased patients in
the 12-month period of study were matched with two
surviving controls. The laboratory database was then
analysed for admission investigations, including
serum sodium, plasma glucose, and white blood
cell (WCC) count. Abnormalities of these variables
were then compared between cases (those who sub-
sequently died), and controls (those who survived).
Results: There were 16 219 admissions, with
an overall mortality of 7.6%. We investigated
(glucose 411.0 mmol/l) (OR 2.0, p < 0.0001);
severe hyponatraemia (sodium <125 mmol/l)
(OR 4.0, p < 0.0001); and leukocytosis (WCC
410
109/l) (OR 2.0, p < 0.001) were significantly
associated with mortality. The respective asso-
ciations on logistic regression analysis were:
glucose, OR 1.7, p ¼ 0.02; sodium, OR 4.4,
p < 0.0001; WCC, OR 1.5, p ¼ 0.006. Low glucose
levels, high sodium levels, and low WCC levels
were also associated with increased mortality,
leading to ‘U-shaped’ mortality associations.
The effect of more than one laboratory abnor-
mality being present was cumulative, in a linear
fashion.
Discussion: Plasma glucose, serum sodium and
WCC are measured in most acutely admitted
patients, and abnormalities of these variables have
associations with in-hospital mortality. This may
provide the basis for the development of a mortality
risk scoring system.

Introduction
The ability to predict likely outcome in acutely
admitted hospital patients can be beneficial in
several ways. High-risk patients can receive espe-
cially intensive management from health workers,
or in cases of extreme adverse prognosis, intensive
management may be curtailed in favour of a more
palliative approach. For patients and their relatives,
an accurate assessment of likely outcome may be
helpful on humanitarian grounds.
There are two approaches to such outcome
assessment measures: one essentially clinical,
the other investigative. Clinical risk scores have
been used for many years, particularly in intensive
care unit (ICU) situations. The APACHE II system is
a well-known example of this, and uses mainly
various clinical parameters to predict outcome on
admission to an ICU.1 Outside ICU situations, the
MEWS score similarly assesses risk stratification,

