Elevated Albumin to Globulin Ratio on Day 7 is Associated with Improved Function Outcomes in Acute Ischemic Stroke Patients with Intravenous Thrombolysis

Figures & data

Figure 1 Flow chart for patients’ selection.

Table 1 Characteristics of AIS Patients with or Without Available Blood Samples in Each Time Point

Characteristics	Admission			24 Hours			7 Days
	Without (n = 51)	With (n = 260)	p value	Without (n = 15)	With (n = 296)	p value	Without (n = 185)	With (n = 126)	p value
Demographic data
Age, (years)	69.08 ± 12.55	67.90 ± 13.06	0.555	67.13 ± 14.77	68.15 ± 12.90	0.769	67.16 ± 13.31	69.47 ± 12.37	0.124
Sex, (male, n.%)	27 (52.94)	169 (65.00)	0.103	8 (53.33)	188 (63.51)	0.426	123 (66.84)	73 (57.48)	0.093
Stroke risk factors
Current smoking, n (%)	12 (23.53)	68 (26.15)	0.695	4 (26.67)	76 (25.68)	1.000	47 (25.54)	33 (25.98)	1.000
Hypertension, n (%)	36 (70.59)	169 (65.00)	0.441	9 (60.00)	196 (66.21)	0.620	125 (67.93)	80 (62.99)	0.366
Diabetes, n (%)	11 (21.57)	52 (20.00)	0.799	1 (6.67)	62 (20.95)	0.311	34 (18.48)	29 (22.83)	0.347
Hyperlipidemia, n (%)	16 (31.37)	22 (8.46)	< 0.001	3 (20.00)	35 (11.82)	0.590	24 (13.04)	14 (11.02)	0.593
Atrial fibrillation, n (%)	16 (31.37)	54 (20.76)	0.097	5 (33.33)	65 (21.96)	0.476	43 (23.37)	27 (21.26)	0.661
Prior stroke, n (%)	3 (5.88)	36 (13.85)	0.116	1 (6.67)	38 (12.84)	0.761	19 (10.33)	20 (15.75)	0.156
Laboratory data
TC (mmol/L)	4.84 ± 1.07	4.59 ± 1.09	0.151	NA	4.63 ± 1.09		4.62 ± 1.02	4.65 ± 1.17	0.848
TG (mmol/L)	1.69 ± 1.54	1.49 ± 1.07	0.272	NA	1.51 ± 1.15		1.56 ± 1.13	1.45 ± 1.19	0.406
HDL (mmol/L)	1.15 ± 0.22	1.10 ± 0.28	0.222	NA	1.10 ± 0.27		1.11 ± 0.28	1.09 ± 0.25	0.557
LDL (mmol/L)	3.00 ± 0.95	2.91 ± 0.95	0.559	NA	2.93 ± 0.94		2.88 ± 0.87	3.00 ± 1.03	0.303
FBG (mmol/L)	6.20 ± 2.53	6.27 ± 2.49	0.874	6.94 ± 1.39	6.24 ± 2.50	0.633	6.27 ± 2.58	6.24 ± 2.37	0.905
Clinical data
SBP (mmHg)	161.60 ± 27.28	163.83 ± 26.36	0.585	173.93 ± 30.66	163.00 ± 26.19	0.117	164.35 ± 26.70	162.16 ± 26.21	0.474
DBP (mmHg)	88.75 ± 16.26	90.63 ± 16.43	0.454	94.87 ± 18.29	90.09 ± 16.29	0.271	91.49 ± 16.25	88.60 ± 16.51	0.126
DNT (minute)	60 (50–72)	55 (44–73)	0.183	63 (57–69)	56 (45–73)	0.523	59 (46–73)	54 (43–73)	0.132
ONT (minute)	158 (124–213)	154 (125–197)	0.714	145 (114–194)	155 (126–200)	0.279	150 (120–195)	161 (130–209)	0.123
NIHSS at admission	7 (5–9)	7 (5–12)	0.530	11 (6–17)	7 (5–11)	0.055	7 (4–11)	7 (5–11)	0.930
NIHSS at 24 h	4 (2–8)	5 (2–9)	0.457	21 (12–35)	4 (2–8)	< 0.001	4 (2–9)	5 (2–9)	0.644
Stroke subtype, n (%)			0.543			0.290			0.618
CE	18 (35.29)	90 (34.72)		5 (33.33)	103 (34.80)		64 (34.78)	44 (34.65)
LAA	19 (37.25)	109 (41.94)		7 (46.67)	121 (20.88)		77 (41.85)	51 (40.16)
SAO	6 (11.76)	37 (14.23)		0 (0)	43 (14.53)		28 (15.22)	15 (11.81)
SOE/SUE	8 (15.69)	24 (9.23)		3 (20.00)	29 (9.80)		16 (8.70)	16 (12.60)

Abbreviations: TC, total cholesterol; TG, triglyceride; LDL, low-density lipoprotein; HDL, high-density lipoprotein; FBG, fasting blood glucose; SBP, systolic blood pressure; DBP, diastolic blood pressure; DNT, Door to needle time; ONT, Onset to needle time; NIHSS, National Institute of Health Stroke Scale; LAA, large artery atherosclerosis; CE, cardioembolism; SAO, small-artery occlusion; SOE, stroke of other determined etiology; SUE, stroke of undetermined etiology.

