Article Figures & Data
Figures
- Figure 1.
PRISMA flow chart.
- Figure 2.
Risk of bias summary using the QUADAS-2. Zhang et al. 2020_a refers to L. J. Zhang et al., 2020, Zhang et al. 2020_b refer to H. T. Zhang et al., 2020.
- Figure 3.
SROC for all studies. AUC, 0.89. SROC, summary receiver operating characteristic; AUC, area under the curve.
- Figure 4.
Forest plots of sensitivity and specificity of blood biomarkers for diagnosis of IS. The pooled sensitivity is 0.76 (0.74–0.78); the pooled specificity is 0.84 (0.83–0.86).
- Figure 5.
Univariable meta-regression and subgroup analyses for the heterogeneity.
- Figure 6.
Deek's funnel plot to estimate publication bias.
- Figure 7.
Fagan nomogram to evaluate the clinical utility of blood biomarkers for diagnosis of IS.
Tables
Inclusion criteria Human participants of age ≥18 years old (both male and female)
Original studies primarily aimed to investigate blood biomarkers for the diagnosis of IS, including prospective comparative studies, cohort, case control, case series or case reports (≥10 patients), and diagnostic randomized controlled trials. Case series and case reports were excluded from the meta-analysis and included only in the review
Original studies reporting the following result: TP, FP, TN, FN, sensitivity, specificity, PLR, NLR, the AUC, or DOR, or data suffice to construct two-by-two contingency tables to compute the diagnostic accuracy
Included participants diagnosed with IS, including IS (thrombotic strokes or embolic strokes) or TIA
All types of settings are acceptable, including inpatient, outpatient, community, or home
Described in the English language
Full-text availability
Exclusion criteria The study did not include the population of interest or concerned animal subjects
Conference proceedings, abstracts, review articles, theoretical papers, pilot studies, protocols, dissertations, letters to the editor, opinions (viewpoint), statement papers, government documents, or working papers
- Reference - Published Year - Country Study design - Study setup - Setting - Sample size (total) (IS/C)) (n)a - Target IS population - Comorbidities - Age (median or mean) (range) (in a year) - Male/female (n/n) Prevalence
of IS (%)All included blood biomarkers Blood biomarker with
optimal performanceBlood biomarker with optimal performance TP FP TN FN Sen (95% CI) Spe (95% CI) AUC (95% CI) - (Fan et al., 2018)
- 2018
- China
Prospective study - Single-center
- Inpatient
- 389 (133/144)
- Acute lacunar infarction
- Comorbidities: Hypertension, diabetes mellitus, hyperlipidemia, CAD, and atrial fibrillation
- Acute lacunar infarction 69 (59.5–75.5), control 66.5 (59.25–71)
- 227/112
34.19% - Homocysteine (Hcy)
- Fibrinogen
Hcy 128 0 192 69 0.65 (0.58–0.72) 1.00 (0.98–1.00) 0.88 (0.84–0.92) - (Q. X. Qin et al., 2018)
- 2018
- China
Retrospective study - Multicenter
- Inpatient
- 228 (114/114)
- AIS with active colorectal cancer (CRCIS)
- Comorbidities: Colorectal cancer
- CRCIS 65.33 ± 12.45, healthy control (HC) 63.67 ± 9.18
- 156/72
50.00% - D-dimer
- Neutrophil count (NC)
- Carcinoembryonic antigen (CEA)
- Cancer antigen 125 (CA125)
D-dimer + CEA + NC 98 23 91 16 0.86 (0.78–0.92) 0.80 (0.71–0.87) 0.89 (0.85–0.93) - (Fang et al., 2018)
