Abstract

Leukocytosis (raised concentration of white cells in the blood) is commonly associated with infection or inflammation, but can occur in a wide variety of other conditions. Leukocytosis has also been linked with increased mortality and morbidity in a number of studies. We have systematically reviewed the relevant literature, which clearly demonstrates an association between leukocytosis and mortality—particularly due to cardiovascular or cerebrovascular causes. The mechanisms of this effect are uncertain but, when combined with other markers predictive of death, leukocytosis may contribute to modelling systems to predict in-patient mortality risk.

Introduction

Leukocytosis is an elevation of the concentration of leukocytes or white blood cells in blood, and is generally considered to be present when the white cell count (WCC) exceeds 11 × 109/l. Widely considered to be an indicator of infection or inflammation, leukocytosis can also occur in a variety of other clinical situations, such as trauma, exercise, therapy with drugs such as steroids or lithium, malignancy, poisoning, psychosis and diabetic ketoacidosis.1–6

It is less well appreciated that leukocytosis can be associated with increased mortality and morbidity risk. This effect is well described for coronary heart disease (CHD)8–10 and cerebrovascular disease (CVD),11 but associations are also reported with hypertension,12 glucose intolerance13 and general mortality risk.7

In this article, we have systematically reviewed the literature on leukocytosis, mortality and morbidity in the absence of overt infection, to assess the strength and validity of these described associations and to explore possible causative mechanisms.

Methods

We interrogated the search engines Medline, PubMed, Athens, Ovid and Google scholar, using the key words ‘white blood cell count’, ‘white cell count’, ‘WBC’, ‘leukocytosis’, ‘mortality’, ‘morbidity’ and ‘risk factor’—both alone and in combinations. No date limits were set, but the search was limited to human studies and reports in the English language. A total of 447 papers were found, of which 394 were rejected: 18 were case reports or letters, 15 were duplicates and 361 were irrelevant to mortality or morbidity. This left 53 articles, which were reviewed in detail.

Leukocytosis and mortality

There is a considerable evidence that leukocytosis may be an independent predictor for death.7,9,10 A study from Spain investigated the relationship of the WCC to 5-year mortality among 152 men who had proven CHD, but no myocardial infarction or source of infection.8 The severity of CHD was assessed by the number of main coronary arteries with significant stenosis. The WCC was significantly higher in patients with triple vessel disease and the total leukocyte count differed significantly among those who died, compared with those who survived. The authors concluded that there was an association between increased WCC and a shorter subsequent survival time. de Labry and others analysed the WCC in prospective examinations of 2011 initially healthy men in the Normative Aging Study (mean age: 47 years), followed for an average of 13 years.7 Mortality for those with a baseline WCC over 9 × 109/l was 12.2/1000 person-years, which was 1.8 times greater than those with a lower WCC. They found that, even within the normal range, an increase of 1 × 109/l in the initial count increased the risk ratio (RR) by 1.2, and it was concluded that the WCC was an independent predictor of all-cause mortality.

Among 7651 patients attending an American hospital with acute coronary syndromes, a WCC >10 × 109/l was associated with increased 30-day mortality.10 A further study from Poland was carried out to determine whether the WCC at diagnosis in patients with acute stroke had a predictive value for subsequent clinical outcome.11 A WCC > 10 × 109/l was associated with a >70-fold risk for death [odds ratio (OR) = 75.2; 95% confidence interval (CI): 8.9–635.8; P = 0.0001]. Also, each 1 × 109/l increase in WCC on admission was associated with an increased risk for in-hospital mortality (OR = 2.2; 95% CI: 1.4–3.6; P = 0.0008). They concluded that an increase in the WCC within the first 12 hours of stroke was an independent and strong predictive factor for mortality.

A US study examined the Co-operative Cardiovascular Project (CCP) database of acute myocardial infarction (MI) patients.9 Out of 153 213 patients, approximately one-third had an elevated WCC (>12 × 109/l). There was a significantly higher risk of in-hospital and 30-day mortality with increasing WCC. Patients in the highest quintile (WCC of 13–19.8 × 109/l) compared to those in the lowest quintile (6–7.5) were >3 times likely to have died at 30 days (32 vs. 10%; P = 0.001).