Table 2 Characteristics of AIS Patients with or Without Poor Function Outcomes

Characteristics	Available Cases	Function Outcomes
		mRS 0–2 (n = 210)	mRS 3–6 (n = 101)	p value
Demographic data
Age (years)	311 (100)	65.24 ± 12.71	74.04 ± 11.43	< 0.001
Sex (male, n, %)	311 (100)	141 (67.14)	55 (54.46)	0.030
Stroke risk factors
Current smoking, n (%)	311 (100)	66 (31.43)	14 (13.86)	0.001
Hypertension, n (%)	311 (100)	130 (61.90)	75 (74.26)	0.031
Diabetes, n (%)	311 (100)	43 (20.48)	20 (19.80)	0.890
Hyperlipidemia, n (%)	311 (100)	21 (10.00)	17 (16.83)	0.085
Atrial fibrillation, n (%)	311 (100)	39 (18.57)	31 (30.69)	0.017
Prior stroke, n (%)	311 (100)	19 (9.05)	20 (19.80)	0.007
Laboratory data
TC (mmol/L)	286 (91.96)	4.61 ± 1.03	4.69 ± 1.21	0.556
TG (mmol/L)	286 (91.96)	1.58 ± 1.26	1.37 ± 0.82	0.152
HDL (mmol/L)	286 (91.96)	1.10 ± 0.26	1.12 ± 0.30	0.634
LDL (mmol/L)	286 (91.96)	2.89 ± 0.91	3.04 ± 1.01	0.236
FBG (mmol/L)	294 (94.53)	5.79 ± 1.97	7.36 ± 3.17	< 0.001
Admission-Alb (g/L)	260 (83.60)	41.31 ± 2.90	39.59 ± 3.68	< 0.001
Admission-Glb (g/L)	260 (83.60)	33.18 ± 4.64	34.39 ± 4.78	0.053
Admission-A/G	260 (83.60)	1.27 ± 0.18	1.18 ± 0.21	< 0.001
24 h-Alb (g/L)	296 (95.18)	38.08 ± 3.03	37.90 ± 3.49	0.624
24 h-Glb (g/L)	296 (95.18)	26.77 ± 4.12	29.36 ± 4.85	< 0.001
24 h-A/G	296 (95.18)	1.46 ± 0.24	1.33 ± 0.27	< 0.001
7 day-Alb (g/L)	126 (40.51)	37.50 ± 3.15	35.14 ± 3.05	< 0.001
7 day-Glb (g/L)	126 (40.51)	27.42 ± 4.63	31.26 ± 4.78	< 0.001
7 day-A/G (g/L)	126 (40.51)	1.41 ± 0.25	1.15 ± 0.19	< 0.001
Clinical data
SBP (mmHg)	311 (100)	161.29 ± 26.40	168.40 ± 26.08	0.022
DBP (mmHg)	311 (100)	90.96 ± 16.58	88.98 ± 15.99	0.319
DNT (minute)	311 (100)	55 (45–73)	60 (46–74)	0.334
ONT (minute)	311 (100)	150 (124–196)	159 (127–200)	0.413
NIHSS at admission	310 (99.68)	6 (4–8)	13 (7–18)	< 0.001
NIHSS at 24 h	295 (94.86)	4 (2–6)	12 (7–19)	< 0.001
Stroke subtype, n (%)	311 (100)			< 0.001
CE		57 (27.14)	51 (50.49)
LAA		88 (41.90)	40 (39.60)
SAO		43 (20.48)	0 (0)
SOE/SUE		22 (10.47)	10 (9.90)

Abbreviations: TC, total cholesterol; TG, triglyceride; LDL, low-density lipoprotein; HDL, high-density lipoprotein; FBG, fasting blood glucose; Alb, albumin; Glb, globulin; A/G, albumin to globulin ratio; SBP, systolic blood pressure; DBP, diastolic blood pressure; DNT, Door to needle time; ONT, Onset to needle time; NIHSS, National Institute of Health Stroke Scale; LAA, large artery atherosclerosis; CE, cardioembolism; SAO, small-artery occlusion; SOE, stroke of other determined etiology; SUE, stroke of undetermined etiology.

Figure 2 Dynamic changes in concentration (mean ± SD) of (A) albumin; (B) globulin and (C) albumin-globulin ratio (A/G) according to AIS outcomes. The data are summarized in Tables 2 and S1.

