Associations of Interleukin 10, Matrix Metallopeptidase 9, and Legumain with Blood Pressure Variability and Neurologic Outcomes in Patients with Ischemic Stroke

Figures & data

Table 1 Baseline Characteristics of the Study Subjects

Variables	All Subjects (n=349)	Non-Progressive Ischemic Stroke (n=265)	Progressive Ischemic Stroke (n=84)	P
Age, years	72.97±11.47	73.08±11.34	72.60±11.93	0.739
Male	202 (57.88%)	158 (59.62%)	44 (52.38%)	0.241
Current smoking	112 (32.09%)	86 (32.45%)	26 (30.95%)	0.797
Alcohol use	67 (19.20%)	48 (18.11%)	19 (22.62%)	0.361
Interleukin 10 (pg/mL)	4.81 (2.78–7.72)	4.28 (2.66–7.45)	5.71 (4.08–8.10)	0.004
Matrix metallopeptidase 9 (mg/L)	753.82 (639.88–954.83)	715.65 (635.04–891.42)	870.81 (698.83–1345.70)	<0.001
Legumain (ng/mL)	5.37 (4.52–7.02)	5.14 (4.49–6.63)	6.01 (4.64–11.41)	0.002
Comorbidity
Hypertension	263 (75.36%)	191 (72.08%)	72 (85.71%)	0.011
Coronary heart disease	36 (10.32%)	27 (10.19%)	9 (10.71%)	0.840
Atrial fibrillation	57 (16.33%)	43 (16.23%)	14 (16.67%)	0.924
Hyperlipidemia	139 (39.83%)	96 (36.23%)	43 (51.19%)	0.015
Diabetes	155 (44.41%)	110 (41.51%)	45 (53.57%)	0.053
Cerebral infarction history	90 (25.79%)	69 (26.04%)	21 (25.00%)	0.850
Cerebral hemorrhage history	4 (1.15%)	2 (0.75%)	2 (2.38%)	0.245
Blood test
White blood cells (×10^9/L)	6.73 (5.58–8.18)	6.59 (5.56–7.98)	6.99 (5.67–8.58)	0.344
Hemoglobin (g/L)	133 (121–145)	132 (120–145)	137 (124–147.5)	0.101
Platelet (×10^9/L)	206 (171–245)	205 (170–246)	215.5 (172.75–243.25)	0.357
Random glucose (mmol/L)	7.70 (6.30–11.40)	7.60 (6.30–10.70)	8.42 (6.28–13.67)	0.078
Fasting blood sugar (mmol/L)	5.59 (4.88–7.47)	5.49 (4.87–6.99)	5.97 (5.07–8.72)	0.018
Hemoglobin A1C (%)	6.20 (5.80–7.70)	6.20 (5.80–7.50)	6.30 (5.60–8.62)	0.764
C-reactive protein (mg/L)	3.20 (1.30–7.80)	3.10 (1.30–7.30)	3.85 (1.25–9.43)	0.709
International Normalized Ratio	0.93 (0.89–0.98)	0.93 (0.89–0.98)	0.94 (0.89–0.98)	0.692
D-dimer (mg/L)	0.41 (0.23–0.98)	0.39 (0.23–0.86)	0.52 (0.22–1.42)	0.230
Total cholesterol (mmol/L)	4.57 (3.82–5.32)	4.49 (3.82–5.23)	4.78 (3.85–5.60)	0.141
HDL cholesterol (mmol/L)	1.12 (0.93–1.33)	1.10 (0.91–1.30)	1.16 (1.04–1.44)	0.005
LDL cholesterol (mmol/L)	2.68 (2.13–3.31)	2.66 (2.23–3.28)	2.79 (1.73–3.38)	0.355
Triglyceride (mmol/L)	1.21 (0.92–1.71)	1.19 (0.92–1.66)	1.27 (0.92–1.93)	0.496
Urea nitrogen (mmol/L)	5.52 (4.40–6.70)	5.52 (4.40–6.61)	5.54 (4.36–6.86)	0.665
Creatinine (mmol/L)	72.00 (60.20–86.00)	73.30 (62.80–86.90)	66.45 (54.33–80.55)	0.003
Uric acid (mmol/L)	330.45 (273.68–392.32)	332.00 (277.40–395.30)	322.20 (258.65–380.55)	0.176
Homocysteine (μmol/L)	15.40 (12.80–19.30)	15.10 (12.70–18.90)	16.00 (12.88–20.10)	0.516
Cystatin C (mg/L)	0.86 (0.84–0.89)	0.86 (0.83–0.89)	0.86 (0.85–0.89)	0.350
Location of ischemic stroke				0.126
Anterior circulation	225 (64.47%)	165 (62.26%)	60 (71.43%)
Posterior circulation	124 (35.53%)	100 (37.74%)	24 (28.57%)
Subtypes of ischemic stroke				0.079
Large-artery atherosclerosis	148 (42.41%)	106 (40.00%)	42 (50.00%)
Cardioembolism	62 (17.77%)	46 (17.36%)	16 (19.05%)
Small-vessel occlusion	133 (38.11%)	108 (40.75%)	25 (29.76%)
Stroke of other determined etiology	1 (0.29%)	0 (0.00%)	1 (1.19%)
Stroke of undetermined etiology	5 (1.43%)	5 (1.89%)	0 (0.00%)