Population-based studies have also shown a relationship between raised WCC and mortality.7,16–22 A study from the USA followed up healthy older women (65–101 years) for 5 years and reported that baseline WCC was independently related to mortality.17 Another study in South Korea followed a healthy population (age 40–95 years) that received health insurance for 10 years, and reported that a raised WCC was related to all-cause mortality (hazard ratio for highest quartile vs. lowest was 1.5).18 A study from the Netherlands followed healthy randomly selected men (age 64–84 years) for 5 years and reported that a raised WCC predicted CHD and all-cause mortality independently of conventional risk factors.19 Three further population-based studies, one from Japan20 and two from Australia,21,22 compared mortality in those with the highest vs. lowest quartiles of WCC. A mortality RR of 2.01 was shown for cardiovascular mortality,20 1.68 for all-cause mortality21 and 1.73 for cancer mortality.22

The WCC has also been shown to be a mortality predictor in a range of other diseases, including respiratory disease,14 malignancy23 and head trauma.24 Our own studies have shown that leukocytosis (WCC > 10 × 109/l) at the time of hospital admission for any reason strongly predicts in-patient mortality (OR = 2.0; P<0.0001).25

One negative study was reported by Chalasani and colleagues in the USA,26 although this concerned only patients with upper gastro-intestinal bleeding, and their criterion for leukocytosis was relatively low at 8.5 × 109/l. Using this definition, there was no difference in mortality between those above and below this cut-off level (8.7 vs. 6.4%; P = 0.27).

The studies discussed above, and others, are summarized in Tables 1 (WCC and cardiovascular mortality) and 2 (WCC and mortality in healthy populations, and in other illnesses).

Table 1

Summary of cardiovascular studies relating raised WCC and mortality

Study Year of publication Country of study Type of study Patients studied Mean age/age group (in years) Number of patients WCC × 109/l Mortality 

 
Pitsavos et al.27 2008 Greece Retrospective Patients with acute coronary syndrome – 2172 – Raised WCC was an independent predictor for in-hospital mortality among former and current smokers 
Newall et al.28 2006 UK Prospective Patients with coronary artery bypass grafting – 3024 – High preoperative WCC was independently related to one year mortality 
Lipinski et al.29 2006 USA Retrospective Patients with ischemic left ventricular dysfunction undergoing percutaneous coronary intervention 57 238 ≥10 compared to <10 One year survival was 86 vs. 96% and 3 year survival was 79 vs. 89% 
Nunez et al.30 2005 Spain Prospective AMI patients (ST and non-ST elevated) – 1118 >10 compared to <10, ≥15 compared to <10 HR for non-ST elevated patients was 2.07 and 1.6 and for ST elevated patients was 2.07 and 2.2, respectively (one year follow-up) 
Stewart et al.32 2005 New Zealand Clinical trial Patients with previous MI or unstable angina – 9014 >8.2 compared to <5.9 Mortality prevention after treatment with pravastatin at the highest quartile compared to the lowest was 38 per 1000 patients 
Comparan et al.41 2005 Mexico Prospective Cardiovascular disease/MI patients – 271 >10 compared to <10 32 vs. 14% 
Rajagopal et al.33 2004 USA Retrospective Patients undergoing percutaneous coronary intervention – – – Post-procedural WCC was independently related to long-term mortality 
Grzybowski et al.33 2004 USA Retrospective AMI patients – 115 273 WCC > 5 was divided into quartiles J-shaped curve. Independent predictor for in-hospital AMI mortality 
Dacey et al.34 2003 USA Prospective Patients with coronary artery bypass grafting – 11 270 ≥12 compared to <6 4.8 vs. 1.7% 
Mueller et al.35 2003 Germany Prospective Non-ST elevation patients with acute coronary syndrome undergoing revascularization – 1391 >10 compared to <10 Patients with raised WCC were 3 times more likely to die (HR = 3.2, CI = 1.5–7.1) than others 
Gurm et al.36 2003 USA Retrospective Patients with percutaneous coronary intervention – 7179 – A raised pre-procedural WCC was associated with long-term mortality 
Bhatt et al.37 2003 USA Retrospective Patients with acute coronary syndrome – 10 480 – 4% lowest quartile, 5.8% second quartile, 6.7% third quartile, 8% fourth quartile 
Sabatine et al.38 2002 USA – Patients with coronary artery diseases – 2208 – Higher baseline WCC was independently related to 6 month mortality ranging from 1.5 to 3.6 to 5.1% for patients with low, intermediate and high WCC, respectively 
Barron et al.9 2001 USA Retrospective MI patients 65 153 213 – Strong independent indicator of mortality 
Cannon et al.10 2001 USA Retrospective Patients with cardiovascular disease – 7651 >10 compared to <10 6.3 vs. 3.6% in 30 days 
Lee et al.39 2001 USA Retrospective CHD, Stroke, AMI patients (ARIC study) – 13 555 ≥7 compared to <4.8 Patients in the highest quartile had 1.9 times the risk of incident CHD, 1.9 stroke risk and 2.3 CVD mortality 
Grimm et al.40 1985 USA Prospective CHD patients Middle age men 6222 – Strong relationship with mortality, independent of smoking; each 1 × 109/l decrease of WCC = 14% mortality decrease 
Study Year of publication Country of study Type of study Patients studied Mean age/age group (in years) Number of patients WCC × 109/l Mortality 