Address correspondence to Professor G.V. Gill, Liverpool School of Tropical Medicine, Pembroke Place,
Liverpool L3 5QA. email: g.gill@liv.ac.uk
! The Author 2007. Published by Oxford University Press on behalf of the Association of Physicians.
All rights reserved. For Permissions, please email: journals.permissions@oxfordjournals.org
502 K. Asadollahi et al.
though this is designed mainly to identify patients
who may benefit from higher-dependency care.2
Risk assessment on the basis of laboratory
investigations is also commonly used, but is usually
applied in specific disease situations, and generally
gives arbitrary (rather than numerical) assessments
of risk. Examples include the degree of elevation
of serum troponin T and abnormalities of the
electrocardiogram (ECG) in patients with myo-
cardial infarction,3 or the degree of plasma hyper-
osmolality in diabetic patients with hyperglycaemic
emergencies.4
There are, however, common laboratory measure-
ments which appear to be associated with general
mortality risk in hospital patients. For example,
hyponatraemia (particularly of severe degrees) has
been known for many years to be associated with
high mortality in general hospital patients.5–8 More
recently, leukocytosis (in non-infective situations)
has been shown to be associated with increased
coronary and general mortality.9–11 Finally, admis-
sion plasma or blood glucose (in non-diabetic
situations) strongly predicts mortality in patients
admitted with myocardial infarction,12–14 stroke,15
and other general medical problems.16 Of particular
interest and importance, reduction of glucose
levels in critically ill patients by insulin treatment
improves outcome,17 suggesting that this laboratory
abnormality at least is a modifiable variable.
Fortuitously, the vast majority of acutely ill
patients admitted to Western hospitals have all
three of these variables measured routinely. Serum
or plasma sodium (Na) is measured as part of ‘U&E’
(urea and electrolytes), or a ‘renal profile’. The white
blood cell count (WCC) is included in a ‘full blood
count’ or ‘haematogram’; and plasma or blood
glucose is also usually routinely measured. We have
therefore undertaken a large database exploration
of these measurements and their effect on in-patient
mortality, in a large British teaching hospital.
In particular, we have case-controlled deceased
patients, and explored causes as well as occurrence
of death, and the cumulative effects when more than
one of the abnormal laboratory variables is present.
Methods
A computerized hospital database analysis was
carried out in a single calendar year (January to
December 2002) of all acute admissions to a British
urban teaching hospital (Royal Liverpool University
Hospital). An acute admission was defined as a
patient admitted after presenting to the accident and
emergency department, or referred by their general
practitioner with an acute medical or surgical event.
There were 16 219 such acute admissions of
whom 1227 (7.6%) died during hospitalization.
All the deceased patients were electronically
selected as cases, and for each case, two controls
were sought from the admission lists, matched for
sex, age band (10-year intervals), hospital specialty,
and the nearest sequential date of admission.
For some patients—notably those admitted to the
intensive care unit (ICU)—it was not possible to
select a second control; and for other patients,
no appropriate matching control could be found.
Of the 602 cases, 123 were matched to two
controls, 405 to a single control, and 74 were
unmatched. Of the controls, 422 were not matched
to cases. Some patients had missing laboratory
variables as follows: sodium 1, glucose 271,
chloride 2, potassium 97, bicarbonate 1, urea 1,
creatinine 1, anion gap 103, platelets 7, neutrophils
27 and lymphocytes 27. The final group for
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analysis was thus 602 cases (deceased) and 1073
controls (survivors)
For the purposes of analysis, we defined hyper-
glycaemia as a random plasma glucose
47.0 mmol/l, hyponatraemia as a plasma sodium
(Na) <135 mmol/l, and leukocytosis as white blood
cell (WBC) count 410.0
109/l. As well as our
major test variables of serum sodium, plasma
glucose, and white blood cell count, we also
analysed the effect of other measurements available
with these: serum potassium and urea (with the renal
profile), and haemoglobin, platelets, neutrophils
and lymphocytes (with the blood count). For each
variable, we designed ‘bandings’ of ranges.
For example, 2.5–7.0 mmol/l was the normal band
for serum urea, and the high and low bands were
47.0 and <2.5 mmol/l, respectively. For sodium and
glucose (which we wished to investigate in more
detail), more bandings were chosen. Mortality odd
ratios (OR) were determined for these bandings,
against the mortality for these in the normal ranges.
Data analysis used the Statistical Package for
Social Sciences (SPSS), version 14. Univariate
analysis of 2
2 tables was by Fischer’s exact
test or 2 tests (depending on number of observa-
tions). Logistic regression analysis was performed to
simultaneously investigate the impact of the mea-
