The Association Between Absolute Lymphocyte Count and Long-Term Mortality in Critically Ill Medical Patients: Propensity Score-Based Analyses

Figures & data

Table 1 Characteristics of Critically Ill Patients Categorized by One-Year Mortality

	All	Survivor	Non-Survivor	p value
	n=5722	n=3154	n=2568
Basic characteristics comorbidities
Age, years	68 [57–80]	66 [54–77]	71 [60–82]	<0.01
Sex (male)	3633 (63.5%)	1922 (60.9%)	1711 (66.6%)	<0.01
Body mass index	23.2 [20.4–26.3]	23.6 [20.8–26.7]	22.7 [20.1–25.9]	<0.01
Charlson Comorbidity Index	2 [1–3]	2 [1–3]	2[1–4]	<0.01
Severity and managements
APACHE II score	25 [19–30]	23 [17–28]	27 [22–32]	<0.01
Presence of septic shock	986 (17.20%)	320 (10.10%)	666 (25.90%)	<0.01
Receiving mechanical ventilation	4234 (74%)	2078 (65.9%)	2156 (84%)	<0.01
Fluid balance day 1–3, positive	3684 (64.4%)	1784 (56.6%)	1900 (74%)	<0.01
Blood transfusion in ICU	2944 (51.5%)	1204 (38.2%)	1740 (67.8%)	<0.01
Main organ dysfunction/failure
Acute respiratory failure	2860 (50.0%)	1308 (41.6%)	1552 (60.4%)	<0.01
Acute neurological dysfunction	544 (9.5%)	362 (11.5%)	182 (7.1%)
Acute cardiac dysfunction	500 (8.7%)	348 (11.0%)	152 (5.9%)
Acute renal failure	219 (3.8%)	135 (4.3%)	84 (3.3%)
Others	1599 (27.9%)	1001 (31.7%)	598 (23.3%)
Laboratory data
White blood cell count (10^3/μL)	13.3 [10.2–16.5]	12.8 [9.8–16.0]	14.0 [10.8–17.0]	<0.01
Haemoglobin (g/dL)	12.6 [11.2–14.1]	13.0 [11.5–14.5]	12.1 [11.0–13.5]	<0.01
Platelet (10^3/μL)	248 [203–303]	253 [207–306]	243 [197–300]	<0.01
Albumin (g/dL)	3.1 [2.6–3.6]	3.3 [2.8–3.8]	2.9 [2.5–3.4]	<0.01
Creatinine (mg/dL)	1.1 [0.8–1.4]	1.0 [0.8–1.3]	1.1 [0.8–1.5]	<0.01
Lactate (mg/dL)	15.20 [11.3–19.4]	14.8 [11.0–19.1]	15.5 [11.8–20.0]	<0.01
Absolute lymphocyte count (/μL)	1774 [1202–2620]	1948 [1373–2743]	1549 [1027–2388]	<0.01
Outcome
ICU length of stay, days	8 [4–15]	6 [3–12]	10 [6–18]	<0.01
Hospital length of stay, days	20 [11–34]	18 [10–31]	23 [12–37]	<0.01

Note: Data are shown as mean ± standard deviation and number (percentages).

Abbreviations: COPD, chronic obstructive pulmonary disease; APACHE, acute physiology and chronic health evaluation; ICU, intensive care unit.

Figure 1 Flowchart of subject enrollment.

Abbreviations: ICUs, intensive care units; TCVGH, Taichung Veterans General Hospital.

Table 2 Cox Proportional Hazard Regression Analysis for Long-Term Mortality Among the 5722 Critically Ill Patients