- 2018
- China
Retrospective, case-control study - Single-center
- Inpatient
- 462 (262/200)
- AIS
- Comorbidities: Hypertension, diabetes, hyperlipidemia
- AIS 62.5 ± 11.5, HC 61.8 ± 10.8
- 261/201
56.71% - S100 calcium-binding protein B (S100B)
- C-reactive protein (CRP)
- IL-6
- Plasminogen activator inhibitor-1 (PAI-1)
- Matrix metallopeptidase 9 (MMP-9)
- P-selectin
- Intercellular adhesion molecule 1 (ICAM-1)
- Tumor necrosis factor α (TNF-α)
- Low-density lipoprotein cholesterol
- IL-10
- Nitric oxide (NO)
- Glial fibrillary acidic protein
CRP NA NA NA NA NA NA 0.99 (0.98–1.00) IL-6 NA NA NA NA NA NA 0.96 (0.94–0.98) PAI-1 NA NA NA NA NA NA 0.99 (0.98–1.00) P-selectin NA NA NA NA NA NA 0.91 (0.88–0.94) TNF-α NA NA NA NA NA NA 0.99 (0.98–1.00) - (Mohamed et al., 2019)
- 2019
- Egypt
A prospective, case-control study - Single-center
- Inpatient
- 96 (48/48)
- CES
- Comorbidities: N/A
- NA
- NA
50.00% - Brain natriuretic peptide (BNP)
- D-dimer
- Creatine–kinase-MB (CK-MB)
- CRP
- Globulin/albumin ratio
BNP 36 18 30 12 0.75 (0.60–0.86) 0.63 (0.47–0.76) 0.80 (0.71–0.89) D-dimer 44 16 32 4 0.91 (0.79–0.97) 0.66 (0.51–0.79) 0.79 (0.70–0.88) CK-MB 41 12 36 7 0.85 (0.71–0.93) 0.75 (0.60–0.86) 0.91 (0.85–0.97) - (Zuo et al., 2020)
- 2020
- China
A prospective, cohort study - Dual-center
- Inpatient
- 300 (200/100)
- AIS
- Comorbidities: N/A
- AIS 72 (61–82), HC 64 (59–71)
- 188/112
66.67% - circFUNDC1
- circPDS5B
- circCDC14A
- Combination of the above three circRNAs
Combination of three circRNAs (circFUNDC1, circPDS5B, circCDC14A) 144 9 91 56 0.72 (0.65–0.78) 0.91 (0.83–0.96) 0.88 (0.84–0.91) - (O'Connell et al., 2017)
- 2017
- USA
Prospective study - Single-center
- Inpatient
- 63 (43/20)
- AIS
- Comorbidities: Hypertension, dyslipidemia, diabetes, atrial fibrillation
- AIS 72.5 ± 15.5, mimic stroke 58.0 ± 17.0
- 29/31
68.25% Peripheral blood cell-free DNA (cfDNA) cfDNA 37 5 15 6 0.86 (0.72–0.95) 0.75 (0.51–0.91) 0.90 (0.72–0.95) - (Nezu et al., 2022)
- 2022
- Japan
Prospective study - Multicenter
- Inpatient
- 120 (47/73)
- CAS
- Comorbidities: Hypertension, diabetes mellitus, dyslipidemia, chronic kidney disease, atrial fibrillation, cancer
- AIS patients with active cancer and CAS 72.4 ± 11.5, AIS patients with active cancer 76.3 ± 10.2
- 74/46
39.17% - Carbohydrate antigen (CA) 125
- CEA
- CA 19–9
CA 125 35 16 57 12 0.75 (0.59–0.86) 0.78 (0.67–0.87) 0.81 (0.72–0.88) - (Comertpay et al., 2020)
- 2020
- Turkey
A prospective, case-control study - Single-center
- Inpatient
- 72 (36/36)
- AIS
- Comorbidities: N/A
- AIS 66.06 ± 14.59 (23–94), HC 66.1 ± 14.4 (25–94)
- 46/26
50.00% Soluble tumor necrosis factor-like weak inducer of apoptosis (sTWEAK) sTWEAK 28 3 33 8 0.78 (0.60–0.89) 0.92 (0.76–0.98) 0.84 (0.74–0.94) - (C. Tian et al., 2022)
- 2022
- China
A prospective, case-control study - Single-center
- Inpatient
- 78 (39/39)
- AIS
- Comorbidities: Diabetes mellitus, hypertension, hyperlipidemia, coronary heart disease
- AIS 74, control 76.62 ± 10.34
- 36/42
50.00% - nc-KRTCAP3-2:1
- Inc-OSBPL10
- nc-OSBPL10-2:1
- NR_120420
- Inc-AP002414.1.1
- nc-AP002414.1.1-5:8
- nc-GCH1-2:3
- NR_003529.
