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Table 4 Study characteristic

From: Malondialdehyde (MDA) and 8-hydroxy-2′-deoxyguanosine (8-OHdG) in ischemic stroke: a systematic review

No.

First author, country, year

Study design

Sample (n)

Sample characteristic: age (year), gender (male, female)

Outcome measure

Result

1.

Aygul, Turkey, 2006 [13]

Cross-sectional

AIS: 19

Healthy: 20

AIS

Age: 64.7 ± 7.9

Gender: 11, 8

Healthy

Age: 62.5 ± 8.3

Gender: 12, 8

Oxidative stress biomarker of AIS

CSF MDA level in IS group was significantly higher than control group (16.5 ± 3.5 vs 14.4 ± 3.4 nmol/mL, p < 0.05)

2.

Aygul, Turkey, 2008 [29]

Prospective study

IS: 29

Healthy: 13

IS

Age: 61. 9 ± 10. 4

Gender: 12, 17

Healthy

Age: 58.1 ± 6.8

Gender: 6, 7

Oxidative stress biomarker of IS

MDA level in IS group within 3–4 d after onset was significantly higher than control group (14.3 vs 10.6 µmol/L, p: .004)

3.

Bir, Turkey, 2006 [41]

Cross-sectional

IS

Atherothrombotic: 19

Lacunar: 19

Healthy: 30

Atherothrombotic

Age: 69 (38–79)

Gender: 10, 9

Lacunar

Age: 58 (30–79)

Gender: 10, 9

Healthy

Age: 59 (40–69)

Gender: 16, 14

Oxidative stress biomarker of chronic IS

MDA level in chronic IS (atherothrombotic & lacunar) was significantly higher than control group (3.5 vs 1.69 nmol/mL, p < 0.001; 3.83 vs 1.69 nmol/mL, p < 0.001)

4.

Cano, Venezuela, 2003 [30]

Prospective study (24 h)

AIS: 15

Healthy: 15

AIS

Age: 64 ± 3.6

Gender: 8, 7

Healthy

Age: 56.7 ± 1.3

Gender: 8, 7

Oxidative stress biomarker of AIS (thrombotic stroke)

MDA level in AIS within 24 h after onset was significantly higher than control group (47.9 ± 7.1 vs 1.7 ± 0.2 µmol/L, p < 0.001)

5.

Chen, China, 2018 [48]

Cross-sectional

PSD: 70

Non-PSD: 69

PSD

Age: 65.8 (55.9–74.2)

Gender: 48, 22

Non-PSD

Age: 59.7 (53.6–72.1)

Gender: 49. 20

PSD predictor

Urinary 8-OHdG level in PSD group was insignificantly higher than control group (40.1 vs 38.6 ng/mgCr, p: 0.056). Urinary 8-OHdG level was positively correlated with PSD (r: 0.202, p: 0.017)

6.

Cojocaru, Romania, 2013 [31]

Prospective study (7 d)

AIS: 57

Healthy: 51

AIS

Age: 73.4 ± 6.5

Gender: 33, 24

Oxidative stress biomarker of AIS

MDA level in AIS within 24 h and 7 d after onset was significantly higher than control group (2.36 vs 1.32, p < 0.05; 3.14 vs 1.32, p < 0.001)

7.

Demirkaya, Turkey, 2001 [42]

Cross-sectional

AIS: 34

Healthy: 30

AIS

Age: 59.3 ± 12.6

Gender: 20, 14

Healthy

Age: 54.4 ± 8.7

Gender: 19, 11

Oxidative stress biomarker of AIS, outcome predictor

MDA level within 1 day after AIS onset was higher significantly than control group (349.7 ± 60.5 vs 200 ± 65.7 mol/gHb, p < 0.001). Higher MDA level within 1 day was significantly associated with infarct size, stroke severity, poor short-term clinical outcome, and prognosis (r: 9.964, p < 0.001; r: 0.846, p: 0.004; r: 0.557, p < 0.001; p: 0.021)

8.