	Univariable Analysis		Multivariable Analysis
	HR (95% CI)	p value	HR (95% CI)	p value
Basic characteristics
Age, years	1.014 (1.012–1.017)	<0.001	1.006 (1.003–1.009)	<0.001
Sex (male)	1.190 (1.096–1.292)	<0.001	1.251 (1.151–1.361)	<0.001
Body mass index	0.979 (0.970–0.987)	<0.001	0.999 (0.991–1.008)	0.879
CCI≥2	1.575 (1.443–1.719)	<0.001	1.317 (1.205–1.441)	<0.001
Severity and managements
APACHE II score	1.060 (1.054–1.065)	<0.001	1.029 (1.023–1.035)	<0.001
Presence of septic shock	2.347 (2.148–2.564)	<0.001	1.507 (1.372–1.656)	<0.001
Receiving mechanical ventilation	2.165 (1.949–2.406)	<0.001	1.270 (1.131–1.425)	<0.001
Fluid balance day 1–3, positive	1.915 (1.753–2.091)	<0.001	1.552 (1.418–1.699)	<0.001
Blood transfusion in ICU	2.458 (2.262–2.671)	<0.001	1.527 (1.391–1.676)	<0.001
Main organ dysfunction/failure
Acute respiratory failure	Reference		Reference
Acute cardiac dysfunction	0.480 (0.406–0.567)	<0.001	0.776 (0.653–0.922)	0.004
Acute neurological dysfunction	0.533 (0.457–0.621)	0.343	1.088 (0.925–1.280)	0.308
Acute renal failure	0.652 (0.524–0.812)	0.066	0.967 (0.775–1.208)	0.770
Laboratory data
WBC, per 10^3 /μL increment	1.038 (1.028–1.049)	<0.001	1.013 (1.003–1.024)	0.013
Albumin (g/dl)	0.863 (0.844–0.882)	<0.001	0.955 (0.932–0.978)	<0.001
Platelet (10^3/μL)	0.998 (0.998–0.999)	<0.001	0.999 (0.998–0.999)	<0.001
Haemoglobin (g/dL)	0.531 (0.499–0.564)	<0.001	0.724 (0.676–0.775)	<0.001
Creatinine (mg/dL)	1.471 (1.330–1.628)	<0.001	1.098 (0.990–1.219)	0.077
Lactate (mg/dL)	1.020 (1.012–1.028)	<0.001	1.009 (1.002–1.017)	0.017
ALC, per 10^3/μL decrement	1.212 (1.166–1.260)	<0.001	1.091 (1.050–1.134)	<0.001

Abbreviations: CCI, Charlson Comorbidity Index; APACHE, acute physiology and chronic health evaluation; WBC, white blood cell; ALC, absolute lymphocyte counts.

Table 3 Stratified Analyses of Modification Effect on the Association Between the Absolute Lymphocyte Count Cut by 1500 Counts/μL and Risk of Mortality

Variables	Crude HR (95% CI)	p value	Adjusted HR (95% CI)	p value
Age, years		0.014		0.026
<65	1.813 (1.591–2.066)		1.715 (1.503–1.958)
≥65	1.538 (1.396–1.694)		1.524 (1.382–1.680)
Sex		0.161		0.117
Female	1.531 (1.339–1.752)		1.493 (1.303–1.710)
Male	1.735 (1.578–1.908)		1.673 (1.502–1.842)
Body mass index		0.242		0.206
<23.7	1.601 (1.446–1.772)		1.558 (1.407–1.726)
≥23.7	1.701 (1.507–1.920)		1.682 (1.490–1.900)
Charlson Comorbidity Index		0.011		0.022
<2	1.886 (1.623–2.192)		1.731 (1.486–2.018)
≥2	1.522 (1.390–1.666)		1.500 (1.369–1.643)
APACHE II score		0.024		0.027
<24.5	1.774 (1.559–2.019)		1.672 (1.467–1.906)
≥24.5	1.459 (1.324–1.608)		1.455 (1.32–1.605)
Presence of septic shock		0.281		0.352
No	1.666 (1.522–1.823)		1.593 (1.454–1.745)
Yes	1.453 (1.247–1.692)		1.464 (1.255–1.707)
Main organ dysfunction/failure		0.382		0.405
Acute respiratory failure	1.484 (1.343–1.640)		1.465 (1.324–1.620)
Acute neurological disorders	1.700 (1.244–2.322)		1.620 (1.183–2.218)
Acute cardiac disorders	1.836 (1.335–2.524)		1.793 (1.303–2.469)
Acute renal disorders	1.284 (0.824–2.001)		1.332 (0.852–2.083)
Receiving mechanical ventilation		0.004		0.006
No	2.112 (1.741–2.562)		1.902 (1.562–2.316)
Yes	1.547 (1.422–1.684)		1.531 (1.406–1.668)
Fluid balance during day 1–3, positive		0.009		0.011
No	1.966 (1.689–2.288)		1.874 (1.607–2.187)
Yes	1.504 (1.375–1.646)		1.474 (1.346–1.614)
White blood cell count (10^3/μL)		0.210		0.237
<13.2	1.854 (1.647–2.087)		1.775 (1.575–2.001)
≥13.2	1.657 (1.493–1.840)		1.622 (1.459–1.803)
Albumin (g/dl)		0.192		0.192
<3.1	1.484 (1.343–1.640)		1.493 (1.349–1.651)
≥3.1	1.658 (1.465–1.876)		1.560 (1.377–1.767)
Platelet (10^3/μL)		0.153		0.248
<255.5	1.562 (1.408–1.732)		1.537 (1.385–1.707)
≥255.5	1.778 (1.581–1.998)		1.705 (1.514–1.919)
Haemoglobin (g/dL)		<0.001		<0.001
<12.8	1.435 (1.300–1.585)		1.429 (1.293–1.578)
≥12.8	1.902 (1.678–2.156)		1.798 (1.584–2.041)
Creatinine (mg/dL)		0.002		0.001
<1.1	1.887 (1.690–2.107)		1.834 (1.641–2.050)
≥1.1	1.461 (1.310–1.629)		1.417 (1.269–1.583)

