Predictive Role of Coagulation, Fibrinolytic, and Endothelial Markers in Patients with Atrial Fibrillation, Stroke, and Thromboembolism: A Meta-Analysis, Meta-Regression, and Systematic Review

Alexander Weymann; Anton Sabashnikov; Sadeq Ali-Hasan-Al-Saegh; Aron-Frederik Popov; Seyed Jalil Mirhosseini; William L. Baker; Mohammadreza Lotfaliani; Tong Liu; Hamidreza Dehghan; Senol Yavuz; Michel Pompeu Barros de Oliveira Sá; Jae-Sik Jang; Mohamed Zeriouh; Lei Meng; Fabrizio D’Ascenzo; Abhishek J. Deshmukh; Guiseppe Biondi-Zoccai; Pascal M. Dohmen; Hugh Calkins; Integrated Meta-Analysis of Cardiac Cardiac Surgery and Cardiology-Group IMCSC-Group]

doi:10.12659/MSMBR.902558

31 March 2017 : Meta-Analysis

Predictive Role of Coagulation, Fibrinolytic, and Endothelial Markers in Patients with Atrial Fibrillation, Stroke, and Thromboembolism: A Meta-Analysis, Meta-Regression, and Systematic Review

Alexander Weymann^{ABCDEFG 1*}, Anton Sabashnikov^{ABCDEFG 2,3}, Sadeq Ali-Hasan-Al-Saegh^{ABCDEFG 4}, Aron-Frederik Popov^{ABCDEFG 5}, Seyed Jalil Mirhosseini^{ABCDEFG 4}, William L. Baker^{ABCDEFG 6}, Mohammadreza Lotfaliani^{ABCDEFG 4}, Tong Liu^{ABCDEFG 7}, Hamidreza Dehghan^{ABCDEFG 8}, Senol Yavuz^{ABCDEFG 9}, Michel Pompeu Barros de Oliveira Sá^{ABCDEFG 10,11,12}, Jae-Sik Jang^{ABCDEFG 13}, Mohamed Zeriouh^{ABCDEFG 2,3}, Lei Meng^{ABCDEFG 14}, Fabrizio D’Ascenzo^{ABCDEFG 15}, Abhishek J. Deshmukh^{ABCDEFG 16}, Guiseppe Biondi-Zoccai^{ABCDEFG 17,18}, Pascal M. Dohmen^{ABCDEFG 1}, Hugh Calkins^{ABCDEFG 19}, Integrated Meta-Analysis of Cardiac Cardiac Surgery and Cardiology-Group IMCSC-Group]

DOI: 10.12659/MSMBR.902558

Med Sci Monit Basic Res 2017; 23:97-140

Authors information Article notes Copyright and License information

¹Department of Cardiac Surgery, University Hospital Oldenburg, European Medical School Oldenburg-Groningen, Carl von Ossietzky University Oldenburg, Oldenburg, Germany
²Department of Cardiothoracic Transplantation and Mechanical Circulatory Support, Royal Brompton and Harefield NHS Foundation Trust, Harefield Hospital, Harefield Middlesex, United Kingdom
³Department of Cardiothoracic Surgery, University Hospital Cologne, Cologne, Germany
⁴Cardiovascular Research Center, Shahid Sadoughi University of Medical Sciences, Yazd, Iran
⁵Department of Cardiac Surgery, University Hospital Frankfurt am Main, Frankfurt am Main, Germany
⁶ University of Connecticut/Hartford Hospital Evidence-Based Practice Center, Hartford, USA
⁷Tianjin Key Laboratory of Ionic-Molecular Function of Cardiovascular Disease, Department of Cardiology, Tianjin Institute of Cardiology, 2nd Hospital of Tianjin Medical University, Tianjin, China
⁸Department of Health Technology Assessment, Shahid Sadoughi University of Medical Sciences and Health Services, Yazd, Iran
⁹Department of Cardiovascular Surgery, Bursa Yuksek Ihtisas Training and Research Hospital, Bursa, Turkey
¹⁰Division of Cardiovascular Surgery, Pronto Socorro Cardiológico de Pernambuco – PROCAPE, Recife, Brazil
¹¹ Nucleus of Postgraduate and Research in Health Sciences of Faculty of Medical Sciences and Biological Sciences Institute (FCM/ICB), Recife, Brazil
¹² University of Pernambuco – UPE, Recife, Brazil
¹³Department of Cardiology, Busan Paik Hospital, Inje University College of Medicine, Busan, South Korea
¹⁴Division of Cardiology, Department of Medical Sciences, Città della Salute e della Scienza Hospital, University of Turin, Turin, Italy
¹⁵Mayo Clinic Heart Rhythm Section, Cardiovascular Diseases, Mayo Clinic, Rochester, USA
¹⁶Department of Medico-Surgical Sciences and Biotechnologies, Sapienza University of Rome, Rome, Italy
¹⁷Department of AngioCardioNeurology, IRCCS Neuromed, Pozzilli, Italy
¹⁸Department of Cardiology, Johns Hopkins Medical Institutions, Baltimore, USA