Dogan, Turkey, 2018 [43]

Cross-sectional

IS: 20

IS risk: 22

Healthy: 27

IS

Age: 64.2 ± 14.04

Gender: 11, 9

IS risk

Age: 59.2 ± 8.74

Gender: 12, 10

Healthy

Age: 12, 15

Gender: 59.1 ± 12.09

Oxidative stress biomarker of IS

MDA level in IS group was significantly higher than control group (p < 0.05)

9.

Dominguez, Spain, 2010 [32]

Prospective study (24 h)

AIS: 160

Healthy: 60

AIS

Age: 74 (65–78)

Gender: 88, 72

Oxidative stress biomarker of AIS

MDA level in AIS group was significantly higher than control group (1.13 ± 0.33 vs 0.69 ± 0.24 µmol/L, p < 0.01) and significantly increased within hours (1, 2, 12, 24 h; p < 0.001). Higher MDA level in AIS group was associated with stroke severity, clinical outcome, and hemorrhagic complications (p < 0.05)

10.

Elsayed, Egypt, 2020 [18]

Prospective study (3 mo)

AIS: 42

Age: 62.95 ± 4.21

Gender, 20, 22

Functional outcome predictor

Higher MDA level was significantly correlated with mRS score (r: 0.54, p: 0.001)

11.

Haritha, India, 2020 [19]

Cross-sectional

IS: 60

Healthy: 30

IS

Age: 55.95 ± 7.98

Gender: 39, 21

Healthy

Age: 56.20 ± 7.48

Gender: 20, 10

Oxidative stress biomarker of IS

MDA level in IS group was significantly higher than control group (5.18 ± 1.26 vs 3.27 ± 1.26, p < 0.001)

12.

Liu, China, 2017 [17]

Prospective study (30 d)

PSCI: 101

Non-PSCI: 92

PSCI

Age: 66 (56–72)

Gender: 56, 45

Non-PSCI

Age: 65, 27

Gender: 60 (52.3–65.8)

PSCI predictor

MDA and 8-OHdG level in PSCI group were significantly higher than control group (3.6 vs 2.3, p < 0.001; 217.5 vs 159.4, p < 0.001). MDA (> 2.59 nmol/ml) and 8-OHdG (> 158.63 ng/L) level were associated with PSCI (p < 0.05)

13.

Liu, China, 2018 [11]

Prospective study (30 d)

PSD: 70

Non-PSD: 171

PSD

Age: 64 (57–71)

Gender: 45, 25

Non-PSD

Age: 64 (56–70)

Gender: 110, 61

PSD predictor

8-OHdG level in PSD group was significantly higher than control group (218 vs 164.8 ng/L, p < 0.001). 8-OHdG level (≥ 200 ng/L) was positively correlated with PSD (r: 0.129, p: 0.046)

14.

Lorente, Spain, 2015 [33]

Prospective study (30 d)

IS non-survivor: 26

IS survivor: 24

Healthy: 100

IS non-survivor

Age: 66 (45–76)

Gender: 17, 9

IS survivor

Age: 47 (32–67)

Gender: 16, 8

Healthy

Age: 59 (47–71)

Gender: 62, 38

Oxidative stress biomarker of IS, mortality predictor

MDA level in IS group was significantly higher than control group (2.16 vs 1.11, p < 0.001), and in non-survivor group was significantly higher that survivor group (2.95 vs 1.83, p < 0.001). Higher MDA level (> 2.27 nmol/mL) was associated with 30-day mortality of IS patients (OR: 7.23, 95% CI: 1.84–28.73, p: 0.005)

15.

Lorente, Spain, 2016 [34]

Prospective study (30 d)

Non-survivor: 29

Survivor: 29

Non-survivor

Age: 64 (54–70)

Gender: 18, 11

Survivor

Age: 57 (47–67)

Gender: 16, 13

Mortality predictor

MDA level in non-survivor group was significantly higher than survivor group (2.93 vs 1.9 nmol/mL, p: 0.004)

16.

