Heparin-binding protein as a predictor of mortality in patients with diabetes mellitus and community-acquired pneumonia in intensive care unit : a propensity score matched study

doi:10.5847/wjem.j.1920-8642.2024.033

Abstract

Abstract:

BACKGROUND: Patients with diabetes mellitus (DM) are vulnerable to community-acquired pneumonia (CAP), which have a high mortality rate. We aimed to investigate the value of heparin-binding protein (HBP) as a prognostic marker of mortality in patients with DM and CAP.

METHODS: This retrospective study included CAP patients who were tested for HBP at intensive care unit (ICU) admission from January 2019 to April 2020. Patients were allocated to the DM or non-DM group and paired with propensity score matching. Baseline characteristics and clinical outcomes up to 90 days were evaluated. The primary outcome was the 10-day mortality. Receiver operating characteristic (ROC) curves, Kaplan-Meier analysis, and Cox regression were used for statistical analysis.

RESULTS: Among 152 enrolled patients, 60 pairs were successfully matched. There was no significant difference in 10-day mortality, while more patients in the DM group died within 28 d (P=0.024) and 90 d (P=0.008). In the DM group, HBP levels at ICU admission were higher in 10-day non-survivors than in 10-day survivors (median 182.21 [IQR: 55.43-300] ng/ml vs. median 66.40 [IQR: 34.13-107.85] ng/mL, P=0.019), and HBP levels could predict the 10-day mortality with an area under the ROC curve of 0.747. The cut-off value, sensitivity, and specificity were 160.6 ng/mL, 66.7%, and 90.2%, respectively. Multivariate Cox regression analysis indicated that HBP was an independent prognostic factor for 10-day (HR 7.196, 95%CI: 1.596-32.455, P=0.01), 28-day (HR 4.381, 95%CI: 1.449-13.245, P=0.009), and 90-day mortality (HR 4.581, 95%CI: 1.637-12.819, P=0.004) in patients with DM.

CONCLUSION: Plasma HBP at ICU admission was associated with the 10-day, 28-day, and 90-day mortality, and might be a prognostic factor in patients with DM and CAP.

Key words: Community-acquired pneumonia, Diabetes mellitus, Heparin-binding protein, Propensity score match

Yuhan Sun, Baoqing Sun, Zhigang Ren, Mingshan Xue, Changju Zhu, Qi Liu. Heparin-binding protein as a predictor of mortality in patients with diabetes mellitus and community-acquired pneumonia in intensive care unit : a propensity score matched study[J]. World Journal of Emergency Medicine, 2024, 15(4): 263-272.

Figures/Tables 6

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Characteristics	DM group (n=68)	Non-DM group (n=84)	χ²/Z value	P-value
Demography
Age, years, median (IQR)	68 (55-74)	57 (44-71)	-2.421	0.015
Male, n (%)	46 (67.6)	60 (71.4)	0.255	0.614
Comorbidity, n (%)
Hypertension	39 (57.4)	20 (23.8)	17.804	<0.001
COPD	8 (11.8)	17 (20.2)	1.963	0.161
ACD	13 (19.1)	9 (10.7)	2.144	0.143
Cor pulmonale	6 (8.8)	7 (8.3)	0.012	0.914
Cardiac arrhythmia	7 (10.3)	9 (10.7)	0.007	0.933
Remote cerebral infarction	14 (20.6)	8 (9.5)	3.716	0.054
CKD	7 (10.3)	3 (3.6)	2.763	0.096
Others	6 (8.8)	9 (10.7)	0.151	0.698
Laboratory tests, median (IQR)
HBP, ng/mL	67.55 (37.87-115.27)	54.04 (28.07-109.57)	-1.162	0.245
PO₂/FiO₂, mmHg	162.4 (118.2-216.9)	204.1 (129.2-261.95)	-2.162	0.031
Glucose, mmol/L	10.42 (7.93-14.15)	6.40 (5.53-7.70)	-8.148	<0.001
WBC,×10⁹/L	9.73 (6.97-12.88)	7.47 (5.05-11.5)	-2.412	0.016
NEUT, %	7.74 (5.98-11.03)	5.62 (3.70-9.89)	-2.548	0.011
CRP, mg/L	75.11 (39.25-124.28)	59.46 (16.82-98.48)	-2.212	0.027
PCT, ng/L	0.47 (0.140-1.076)	0.27 (0.071-0.783)	-1.595	0.111
ESR, mm/h	54 (30-77)	31 (14-66)	-2.539	0.011
Clinical evaluation, median (IQR)
APACHE II	13 (8-18)	8 (6-12)	-4.425	<0.001
SOFA score	4 (3-6)	3 (2-4)	-4.498	0.008

