The Neutrophil-to-Albumin Ratio as a New Predictor of All-Cause Mortality in Patients with Heart Failure

Figures & data

Table 1 Baseline Characteristics of the Study Population

Characteristics	The Level of NPAR			P value
	<22.56 (n=980)	22.56–27.64 (n=980)	>27.64 (n=982)
NPAR, dl/g	18.55 ± 4.19	25.03 ± 1.40	33.82 ± 6.40	<0.001
Clinical parameters
Age, years	72.13 ± 13.95	72.99 ± 13.52	73.11 ± 14.13	0.237
Gender, n(%)				0.420
Male	520 (53.06)	497 (50.71)	494 (50.31)
Female	460 (46.94)	483 (49.29)	488 (49.69)
Ethnicity, n(%)				<0.001
White	687 (70.10)	712 (72.65)	724 (73.73)
Black	153 (15.61)	107 (10.92)	88 (8.96)
Other	140 (14.29)	161 (16.43)	170 (17.31)
Vital signs
SBP, mmHg	118.54 ± 18.36	117.26 ± 17.13	113.45 ± 16.82	<0.001
DBP, mmHg	60.11 ± 11.80	58.02 ± 10.17	55.95 ± 10.38	<0.001
MAP, mmHg	77.31 ± 11.89	75.65 ± 10.49	73.38 ± 11.01	<0.001
Heart rate, beats/minute	83.32 ± 16.61	84.45 ± 16.19	87.92 ± 16.11	<0.001
RR, times/minute	19.79 ± 3.92	20.16 ± 4.07	20.34 ± 4.16	0.009
Temperature, °C	36.75 ± 0.65	36.78 ± 0.67	36.74 ± 0.70	0.461
SpO2, %	96.89 ± 2.07	96.77 ± 2.63	96.99 ± 2.83	0.170
Comorbidities, n(%)
CHF	942 (96.12)	944 (96.33)	956 (97.35)	0.273
Cardiac arrhythmias	526 (53.67)	571 (58.27)	559 (56.92)	0.109
Infected	412 (42.04)	547 (55.82)	691 (70.37)	<0.001
Valvular disease	245 (25.00)	246 (25.10)	195 (19.86)	0.007
Pulmonary circulation	134 (13.67)	137 (13.98)	109 (11.10)	0.113
Chronic pulmonary	324 (33.06)	354 (36.12)	306 (31.16)	0.063
Hypertension	636 (64.90)	634 (64.69)	528 (53.77)	<0.001
Renal failure	330 (33.67)	341 (34.80)	325 (33.10)	0.721
Laboratory parameters
Albumin, g/dl	3.73 ± 0.48	3.31 ± 0.34	2.62 ± 0.41	<0.001
Serum creatinine, mg/dl	2.14 ± 2.11	2.10 ± 1.91	2.10 ± 1.75	0.838
Glucose, mg/dl	160.28 ± 93.25	168.67 ± 96.08	155.49 ± 98.02	0.009
Serum urea nitrogen, mg/dl	38.63 ± 27.12	40.65 ± 27.80	44.10 ± 29.20	<0.001
Hematocrit, %	35.18 ± 6.73	33.29 ± 6.57	31.49 ± 5.71	<0.001
Hemoglobin, g/dl	11.66 ± 2.28	10.98 ± 2.23	10.30 ± 1.94	<0.001
WBC, 10^9/l	11.90 ± 13.77	13.10 ± 7.37	15.25 ± 8.63	<0.001
Neutrophil percentage, %	69.53 ± 17.54	82.78 ± 8.00	86.53 ± 6.97	<0.001
Platelet, 10^9/l	234.15 ± 119.42	251.99 ± 118.31	266.00 ± 140.54	<0.001
RDW, fl	15.50 ± 2.18	15.65 ± 2.18	16.26 ± 2.30	<0.001
Sodium, mmol/l	137.87 ± 5.28	138.04 ± 5.44	138.36 ± 5.90	0.135
Potassium, mmol/l	4.42 ± 0.88	4.38 ± 0.78	4.29 ± 0.78	0.002
Bicarbonate, mmol/l	24.68 ± 5.83	24.20 ± 5.89	23.60 ± 5.90	<0.001
Anion gap, mmol/l	16.92 ± 4.63	16.52 ± 4.50	15.78 ± 4.45	<0.001
APTT, second	38.58 ± 25.17	38.91 ± 24.87	40.37 ± 25.11	0.256
INR	1.76 ± 1.46	1.92 ± 1.94	1.87 ± 1.74	0.126
PT, second	17.52 ± 9.58	18.74 ± 13.45	19.03 ± 15.55	0.029
Scoring systems
SAPSII	40.07 ± 12.80	40.88 ± 11.57	45.41 ± 14.03	<0.001
APSIII	49.55 ± 18.08	50.97 ± 16.63	59.91 ± 20.80	<0.001
In-hospital management, n(%)
Vasopressin use	336 (34.29)	368 (37.55)	470 (47.86)	<0.001
RRT	71 (7.24)	69 (7.04)	89 (9.06)	0.184
Mechanical ventilation	382 (38.98)	424 (43.27)	486 (49.49)	<0.001
Primary outcome, n(%)
30-day mortality	137 (13.98)	170 (17.35)	291 (29.63)	<0.001
Secondary outcomes
In-hospital mortality, n(%)	115 (11.73)	126 (12.86)	228 (23.22)	<0.001
90-day mortality, n(%)	212 (21.63)	263 (26.84)	404 (41.14)	<0.001
365-day mortality, n(%)	347 (35.41)	408 (41.63)	566 (57.64)	<0.001
Hospital LOS, day	10.79 ± 10.92	11.53 ± 9.30	14.66 ± 12.68	<0.001