- Inc-DENR
- nc-DENR-2:3
- nc-CMPK2-5:39
NR_120420 (total anterior circulation infarction subgroup) 34 6 33 5 0.86 (0.69–0.94) 0.85 (0.69–0.94) 0.86 (0.73–0.99) - (P. F. Liu et al., 2017)
- 2017
- China
A prospective, case-control study - Single-center
- Inpatient
- 49 (26/23)
- AIS
- Comorbidities: hypertension, hyperlipidemia
- AIS 59.08 ± 8.51, control 56.96 ± 2.70
- 33/16
53.06% - Ornithine
- Proline
- Acetylcarnitine
- Threonine
- PC (1:0/16:0)
- LysoPC (16:0)
- LysoPE (20:4)
- Carnitine
- Lysine
- Aspartic acid
- LysoPE (18:2)
- Betaine
- Isoleucine
- Serine
PC (5:0/5:0)
Combination of five biomarkers (serine, isoleucine, betaine, PC (5:0/5:0), LysoPE (18:2)) NA NA NA NA NA NA 0.97 (0.92–1.02) - (Cheng et al., 2018)
- 2018
- China
A prospective, case-control study - Single-center
- Inpatient
- 119 (77/42)
- AIS
- Comorbidities: Hypertension, diabetes mellitus
- AIS 61 ± 10.4, control 59 ± 4.7
- 35–79 (61)
- 83/36
64.71% - miR-148b-3p
- miR-151b
- miR-27b-3p
Combination of miR-148b-3p and miR-27b-3p 52 3 39 25 0.67 (0.46–0.67) 0.93 (0.70–0.97) 0.81 (0.70–0.92) - (H. Tian et al., 2021)
- 2021
- China
A prospective, case-control study - Single-center
- Inpatient
- 140 (76/64)
- AIS
- Comorbidities: Hypertension, diabetes, hyperlipidemia
- AIS 57.0 ± 6.4, control 56.4 ± 6.2
- 87/53
54.29% - miR-210
- miR-137
- miR-153
miR-210 46 14 62 18 0.72 (0.59–0.82) 0.82 (0.71–0.89) 0.82 (0.76–0.91) miR-137 45 11 65 19 0.70 (0.57–0.81) 0.86 (0.75–0.92) 0.84 (0.78–0.91) miR-153 52 20 56 12 0.81 (0.69–0.90) 0.74 (0.62–0.83) 0.84 (0.78–0.91) - (Wang et al., 2017)
- 2017
- China
A prospective, case-control study - Single-center
- Inpatient
- 69 (40/29)
- AIS
- Comorbidities: Hypertension, diabetes mellitus, atrial fibrillation
- AIS 65.7, control 61.0
- 38/31
57.97% - Alanine
- Citrate
- Glycine
- Leucine
- Isoleucine
- Serine
- Tyrosine
- Methionine
- Tryptophan
- Erythronic acid
- Urea
- Purine
- Proline
- Hypoxanthine
Tyrosine, lactate, and tryptophan panel NA NA NA NA NA NA NA - (D. Lu et al., 2020)
- 2020
- China
Phase 1: Experimental design
Phase 2: Bioinformatics analysis, case-control study
- Multicenter
- Inpatient
- 16 (8/8)
- AIS
- Comorbidities: N/A
- AIS 55.4 ± 12.3, control 54.11 ± 10.1
- 14/2
50.00% 140,732 out of 140,790 human circRNAs - circPHKA2
- circBBS2
NA NA NA NA NA NA NA - (Augello et al., 2018)
- 2018
- USA
A prospective, case-control study - Single-center
- Inpatient and outpatient
- 50 (24/26)
- AIS
- Comorbidities: Hypertension, CAD, CAD, diabetes mellitus, atrial fibrillation
- AIS 58 (51–74), control 61 (51–76)
- 31/19
48.00% - Gp130/sIL-6Rb
- IFN-β