Characteristics	DM group (n=60)	Non-DM group (n=60)	χ²/Z value	P-value
Demographic characteristic
Age, years, median (IQR)	64 (54-74)	64 (55-74)	-0.200	0.842
Male, n (%)	41 (68.3)	41(68.3)	0.000	1.000
Comorbidity, n (%)
Hypertension	33 (55.0)	17 (28.3)	8.777	0.003
COPD	6 (10.0)	17 (28.3)	6.508	0.011
ACD	9 (15.0)	9 (15.0)	0.000	1.000
Cor pulmonale	5 (8.3)	7 (11.7)	0.370	0.543
Cardiac arrhythmia	5 (8.3)	7 (11.7)	0.370	0.543
Remote cerebral infarction	10 (16.7)	8 (13.3)	0.261	0.609
CKD	7 (11.7)	1 (1.7)	4.821	0.061
Others	6 (10.0)	9 (15.0)	0.686	0.408
Laboratory tests, median (IQR)
HBP, ng/mL	69.71 (34.57-134.35)	54.93 (27.05-91.86)	-1.220	0.222
PO₂/FiO₂, mmHg	160.1 (113.35-202.7)	209.4 (171.8-263.6)	-3.727	<0.001
Glucose, mmol/L	11.34 (8.50-15.22)	6.30 (5.43-7.20)	-8.021	<0.001
WBC,×10⁹/L	9.73 (7.07-13.28)	7.58 (5.23-11.17)	-2.181	0.029
NEUT, %	84.95 (77.40-91.78)	83.80 (74.50-89.73)	-0.562	0.574
CRP, mg/L	75.11 (39.25-127.17)	49.78 (12.98-88.35)	-2.590	0.010
PCT, ng/L	0.46 (0.11-0.99)	0.17 (0.07-0.56)	-2.000	0.046
ESR, mm/h	53 (26.2-77)	34 (14.3-68.5)	-1.913	0.056
Clinical evaluation and clinical outcomes
APACHE II, median (IQR)	12 (8-17)	9 (6-12)	-3.127	0.002
SOFA, median (IQR)	4 (3-6.75)	3 (2-4)	-4.627	<0.001
SRF, n (%)	19 (31.7)	5 (8.3)	10.208	0.001
ARDS, n (%)	36 (60.0)	19 (31.7)	9.701	0.002
Severe pneumonia, n (%)	43 (71.7)	30 (50.0)	5.911	0.015
Invasive ventilation, n (%)	19 (31.7)	6 (10.0)	8.539	0.003
Length of ICU stay, d, median (IQR)	5 (3-11)	3 (2-6)	-3.073	0.002
10-day mortality, n (%)	9 (15.0)	4 (6.7)	2.157	0.142
28-day mortality, n (%)	14 (23.3)	5 (8.3)	5.065	0.024
90-day mortality, n (%)	16 (26.7)	5 (8.3)	6.984	0.008