^*Corresponding Author: Alexander Weymann, e-mail: [email protected]

^AStudy design/planning
^BData collection/entry
^CData analysis/statistics
^DData interpretation
^EPreparation of manuscript
^FLiterature analysis/search
^GFunds collection

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Supplementary Table 3 Subgroup-analysis and meta-regression.

Subgroup	Studies (N)	WMD (95% CI)	I-squared and P-value respectively	P-value of meta-regression


Year of publication				0.845
>2000	25	243.7 (209.1 to 278.2)	99.8% and 0.001
≤2000	16	137.3 (103.6 to 171.1)	99.1% and 0.001

Geographic area				0.008
Asian	13	144.4 (108.8 to 180.1)	99.7% and 0.001
European	24	242.5 (199.4 to 285.7)	99% and 0.001
Africa	1	0.83 (0.28 to 1.38)	–
North American	2	65.11 (−62.93 to 193.1)	98.2% and 0.001
South American	–	–	–
Australia	1	472 (429.3 to 514.6)	–

Design of study				0.001
Cohort	35	176.1 (153.7 to 198.4)	99.7% and 0.001
Case-control	6	290.2 (189.5 to 390.8)	99.8% and 0.001

Number of population				0.49
>300	2	65.1 (−62.9 to 193.1)	99.9% and 0.001
≤300	39	204.4 (179.9 to 229)	99.4% and 0.001

Mean Age				0.92
>60 years	26	226.7 (188.6 to 264.8)	99.7% and 0.001
≤60 years	9	160.7 (77 to 244.4)	99.6% and 0.001

Male				0.94
>70%	3	113.7 (22.2 to 205.1)	98.9% and 0.001
≤70%	26	227.8 (187.8 to 267.8)	99.6% and 0.001

Diabetes mellitus				0.47
>30%	2	290 (271.6 to 308.4)	73.3% and 0.001
≤30%	20	264.8 (205.7 to 323.8)	99.7% and 0.001

Hypertension				0.96
>70%	1	96.1 (47.2 to 144.7)	–
≤70%	19	258.6 (194.7 to 321.9)	99.8% and 0.001

History of myocardial infarction				0.95
>20%	1	−0.16 (−0.42 to 0.107)	–
≤20%	4	761.7 (140.3 to 1383.2)	98.2% and 0.001

Anti-coagulant status codes				0.91
1	18	215.3 (172 to 258.6)	98.9% and 0.001
2	–	–	–
3	2	154 (−110.2 to418.4)	97.6% and 0.001
4	11	331.3 (225.5 to 437.1)	99.6% and 0.001
5	10	91.1 (56 to 126.3)	99.9% and 0.001
6	–	–	–

AF				0.015
Chronic	14	261.3 (208.9 to 313.8)	99.6% and 0.001
Non-chronic	11	104.7 (29.6 to 179.8)	99.4% and 0.001

Type of AF				0.254
Paroxysmal	5	19.6 (12.5 to 26.8)	0.0% and 0.78
Persistent	–	–	–
Permanent	4	512.5 (135.3 to 889.8)	99% and 0.001

Cigarette smoking				0.132
>30%	7	111.1 (106.1 to 116)	99.7% and 0.001
≤30%	8	−0.136 (−0.403 to 0.131)	98.3% and 0.001