 
Pitsavos et al.27 2008 Greece Retrospective Patients with acute coronary syndrome – 2172 – Raised WCC was an independent predictor for in-hospital mortality among former and current smokers 
Newall et al.28 2006 UK Prospective Patients with coronary artery bypass grafting – 3024 – High preoperative WCC was independently related to one year mortality 
Lipinski et al.29 2006 USA Retrospective Patients with ischemic left ventricular dysfunction undergoing percutaneous coronary intervention 57 238 ≥10 compared to <10 One year survival was 86 vs. 96% and 3 year survival was 79 vs. 89% 
Nunez et al.30 2005 Spain Prospective AMI patients (ST and non-ST elevated) – 1118 >10 compared to <10, ≥15 compared to <10 HR for non-ST elevated patients was 2.07 and 1.6 and for ST elevated patients was 2.07 and 2.2, respectively (one year follow-up) 
Stewart et al.32 2005 New Zealand Clinical trial Patients with previous MI or unstable angina – 9014 >8.2 compared to <5.9 Mortality prevention after treatment with pravastatin at the highest quartile compared to the lowest was 38 per 1000 patients 
Comparan et al.41 2005 Mexico Prospective Cardiovascular disease/MI patients – 271 >10 compared to <10 32 vs. 14% 
Rajagopal et al.33 2004 USA Retrospective Patients undergoing percutaneous coronary intervention – – – Post-procedural WCC was independently related to long-term mortality 
Grzybowski et al.33 2004 USA Retrospective AMI patients – 115 273 WCC > 5 was divided into quartiles J-shaped curve. Independent predictor for in-hospital AMI mortality 
Dacey et al.34 2003 USA Prospective Patients with coronary artery bypass grafting – 11 270 ≥12 compared to <6 4.8 vs. 1.7% 
Mueller et al.35 2003 Germany Prospective Non-ST elevation patients with acute coronary syndrome undergoing revascularization – 1391 >10 compared to <10 Patients with raised WCC were 3 times more likely to die (HR = 3.2, CI = 1.5–7.1) than others 
Gurm et al.36 2003 USA Retrospective Patients with percutaneous coronary intervention – 7179 – A raised pre-procedural WCC was associated with long-term mortality 
Bhatt et al.37 2003 USA Retrospective Patients with acute coronary syndrome – 10 480 – 4% lowest quartile, 5.8% second quartile, 6.7% third quartile, 8% fourth quartile 
Sabatine et al.38 2002 USA – Patients with coronary artery diseases – 2208 – Higher baseline WCC was independently related to 6 month mortality ranging from 1.5 to 3.6 to 5.1% for patients with low, intermediate and high WCC, respectively 
Barron et al.9 2001 USA Retrospective MI patients 65 153 213 – Strong independent indicator of mortality 
Cannon et al.10 2001 USA Retrospective Patients with cardiovascular disease – 7651 >10 compared to <10 6.3 vs. 3.6% in 30 days 
Lee et al.39 2001 USA Retrospective CHD, Stroke, AMI patients (ARIC study) – 13 555 ≥7 compared to <4.8 Patients in the highest quartile had 1.9 times the risk of incident CHD, 1.9 stroke risk and 2.3 CVD mortality 
Grimm et al.40 1985 USA Prospective CHD patients Middle age men 6222 – Strong relationship with mortality, independent of smoking; each 1 × 109/l decrease of WCC = 14% mortality decrease 

AMI, acute myocardial infarction; HR, hazard ratio.

