Low HALP (Hemoglobin, Albumin, Lymphocyte, and Platelet) Score Increases the Risk of Post-Stroke Cognitive Impairment: A Multicenter Cohort Study

Figures & data

Table 1 Demographic, Clinical Characteristics and Outcomes of Patients with Different HALP Score Ranges

	Q1, n=257 (<36.56)	Q2, n=258 (36.56–48.83)	Q3, n=251 (48.83–65.08)	Q4, n=256 (>65.08)	P value
Demographic characteristics
Average Age (year)	64±11	61±11	60±11	60±10	<0.0001**
Gender (Male,%)	158(24.26)	181(24.26)	195(26.14)	212(28.42)	<0.0001**
Education level (n,%)					0.522
Elementary or below	72(28.24)	87(24.10)	85(23.81)	13(26.53)
Middle school	63(24.71)	94(26.04)	90(25.21)	11(22.45)
High school or above	63(24.71)	89(24.65)	86(24.09)	13(26.53)
Unknown	57(22.35)	91(25.21)	96(26.89)	12(24.49)
Medical history (n,%)
Current smoker	35(19.44)	49(27.22)	49(27.22)	47(26.11)	0.309
Second and smoking	51(18.89)	74(27.41)	74(27.41)	71(26.30)	0.060
Heavy drinker (>60g/d)	29(17.68)	42(25.61)	38(23.17)	55(33.54)	0.018**
Stroke	55(26.96)	53(25.98)	50(24.51)	46(22.55)	0.795
TIA	11(28.95)	5(13.16)	12(31.58)	10(26.32)	0.344
Hypertension	163(25.15)	170(26.23)	152(33.46)	163(25.15)	0.666
Diabetes	47(19.58)	61(25.42)	61(25.42)	71(29.58)	0.089
Hypercholesterolemia	28(25.00)	24(21.43)	31(27.68)	29(25.89)	0.739
Coronary heart disease	1(20.00)	2(40.00)	1(20.00)	1(20.00)	0.815
Heart failure	2(25.00)	3(37.50)	1(12.50)	2(25.00)	0.612
Atrial fibrillation	11(19.64)	16(28.57)	14(25.00)	15(26.79)	0789
BMI	24.49±3.38	24.66±3.16	25.01±3.07	25.61±3.20	0.0004**
TOAST classification (n,%)					0.517
Large artery atherosclerosis	75(29.18)	57(22.18)	63(24.51)	62(24.12)
Cardiogenic embolism	16(24.62)	19(29.23)	13(20.00)	17(26.15)
Small artery occlusion	55(22.82)	57(23.65)	63(26.14)	66(27.39)
Others	4(50.00)	3(37.50)	1(12.50)	0(0.00)
Unknown	107(23.73)	122(27.05)	111(24.61)	111(24.61)
Baseline neurological function (n,%)					0.098
NIHSS=0	33(22.30)	35(23.65)	34(22.97)	46(31.08)
NIHSS=1	32(20.92)	34(22.22)	43(28.10)	44(28.76)
NIHSS=2	39(23.64)	53(32.12)	38(23.03)	35(21.21)
NIHSS=3	39(27.27)	36(25.17)	33(23.08)	35(24.48)
NIHSS>3	114(27.60)	100(24.21)	103(24.94)	96(23.24)
Affective symptoms (mean±SD)
GAD-7 at 2 weeks	3.54±4.45	2.93±3.87	3.33±4.31	3.32±4.07	0.126
PHQ-9 at 2 weeks	20.76±6.16	21.29±6.08	21.23±6.13	21.96±5.57	0.231
MoCA at 2 weeks	20.61±6.27	21.09±5.99	21.39±6.11	25.57±3.20	0.028**
MoCA at 12 months	23.20±5.66	24.10±4.71	23.81±4.89	24.57±4.38	0.028**
Visuoexecutive	3.16±1.65	3.36±1.54	3.60±1.50	3.60±1.48	0.003**
Naming	2.66±0.73	2.74±0.70	2.74±0.69	2.82±0.56	0.017**
Attention	5.18±1.28	5.39±1.54	5.42±1.15	5.42±1.03	0.044**
Language	2.18±0.90	2.24±0.87	2.24±0.88	2.32±0.83	0.300
Abstraction	1.41±0.76	1.46±0.70	1.46±0.70	1.53±0.67	0.482
Recalls	2.63±1.66	2.67±1.57	2.67±1.57	2.92±1.53	0.162
Orientation	5.64±0.84	5.55±1.00	5.54±1.00	5.73±0.62	0.227
Decline—from 2 weeks to 12 months (%)	28(25.23)	29(26.13)	30(27.03)	24(21.62)	0.818
Baseline pre-mRS≥2 (n,%)	128(49.81)	106(41.09)	109(43.43)	81(31.64)	0.0004**
Baseline pre-mRS	1.78±1.28	1.62±1.23	1.64±1.22	1.36±1.15	0.0007**
mRS at 2 weeks	1.68±1.09	1.07±0.99	1.05±1.04	0.91±0.92	0.055

Note: **p<0.01.

Abbreviations: BMI, Body Mass Index; NIHSS, National Institutes of Health Stroke Scale; MoCA, Montreal Cognitive Assessment; mRS, modified Rankin scale; GAD-7, 7-item Generalized Anxiety Disorder Scale; PHQ-9, Patient Health Questionnaire-9; TOAST, Trial of ORG 10172 in Acute Stroke Treatment (TOAST) type.