Year of publication				0.02
>2000	46	0.29 (0.24 to 0.35)	96.1% and 0.001
≤2000	12	0.75 (0.54 to 0.96)	96.4% and 0.001

Geographic area				0.04
Asian	9	0.35 (0.24 to 0.47)	95% and 0.001
European	40	0.53 (0.38 to 0.68)	97.9% and 0.001
Africa	–	–	–
North American	9	0.10 (0.02 to 0.19)	97.3% and 0.001
South American	–	–	–
Australia	–	–	–

Design of study				0.44
Cohort	15	0.22 (0.15 to 0.29)	98.2% and 0.001
Case-control	43	0.52 (0.36 to 0.69)	97.4% and 0.001

Number of population				0.053
>300	11	0.15 (0.05 to 0.25)	98.4% and 0.001
≤300	47	0.52 (0.39 to 0.64)	98% and 0.001

Mean Age				0.94
>60 years	43	0.48 (0.37 to 0.59)	98.7% and 0.001
≤60 years	13	0.26 (0.17 to 0.34)	95% and 0.001

Male				0.468
>70%	13	0.56 (0.35 to 0.77)	93.9% and 0.001
≤70%	37	0.40 (0.31 to 0.48)	98.9% and 0.001

Diabetes mellitus				0.97
>30%	6	0.40 (0.11 to 0.69)	96.5% and 0.001
≤30%	37	0.35 (0.28 to 0.43)	97.3% and 0.001

Hypertension				0.60
>70%	3	0.17 (0.004 to 0.35)	87.1% and 0.001
≤70%	40	0.36 (0.29 to 0.43)	97.5% and 0.001

History of myocardial infarction				0.58
>20%	4	0.01 (−0.11 to 0.13)	75.6% and 0.006
≤20%	16	0.42 (0.26 to 0.58)	96.5% and 0.001

Anti-coagulant status codes				0.26
1	16	0.45 (0.23 to 0.68)	98.5% and 0.001
2	–	–	–
3	8	0.62 (0.19 to 1.05)	95.3% and 0.001
4	16	0.20 (0.14 to 0.25)	92.7% and 0.001
5	17	0.53 (0.33 to 0.73)	98.6% and 0.001
6	1	0.05 (−0.13 to 0.23)	–

AF				0.23
Chronic	18	0.7 (0.42 to 0.97)	97.6% and 0.001
Non-chronic	16	0.24 (0.16 to 0.33)	92.6% and 0.001

Type of AF				0.43
Paroxysmal	8	0.38 (0.18 to 0.58)	83.9% and 0.78
Persistent	4	0.42 (0.11 to 0.74)	90.2% and 0.001
Permanent	9	0.54 (0.21 to 0.87)	93.6% and 0.001

Cigarette smoking				0.47
>30%	11	0.51 (0.47 TO 0.56)	98.3% and 0.001
≤30%	26	0.09 (0.78 to 0.103)	96.5% and 0.001



Year of publication				–
>2000	7	0.79 (−0.39 to 1.98)	98.1% and 0.001
≤2000	2	0.97 (−0.54 to 2.49)	99.8% and 0.001

Geographic area				–
Asian	3	0.52 (0.23 to 0.82)	99.7% and 0.001
European	6	0.47 (0.34 to 0.64)	94.8% and 0.001
Africa	–	–	–
North American	–	–	–
South American	–	–	–
Australia	–	–	–

Design of study	All of them are case–control
Cohort
Case-control

Number of population				–
>300	1	0.36 (0.33 to 0.39)	–
≤300	8	0.46 (0.29 to 0.62)	99.2% and 0.001

Mean Age				–
>60 years	6	0.82 (0.26 to 1.37)	99% and 0.001
≤60 years	–	–	–

Male				–
>70%	1	1.75 (1.61 to 1.88)	–
≤70%	5	0.58 (0.25 to 0.91)	95.5% and 0.001