Indicators	Maximum Youden index	Cut-off value	Sensitivity	Specificity	AUC	95%CI
Panel A: CAP patients with DM
10-day mortality
HBP	0.569	160.6 ng/mL	0.667	0.902	0.747	0.54-0.96
PCT	0.477	1.805 ng/L	0.556	0.921	0.732	0.56-0.91
ESR	0.301	63.5 mm/h	0.889	0.412	0.614	0.41-0.82
CRP	0.216	74.97 mg/L	0.667	0.549	0.536	0.35-0.72
28-day mortality
HBP	0.320	160.6 ng/mL	0.429	0.891	0.576	0.38-0.77
PCT	0.354	0.8085 ng/L	0.571	0.783	0.683	0.53-0.83
ESR	0.161	76.5 mm/h	0.857	0.304	0.549	0.37-0.73
CRP	0.214	85.8 mg/L	0.714	0.500	0.545	0.38-0.71
90-day mortality
HBP	0.347	160.6 ng/mL	0.436	0.909	0.624	0.44-0.81
PCT	0.358	0.8085 ng/L	0.563	0.796	0.675	0.52-0.83
ESR	0.119	36.2 mm/h	0.438	0.682	0.523	0.35-0.70
CRP	0.188	85.8 mg/L	0.688	0.500	0.551	0.39-0.72
Panel B: CAP patients without DM
10-day mortality
HBP	0.429	83.48 ng/mL	0.750	0.679	0.714	0.46-0.97
PCT	0.536	0.542 ng/L	0.750	0.786	0.690	0.38-1.0
ESR	0.232	2.5 mm/h	0.250	0.982	0.540	0.22-0.87
CRP	0.714	162.7 mg/L	0.750	0.964	0.763	0.40-1.00
28-day and 90-day mortality﹡
HBP	0.436	73.66 ng/mL	0.800	0.636	0.698	0.49-0.92
PCT	0.546	0.397 ng/L	0.800	0.746	0.700	0.45-0.95
ESR	0.327	6.2 mm/h	0.400	0.927	0.622	0.33-0.91
CRP	0.564	162.7 mg/L	0.600	0.964	0.687	0.37-1.00

Factors	Univariate analysis		Multivariate analysis
Factors	HR (95%CI)	P-value	HR (95%CI)	P-value
10-day mortality
HBP>160.6 ng/mL	11.917 (2.961-47.961)	0.000	7.196 (1.596-32.455)	0.010
PCT>1.805 ng/L	9.405 (2.509-135.254)	0.001	4.231 (0.865-20.699)	0.075
SRF	4.877 (1.217-19.552)	0.025	2.015 (0.380-10.680)	0.410
CRP>74.97 mg/L	0.458 (0.115-1.833)	0.458
ESR>63.5 mm/h	0.202 (0.025-1.614)	0.202
Age	0.998 (0.953-1.044)	0.917
Male	0.558 (0.150-2.078)	0.384
Diabetes duration	0.979 (0.895-1.072)	0.646
HbA1c	1.051 (0.754-1.465)	0.768
Hypertension	1.654 (0.414-6.614)	0.477
COPD	1.048 (0.131-8.384)	0.965
28-day mortality
HBP>160.6 ng/mL	5.291 (1.819-15.393)	0.002	4.381 (1.449-13.245)	0.009
PCT>0.809 ng/L	3.873 (1.341-11.191)	0.012	2.791 (0.944-8.253)	0.063
SRF	5.188 (1.728-15.576)	0.003	4.754 (1.546-14.619)	0.007
CRP>85.8 mg/L	0.477 (0.150-1.521)	0.211
ESR>76.5 mm/h	0.471 (0.106-2.107)	0.325
Age	1.013 (0.975-1.052)	0.515
Male	0.792 (0.265-2.365)	0.677
Diabetes duration	0.948 (0.865-1.039)	0.258
HbA1c	0.907 (0.673-1.222)	0.520
Hypertension	1.544 (0.517-4.609)	0.436
COPD	1.467 (0.328-6.559)	0.616
90-day mortality
HBP>160.6 ng/mL	5.560 (2.052-15.062)	0.001	4.581 (1.637-12.819)	0.004
PCT>0.809 ng/L	3.776 (1.402-10.169)	0.009	2.719 (0.985-7.504)	0.054
SRF	4.861 (1.756-13.455)	0.002	4.405 (1.557-12.461)	0.005
CRP>85.8 mg/L	0.539 (0.187-1.551)	0.252
ESR>36.2 mm/h	0.786 (0.286-2.163)	0.641
Age	0.998 (0.964-1.033)	0.920
Male	0.730 (0.265-2.008)	0.542
Diabetes duration	0.949 (0.872-1.033)	0.230
HbA1c	0.947 (0.725-1.237)	0.690
Hypertension	1.894 (0.658-5.452)	0.237
COPD	1.265 (0.287-5.567)	0.756