- IL-28A/IFN-λ2
- MMP-2
- Osteopontin (OPN)
- sTNF-R1
- sTNF-R2
- TSL
IL-28A/IFN-λ2, MMP-2, sTNF-R2, and TSLP panel 21 1 25 3 0.88 (0.67–0.97) 0.96 (0.78–1.00) 0.96 (0.89–1.02) - (Guo et al., 2018)
- 2018
- China
A prospective, case-control study - Single-center
- Inpatient
- 20 (10/10)
- AIS
- Comorbidities: N/A
- AIS 63.2 ± 10.7, control 69.3 ± 5.9
- 14/6
50.00% 560 upregulated and 690 downregulated differentially expressed lncRNAs Combination of lncRNAs (lncRNA-ENST00000568297, lncRNA-ENST00000568243, and lncRNA-NR_046084) 8 2 8 2 0.83 (0.44–0.96) 0.80 (0.44–0.96) 0.84 (0.66–1.02) - (Huang et al., 2021)
- 2021
- China
A prospective, cohort study - Single-center
- Inpatient
- 305 (155/150)
- AIS
- Comorbidities: Hypertension
- AIS 56.0 (median), control 55.0 (median)
- AIS 84/71, control 76/74
50.82% - Serum Interleukin-34 (IL-34)
- Glycosylated hemoglobin (HbA1c)
IL-34 106 5 145 49 0.68 (0.60–0.75) 0.97 (0.92–0.98) 0.87 (0.83–0.91) - (L. J. Zhang et al., 2020)
- 2020
- China
Prospective study - NA
- NA
- 78 (48/30)
- Fist-ever IS (FS) and recurrent IS (RS)
- Comorbidities: High blood pressure, coronary heart disease, valvular disease of the heart, heart failure, atrial fibrillation
- FS 64.2 ± 8.9, RS 75.8 ± 9.4, HC 65.5 ± 8.2
- FS 21/17, RS 7/3, HC 17/13
61.54% - Model 1: fatty acid metabolite levels including DHA, 8-iso-PGF3α, arachidonic acid, 8-iso-15-keto-PGF2a, 13-HODE, and 14,15-DHET
- Model 2: clinical biochemical parameter levels, including HDL, blood glucose, and TG
- Model 3: both fatty acid metabolites and clinical biochemical parameters: arachidonic acid, DHA, 13-HODE, 8-iso-15-keto-PGF2a, and HDL
Model 3: both fatty acid metabolites and clinical biochemical parameters: arachidonic acid, DHA, 13-HODE, 8-iso-15-keto-PGF2a, and HDL 48 2 28 0 1.00 (0.91–1.00) 0.93 (0.77–0.99) 0.99 (0.98–1.00) - (Rahmati et al., 2021)
- No. 22
- 2021
- Iran
Prospective study - Single-center
- Inpatient
- 104 (52/52)
- IS
- Comorbidities: N/A
- NA
- NA
50.00% - micronRNA-210 (miR-210)
- Hypoxia inducible factor-1α (HF-1α)
HF-1α 34 20 32 18 0.65 (0.50–0.78) 0.62 (0.47–0.75) 0.73 (0.64–0.82) - (Zhao et al., 2021)
- 2021
- China
Prospective study - Single-center
- Inpatient
- 100 (50/50)
- IS
- Comorbidities: Hypertension, diabetes mellitus
- IS 66.76 (median), control 66.74 (median)
- IS 31/19, control 30/20
50.00% - microRNA-148a (has-miR-148a)
- microRNA-342-3p (has-miR-342-3p)
- microRNA-19a (has-miR-19a)
- microRNA-320d (has-miR320d)
- has-miR-148a + has-miR-342-3p
- has-miR148a + has-miR-342-3p + has-miR-19a
- has-miR148a + has-miR-342-3p + has-miR-19a + has-miR-320d