Table 2 Logistic Regression Analysis of Cognitive Outcomes at 2 Weeks in AIS/TIA Participants

Outcome	Events n (%)	Unadjusted, OR (95% CI)	P value	Model 1	P value	Model 2	P value
MoCA≤22
HALP score Q1	141(54.86)	1.47(1.04~2.08)	0.031*	1.25(0.86~1.80)	0.24	1.47(0.07~32.96)	0.81
Q2	121(46.90)	1.07(0.75~1.51)	0.718	1.01(0.71~1.45)	0.95	0.76(0.03~20.64)	0.87
Q3	125(49.80)	1.20(0.85~1.70)	0.312	1.19(0.83 ~1.71)	0.35	0.79(0.05~13.33)	0.87
Q4	116(45.31)	Reference		Reference		Reference

Notes: Model 1: adjusted for age, gender, and education. Model 2: adjusted for age, gender, education, smoking, history of stroke, hypertension, diabetes, coronary heart disease, atrial fibrillation, TOAST type, NIHSS score, mRS, and baseline MoCA. *p<0.05.

Table 3 Logistic Regression Analysis of Cognitive Outcomes at 12 Months in AIS/TIA Participants

Outcome	Events n (%)	Unadjusted, OR (95% CI)	P value	Model 1	P value	Model 2	P value
MoCA≤22
HALP score Q1	105(40.84)	1.91(1.32~2.77)	0.001**	1.61(1.09~2.38)	0.018	1.57(1.02~2.41)	0.039*
Q2	82(31.78)	1.29(0.88~1.89)	0.194	1.23(0.83~1.83)	0.31	1.16(0.75~1.77)	0.506
Q3	76(30.28)	1.20(0.82~1.77)	0.354	1.19(0.79 ~1.77)	0.40	1.13(0.75~1.75)	0.573
Q4	68(26.56)	Reference		Reference		Reference

Notes: Model 1: adjusted for age, gender, and education. Model 2: adjusted for age, gender, education, smoking, history of stroke, hypertension, diabetes, coronary heart disease, atrial fibrillation, TOAST type, NIHSS score, mRS, and baseline MoCA. *p<0.05; **p<0.01.

Figure 1 Percentage of patients with PSCI at 1 year.

Table 4 Subgroup Analysis of Association Between HALP Score and Cognitive Function

Subgroup		Outcome	Events (%)	Unadjusted, OR (95% CI)	P value	Interaction P
Age						0.2449
	<60 years	HALP Q1	23(23.00)	1.901(1.198~3.016)	0.201
		Q2	29(29.00)	1.142(0.703~1.857)	0.197
		Q3	25(25.00)	1.570(0.948~2.603)	0.853
		Q4	23(23.00)	Reference
	≥60years	HALP Q1	82(35.50)	1.901(1.198 3.016)	0.006**
		Q2	53(22.94)	1.142(0.703 1.857)	0.59
		Q3	51(22.08)	1.570(0.948 2.603)	0.080
		Q4	45(19.48)	Reference
Gender	Male	HALP Q1	64(28.19)	1.992(1.279 3.103)	0.002**	0.172
		Q2	58(25.55)	1.380(0.889 2.141)	0.151
		Q3	51(22.47)	1.036(0.664 1.616)	0.875
		Q4	54(23.79)	Reference
	Female	HALP Q1	41(39.42)	1.515(0.716~3.206)	0.278
		Q2	24(23.08)	0.970(0.437~2.153)	0.941
		Q3	25(24.04)	1.728(0.758~3.942)	0.194
		Q4	14(13.46)	Reference
TOAST type	Large artery atherosclerosis	HALP Q1	41(40.59)	2.53(1.26~5.10)	0.009**	0.7332
		Q2	21(20.79)	1.23(0.58~2.61)	0.599
		Q3	19(18.81)	0.91(0.43~1.93)	0.800
		Q4	20(19.80)	Reference
	Cardiogenic embolism	HALP Q1	8(29.63)	2.399(0.573 10.040)	0.231
		Q2	7(25.93)	1.400(0.345 5.670)	0.638
		Q3	7(25.93)	2.799(0.619 12.660)	0.181
		Q4	5(18.52)	Reference
	Small artery occlusion	HALP Q1	21(31.34)	2.10(0.95~4.64)	0.066
		Q2	17(25.37)	1.45(0.64~3.24)	0.372
		Q3	14(20.90)	0.97(0.43~2.22)	0.945
		Q4	15(22.39)	Reference
	Unknown	HALP Q1	34(25.76)	1.381(0.765 2.493)	0.285
		Q2	34(25.76)	1.145(0.639 2.052)	0.649
		Q3	36(27.27)	1.423(0.793 2.552)	0.237
		Q4	28(21.21)	Reference
Education level	Elementary or below	HALP Q1	38(30.89)	2.068(1.012~4.223)	0.046*	0.140
		Q2	35(28.46)	2.312(1.107~4.831)	0.026**
		Q3	30(24.39)	1.682(0.806~3.508)	0.166
		Q4	20(16.26)	Reference
	Middle school	HALP Q1	32(29.09)	1.379(0.737~2.580)	0.314
		Q2	25(22.73)	0.859(0.452~1.631)	0.642
		Q3	26(23.64)	0.978(0.515~1.857)	0.946
		Q4	27(24.55)	Reference
	High school or above	HALP Q1	28(35.00)	1.991(1.013~3.913)	0.046*
		Q2	15(18.75)	0.811(0.38~1.71)	0.582
		Q3	18(22.50)	1.073(0.52~2.21)	0.849
		Q4	19(23.75)	Reference

Notes: *p<0.05; **p<0.01.

Figure 2 Subgroup analysis of association between HALP score quartiles and 1-year post-stroke cognitive impairment (PSCI) in patients with acute ischemic stroke/transient ischemic attack recurrence.