Note: The data came from patients in MIMIC III database.

Abbreviations: NPAR, ratio of neutrophil to albumin; SBP, systolic blood pressure; DBP, diastolic blood pressure; MAP, mean arterial pressure; RR, respiratory rate; SpO₂, pulse oximetry-derived oxygen saturation; CHF, congestive heart failure; WBC, white blood cell count; RDW, red blood cell distribution width; APTT, activated partial thromboplastin time; INR, international normalized ratio; PT, prothrombin time; SAPSII, simple acute physiology score II; APSIII, acute physiology score III; RRT, renal replacement treatment; LOS, length of stay.

Figure 1 Flow chart of cohort selection.

Abbreviations: ICU, intensive care unit; MIMIC-III, Medical Information Mart for Intensive Care-III.

Table 2 HR (95% CI) or β (95% CI) for Outcomes Across Groups of Neutrophil-to-Albumin Ratios

	Non-Adjusted		Adjust I		Adjust II
Mortality	HR (95% CI)	P value	HR (95% CI)	P value	HR (95% CI)	P value
30-Day all-cause mortality
NPAR	1.04 (1.03, 1.05)	<0.001	1.04 (1.03, 1.05)	<0.001	1.02 (1.01, 1.03)	<0.001
Tertiles
<22.56	1.00		1.00		1.00
22.56–27.64	1.27 (1.01, 1.59)	0.037	1.22 (0.97, 1.53)	0.085	1.18 (0.93, 1.49)	0.171
>27.64	2.29 (1.87, 2.81)	<0.001	2.18 (1.78, 2.67)	<0.001	1.52 (1.22, 1.90)	<0.001
P for trend		<0.001		<0.001		<0.001
In-hospital all-cause mortality
NPAR	1.02 (1.00, 1.03)	0.004	1.01 (1.00, 1.02)	0.017	1.00 (0.99, 1.02)	0.416
Tertiles
<22.56	1.00		1.00		1.00
22.56–27.64	1.01 (0.78, 1.30)	0.968	0.96 (0.74, 1.24)	0.752	0.99 (0.76, 1.29)	0.962
>27.64	1.37 (1.10, 1.72)	0.006	1.31 (1.04, 1.64)	0.020	1.09 (0.85, 1.40)	0.483
P for trend		0.002		0.007		0.436
90-Day all-cause mortality
NPAR	1.04 (1.03, 1.04)	<0.001	1.04 (1.03, 1.05)	<0.001	1.02 (1.01, 1.03)	<0.001
Tertiles
<22.56	1.00		1.00		1.00
22.56–27.64	1.28 (1.07, 1.53)	0.007	1.24 (1.03, 1.48)	0.022	1.19 (0.99, 1.43)	0.069
>27.64	2.17 (1.84, 2.56)	<0.001	2.09 (1.77, 2.47)	<0.001	1.46 (1.22, 1.75)	<0.001
P for trend		<0.001		<0.001		<0.001
365-Day all-cause mortality
NPAR	1.03 (1.03, 1.04)	<0.001	1.04 (1.03, 1.04)	<0.001	1.02 (1.01, 1.03)	<0.001
Tertiles
<22.56	1.00		1.00		1.00
22.56–27.64	1.24 (1.07, 1.43)	0.004	1.20 (1.04, 1.39)	0.012	1.14 (0.99, 1.33)	0.075
>27.64	2.01 (1.76, 2.30)	<0.001	1.97 (1.72, 2.26)	<0.001	1.43 (1.24, 1.66)	<0.001
P for trend		<0.001		<0.001		<0.001
Hospital LOS, day	β (95% CI)	P value	β (95% CI)	P value	β (95% CI)	P value
NPAR	0.19 (0.14, 0.24)	<0.001	0.19 (0.14, 0.24)	<0.001	0.07 (0.01, 0.12)	0.017
Tertiles
<22.56	0.00		0.00		0.00
22.56–27.64	0.74 (−0.24, 1.72)	0.139	0.80 (−0.18, 1.77)	0.109	−0.23 (−1.18, 0.73)	0.643
>27.64	3.87 (2.89, 4.85)	<0.001	3.93 (2.95, 4.90)	<0.001	1.38 (0.35, 2.40)	0.008
P for trend		<0.001		<0.001		0.006

Notes: Non-adjusted and Adjust I and II were derived from Cox proportional hazards regression models: Adjust I covariates were adjusted for age, gender and ethnicity; Adjust II covariates were adjusted for age, gender, ethnicity, anion gap, bicarbonate, APTT, INR, PT, serum urea nitrogen, RDW, heart rate, SBP, DBP, RR, temperature, SpO_2, cardiac arrhythmias, hypertension, vasopressin use, mechanical ventilation, infected, SAPSII, APSIII. The data came from patients in MIMIC III database.