has-miR148a + has-miR-342-3p + has-miR-19a + has-miR-320d 47 9 41 3 0.94 (0.83–0.98) 0.82 (0.68–0.91) 0.89 (0.77–1.00) - (Park et al., 2018)
- 2017
- USA
A prospective, case-control study - Multicenter
- Inpatient and outpatient
- 305 (172/133)
- AIS
- Comorbidities: Hypertension, diabetes mellitus, hyperlipidaemia, CAD, atrial fibrillation
- AIS 68.8 ± 14.7, control 71.0 ± 10.5
- 147/158
56.39% - Glycogen phosphorylase isoenzyme BB (GPBB)
Glycogen phosphorylase isoenzyme BB (GPBB) 160 9 124 12 0.93 (0.88–0.96) 0.93 (0.87–0.97) 0.96 (0.94–0.98) - (H. T. Zhang et al., 2020)
- 2020
- China
Case-control study - Single-center
- Inpatient
- 163 (93/70)
- IS
- Comorbidities: Hypertension, diabetes mellitus
- IS 67.5 ± 11.2, control 66.2 ± 10.8
- 96/67
57.06% - Endothelial microvesicles (EMVs)
- EMVs carrying miRNA-155
EMVs + EMVs-miR-155 70 8 85 23 0.75 (0.65–0.83) 0.91 (0.83–0.96) 0.89 (0.84–0.94) - (Sun et al., 2017)
- 2017
- China
Case-control study - Single-center
- Inpatient and outpatient
- 60 (30/30)
- IS
- Comorbidities: N/A
- IS 59.77 ± 12.41, control 57.83 ± 11.08
- 34/26
50.00% 12 Metabolites - Uric acid
- LysoPE (0:0/18:3)
- LysoPC (18:2)
- Bilirubin
- Sphinganine
- Linoelaidyl carnitine
- LysoPC (16:0)
- Adrenoyl ethanolamide
- PE (15:0/22:1)
- PS (14:1/22:6)
- PC (14:0/20:4)
- PC (16:0/22:6)
Uric acid 22 7 23 8 0.73 (0.54–0.87) 0.77 (0.57–0.89) 0.78 (0.66–0.90) Sphinganine 21 5 25 9 0.70 (0.50–0.85) 0.83 (0.65–0.94) 0.75 (0.63–0.88) Adrenoyl ethanolamide 23 7 23 7 0.77 (0.57–0.89) 0.77 (0.57–0.89) 0.81 (0.70–0.92) - (C. Qin et al., 2019)
- 2019
- China
- A retrospective, case-control study
- Single-center
- Inpatient
- 66 (33/33)
- AIS due to large-vessel occlusion (LVO)
- Comorbidities: Hypertension, diabetes mellitus, coronary heart disease, hypercholesterolemia
- AIS due to LVO 54 (46–59), HC 55 (45–62)
- 41/25
50.00% - IGF2
- LYVE1
- PPBP, THBS1
The 4-protein panel (IGF2, LYVE1, PPBP, THBS1) NA NA NA NA NA NA 0.95 (0.90–1.01) - (Lee et al., 2020)
- 2020
- South Korea
A prospective, case-control study - Single-center
- Inpatient
- 61 (30/31)
- AIS
- Comorbidities: Cardiovascular disease, hypertension, diabetes, atrial fibrillation
- AIS 59.9 ± 10.9, HC 56.12 ± 5.6
- 30/31
49.18% - Prothrombin (F2)
- Plasminogen (PLG)
- Fibrinogen alpha chain (FGA)
- Histidine-rich glycoprotein (HRG)
F2 26 4 27 4 0.87 (0.68–0.96) 0.87 (0.69–0.96) 0.92 (0.84–0.99) PLG 29 1 30 1 0.97 (0.81–1.00) 0.97 (0.82–1.00) 0.98 (0.94–1.02) FGA 27 2 29 3 0.90 (0.72–0.97) 0.93 (0.77–0.99) 0.92 (0.85–0.99) HRG 29 1 30 1 0.97 (0.81–1.00) 0.97 (0.815–1.00) 0.98 (0.944–1.02) - (Tiedt et al., 2017)