Note: A P-value <0.05 was presented in bold.

Table 2 Blood Pressure Variability and Prognosis of the Study Subjects

Variables	All Subjects (n=349)	Non-Progressive Ischemic Stroke (n=265)	Progressive Ischemic Stroke (n=84)	P
Blood pressure variability
SBP at admission, mmHg	139.94±17.93	138.52±16.90	144.40±20.32	0.009
DBP at admission, mmHg	81.37±10.44	81.01±10.14	82.50±11.32	0.255
Average SBP (24h), mmHg	145.42±15.16	144.16±14.06	149.42±17.70	0.005
CV of average SBP (24h)	10.98±3.17	10.74±3.04	11.73±3.48	0.013
Average DBP (24h), mmHg	80.60±9.27	80.35±9.13	81.37±9.70	0.383
CV of average DBP (24h)	13.50±4.62	13.29±4.33	14.14±5.43	0.144
Average SBP (day), mmHg	146.70±15.28	145.50±14.27	150.50±17.67	0.009
CV of average SBP (day)	10.55±3.61	10.26±3.44	11.46±3.96	0.008
Average DBP (day), mmHg	81.27±9.53	81.09±9.39	81.82±10.01	0.541
CV of average DBP (day)	13.31±5.13	12.94±4.84	14.49±5.82	0.015
Average SBP (night), mmHg	141.72±18.44	140.23±17.18	146.42±21.38	0.007
CV of average SBP (night)	10.09±4.36	10.13±4.39	9.98±4.29	0.788
Average DBP (night), mmHg	78.77±11.43	78.37±11.35	80.05±11.62	0.240
CV of average DBP (night)	12.30±5.18	12.20±5.22	12.63±5.09	0.506
NIH Stroke Scale
At admission	4 (2–6)	4 (2–6)	5 (3–9.25)	<0.001
At discharge	3 (2–6)	3 (1–4)	7 (4–10.25)	<0.001
Modified Rankin Scale
Before admission	0 (0–1)	0 (0–1)	0 (0–1)	0.062
At discharge	2 (2–4)	2 (1–3)	4 (2–5)	<0.001
After 6 months	2 (1–3)	2 (1–2)	3 (2–4)	<0.001
Prognosis*
Improved at discharge	176 (50.43%)	134 (50.57%)	42 (50.00%)	0.928
Improved at 6 months	253 (72.49%)	202 (76.23%)	51 (60.71%)	0.006

Notes: *Improved prognosis was defined by the Modified Rankin Scale ≤2. A P-value <0.05 was presented in bold.

Abbreviations: SBP, systolic blood pressure; DBP, diastolic blood pressure; CV, coefficients of variation.

Table 3 Correlation Coefficient of Interleukin 10, Legumain, Matrix Metallopeptidase 9 with Blood Pressure Variability

Variables	Interleukin 10 (pg/mL)		Matrix Metallopeptidase 9 (mg/L)		Legumain (ng/mL)
	Correlation	P	Correlation	P	Correlation	P
SBP at admission, mmHg	−0.0626	0.244	0.0144	0.789	−0.0160	0.766
DBP at admission, mmHg	−0.0555	0.301	0.0065	0.904	0.0138	0.798
Average SBP (24h), mmHg	0.0139	0.795	0.0507	0.345	−0.0031	0.954
CV of average SBP (24h)	0.0405	0.451	0.3742	<0.001	0.0003	0.995
Average DBP (24h), mmHg	0.0214	0.691	0.0498	0.354	−0.0859	0.109
CV of average DBP (24h)	−0.0505	0.347	0.2201	<0.001	0.0007	0.989
Average SBP (day), mmHg	0.0125	0.816	0.0523	0.310	−0.0068	0.899
CV of average SBP (day)	0.0498	0.353	0.3162	<0.001	−0.0006	0.990
Average DBP (day), mmHg	0.0290	0.589	0.0500	0.352	−0.0842	0.117
CV of average DBP (day)	−0.0543	0.312	0.1905	<0.001	0.0144	0.788
Average SBP (night), mmHg	0.0166	0.757	0.0212	0.693	0.0030	0.955
CV of average SBP (night)	−0.0841	0.117	0.1875	<0.001	0.0021	0.969
Average DBP (night), mmHg	−0.0086	0.872	0.0073	0.891	−0.0468	0.383
CV of average DBP (night)	−0.0465	0.387	0.1340	0.012	0.0119	0.824