Diabetes mellitus				–
>30%	–	–	–
≤30%	5	0.58 (0.25 to 0.91)	95.5% and 0.001

Hypertension				–
>70%	–	–	–
≤70%	5	0.38 (0.17 to 0.59)	99.7% and 0.001

History of myocardial infarction				–
>20%	–	–	–
≤20%	1	0.67 (0.57 to 0.76)	–

Anti-coagulant status codes				–
1	2	0.46 (−0.21 to 1.42)	72.9% and 0.05
2	–	–	–
3	–	–	–
4	5	0.84 (0.31 to 1.36)	99% and 0.001
5	2	−0.04 (−0.07 to 0.01)	77.1% and 0.03
6	–	–	–

AF				–
Chronic	2	1.20 (0.15 to 2.26)	99.4% and 0.001
Non-chronic	–	–	–

Type of AF				–
Paroxysmal	–	–	–
Persistent	–	–	–
Permanent	–	–	–

Cigarette smoking	No Data
>30%
≤30%



Year of publication				–
>2000	4	5.80 (−1.006 to 12.78)	99.7% and 0.001
≤2000	4	4.57 (1.77 to 7.36)	85.4% and 0.001

Geographic area				–
Asian	5	6.93 (2.18 to 11.68)	98.1% and 0.001
European	2	5.46 (3.43 to 7.48)	41.4% and 0.19
Africa	–	–	–
North American	1	0.05 (0.01 to 0.093)	–
South American	–	–	–
Australia	–	–	–

Design of study	All of them are case–control
Cohort
Case-control

Number of population	All of them are less than 300 cases
>300
≤300

Mean Age				–
>60 years	3	5.79 (3.63 to 7.96)	37.5% and 0.202
≤60 years	3	7.89 (2.09 to 13.68)	98.8% and 0.001

Male				–
>70%	–	–	–
≤70%	5	7.87 (4.43 to 11.32)	98.3% and 0.001

Diabetes mellitus				–
>30%	–	–	–
≤30%	2	5.46 (3.43 to 7.48)	41.4% and 0.191

Hypertension				–
>70%	–	–	–
≤70%	2	5.46 (3.43 to 7.48)	41.4% and 0.191

History of myocardial infarction	No Data
>20%
≤20%

Anti-coagulant status codes	All of them are Code–1
1
2
3
4
5
6

AF				–
Chronic	–	–	–
Non-chronic	2	2.47 (0.55 to 4.39)	27.4% and 0.24

Type of AF				–
Paroxysmal	5	2.47 (0.55 to 4.39)	27.4% and 0.24
Persistent	–	–	–
Permanent	–	–	–

Cigarette smoking	No sufficient data
>30%
≤30%



Year of publication				–
>2000	3	4.26 (−8.76 to 17.28)	91% and 0.001
≤2000	3	46.78 (36.8 to 56.70)	0% and 0.833

Geographic area	All of them are European
Asian
European
Africa
North American
South American
Australia

Design of study	All of them are case–control
Cohort
Case-control

Number of population	All of studies have less than 300 cases
>300
≤300

Mean Age				–
>60 years	2	22.65 (−32.07 to 77.37)	94.2% and 0.001
≤60 years	3	18.96 (0.16 to 37.65)	91.1% and 0.001

Male				–
>70%	1	−3.80 (−8.98 to 1.38)	–
≤70%	1	43.55 (28.29 to 58.80)	–

Diabetes mellitus				–
>30%	–	–	–
≤30%	5	30.21 (11.99 to 48.42)	91.3% and 0.001

Hypertension				–
>70%	–	–	–
≤70%	2	8.65 (−6.11 to 23.43)	85.3% and 0.009

History of myocardial infarction	No data
>20%
≤20%

Anti-coagulant status codes				–
1	3	46.78 (36.85 to 56.70)	0.0% and 0.833
2	–	–	–
3	1	−3.80 (−8.98 to 1.38)	–
4	–	–	–
5	2	8.65 (−6.11 to 23.43)	85.3% and 0.009
6	–	–	–

AF				–
Chronic	2	22.65 (−32.07 to 77.37)	94.2% and 0.001
Non-chronic	–	–	–

Type of AF				–
Paroxysmal	–	19.6 (12.5 to 26.8)	–
Persistent	–	–	–
Permanent	1	−3.80 (−8.98 to 1.38)	–