- 2017
- Germany
Case-control study - Single-center
- Inpatient
- 300 (200/100)
- IS
- Comorbidities: Hypertension, hypercholesterolemia, diabetes mellitus
- IS 74.1 ± 13.4, HC 65.6 ± 13.4
- 148/152
66.67% - 33 microRNAs (miRNAs)
A set of miR-125a-5p, miR-125b-5p and miR-143-3p 171 24 76 29 0.86 (0.80–0.90) 0.76 (0.66–0.84) 0.90 (0.87–0.93) - (L. S. Dolmans et al., 2019)
- 2019
- the Netherlands
Cross-sectional study - NA
- Outpatient and home
- 206 (126/80)
- TIA
- Comorbidities: Hypertension, diabetes mellitus, hyperlipidemia, cerebrovascular disease, renal insufficiency, migraine, epilepsy
- TIA 71.4 ± 12.0, control 62.0 ± 14.2
- 122/84
61.17% - NR2
- NR2Ab
- B-FABP
- H-FABP
- NDKA
- UFD1
- PARK7
H-FABP 44 28 52 82 0.35 (0.27–0.44) 0.65 (0.53–0.75) NA - (J. Liu et al., 2020)
- 2020
- China
Prospective study - Single-center
- Inpatient
- 137 (72/65)
- AIS
- Comorbidities: Hypertension, diabetes mellitus, dyslipidemia, cervical artery plaques
- AIS 58.7 ± 9.7, control 56.6 ± 8.5
- 81/56
52.55% - Sphingosine 1-phosphate (S1P)
- High-density lipoprotein cholesterol (HDL-C)
S1P 44 25 40 28 0.61 (0.49–0.72) 0.62 (0.49–0.73) 0.62 (0.53–0.72) S1P within 24 h of symptom onset 49 8 57 23 0.68 (0.56–0.78) 0.87 (0.77–0.94) 0.83 (0.74–0.92) - (Z. Z. Chen et al., 2018)
- 2018
- China
Prospective study - NA
- Inpatient
- 230 (128/102)
- AIS
- Comorbidities: Hypertension, diabetes, coronary disease, dyslipidemia
- AIS 68.42 ± 17.26, control 65.36 ± 16.32
- 109/19
55.65% - Plasma hs-CRP
- Serum miR-146b, miR-21, miR-145, miR-29b, miR-221
- Interleukin (IL-6)
Combination of hs-CRP, IL-6 and miR-146b NA NA NA NA NA NA 0.87 (0.80–0.93) IS, ischemic stroke group; C, control group; TP, true positive; FP, false positive; TN, true negative; FN, false negative; Sen, sensitivity; Spe, specificity; AUC, area under the curve; N/A, not applicable.
↵a The one generated the final diagnostic value.
Subgroup Number of included studies Total sample size AUC Sen (95% CI) Spe (95% CI) PLR (95% CI) NLR (95% CI) DOR (95% CI) All combined 23 3,494 0.89 0.76 (0.74–0.78) 0.84 (0.83–0.86) 4.91 (3.69–6.53) 0.26 (0.20–0.32) 23.14 (14.15–37.84) Setting Inpatient 18 2,795 0.88 0.76 (0.74–0.78) 0.84 (0.83–0.86) 4.85 (3.64–6.45) 0.28 (0.23–0.33) 21.66 (14.15–33.16) Othersa 4 621 0.91 0.71 (0.66–0.75) 0.83 (0.78–0.87) 4.40 (1.54–12.60) 0.27 (0.09–0.83) 16.95 (2.41–119.25) Sample size <100 9 578 0.92 0.86 (0.82–0.88) 0.82 (0.79–0.86) 4.95 (3.44–7.12) 0.20 (0.14–0.27) 30.87 (16.31–58.42) ≥100 14 2,916 0.86 0.73 (0.71–0.75) 0.85 (0.83–0.87) 4.73 (3.11–7.19) 0.31 (0.23–0.41) 17.57 (8.84–34.91) Target