sured variables on mortality. Because for some cases
no matching control could be found, an uncondi-
tional logistic regression (i.e. ignoring matching)
was carried out. This allowed the whole dataset to
be analysed and, more importantly, meant that
unmatched cases were not dropped, which could
have introduced selection bias.
Ethical approval was obtained from the Ethical
Committees of the Royal Liverpool University
Hospital and the Liverpool School of Tropical
Medicine.
 Admission variables and mortality
Results
Group characteristics
The 602 deceased patients were of mean (SD) age
75  13 years; 79% were acute medical admissions
and 21% surgical, and the duration of hospital stay
was 20  26 days (meanSD). The 1073 controls
(survivors) had a mean age of 76  12 years, 85%
were medical, and the mean length of hospitaliza-
tion was 18  23 days. None of these parameters
were significantly different between patients and
controls.
Mortality risk factors
The risk of mortality for each of the measured
laboratory variables, together with appropriate
confidence intervals and levels of significance, is
shown in Table 1, both for univariate analysis and
logistic regression. Because many variables were
correlated with each other (Table 2), we relied on
logistic regression to indicate true mortality links.
The latter analysis showed particularly strong
statistical associations of mortality with hyponatrae-
mia, hypernatraemia, leukopenia, thrombocytope-
nia and raised creatinine.
Mortality pattern for major laboratory
variables
Figures 1–3 show the pattern of mortality risk for the
three main laboratory variables: plasma glucose
(Figure 1), serum sodium (Figure 2), and white
blood cell count (Figure 3). It can be seen that using
the bandings from Table 1, in each case there was a
‘U’-shaped curve, with higher mortality risk at both
abnormally high and low levels. The effect was
particularly marked for sodium.
Cumulative effect of laboratory variables
Figure 4 shows the mortality risk of abnormalities of
the three major variables (hyperglycaemia, hypona-
traemia, and leukocytosis) individually, and also in
combination. It can be seen that combinations of
these abnormalities led to a graded and approxi-
mately linear increase in mortality risk.
Mortality causes
Using standard coded causes of death (ICD-10),
and the major significant risk factors of hyponatrae-
mia, leukocytosis, and hyperglycaemia; mortality
causes were compared between those with and
without these laboratory variables for each diag-
nostic category. Comparing hyponatraemia and
normonatraemic patients, only pneumonia was
503
over-represented in those with hyponatraemia
(mortality 11.8% vs. 7.8%, p ¼ 0.04). Similarly
with leukocytosis, again only pneumonia showed
a significant excess (13.3% vs. 4.3%, p < 0.0001).
For hyperglycaemia, there was a significant excess
of myocardial infarction (6.9% vs. 2.7%, p < 0.001),
as well as pneumonia (11.9% vs. 7.1%, p < 0.01).
Discussion
Despite the considerable importance of hospital
mortality, there has been little robust research on
early predictive factors. Our study involved a large
cohort, with a carefully selected group of case-
controls, and we also studied acute general admis-
sions. Previous research in the area has tended to
concentrate on specific diagnostic categories
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(e.g. myocardial infarction12–14 or stroke15) or
especially high-risk groups of patients (e.g. in
intensive care units1). Also, we investigated the
effect of laboratory variables which are almost
universally measured in all patients admitted to
Western hospitals: electrolytes, renal function
tests, plasma glucose, haemoglobin and white
blood cell count.
Univariate analysis showed statistically significant
associations with mortality for abnormal levels of
most of the variables tested (Table 1), but the more
critical logistic regression analysis did not always
confirm these associations. In particular, the rela-
tionship between hyperglycaemia and mortality was
greatly reduced in significance. It may be that at
least some of the findings significant on univariate
analysis are age-dependent, a hypothesis that could
be tested using a different control group that is not
age-matched. Hypernatraemia (4145 mmol/l) and
severe hyponatraemia (<125 mmol/l) maintained
highly significant mortality associations with logistic
regression; as did uraemia, thrombocytopenia,
leukocytosis, and lymphopenia.
An especially interesting finding was that for the
common variables of plasma glucose, serum
sodium, and white blood cell count, there was a
‘U-shaped’ relationship between their levels and
mortality (Figures 1–3). Thus both low and high
levels were associated with excess death risk,
compared to levels within the normal range. This
common effect has not been previously described to
our knowledge.
Perhaps not surprisingly, when hyponatraemia,
hyperglycaemia and leukocytosis existed together
(either two of the three, or all three), there was a
cumulative effect on mortality. Figure 4 suggests that
the cumulative effect is linear. The odds ratio (OR)
504 K. Asadollahi et al.