Table 2

Summary of studies on healthy populations and other conditions relating raised WCC and mortality

Medical condition Study Year of publication Country of study Type of study Patients studied Age group/ mean age (in years) Number of patients WCC × 109/l Mortality 

 
Cerebro-vascular diseases Kazmierski et al.42 2004 Poland Prospective Stroke patients 67.5 400 >9.7 compare to <9.7 Raised WCC was related to mortality with OR = 8.26 
 Brown et al.43 2004 USA Retrospective Patients with CVD 30–75 8459 >8.2 compared to <5.7 RR for mortality = 2.1 
 Lee et al.40 2001 USA Retrospective CHD, Stroke, AMI patients(ARIC study) – 13 555 ≥7 compared to <4.8 Patients in the highest quartile had 1.9 times the risk of incident CHD, 1.9 stroke and 2.3 CVD mortality 
 Kazmierski et al.11 2001 Poland Retrospective Stroke patients – 100 >10 WCC >10 cells × 109/l was associated with a >70-fold greater risk for death (P = 0.0001) 
Healthy populations Ruggiero et al.16 2007 USA Retrospective Healthy patients in the Baltimore Longitudinal Study of Ageing – 2803 >6 compared to 3.5–6 Non-linearly related to all cause mortality and linearly related to cardiovascular mortalities 
 Tamakoshi et al.20 2007 Japan Retrospective Population-based study (patients without a history of CVD) – 9756 9-10 compared to 4–4.9 Patients in the higher quartile compared to the lower had a RR of 1.79 for mortality 
 Shankar et al.21 2007 Australia Prospective Population-based study 49–84 2904 ≥6.8 compared to ≤4.8 Patients in the highest quartile compared to the lowest had a RR of 2.01 for cardiovascular and 1.68 for all cause of mortality 
 Shankar et al.22 2006 Australia Prospective Population-based study 49–84 3189 ≥7.4 compared to ≤5.3 Patients in the highest quartile compared to the lowest had a RR of 1.73 for cancer mortality 
 Leng et al.17 2005 USA Prospective Community-dwelling older women 65–101 624 – Baseline total higher WCC was independently related to mortality (5-year follow-up) 
 Jee et al.18 2005 South Korea Prospective Population that received health insurance 40–95 437 454 – Raised WCC was related to all cause mortality. HR for highest quartile vs. lowest was 1.5 (10-year follow-up) 
 Weijenberg et al.19 1996 Netherlands Prospective Randomly selected men 64–84 884 – Raised WCC predicted CHD and all-cause mortality, independently of the conventional risk factors (5-year follow-up) 
 De Labry et al.7 1990 USA Prospective Healthy men in the Normative Ageing Study 47.5 2011 >9 compared to <9 1.8–2.5 times higher. Even in normal ranges, each WCC increase of 1 × 109/l had a RR =1.2 (13.6-year follow-up) 
Other conditions Asadollahi et al.25 2007 UK Retrospective General in-hospital admissions 61 1675 ≥10 deceased patients compared to survivors Significant relationship between leukocytosis and mortality (OR = 2.0; P < 0.001) 
 De Campos et al.44 2008 Brazil Prospective Patients with acute pancreatitis – 39 ≥19 7.7% 
 Erlinger et al.23 2004 USA Retrospective Cancerous patients – 7674 – Independent risk factor for mortality 
 James et al.14 1999 Australia Prospective Patients with respiratory and cardiac illnesses – 4291 – Increased WCC was independently associated with mortality 
 Keskil et al.24 1994 Turkey Prospective Patients with head trauma – 153 >20 compared to <20 Mortality rate = 96 vs. 23% 
Medical condition Study Year of publication Country of study Type of study Patients studied Age group/ mean age (in years) Number of patients WCC × 109/l Mortality 