Lorente, Spain, 2021 [35]

Prospective study (30 d)

Non-survivor: 34

Survivor: 34

Non-survivor

Age: 63 (53–70)

Gender: 21, 13

Survivor

Age: 59 (47–68)

Gender: 20, 14

Mortality predictor

8-OHdG level in non-survivor group was significantly higher than survivor group (6 vs 3.86, p < 0.001). Higher 8-OHdG level (> 4.82 ng/mL) was associated with 30-day mortality of IS (OR: 1.568, 95% CI: 1.131–2.174, p: 0.01)

17.

Lorenzano, USA, 2018 [36]

Prospective study (9 h)

Infarct growth: 170

No Infarct growth: 50

Infarct growth

Age: 69.9 ± 14.0

Gender: 107, 63

No Infarct growth

Age: 67.9 ± 17.2

Gender: 23, 27

Infarct growth of AIS

8-OHdG level in infarct growth group was insignificantly higher than control group (5.6 vs 3.4 ng/mL, p: 0.18)

18.

Menon, India, 2020 [14]

Case–control

AIS:

100

Healthy: 99

AIS

Age: 55.54 ± 11.57

Gender: Male 74%

Healthy

Age: 57.39 ± 10.53

Gender: Male 74%

Oxidative stress biomarker of AIS

MDA level in AIS group was significantly higher than control group (7.11 ± 1.67 vs 1.64 ± 0.82, p < 0.05)

19.

Milanlioglu, Turkey, 2016 [16]

Case–control

AIS: 45

Healthy: 30

AIS

Age: 64 ± 15

Gender: 30, 15

Healthy

Age: 62 ± 8

Gender: 20, 10

Oxidative stress biomarker of AIS

MDA level in AIS group within 24 h after onset was significantly higher than control group (6.77 ± 1.44 vs 5.9 ± 1.62, p < 0.05)

20.

Mizukoshi, Japan, 2005 [37]

Prospective study (3–5 d)

AIS: 7

Healthy: 6

AIS

Age: 73

Gender: 4, 3

Healthy

Age: 67

Gender: 4, 2

Oxidative stress biomarker of AIS (cardioembolic stroke)

Higher urinary 8-OHdG level within 3–5 days after onset was significantly associated with acute cardioembolic stroke (p < 0.01)

21.

Moon, Korea, 2014 [44]

Cross-sectional

AIS: 71

CIS: 28

AIS

Age: 66.8 ± 10.7

Gender: 46, 25

CIS

Age: 66.1 ± 11.1

Gender: 12, 16

Oxidative stress biomarker of IS (atherosclerotic)

Higher MDA level was significantly correlated with infarct volume of AIS (r: 0.551, p < 0.05)

22.

Mueangson, Thailand, 2020 [45]

Cross-sectional

IS:

91

Healthy:

91

IS

Age: 69 ± 14

Gender: 59, 32

Healthy

Age: 68 ± 13

Gender: 59, 32

Oxidative stress biomarker of IS, HGS biomarker

MDA level in IS group was significantly higher than control group (7.05 ± 3.49 vs 5.98 ± 5.68, p: 0.022). Higher MDA level was associated with low HGS in the non-paretic limbs of IS patients (AOR: 1.280, 95% CI: 1.024–1.6, p: 0.03)

23.

Nakajima, Japan, 2012 [12]

Prospective study (7 d)

Lacunar: 9 Atherothrombotic: 22

Cardioembolic: 13

Poor outcome 25

Good outcome: 19

Lacunar

Age: 74

Gender: 5, 4

Atherothrombotic

Age: 69

Gender: 8, 14

Cardioembolic

Age: 74

Gender: 7, 6

Poor outcome

Age: 72

Gender: 13, 12

Good outcome

Age: 70

Gender: 12, 7

Clinical outcome predictor

Δ 8-OHdG level (day 0 to 7) in atherothrombotic group was significantly higher than lacunar group (33.8 vs 6.3, p: 0.048). Δ 8-OHdG level (day 0 to 7) in poor outcome was significantly higher than good outcome (39.44 vs 2.54, p: 0.004)

24.