Note: A P-value <0.05 was presented in bold.

Abbreviations: SBP, systolic blood pressure; DBP, diastolic blood pressure; CV, coefficients of variation.

Table 4 Correlation Coefficient of MRS with Blood Pressure Variability

Variables	MRS at Discharge		MRS After 6 Months
	Correlation	P	Correlation	P
SBP at admission, mmHg	0.1030	0.055	0.0969	0.071
DBP at admission, mmHg	−0.0345	0.521	−0.0639	0.234
Average SBP (24h), mmHg	0.1574	0.003	0.1383	0.010
CV of average SBP (24h)	0.1727	0.001	0.1855	<0.001
Average DBP (24h), mmHg	0.0754	0.160	0.0504	0.348
CV of average DBP (24h)	0.0951	0.076	0.1053	0.049
Average SBP (day), mmHg	0.1450	0.007	0.1399	0.009
CV of average SBP (day)	0.1671	0.002	0.1681	0.002
Average DBP (day), mmHg	0.0761	0.156	0.0535	0.319
CV of average DBP (day)	0.0643	0.231	0.0720	0.180
Average SBP (night), mmHg	0.1512	0.005	0.1063	0.047
CV of average SBP (night)	0.0680	0.205	0.0844	0.116
Average DBP (night), mmHg	0.0564	0.293	0.0267	0.619
CV of average DBP (night)	0.1227	0.022	0.1241	0.020

Note: A P-value <0.05 was presented in bold.

Abbreviations: MRS, Modified Rankin Scale; SBP, systolic blood pressure; DBP, diastolic blood pressure; CV, coefficients of variation.

Table 5 Correlation Coefficient of Interleukin 10, Legumain, Matrix Metallopeptidase 9 with MRS

Variables	Interleukin 10 (pg/mL)		Matrix Metallopeptidase 9 (mg/L)		Legumain (ng/mL)
	Correlation	P	Correlation	P	Correlation	P
MRS at discharge	0.1927	<0.001	0.3770	<0.001	0.0376	0.483
MRS after 6 months	0.1789	<0.001	0.3816	<0.001	0.0459	0.392

Note: A P-value <0.05 was presented in bold.

Abbreviation: MRS, Modified Rankin Scale.

Table 6 Association of Interleukin 10, Legumain, Matrix Metallopeptidase 9 with MRS

Exposure	Crude			Adjust Model 1*			Adjust Model 2^§
	β	95% CI	P	β	95% CI	P	β	95% CI	P
MRS at discharge
Interleukin 10 (per SD increase)	0.25	0.11–0.40	<0.001	0.12	−0.01–0.25	0.065	0.04	−0.07–0.16	0.438
Matrix metallopeptidase 9 (per SD increase)	0.62	0.49–0.75	<0.001	0.39	0.26–0.52	<0.001	0.23	0.11–0.35	<0.001
Legumain (per SD increase)	0.14	−0.01–0.29	0.060	0.15	0.03–0.28	0.018	−0.07	−0.18–0.05	0.274
MRS after 6 months
Interleukin 10 (per SD increase)	0.26	0.12–0.41	<0.001	0.11	−0.01–0.23	0.071	0.04	−0.06–0.15	0.437
Matrix metallopeptidase 9 (per SD increase)	0.72	0.59–0.85	<0.001	0.45	0.34–0.57	<0.001	0.32	0.20–0.43	<0.001
Legumain (per SD increase)	0.11	−0.04–0.26	0.1382	0.12	0.01–0.24	0.037	−0.07	−0.18–0.04	0.224

Notes: *Adjusted for age, sex, and MRS before admission. §Adjusted for age, sex, MRS before admission, and type of ischemic stroke (progressive or not). A P-value <0.05 was presented in bold.

Abbreviations: MRS, Modified Rankin Scale; SD, standard deviation; CI, confidence interval.