 
Cerebro-vascular diseases Kazmierski et al.42 2004 Poland Prospective Stroke patients 67.5 400 >9.7 compare to <9.7 Raised WCC was related to mortality with OR = 8.26 
 Brown et al.43 2004 USA Retrospective Patients with CVD 30–75 8459 >8.2 compared to <5.7 RR for mortality = 2.1 
 Lee et al.40 2001 USA Retrospective CHD, Stroke, AMI patients(ARIC study) – 13 555 ≥7 compared to <4.8 Patients in the highest quartile had 1.9 times the risk of incident CHD, 1.9 stroke and 2.3 CVD mortality 
 Kazmierski et al.11 2001 Poland Retrospective Stroke patients – 100 >10 WCC >10 cells × 109/l was associated with a >70-fold greater risk for death (P = 0.0001) 
Healthy populations Ruggiero et al.16 2007 USA Retrospective Healthy patients in the Baltimore Longitudinal Study of Ageing – 2803 >6 compared to 3.5–6 Non-linearly related to all cause mortality and linearly related to cardiovascular mortalities 
 Tamakoshi et al.20 2007 Japan Retrospective Population-based study (patients without a history of CVD) – 9756 9-10 compared to 4–4.9 Patients in the higher quartile compared to the lower had a RR of 1.79 for mortality 
 Shankar et al.21 2007 Australia Prospective Population-based study 49–84 2904 ≥6.8 compared to ≤4.8 Patients in the highest quartile compared to the lowest had a RR of 2.01 for cardiovascular and 1.68 for all cause of mortality 
 Shankar et al.22 2006 Australia Prospective Population-based study 49–84 3189 ≥7.4 compared to ≤5.3 Patients in the highest quartile compared to the lowest had a RR of 1.73 for cancer mortality 
 Leng et al.17 2005 USA Prospective Community-dwelling older women 65–101 624 – Baseline total higher WCC was independently related to mortality (5-year follow-up) 
 Jee et al.18 2005 South Korea Prospective Population that received health insurance 40–95 437 454 – Raised WCC was related to all cause mortality. HR for highest quartile vs. lowest was 1.5 (10-year follow-up) 
 Weijenberg et al.19 1996 Netherlands Prospective Randomly selected men 64–84 884 – Raised WCC predicted CHD and all-cause mortality, independently of the conventional risk factors (5-year follow-up) 
 De Labry et al.7 1990 USA Prospective Healthy men in the Normative Ageing Study 47.5 2011 >9 compared to <9 1.8–2.5 times higher. Even in normal ranges, each WCC increase of 1 × 109/l had a RR =1.2 (13.6-year follow-up) 
Other conditions Asadollahi et al.25 2007 UK Retrospective General in-hospital admissions 61 1675 ≥10 deceased patients compared to survivors Significant relationship between leukocytosis and mortality (OR = 2.0; P < 0.001) 
 De Campos et al.44 2008 Brazil Prospective Patients with acute pancreatitis – 39 ≥19 7.7% 
 Erlinger et al.23 2004 USA Retrospective Cancerous patients – 7674 – Independent risk factor for mortality 
 James et al.14 1999 Australia Prospective Patients with respiratory and cardiac illnesses – 4291 – Increased WCC was independently associated with mortality 
 Keskil et al.24 1994 Turkey Prospective Patients with head trauma – 153 >20 compared to <20 Mortality rate = 96 vs. 23% 

AMI, acute myocardial infarction; HR, hazard ratio.

Leukocytosis and morbidity

In addition to mortality effects, a raised WCC has been reported in different studies to have links with morbidity.6,12,13,15 A cohort study from Japan followed 9383 patients who were initially hypertension free, and reported that a raised WCC predicted a future increased incidence of hypertension.12 A prospective German study of 887 randomly selected non-diabetic individuals showed that leukocytosis was positively correlated with deterioration in glucose tolerance, and negatively with insulin sensitivity.13 Leukocytosis has also been reported as a prognostic marker for organ damage among healthy young soldiers (mean age 24–36 years) participating in a strenuous physical exercise in a study from Japan.15 A cohort study in the USA reported that a raised WCC was independently related to angiographically documented CHD, and it also predicted the presence of multivessel disease among 389 patients who underwent coronary angiography.6 Finally, an association between leukocytosis and major depression has been reported by Zorilla and others from the USA.45

Discussion

The literature reviewed in this article provides compelling evidence for an independent association between leukocytosis and mortality (particularly coronary and cerebrovascular). There are also various reported morbidity associations, though the evidence is less strong than for mortality. The reasons for the association between raised WCC and mortality are uncertain. Leukocytosis is a non-specific reaction to a variety of illnesses and conditions, and it may represent an ‘acute phase marker’ analogous to C-reactive protein (CRP) or the erythrocyte sedimentation rate (ESR). Interestingly, raised circulating catecholamines can cause leukocytosis, perhaps as part of a generalized stress response.46

Further research is needed to elucidate the mechanisms and significance of leukocytosis as a mortality risk. It is possible that the WCC, either alone or with other clinical and laboratory parameters, may be a potential measure of mortality risk in acutely ill hospitalized patients.25

Funding

KA was supported by the Iranian Government.

Conflict of interest: None declared.

References

1
Reding
MT
Hibbs
JR
Morrison
VA
Swain
WR
Filice
GA
Diagnosis and outcome of 100 consecutive patients with extreme granulocytic leukocytosis
Amer J Med
 , 
1998
, vol. 
104
 (pg. 
12
-
16
)
2
McCarthy
DA
Perry
JD
Melsom
RD
Dale
MM
Leukocytosis induced by exercise
Br Med J
 , 
1987
, vol. 
295
 pg. 
636
 