Cigarette smoking	No sufficient data
>30%
≤30%



Year of publication				–
>2000	1	10.05 (9.37 to 10.72)	–
≤2000	3	2.17 (−0.72 to 5.07)	99.4% and 0.001

Geographic area				–
Asian	1	4.60 (4.28 o 4.91)	–
European	3	3.98 (−1.33 to 9.30)	99.7% and 0.001
Africa	–	–	–
North American	–	–	–
South American	–	–	–
Australia	–	–	–

Design of study	All of studies are case–control
Cohort
Case-control

Number of population	All of studies have less than 300 cases
>300
≤300

Mean Age	All of studies have total age higher than 60 years
>60 years
≤60 years

Male				–
>70%	1	4.60 (4.28 o 4.91)	–
≤70%	1	10.05 (9.37 to 10.72)	–

Diabetes mellitus				–
>30%	–	–	–
≤30%	1	10.05 (9.37 to 10.72)	–

Hypertension				–
>70%	–	–	–
≤70%	1	10.05 (9.37 to 10.72)	–

History of myocardial infarction	No data
>20%
≤20%

Anti-coagulant status codes				–
1	3	3.98 (−1.33 to 9.30)	99.7% and 0.001
2	–	–	–
3	–	–	–
4	1	4.60 (4.28 to 4.97)	–
5	–	–	–
6	–	–	–

AF				–
Chronic	1	4.60 (4.28 to 4.97)	–
Non-chronic	1	10.05 (9.37 to 10.72)	–

Type of AF				–
Paroxysmal	1	10.05 (9.37 to 10.72)–	–
Persistent	–	–	–
Permanent	–	–	–

Cigarette smoking				–
>30%	2	5.19 (4.78 to 5.63)	99.7% and 0.001
≤30%	1	0.42 (0.11 to 0.72)	–



Year of publication				–
>2000	9	3.095 (1.52 to 4.66)	95.5% and 0.001
≤2000	5	0.709 (−0.908 to 2.32)	99.2% and 0.001

Geographic area				–
Asian	2	3.78 (3.30 to 4.26)	0.0% and 0.86
European	11	1.86 (0.69 to 3.03)	98.4% and 0.001
Africa	–	–	–
North American	1	1.30 (0.013 to 2.58)	–
South American	–	–	–
Australia	–	–	–

Design of study				–
Cohort	2	1.89 (−1.82 to 5.62)	98.2% and 0.001
Case-control	12	2.16 (0.98 to 3.34)	98.2% and 0.001

Number of population				–
>300	1	3.80 (3.30 to 4.29)	–
≤300	13	1.95 (0.88 to 3.02)	98.1% and 0.001

Mean Age				–
>60 years	10	2.69 (1.56 to 3.83)	96.1% and 0.001
≤60 years	3	1.29 (−1.14 to 3.74)	88.8% and 0.001

Male				–
>70%	4	3.67 (0.40 to 6.94)	96.3% and 0.001
≤70%	6	2.34 (0.56 to 4.13)	99.2% and 0.001

Diabetes mellitus				–
>30%	–	–	–
≤30%	13	1.60 (0.52 to 2.68)	98.3% and 0.001

Hypertension				–
>70%	–	–	–
≤70%	10	2.41 (1.47 to 3.51)	93.5% and 0.001

History of myocardial infarction				–
>20%	2	1.98 (0.81 to 3.14)	53.3% and 0.143
≤20%	2	3.68 (3.26 to 4.10)	0.0% and 0.396

Anti-coagulant status codes				–
1	5	0.21 (−1.50 to 1.93)	99.1% and 0.001
2	–	–	–
3	1	10.57 (8.055 to 13.085)	–
4	3	1.94 (−0.36 to 4.26)	96.8% and 0.001
5	4	3.48 (2.76 to 4.19)	22.6% and 0.275
6	1	1.30 (0.013 to 2.58)	–

AF				–
Chronic	3	4.43 (−1.25 to 10.12)	97.6% and 0.001
Non-chronic	2	2.99 (2.11 to 3.87)	51% and 0.154

Type of AF				–
Paroxysmal	1	2.50 (1.53 to 3.46)	–
Persistent	1	3.40 (2.62 to 4.17)	–
Permanent	1	10.57 (8.055 to 13.085)	–