Abbreviations: NPAR, ratio of neutrophil to albumin; HR, hazard ratio; CI, confidence interval; OR, odds ratio; RRT, renal replacement treatment; APTT, activated partial thromboplastin time; INR, international normalized ratio; PT, prothrombin time; RDW, red blood cell distribution width; SBP, systolic blood pressure; DBP, diastolic blood pressure; RR, respiratory rate; SpO2, pulse oximetry-derived oxygen saturation; SAPSII, simple acute physiology score II; APSIII, acute physiology score III; LOS, length of stay.

Table 3 Subgroup Analysis of the Association Between NPAR and 30-Day Mortality

Variables	No. of Patients	HR	Lower Limit of 95% CI	Upper Limit of 95% CI	P for Interaction
Age, years					0.942
<75	1471	1.04	1.02	1.05
≥75	1471	1.04	1.03	1.05
Gender					0.381
Male	1511	1.04	1.03	1.06
Female	1431	1.04	1.02	1.05
Ethnicity					0.491
White	2123	1.04	1.03	1.05
Black	348	1.04	1.02	1.06
Other	471	1.03	1.00	1.05
MAP, mmHg					0.165
<74	1468	1.03	1.02	1.04
≥74	1469	1.04	1.03	1.06
Heart rate, beats/minute					0.233
<84	1468	1.05	1.04	1.07
≥84	1469	1.03	1.02	1.04
RR, times/minute					0.118
<20	1468	1.04	1.03	1.05
≥20	1469	1.04	1.03	1.05
CHF					0.632
Yes	2842	1.04	1.03	1.05
No	100	1.02	0.95	1.10
Valvular disease					0.292
Yes	686	1.05	1.03	1.08
No	2256	1.04	1.03	1.05
Hypertension					0.447
Yes	1798	1.04	1.03	1.05
No	1144	1.03	1.02	1.05
Renal failure					0.558
Yes	996	1.04	1.03	1.06
No	1946	1.04	1.03	1.05
Serum creatinine, mg/dl					0.768
≤1.4	1455	1.04	1.03	1.05
≥1.5	1487	1.04	1.03	1.05
Glucose, mg/dl					0.761
≤134	1458	1.03	1.02	1.05
≥135	1482	1.05	1.03	1.06
Serum urea nitrogen, mg/dl					0.815
≤32	1454	1.04	1.03	1.05
≥33	1488	1.04	1.02	1.05
RDW, fl					0.636
≤15.2	1421	1.04	1.02	1.06
≥15.3	1518	1.03	1.02	1.04
Anion gap, mmol/l					0.065
≤15	1379	1.04	1.03	1.05
≥16	1563	1.05	1.03	1.06
APTT, second					0.756
≤31	1421	1.04	1.02	1.06
>31	1428	1.04	1.03	1.05
INR					0.114
≤1.2	1147	1.04	1.02	1.06
≥1.3	1699	1.03	1.02	1.04
PT, second					0.103
≤14.5	1416	1.03	1.01	1.05
≥14.6	1430	1.04	1.03	1.05
SAPSII					0.526
≤40	1464	1.04	1.02	1.06
≥41	1478	1.03	1.02	1.04
APSIII					0.614
≤50	1419	1.03	1.01	1.05
≥51	1523	1.03	1.02	1.04

Notes: HR (95% CI) were derived from Cox proportional hazards regression models. The data came from patients in MIMIC III database.

Abbreviations: NPAR, ratio of neutrophil to albumin; HR, hazard ratio; CI, confidence interval; MAP, mean arterial pressure; RR, respiratory rate; CHF, congestive heart failure; RDW, red blood cell distribution width; APTT, activated partial thromboplastin time; INR, international normalized ratio; PT, prothrombin time; SAPSII, simple acute physiology score II; APSIII, acute physiology score III.

Figure 2 ROC curve for combining SAPSII and NPAR. (Model 1: SAPSII+NPAR; model 2: SAPSII).

Note: The data came from patients in MIMIC III database.

Abbreviations: AUC, area under the curve; SAPSII, simple acute physiology score II; APSIII, acute physiology score III; NPAR, ratio of neutrophil to albumin; ROC, receiver operator characteristic curve.

Figure 3 Pearson correlation analysis of the NPAR and hospital LOS.

Note: The data came from patients in the Second Affiliated Hospital of Wenzhou Medical University.

Abbreviations: NPAR, ratio of neutrophil to albumin; LOS, length of stay.