Abbreviation: APACHE, acute physiology and chronic health evaluation.

Table 4 Cox Proportional Hazard Regressions for Estimation of the Association Between the Level of Week-One Absolute Lymphocyte Count and Long-Term All-Cause Mortality in Distinct Patient Populations

	Original Population		PSM		IPTW		CBPS
	HR (95% CI)		HR (95% CI)		HR (95% CI)		HR (95% CI)
Model 1	1.665 (1.541–1.800)	<0.001	1.251 (1.143–1.370)	<0.001	1.220 (1.123–1.325)	<0.001	1.264 (1.165–1.372)	<0.001
Model 2	1.356 (1.253–1.467)	<0.001	1.276 (1.166–1.397)	<0.001	1.271 (1.167–1.384)	<0.001	1.280 (1.177–1.393)	<0.001
Model 3	1.327 (1.224–1.438)	<0.001	1.301 (1.188–1.424)	<0.001	1.292 (1.186–1.407)	<0.001	1.297 (1.191–1.412)	<0.001

Notes: Model 1. Unadjusted. Model 2. Adjusted for demographic data, comorbidities, and critical illness severity/management listed in Table 1. Model 3. Adjusted for variables in model 2, main organ dysfunction/failure, and laboratory data.

Abbreviations: PSM, propensity score matching; IPTW, inverse probability of treatment weighting; CBPS, covariate balancing propensity score; HR, hazard ratio; CI, confidence interval.

Figure 2 Flowchart of propensity score matching.

Abbreviations: ICUs, intensive care units; TCVGH, Taichung Veterans General Hospital.

Figure 3 The strength of association between long-term mortality and week-one absolute lymphocyte count with distinct cut-off values. (A) Original population. (B) Propensity-score matched population.

Table 5 Association Between Absolute Lymphocyte Count Lower Than 1500 per μL and Long-Term Mortality in Critically Ill Patients After Excluding Those Who Died Within Particular Durations

	Crude HR	p value	Adjusted HR	p value
	95% CI		95% CI
Mortality within 1–3 days, n= 208	1.741 (1.606–1.887)	<0.001	1.424 (1.310–1.548)	<0.001
Mortality within 1–5 days, n=342	1.784 (1.642–1.939)	<0.001	1.462 (1.342–1.593)	<0.001
Mortality within 1–7 days, n=462	1.836 (1.686–2.000)	<0.001	1.503 (1.376–1.642)	<0.001
Mortality within 1–10 days, n=623	1.854 (1.696–2.026)	<0.001	1.513 (1.380–1.659)	<0.001
Mortality within 1–14 days, n=801	1.829 (1.666–2.008)	<0.001	1.487 (1.351–1.638)	<0.001

Note: Adjusted covariates demographics, severity, managements and laboratory data as shown in Table 2.