Cigarette smoking				–
>30%	2	4.05 (3.56 to 4.56)	96.3% and 0.001
≤30%	4	2.73 (2.18 to 3.27)	61.6% and 0.051



Year of publication				0.28
>2000	10	6.69 (1.79 to 11.59)	99.5% and 0.001
≤2000	5	20.72 (7.68 to 33.75)	97.4% and 0.001

Geographic area				0.30
Asian	4	15.82 (0.49 to 31.14)	99.5% and 0.001
European	10	10.07 (6.93 to 13.21)	98.4% and 0.001
Africa	–	–	–
North American	1	1.009 (−3.05 to 5.07)	–
South American	–	–	–
Australia	–	–	–

Design of study				0.97
Cohort	1	4.490 (2.71 to 7.08)	–
Case-control	14	11.28 (6.70 to 15.86)	99.4% and 0.001

Number of population				0.98
>300	1	4.490 (2.71 to 7.08)	–
≤300	14	11.28 (6.70 to 15.86)	99.4% and 0.001

Mean Age				0.96
>60 years	9	6.99 (4.31 to 9.67)	91.7% and 0.001
≤60 years	5	10.36 (2.19 to 18.52)	99.8% and 0.001

Male				0.18
>70%	1	36.42 (32.41 to 40.42)	–
≤70%	8	11.28 (3.14 to 19.42)	99.5% and 0.001

Diabetes mellitus				–
>30%	–	–	–
≤30%	12	8.93 (6.03 to 11.88)	98.1% and 0.001

Hypertension				–
>70%	–	–	–
≤70%	9	3.34 (1.30 to 5.39)	96% and 0.001

History of myocardial infarction				0.97
>20%	2	1.55 (−3.66 to 6.78)	84.5% and 0.011
≤20%	2	4.16 (3.29 to 5.03)	0.0% and 0.474

Anti-coagulant status codes				0.014
1	7	21.28 (11.09 to 31.47)	98.9% and 0.001
2	–	–	–
3	1	4.20 (1.09 to 7.31)	–
4	2	3.95 (3.27 to 4.64)	0.0% and 0.831
5	4	1.08 (−0.357 to 2.534)	87.1% and 0.001
6	1	−1.50 (−5.53 to 2.53)	–

AF				0.97
Chronic	3	16.58 (−1.97 to 35.14)	95.6% and 0.001
Non-chronic	2	3.80 (3.16 to 4.44)	0.0% and 0.448

Type of AF				0.26
Paroxysmal	1	3.88 (2.87 to 4.88)	–
Persistent	1	4.03 (3.08 to 4.97)	–
Permanent	1	5.90 (3.49 to 8.31)	–

Cigarette smoking				0.95
>30%	2	5.35 (3.73 to 6.97)	0.0% and 0.568
≤30%	4	3.80 (3.13 to 4.48)	56.9% and 0.07



Year of publication				0.98
>2000	28	27.50 (19.43 to 35.56)	96.3% and 0.001
≤2000	4	23.67 (9.80 to 37.53)	99.5% and 0.001

Geographic area				0.01
Asian	4	15.19 (7.19 to 23.19)	15.4% and 0.315
European	25	30.91 (22.26 to 39.56)	99% and 0.001
Africa	–	–	–
North American	3	13.23 (10.42 to 16.04)	0.0% and 0.423
South American	–	–	–
Australia	–	–	–

Design of study				0.05
Cohort	5	11.70 (6.62 to 16.78)	66.4% and 0.018
Case-control	27	29.97 (21.49 to 38.44)	98.9% and 0.001

Number of population				0.10
>300	4	10.32 (5.54 to 15.09)	63.8% and 0.041
≤300	28	29.78 (21.48 to 38.08)	98.8% and 0.001

Mean Age				0.703
>60 years	22	27.88 (18.70 to 37.07)	99.1% and 0.001
≤60 years	10	23.95 (16.11 to 31.79)	85.4% and 0.001

Male				0.44
>70%	13	27.82 (18.23 to 37.41)	87.9% and 0.001
≤70%	15	28.74 (17.73 to 39.74)	98% and 0.001