Table 1 Comparison of deceased and surviving patients with different laboratory variables

Variables Ranges Number Univariate analysis Logistic regression

(OR, 95%CI, p) (OR, 95%CI, p)
Dead Alive

Glucose (mmol/l) 411.0 64 76 2.0, 1.4–2.9, 0.0001 1.7, 1.1–2.5, 0.02

7.1–11.0 163 262 1.5, 1.2–1.9, 0.002 1.4, 1–1.8, 0.03
5.0–7.0 204 487 Reference range –
<5.0 57 90 1.5, 1–2.2.0, 0.03 1.5, 1–2.3.0, 0.05
Sodium (mmol/l) 4145 46 29 3.6, 2.3–5.9, 0.0001 3.1, 1.8–5.6, 0.0001
135–145 377 866 Reference range –
130–134 118 127 2.1, 1.6–2.8, 0.0001 1.9, 1.3–2.6, 0.0001
125–129 35 35 2.3, 1.4–3.7, 0.001 1.9, 1.0–3.6, 0.04
<125 26 15 4.0, 2.1–7.6, 0.0001 4.4, 2–9.2.0, 0.0001
Potassium (mmol/l) 45.0 71 55 2.7, 1.8–3.9, 0.0001 2.1, 1.2–3.8, 0.02
3.5–5.0 406 843 Reference range –
<3.5 83 119 1.4, 1.3–1.5, 0.02 1.1, 0.6–1.8, 0.8
Urea (mmol/l) 47.0 393 520 2.0, 1.6–2.5, 0.0001 1.4, 1.0–1.9, 0.007

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2.5–7.0 204 536 Reference range –
<2.5 5 17 0.8, 0.3–2.3, 0.7 0.9, 0.3–2.9, 0.8
Platelets (
109/l) 4450 51 62 2.1, 1.5–3, 0.0001 1.4, 0.97–2.1, 0.07
150–450 475 941 Reference range –
<150 71 68 1.5, 1.1–2, 0.01 1.8, 1.2–2.8, 0.006
Leukocytes (
109/l) 410 371 485 2.0, 1.7–2.5, 0.0001 1.5, 1.2–1.95, 0.002
4–9 218 579 Reference range –
<4 12 9 3.5, 1.5–8.5, 0.006 2.8, 1.1–7.4, 0.04
Neutrophils (
109/l) 47 402 553 2.1, 1.7–2.6, 0.0001 1.2, 0.8–1.8, 0.3
2–7 173 504 Reference range –
<2 9 7 3.8, 1.4–10.2, 0.02 1.4, 0.4–5.2, 0.6
Lymphocytes (
109/l) 43 43 65 2.1, 1.7–2.5, 0.0001 1.3, 0.8–2.3, 0.3
1–3 286 696 Reference range –
<1 255 303 1.6, 1.1–2.4, 0.02 1.6, 1.2–2.1, 0.001
Haemoglobin (g/dl) 417 10 8 1.4, 1.1–1.7, 0.004 1.1, 0.3–3.6, 0.9
12–17 351 722 Reference range –
<12 241 343 2.7, 1–6.8.0, 0.04 1.1, 0.9–1.5, 0.4
Chloride (mmol/l) 4109 56 51 2.7, 1.8–4.2, 0.0001 1.5, 0.8–2.5, 0.2
99–109 313 778 Reference range –
<99 233 242 2.4, 1.9–3.0, 0.0001 1.6, 1.1–2.2, 0. 02
Bicarbonate (mmol/l) 433 12 13 2.0, 0.8–4.6, 0.1 1.2, 0.5–3.0, 0.7
22–33 437 929 Reference range –
<22 153 130 2.5, 1.9–3.3, 0.0001 1.3, 0.5–1.9, 0.2
Creatinine (mol/l) 4130 242 239 2.4, 1.9–2.9, 0.0001 1.4, 1.0–2.0, 0.03
50–130 358 832 Reference range –
<50 2 1 4.7, 0.3–129.6, 0.2 –
Anion gap (mmol/l) 416 285 322 2.3, 1.8–2.8, 0.0001 1.2, 0.9–1.6, 0.3
6–16 271 691 Reference range –
<6 2 1 5.1, 0.4–142.5, 0.2 –

OR, odds ratio. Fisher’s exact test.

for mortality ranged from 1.6 to 2.3 for one be restrictive, and coding inaccuracies are well
abnormality, 2.7 to 3.9 for two, and 4.0 for all three. known. Nevertheless, we did show an association
Our data on the cause of mortality should be between hyperglycaemia and myocardial infarction
interpreted with caution. Mortality codings tend to (MI) as a cause of death, as previously reported.12–14
Table 2 Relationships between levels of the 13 variables: correlation coefficients and associated significance levels

Na K Cl BIC U Cr AG Glu Hb PLT WBC N L

Na 1
K 0.08 1
p ¼ 0.003
Cl 0.80 0.10 1
p < 0.0005 p < 0.0005
BIC 0.11 0.33 0.12 1

