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. 2021 May 28;12:638693. doi: 10.3389/fneur.2021.638693

Table 4.

Summary of the biomarkers for the determination of the subtypes of stroke.

Biomarkers Etiology Sample/Methods Cutoff/Time of blood drawing Specificity Sensitivity References
BNP Cardioembolic
CE vs. other strokes subtypes
200 patients (LVD = 18, CE = 82, SVD = 31, and other stroke = 69)
Chemiluminescence enzyme immunoassay
140.0 pg/mL
24 h
80.5%, AUC = 0.87 80.5%, AUC = 0.87 (91)
BNP Cardioembolic
CE vs. all stroke subtypes
707 IS (LVD = 151, CE = 259, SVD = 128, and UE = 169)
ELISA
76 pg/mL
<24 h
69% 72% (92)
BNP and DD Cardioembolic
CE vs. all stroke subtypes
707 IS (LVD = 151, CE = 259, SVD = 128, and UE = 169)
ELISA
BNP>76 pg/mL
DD> 0.96 μg/mL
<24 h
91.3%
AUC = 0.89
66.5% AUC = 0.89 (92)
D-Dimer Cardioembolic
CE vs. all stroke subtypes
707 IS (LVD = 151,CE = 259, SVD = 128, and UE = 169)
ELISA
0.96 μg/mL
<24 h
64% 56% (92)
D-Dimer Cardioembolic
CE vs. LVD + SVD
126 IS (LVD = 34,CE = 34, SVD = 31, and UE = 27), and controls = 63
STA Liatest d-Dimer immunoassay (immunoturbidimetric technology)
2.00μg/mL
>24 h
93.2% 59.3% (93)
NT-proBNP Cardioembolic
CE vs. all stroke subtypes
114 IS (LVD = 27,CE = 34, SVD = 19, and UE = 34)
Human RIAKit Phoenix Pharmaceuticals
200 pg/mL
<6 h
82% 65% (94)
Albumin/globulin ratio (G/A ratio) Cardioembolic
CE vs. all stroke subtypes
114 IS (LVD = 27,CE = 34, SVD = 19, and UE = 34)
Immunoassay or colorimetric assay
0.7
<6 h
31% 91% (94)
NT-proBNP and G/A ratio. Cardioembolic
CE vs. all stroke subtypes
114 IS (LVD = 27,CE = 34, SVD = 19, and UE = 34)
Immunoassay or colorimetric assay
NT-proBNP >200 pg/mL
G/A = 0.7
<6 h
AUC = 0.91 with Atrial Fibrillation (AF)
AUC = 0.84 without AF
(94)
Pro-BNP Cardioembolic
CE vs. all stroke subtypes
262 IS (LVD = 44, CE = 100, SVD = 36, and UE = 82)
Electrochemiluminescence immunoassay “ECLIA”
360 pg/mL
<12 h
83%
AUC = 0.921
87%
AUC = 0.921
(95)
Pro-ANP Cardioembolic
CE vs. all stroke subtypes
262 IS (LVD = 44, CE = 100, SVD = 36, UE = 86)
ELISA
2,266.6 fmol/mL
<12 h
70%
AUC = 0.735
62%
AUC = 0.735
(95)
CK-MB Cardioembolic
CE vs. all stroke subtypes
262 IS (LVD = 44, CE = 100, SVD = 36, and UE = 86)
Electrochemiluminescence immunoassay “ECLIA”
2.6 ng/mL
<12 h
80%
AUC = 0.731
62%
AUC = 0.731
(95)
NT-proBNP Cardioembolic
CE vs. no-CE
Meta-analysis: six studies NT-proBNP prospective cohort 200–360 pg/mL
<72 h
93%
AUC = 0.87
55%
AUC = 0.87
(96)
BNP Cardioembolic
CE vs. no-CE
Meta-analysis: ten studies BNP prospective cohort 64–155 pg/mL
<24 h
85%
AUC = 0.87
65%
AUC = 0.87
(96)
Troponin Embolic stroke of unknown source (ESUS)
ESUS vs. CE, non-CE
1,120 IS [CE = 371, non-CE = 310, and embolic stroke of unknown source (ESUS) = 439]
Sandwich immunoassay
ng/mL
<24 h
95 % 12% (97)
Troponin Cardioembolic
CE vs. ESUS, non-CE
1,120 IS [CE = 371, non-CE = 310, and embolic stroke of unknown source (ESUS) = 439]
Sandwich immunoassay
ng/mL
<24 h
95 % 17% (97)
D-Dimer SVD (lacunar)
SVD vs. CE + LVD
126 patients (LVD = 34,CE = 34, SVD = 31, and UE = 27)
STA Liatest d-Dimer immunoassay (immunoturbidimetric technology)
0.54 μg/mL
>24 h
96.2% 61.3% (93)
Homocysteine (Hcy) Lacunar (SVD)
SVD vs. controls
197 acute lacunar infarction patients and 192 controls
15.5 μmol/L
<24 h
100%
AUC = 0.881
65%
AUC = 0.881
(98)
Fibrinogen Lacunar (SVD)
SVD vs. controls
197 acute lacunar infarction patients and 192 controls
228.55 μg/dL
<24 h
58.3%
AUC = 0.688
83.2%
AUC = 0.688
(98)
Hcy/fibrinogen Lacunar (SVD)
SVD vs. controls
197 acute lacunar infarction patients and 192 controls
15.5 μmol/L
228.55 μg/dL
<24 h
58.3%
AUC = 0.766
94.9%
AUC = 0.766
(98)
GFAP/d-dimer preprint LVD
LVD vs. other strokes
128 patients (LVD = 23, non-LVD = 42, HS = 16, stroke mimic = 31, and TIA = 16)
ELISA
d-dimer
+GFAP = 0.33
92%
AUC = 0.81
57%
AUC = 0.81
(99)

Bold values indicate groups compared in the studies analyzed by Receiver Operating Curve analysis (ROC).