Diabetes mellitus				–
>30%	–	–	–
≤30%	25	25.34 (16.93 to 33.76)	95.6% and 0.001

Hypertension				0.48
>70%	2	16.95 (−1.44 to 35.35)	57% and 0.127
≤70%	24	27.42 (18.17 to 36.13)	96.7% and 0.001

History of myocardial infarction				0.97
>20%	3	20.98 (−14.49 to 0.56.4)	98.7% and 0.001
≤20%	14	26.61 (14.62 to 38.60)	97.2% and 0.001

Anti-coagulant status codes				0.81
1	6	9.66 (5.59 to 13.74)	93.5% and 0.001
2	1	25 (11.14 to 38.85)	–
3	8	33.09 (18.72 to 47.47)	90.9% and 0.001
4	7	34.96 (24.55 to 45.38)	92.4% and 0.001
5	9	30.16 (13.83 to 46.49)	95.9% and 0.001
6	1	5.0 (−9.75 to 19.75)	–

AF				0.65
Chronic	8	43 (29.03 to 56.97)	93% and 0.001
Non-chronic	12	26.73 (16.88 to 36.58)	94.7% and 0.001

Type of AF				0.75
Paroxysmal	4	29.17 (7.99 to 50.34)	96.5% and 0.001
Persistent	5	25.02 (6.51 to 43.52)	96.1% and 0.001
Permanent	4	43.01 (10.43 to 75.59)	95.6% and 0.001

Cigarette smoking				0.98
>30%	4	3.53 (2.48 to 4.58)	95.8% and 0.001
≤30%	21	14.60 (13.67 to 15.53)	98.7% and 0.001



Year of Publication				–
>2000	6	4.36 (2.79 to 5.93)	86.8% and 0.001
≤2000	1	−13.0 (−19.12 to −6.87)	–

Geographic area				–
Asian	–	–	–
European	6	3.81 (0.35 to 7.27)	92.6% and 0.001
Africa	–	–	–
North American	–	–	–
South American	1	1.81 (1.03 to 2.58)	–
Australia	–	–	–

Design of study				–
Cohort	1	2.02 (1.88 to 2.15)	–
Case-control	6	3.87 (0.31 to 7.43)	90.6% and 0.001

Number of population	All of studies have less than 300 cases
>300
≤300

Mean Age				–
>60 years	4	6.04 (2.88 to 9.21)	89.5% and 0.001
≤60 years	2	−5.16 (−19.87 to 9.54)	95.7% and 0.001

Male				–
>70%	2	6.84 (0.02 to 13.65)	86.8% and 0.001
≤70%	4	1.68 (−2.13 to 5.50)	94.3% and 0.001

Diabetes mellitus				–
>30%	–	–	–
≤30%	4	5.10 (2.03 to 8.17)	91.2% and 0.001

Hypertension				–
>70%	–	–	–
≤70%	4	5.10 (2.03 to 8.17)	91.2% and 0.001

History of myocardial infarction				–
>20%	–	–	–
≤20%	3	6.18 (4.78 to 7.58)	0.0% and 0.794

Anti-coagulant status codes				–
1	3	4.36 (−0.52 to 9.25)	56.9% and 0.09
2	–	–	–
3	1	12.28 (6.09 to 18.46)	–
4	2	6.02 (4.61 to 7.50)	0.0% and 0.839
5	1	−5.27 (−19.76 to 9.21)	–
6	–	–	–

AF				–
Chronic	4	3.38 (−5.27 to 12.04)	92.6% and 0.001
Non-chronic	2	2.85 (1.52 to 4.17)	88.7% and 0.001

Type of AF				–
Paroxysmal	1	2.02 (1.88 to 2.15)	–
Persistent	–	–	–
Permanent	1	12.28 (6.09 to 18.46)	–

Cigarette smoking				–
>30%	1	12.28 (6.09 to 18.46)	–
≤30%	3	2.01 (1.88 to 2.14)	56.3% and 0.101

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Predictive Role of Coagulation, Fibrinolytic, and Endothelial Markers in Patients with Atrial Fibrillation, Stroke, and Thromboembolism: A Meta-Analysis, Meta-Regression, and Systematic Review

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