3
Leading Article
“Normal” leukocytosis
Br Med J
 , 
1972
, vol. 
1
 pg. 
328
 
4
Darko
DF
Rose
J
Gillin
JC
Golshan
S
Baird
SM
Neutrophilia and lymphopenia in major mood disorders
Psychiatry Res
 , 
1988
, vol. 
25
 (pg. 
243
-
51
)
5
Abramson
N
Melton
B
Leukocytosis: basics of clinical assessment
Am Fam Physician
 , 
2000
, vol. 
62
 (pg. 
2053
-
60
)
6
Cavusoglu
E
Chopra
V
Gupta
A
Ruwende
C
Yanamadala
S
Eng
C
, et al.  . 
Usefulness of the white blood cell count as a predictor of angiographic findings in an unselected population referred for coronary angiography
Am J Cardiol
 , 
2006
, vol. 
98
 (pg. 
1189
-
93
)
7
de Labry
LO
Campion
EW
Glynn
RJ
Vokonas
PS
White blood cell count as a predictor of mortality: results over 18 years from the Normative Aging Study
J Clin Epidemiol
 , 
1990
, vol. 
43
 (pg. 
153
-
7
)
8
Amaro
A
Gonzalez-Juanatey
JR
Iglesias
C
Martinez-Sande
L
Trillo
R
Garcia-Acuna
J
, et al.  . 
Leukocyte count as a predictor of the severity ischaemic heart disease as evaluated by coronary angiography
Rev Port Cardiol
 , 
1993
, vol. 
12
 (pg. 
913
-
7
)
9
Barron
HV
Harr
SD
Radford
MJ
Wang
Y
Krumholz
HM
The association between white blood cell count and acute myocardial infarction mortality in patients over 65 years of age: findings from the cooperative cardiovascular project
J Am Coll Cardiol
 , 
2001
, vol. 
38
 (pg. 
1654
-
61
)
10
Cannon
CP
McCabe
CH
Wilcox
RG
Bentley
JH
Braunwald
E
Association of white blood cell count with increased mortality in acute myocardial infarction and unstable angina pectoris. OPUS-TIMI 16 Investigators
Am J Cardiol
 , 
2001
, vol. 
87
 (pg. 
636
-
9
)
11
Kazmierski
R
Guzik
P
Ambrosius
W
Kozubski
W
Leukocytosis in the first day of acute ischemic stroke as a prognostic factor of disease progression
Wiad Lek
 , 
2001
, vol. 
54
 (pg. 
143
-
51
)
12
Tatsukawa
Y
Hsu
WL
Yamada
M
Cologne
JB
Suzuki
G
Yamamoto
H
, et al.  . 
White blood cell count, especially neutrophil count, as a predictor of hypertension in a Japanese population
Hypertens Res
 , 
2008
, vol. 
31
 (pg. 
1391
-
7
)
13
Fritsche
A
Haring
H
Stumvoll
M
White blood cell count as a predictor of glucose tolerance and insulin sensitivity. The role of inflammation in the pathogenesis of type 2 diabetes mellitus
Dtsch Med Wochenschr
 , 
2004
, vol. 
129
 (pg. 
244
-
8
)
14
James
AL
Knuiman
MW
Divitini
ML
Musk
AW
Ryan
G
Bartholomew
HC
Associations between white blood cell count, lung function, respiratory illness and mortality: the Busselton Health Study
Eur Respir J
 , 
1999
, vol. 
13
 (pg. 
1115
-
9
)
15
Kayashima
S
Ohno
H
Fujioka
T
Taniguchi
N
Nagata
N
Leukocytosis as a marker of organ damage induced by chronic strenuous physical exercise
Eur J Appl Physiol Occup Physiol
 , 
1995
, vol. 
70
 (pg. 
413
-
20
)
16
Ruggiero
C
Metter
EJ
Cherubini
A
Maggio
M
Sen
R
Najjar
SS
, et al.  . 
White blood cell count and mortality in the Baltimore Longitudinal Study of Aging
J Am Coll Cardiol
 , 
2007
, vol. 
49
 (pg. 
1841
-
50
)
17
Leng
SX
Xue
QL
Huang
Y
Ferrucci
L
Fried
LP
Walston
JD
Baseline total and specific differential white blood cell counts and 5-year all-cause mortality in community-dwelling older women
Exp Gerontol
 , 
2005
, vol. 
40
 (pg. 
982
-
7
)
18
Jee
SH
Park
JY
Kim
HS
Lee
TY
Samet
JM
White blood cell count and risk for all-cause, cardiovascular, and cancer mortality in a cohort of Koreans
Am J Epidemiol
 , 
2005
, vol. 
162
 (pg. 
1062
-
9
)
19
Weijenberg
MP
Feskens
EJ
Kromhout
D
White blood cell count and the risk of coronary heart disease and all-cause mortality in elderly men
Arterioscler Thromb Vasc Biol
 , 
1996
, vol. 
16
 (pg. 
499
-
503
)
20
Tamakoshi
K
Toyoshima
H
Yatsuya
H
Matsushita
K
Okamura
T
Hayakawa
T
, et al.  . 
White blood cell count and risk of all-cause and cardiovascular mortality in nationwide sample of Japanese – results from the NIPPON DATA90
Circ J
 , 
2007
, vol. 
71
 (pg. 
479
-
85
)
21
Shankar
A
Mitchell
P
Rochtchina
E
Wang
JJ
The association between circulating white blood cell count, triglyceride level and cardiovascular and all-cause mortality: population-based cohort study
Atherosclerosis
 , 
2007
, vol. 
192
 (pg. 
177
-
83
)
22
Shankar
A
Wang
JJ
Rochtchina
E
Yu
MC
Kefford
R
Mitchell
P
Association between circulating white blood cell count and cancer mortality: a population-based cohort study
Arch Intern Med
 , 
2006
, vol. 
166
 (pg. 
188
-
94
)
23
Erlinger
TP
Muntner
P
Helzlsouer
KJ
WBC count and the risk of cancer mortality in a national sample of U.S. adults: results from the Second National Health and Nutrition Examination Survey mortality study
Cancer Epidemiol Biomarkers Prev