IS population IS 6 805 0.87 0.82 (0.78–0.85) 0.80 (0.76–0.84) 4.07 (2.65–6.27) 0.26 (0.17–0.40) 17.74 (7.85–40.10) AIS 12 1,650 0.91 0.77 (0.75–0.80) 0.88 (0.85–0.90) 6.78 (4.40–10.44) 0.24 (0.19–0.31) 32.72 (17.38–61.60) Othersb 5 1,039 0.84 0.68 (0.64–0.72) 0.81 (0.78–0.84) 3.00 (1.66–5.42) 0.31 (0.17–0.56) 12.91 (3.69–45.16) Blood biomarker profiling Single 14 2,136 0.88 0.73 (0.71–0.75) 0.84 (0.82–0.86) 4.52 (3.15–6.47) 0.27 (0.21–0.36) 19.74 (10.56–36.89) Multiple 9 1,358 0.91 0.81 (0.78–0.83) 0.86 (0.83–0.88) 5.89 (4.23–8.20) 0.22 (0.16–0.30) 30.20 (19.44–46.91) Ethnicity Asian 17 2,474 0.89 0.75 (0.73–0.77) 0.86 (0.85–0.88) 5.55 (4.00–7.68) 0.29 (0.25–0.35) 23.92 (14.81–38.64) Caucasian 5 924 0.90 0.77 (0.73–0.80) 0.81 (0.77–0.85) 4.53 (1.56–13.14) 0.21 (0.06–0.77) 23.52 (2.93–188.62) African 1 96 0.75 0.84 (0.77–0.90) 0.68 (0.60–0.76) 2.59 (1.92–3.50) 0.23 (0.12–0.46) 11.76 (4.52–30.56) Comorbidities With comorbidities 16 2,537 0.92 0.77 (0.75–0.79) 0.85 (0.83–0.87) 5.56 (3.82–8.09) 0.22 (0.16–0.31) 31.55 (16.00–62.20) N/A 7 957 0.84 0.74 (0.70–0.77) 0.82 (0.79–0.85) 3.99 (2.55–6.25) 0.32 (0.27–0.39) 14.21 (7.71–26.19) Sen, sensitivity; Spe, specificity; PLR, positive likelihood ratio; NLR, negative likelihood ratio; AUC, area under the curve; DOR, diagnostic odds ratio; IS, ischemic stroke; AIS, acute ischemic stroke; N/A, not applicable.
↵a Inpatient and outpatient, outpatient and home.
↵b Acute lacunar infarction, CRCIS, CES, CAS, TIA.
Characteristics Number of included studies (n)a Percentage (%) Publication year 2017 5 17.24 2018 8 27.59 2019 3 10.34 2020 7 24.14 2021 4 13.79 2022 2 6.90 Country China 19 65.52 USA 3 10.34 Egypt 1 3.45 Japan 1 3.45 Turkey 1 3.45 Iran 1 3.45 South Korea 1 3.45 Germany 1 3.45 Netherlands 1 3.45 Study design Prospective study 21 46.67 Case-control study 17 37.78 Retrospective study 3 6.67 Cohort study 2 4.44 Cross-sectional study 1 2.22 Experimental study 1 2.22 Study setup Single center 21 72.41 Multicenter 5 17.24 N/A 3 10.34 Setting Inpatient department 27 84.38 Outpatient department 3 9.38 Home 1 3.13 N/A 1 3.13 Total sample size (n) 1–50 4 13.79 >50–100 10 34.48 >100–200 6 20.69 >200–300 5 17.24 >300–400 3 10.34 >400 1 3.45 Target IS population AIS 20 68.97 IS 6 20.69 Acute lacunar infraction 1 3.45 Cardio embolic stroke 1 3.45 TIA 1 3.45 Age of participants (mean/median in years) 45–59 10 27.78 60–70 16 44.44 >70 8 22.22 NA 2 5.56 Prevalence of IS (%) >20–40 2 6.90 >40–60 21 72.41 >60–80 6 20.69 N/A, not applicable.
↵a One study may have ≥ 1 characteristic.
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