Polidori, Italy, 2002 [38]

Prospective study (7 d)

AIS: 28

Healthy: 76

AIS

Age: 76.9 ± 8.7

Gender: 19. 9

Healthy

Age: 77.3 ± 10.1

Gender: 48, 28

Oxidative stress biomarker of AIS, functional outcome predictor

MDA level in AIS group was significantly higher than control group, and was associated with clinical outcome (p < 0.05)

25.

Sarkar, India, 2009 [46]

Cross-sectional

IS: 100

Healthy: 100

IS

Age: 70 ± 7.5

Gender: 70, 30

Healthy

Age: 68.2 ± 4.1

Gender: 64, 36

Oxidative stress biomarker of IS

MDA level in IS group was significantly higher than control group (6.7 ± 0.1 vs 3.1 ± 1.6, p < 0.001)

26.

Shaafi, Iran, 2021 [9]

Case–control

AIS: 216

AIS risk: 152

Healthy: 188

AIS group

Age: 71.76 ± 9.88

Gender: 148, 68

AIS risk

Age: 71.89 ± 10.22

Gender: 88, 64

Healthy

Age: 73.32 ± 9.43

Gender: 92, 96

AIS development and outcome predictor

MDA level in AIS group was significantly higher than control group (2.08 vs 1.85 µmol/L, p < 0.05). Higher MDA level was associated with the development of AIS (p < 0.001) and negatively correlated with mRS score 3 months of follow-up (p: 0.04, r: -0.26)

27.

Syafrita, Indonesia, 2020 [10]

Case–control

PSD: 36

Non-PSD: 36

PSD

Age: 59.67 ± 11.2

Gender: 19, 17

Non-PSD

Age: 59.64 ± 

Gender: 18, 18

PSD predictor

MDA and 8-OHdG level in PSD group were significantly higher (110.06 ± 33.27 vs 99.98 ± 54.76, p 0.024; 4.39 ± 2.19 vs 3.08 ± 0.73, p < 0.001). MDA and 8-OHdG level were positively correlated with PSD (r: 0.268, p 0.023; r: 0.432, p < 0.001)

28.

Tsai, Taiwan, 2014 [39]

Prospective study (3 mo)

Small-vessel disease: 75

Large-vessel disease: 25

Control: 80

Small-vessel disease age: 61 ± 11.7

Gender: 60, 15

Large-vessel disease age: 64.6 ± 8.8

Gender: 17, 8

Oxidative stress biomarker of AIS, Outcome predictor

MDA level in AIS group was significantly higher than control group on day 1 and 7 after onset and associated with poor outcome (p < 0.05)

29.

Yildirim, Turkey, 2007 [47]

Cross-sectional

AIS: 32

Healthy: 18

AIS

Age: 59.6 ± 10.6

Gender: 17, 15

Healthy

Age: 55.7 ± 9.3

Gender: 10, 8

Oxidative stress biomarker of AIS

Serum and CSF MDA level in AIS group were significantly higher than control group (8.6 ± 1.8 vs 7.1 ± 2.1, p < 0.01; 5.9 ± 2.2 vs 4.2 ± 1.6, p < 0.01)

30.

Zimmermann, Germany, 2004 [40]

Prospective study (7 d)

IS: 11

History of IS: 17

IS

Age: 62.2 ± 8.4

Gender: 6, 5

History of IS

Age: 63.4 ± 7.8

Gender: 3, 14

Oxidative stress biomarker of AIS

MDA level in AIS group (within 48 h of onset) was significantly higher than control group (p < 0.05)

  1. 8-OHdG 8-hydroxy-2′-deoxyguanosine, 95% CI 95% confidence interval, AIS acute ischemic stroke, CIS chronic ischemic stroke, CSF cerebrospinal fluid, d day, h hour, HGS hand grip strength, IS ischemic stroke, L liter, mo month, OR odds ratio, p probability, PSCI post-stroke cognitive impairment, PSD post-stroke depression, r correlation coefficient, MDA malondialdehyde, mL milliliter, mRS modified Rankin scale, ng nanogram