Admission variables and mortality

p < 0.0005 p < 0.0005 p < 0.0005
U 0.10 0.30 – 0.27 1
p < 0.0005 p < 0.0005 p < 0.0005
Cr – 0.34 – 0.34 0.61 1
p < 0.0005 p < 0.0005 p < 0.0005
AG – 0.22 0.25 0.55 0.40 0.42 1
p < 0.0005 p < 0.0005 p < 0.0005 0.0001 p < 0.0005
Glu – – – 0.15 0.10 0.70 0.18 1
p < 0.0005 p ¼ 0.001 p ¼ 0.01 p < 0.0005
HB 0.12 – – 0.10 0.14 0.18 0.05 – 1
p < 0.0005 p < 0.0005 p < 0.0005 p < 0.0005 p ¼ 0.04
PLT 0.05 – – – – – – – 0.11 1
p ¼ 0.05 p < 0.0005
WCC – – 0.10 – 0.10 0.12 0.14 – 0.10 1
p ¼ 0.003 p ¼ 0.008 p < 0.0005 p < 0.0005 p ¼ 0.01
N 0.10 0.12 0.14 0.11 0.17 0.10 0.22 0.13 – 0.23 0.85 1
p ¼ 0.001 p < 0.0005 p < 0.0005 p < 0.0005 p < 0.0005 p < 0.0005 p < 0.0005 p < 0.0005 p < 0.0005 p < 0.0005
L – – – – 0.10 0.10 – – – – 0.50 0.10 1
p ¼ 0.004 p ¼ 0.02 p < 0.0005 p ¼ 0.02

Absence of a p value indicates p40.05. BIC, bicarbonate; U, urea; Cr, creatinine; AG, anion gap; Glu, glucose; Hb, haemoglobin; PLT, platelets; WCC, white cell count;
N, neutrophils; L, lymphocytes.

505
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506 K. Asadollahi et al.

Mortality Mortality
OR OR
6 14

5 12
p =0.0003
10
4
8 p =0.006
3
p =0.04 6
p =0.003
2
4
p =0.0001
1
2
0 0
<5.0 5.0–7.0* 7.1–11.0 >11.0
<4.0 4.0–10.0* >10.0
Plasma glucose levels (mmol/l) WBC (x109/l)
Bars= 95% confidence interval Bars = 95% confidence intervals
* Reference range * Reference range

Figure 1. Mortality odds ratio (with 95%CI) for varying Figure 3. Mortality odds ratio (with 95%CI) for varying
levels of plasma glucose (all levels compared to normal white blood cell counts (all levels compared to normal

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range). range).

Mortality
OR Mortality
14 OR
8
12
p =0.0001 p <0.004
10 7
p <0.04
p =0.0001
8 6
p <0.002
6 p =0.0001 p <0.02
5
4 p =0.001 4.0
p <0.03 3.9
4
2
3.0
3 2.7
0
<125 125–129 130–134 135–145* >145 2.3
2.0
Serum Na levels 2
1.6
Bars=95% confidence intervals
* Reference range 1

Figure 2. Mortality odds ratio (with 95%CI) for varying
levels of serum sodium (all levels compared to normal
range).
We did not, however, find an association between
leukocytosis and MI, which has been described
previously.18
In conclusion, abnormalities of a number of
commonly measured laboratory variables on admis-
sion to hospital were strongly associated with
subsequent in-patient mortality in this patient
group. Particular associations were seen with
severe hyponatraemia, hyperkalaemia, uraemia,
leucocytosis and lymphopoenia. In many cases,
the causal link with mortality remains to be
determined. Our findings raise the possibility of
the development of a laboratory-measurement-
based predictive scoring system, to assess potential
outcome during hospital admission.
0
G WBC Na G + WBC G + Na Na + G + WBC
WBC + Na
bars=95% CI
Figure 4. Odds ratio (with 95%CI) of mortality risk for the
presence of hyperglycaemia (G), hyponatraemia (Na), and
leukocytosis (WBC) alone; as well as varying combination
of abnormalities. G, glucose; Na, sodium; WBC, white
blood cell counts
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