 , 
2004
, vol. 
13
 (pg. 
1052
-
6
)
24
Keskil
S
Baykaner
MK
Ceviker
N
Aykol
S
Head trauma and leukocytosis
Acta Neurochir (Wien)
 , 
1994
, vol. 
131
 (pg. 
211
-
4
)
25
Asadollahi
K
Hastings
IM
Beeching
NJ
Gill
GV
Laboratory risk factors for hospital mortality in acutely admitted patients
QJM
 , 
2007
, vol. 
100
 (pg. 
501
-
7
)
26
Chalasani
N
Patel
K
Clark
WS
Wilcox
CM
The prevalence and significance of leukocytosis in upper gastrointestinal bleeding
Am J Med Sci
 , 
1998
, vol. 
315
 (pg. 
233
-
6
)
27
Pitsavos
C
Kourlaba
G
Panagiotakos
DB
Tsamis
E
Kogias
Y
Stravopodis
P
, et al.  . 
Does smoking status affect the association between baseline white blood cell count and in-hospital mortality of patients presented with acute coronary syndrome? The Greek study of acute coronary syndromes (GREECS)
Int J Cardiol
 , 
2008
, vol. 
125
 (pg. 
94
-
100
)
28
Newall
N
Grayson
AD
Oo
AY
Palmer
ND
Dihmis
WC
Rashid
A
, et al.  . 
Preoperative white blood cell count is independently associated with higher perioperative cardiac enzyme release and increased 1-year mortality after coronary artery bypass grafting
Ann Thorac Surg
 , 
2006
, vol. 
81
 (pg. 
583
-
9
)
29
Lipinski
MJ
Martin
RE
Cowley
MJ
Goudreau
E
Malloy
WN
Johnson
RE
, et al.  . 
Effect of statins and white blood cell count on mortality in patients with ischemic left ventricular dysfunction undergoing percutaneous coronary intervention
Clin Cardiol
 , 
2006
, vol. 
29
 (pg. 
36
-
41
)
30
Nunez
J
Facila
L
Llacer
A
Sanchis
J
Bodi
V
Bertomeu
V
, et al.  . 
Prognostic value of white blood cell count in acute myocardial infarction: long-term mortality
Rev Esp Cardiol
 , 
2005
, vol. 
58
 (pg. 
631
-
9
)
31
Stewart
RA
White
HD
Kirby
AC
Heritier
SR
Simes
RJ
Nestel
PJ
, et al.  . 
White blood cell count predicts reduction in coronary heart disease mortality with pravastatin
Circulation
 , 
2005
, vol. 
111
 (pg. 
1756
-
62
)
32
Rajagopal
V
Gurm
HS
Bhatt
DL
Lincoff
AM
Tcheng
JE
Kereiakes
DJ
, et al.  . 
Relation of an elevated white blood cell count after percutaneous coronary intervention to long-term mortality
Am J Cardiol
 , 
2004
, vol. 
94
 (pg. 
190
-
2
)
33
Grzybowski
M
Welch
RD
Parsons
L
Ndumele
CE
Chen
E
Zalenski
R
, et al.  . 
The association between white blood cell count and acute myocardial infarction in-hospital mortality: findings from the National Registry of Myocardial Infarction
Acad Emerg Med
 , 
2004
, vol. 
11
 (pg. 
1049
-
60
)
34
Dacey
LJ
DeSimone
J
Braxton
JH
Leavitt
BJ
Lahey
SJ
Klemperer
JD
, et al.  . 
Preoperative white blood cell count and mortality and morbidity after coronary artery bypass grafting
Ann Thorac Surg
 , 
2003
, vol. 
76
 (pg. 
760
-
4
)
35
Mueller
C
Neumann
FJ
Perruchoud
AP
Buettner
HJ
White blood cell count and long term mortality after non-ST elevation acute coronary syndrome treated with very early revascularisation
Heart
 , 
2003
, vol. 
89
 (pg. 
389
-
92
)
36
Gurm
HS
Bhatt
DL
Lincoff
AM
Tcheng
JE
Kereiakes
DJ
Kleiman
NS
, et al.  . 
Impact of preprocedural white blood cell count on long term mortality after percutaneous coronary intervention: insights from the EPIC, EPILOG, and EPISTENT trials
Heart
 , 
2003
, vol. 
89
 (pg. 
1200
-
4
)
37
Bhatt
DL
Chew
DP
Lincoff
AM
Simoons
ML
Harrington
RA
Ommen
SR
, et al.  . 
Effect of revascularization on mortality associated with an elevated white blood cell count in acute coronary syndromes
Am J Cardiol
 , 
2003
, vol. 
92
 (pg. 
136
-
40
)
38
Sabatine
MS
Morrow
DA
Cannon
CP
Murphy
SA
Demopoulos
LA
DiBattiste
PM
, et al.  . 
Relationship between baseline white blood cell count and degree of coronary artery disease and mortality in patients with acute coronary syndromes: a TACTICS-TIMI 18 (Treat Angina with Aggrastat and determine Cost of Therapy with an Invasive or Conservative Strategy – thrombolysis in Myocardial Infarction 18 trial) substudy
J Am Coll Cardiol
 , 
2002
, vol. 
40
 (pg. 
1761
-
8
)
39
Lee
CD
Folsom
AR
Nieto
FJ
Chambless
LE
Shahar
E
Wolfe
DA
White blood cell count and incidence of coronary heart disease and ischemic stroke and mortality from cardiovascular disease in African–American and White men and women: atherosclerosis risk in communities study
Am J Epidemiol
 , 
2001
, vol. 
154
 (pg. 
758
-
64
)
40
Grimm
RH
Jr.
Neaton
JD
Ludwig
W
Prognostic importance of the white blood cell count for coronary, cancer, and all-cause mortality
JAMA
 , 
1985
, vol. 
254
 (pg. 
1932
-
7
)
41
Comparan-Nunez
A
Palacios
JM
Jerjes-Sanchez
CD
Leukocytosis associated with higher incidence of adverse cardiovascular events in myocardial infarcts
Arch Cardiol Mex
 , 
2005
, vol. 
75
 