Table 3 Association Between Albumin, Globulin, Albumin/Globulin Ratio in Different Time Points and Function Outcomes After AIS

Characteristics	Death or Major Disability (mRS 3–6)
	Events	OR* (95% CI)	p value
Admission-Albumin
Q1, n = 69 [< 38.6]	35	1
Q2, n = 61 [38.6–41.0]	19	0.462 (0.174–1.228)	0.122
Q3, n = 66 [41.1–43.0]	15	0.477 (0.180–1.263)	0.136
Q4, n = 64 [> 43.0]	16	0.701 (0.256–1.917)	0.489
Per 1-SD increase		0.476 (0.490–1.135)	0.171
Admission-Globulin
Q1, n = 65 [< 30.2]	17	1
Q2, n = 65 [30.2–32.9]	13	0.932 (0.315–2.756)	0.898
Q3, n = 65 [33.0–36.4]	29	1.636 (0.658–4.401)	0.330
Q4, n = 65 [> 36.4]	26	1.564 (0.541–4.520)	0.409
Per 1-SD increase		1.062 (0.732–1.542)	0.751
Admission-A/G ratio
Q1, n = 68 [< 1.12]	39	1
Q2, n = 64 [1.12–1.24]	19	0.486 (0.191–1.237)	0.130
Q3, n = 64 [1.25–1.35]	12	0.173 (0.059–0.508)	0.001
Q4, n = 64 [> 1.35]	15	0.459 (0.161–1.313)	0.147
Per 1-SD increase		0.816 (0.544–1.223)	0.325
24 h-Albumin
Q1, n = 76 [< 36.1]	27	1
Q2, n = 72 [36.1–37.8]	19	0.682 (0.256–1.756)	0.427
Q3, n = 76 [37.9–40.1]	20	0.949 (0.364–2.474)	0.915
Q4, n = 72 [> 40.1]	23	1.477 (0.598–3.650)	0.398
Per 1-SD increase		1.138 (0.810–1.598)	0.457
24 h-Globulin
Q1, n = 74 [< 24.3]	13	1
Q2, n = 75 [24.3–27.3]	15	1.309 (0.458–3.737)	0.615
Q3, n = 74 [27.4–30.0]	27	2.986 (1.112–8.021)	0.030
Q4, n = 73 [> 30.0]	34	3.455 (1.258–9.485)	0.016
Per 1-SD increase		1.499 (1.057–2.126)	0.023
24 h-A/G ratio
Q1, n = 74 [< 1.25]	38	1
Q2, n = 76 [1.25–1.40]	20	0.388 (0.162–0.931)	0.034
Q3, n = 74 [1.41–1.58]	19	0.328 (0.131–0.826)	0.018
Q4, n = 72 [> 1.58]	12	0.279 (0.098–0.790)	0.016
Per 1-SD increase		0.694 (0.469–1.027)	0.067
7 day-Albumin
Q1, n = 32 [< 34.5]	17	1
Q2, n = 32 [34.5–36.8]	11	0.438 (0.110–1.742)	0.241
Q3, n = 32 [36.9–39.1]	8	0.229 (0.052–1.007)	0.051
Q4, n = 30 [> 39.1]	5	0.196 (0.035–1.082)	0.062
Per 1-SD increase		0.401 (0.202–0.794)	0.009
7 day-Globulin
Q1, n = 33 [< 25.5]	4	1
Q2, n = 31 [25.5–28.6]	8	3.902 (0.427–35.659)	0.228
Q3, n = 32 [28.7–31.8]	11	8.496 (0.932–77.451)	0.058
Q4, n = 30 [> 31.8]	18	22.598 (2.415–211.6)	0.006
Per 1-SD increase		2.489 (1.285–4.823)	0.007
7 day-A/G ratio
Q1, n = 32 [< 1.14]	22	1
Q2, n = 32 [1.14–1.34]	12	0.268 (0.069–1.041)	0.057
Q3, n = 34 [1.34–1.51]	4	0.059 (0.011–0.316)	0.001
Q4, n = 29 [> 1.51]	3	0.008 (0.000–0.177)	0.002
Per 1-SD increase		0.182 (0.074–0.446)	< 0.001

Notes: *Adjusted for age, sex, current smoking, hyperlipidemia, atrial fibrillation, prior stroke, systolic blood pressure, fasting glucose and NIHSS at admission.

Table 4 Diagnostic Values of the Albumin, Globulin and Albumin/Globulin Ratio for Death or Major Disability (mRS 3–6)

	AUC (95% CI)	p value	Cut-off Value	Sensitivity (%)	Specificity (%)
Admission-Albumin	0.644 (0.583–0.702)	< 0.001	40.5	62.35	66.29
Admission-Globulin	0.589 (0.527–0.650)	0.019	32.8	67.06	57.14
Admission-A/G ratio	0.653 (0.591–0.710)	< 0.001	1.11	45.88	83.43
24 h-Albumin	0.513 (0.454–0.571)	0.732
24 h-Globulin	0.672 (0.615–0.725)	< 0.001	27.9	62.92	66.97
24 h-A/G ratio	0.677 (0.620–0.730)	< 0.001	1.35	62.92	68.12
7 day-Albumin	0.695 (0.606–0.773)	< 0.001	34.9	53.66	78.82
7 day-Globulin	0.731 (0.645–0.806)	< 0.001	27.8	80.49	58.82
7 day-A/G ratio	0.807 (0.727–0.872)	< 0.001	1.20	73.17	78.82