Suppl. 3
(pg. 
S361
-
8
)
42
Kazmierski
R
Guzik
P
Ambrosius
W
Ciesielska
A
Moskal
J
Kozubski
W
Predictive value of white blood cell count on admission for in-hospital mortality in acute stroke patients
Clin Neurol Neurosurg
 , 
2004
, vol. 
107
 (pg. 
38
-
43
)
43
Brown
DW
Ford
ES
Giles
WH
Croft
JB
Balluz
LS
Mokdad
AH
Associations between white blood cell count and risk for cerebrovascular disease mortality: NHANES II Mortality Study, 1976-1992
Ann Epidemiol
 , 
2004
, vol. 
14
 (pg. 
425
-
30
)
44
De Campos
T
Cerqueira
C
Kuryura
L
Parreira
JG
Solda
S
Perlingeiro
JA
, et al.  . 
Morbimortality indicators in severe acute pancreatitis
JOP
 , 
2008
, vol. 
9
 (pg. 
690
-
7
)
45
Zorilla
EP
Luborsky
L
McKay
JR
Rosenthal
R
Houldin
A
Tax
A
, et al.  . 
The relationship of depression and stressors to imuunological assyas: a meta-analytic review
Brain Behav Immun
 , 
2001
, vol. 
15
 (pg. 
199
-
226
)
46
Benschop
RJ
Rodriguez-Feuerhan
M
Schedlowski
M
Catecholamine-induced leukocytosis; early observations, current research and future directions
Brain Behav Immun
 , 
1996
, vol. 
10
 (pg. 
77
-
9
)