Platelets Cellular and Functional Characteristics in Patients with Atrial Fibrillation: A Comprehensive Meta-Analysis and Systematic Review

Alexander Weymann; Sadeq Ali-Hasan-Al-Saegh; Anton Sabashnikov; Aron-Frederik Popov; Seyed Jalil Mirhosseini; Luis Nombela-Franco; Luca Testa; Mohammadreza Lotfaliani; Mohamed Zeriouh; Tong Liu; Hamidreza Dehghan; Senol Yavuz; Michel Pompeu Barros de Oliveira Sá; William L. Baker; Jae-Sik Jang; Mengqi Gong; Umberto Benedetto; Pascal M. Dohmen; Fabrizio D'Ascenzo; Abhishek J. Deshmukh; Giuseppe Biondi-Zoccai; Hugh Calkins; Gregg W. Stone; Integrated Meta-Analysis of Cardiac Surgery and Cardiology-Group [IMCSC-Group]

doi:10.12659/MSMBR.902557

17 March 2017 : Meta-Analysis

Platelets Cellular and Functional Characteristics in Patients with Atrial Fibrillation: A Comprehensive Meta-Analysis and Systematic Review

Alexander Weymann^{ABCDEFG 1*}, Sadeq Ali-Hasan-Al-Saegh^{ABCDEFG 2}, Anton Sabashnikov^{ABCDEFG 3,4}, Aron-Frederik Popov^{ABCDEFG 5}, Seyed Jalil Mirhosseini^{ABCDEFG 2}, Luis Nombela-Franco^{ABCDEFG 6}, Luca Testa^{ABCDEFG 7}, Mohammadreza Lotfaliani^{ABCDEFG 2}, Mohamed Zeriouh^{ABCDEFG 3,4}, Tong Liu^{ABCDEFG 8}, Hamidreza Dehghan^{ABCDEFG 9}, Senol Yavuz^{ABCDEFG 10}, Michel Pompeu Barros de Oliveira Sá^{ABCDEFG 11,12,13}, William L. Baker^{ABCDEFG 14}, Jae-Sik Jang^{ABCDEFG 15}, Mengqi Gong^{ABCDEFG 8}, Umberto Benedetto^{ABCDEFG 16}, Pascal M. Dohmen^{DFG 1}, Fabrizio D'Ascenzo^{ABCDEFG 17}, Abhishek J. Deshmukh^{ABCDEFG 18}, Giuseppe Biondi-Zoccai^{ABCDEFG 19,20}, Hugh Calkins^{DE 21}, Gregg W. Stone^{DE 22}, Integrated Meta-Analysis of Cardiac Surgery and Cardiology-Group [IMCSC-Group]

DOI: 10.12659/MSMBR.902557

Med Sci Monit Basic Res 2017; 23:58-86

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
²Cardiovascular Research Center, Shahid Sadoughi University of Medical Sciences, Yazd, Iran
³Department of Cardiothoracic Transplantation and Mechanical Circulatory Support, Royal Brompton and Harefield NHS Foundation Trust, Harefield Hospital, Harefield Middlesex, United Kingdom
⁴Department of Cardiothoracic Surgery, University Hospital Cologne, Cologne, Germany
⁵Department of Cardiothoracic Transplantation and Mechanical Circulatory Support, Royal Brompton and Harefield NHS Foundation Trust, London, United Kingdom
⁶Instituto Cardiovascular, Hospital Universitario Clínico San Carlos, Madrid, Spain
⁷Department of Cardiology, IRCCS Pol. S. Donato, S. Donato Milanese, Milan, Italy
⁸Tianjin Key Laboratory of Ionic-Molecular Function of Cardiovascular Disease, Department of Cardiology, Tianjin Institute of Cardiology, Second Hospital of Tianjin Medical University, Tianjin, China
⁹Department of Health Technology Assessment, Shahid Sadoughi University of Medical Sciences and Health Services, Yazd, Iran
¹⁰Department of Cardiovascular Surgery, Bursa Yuksek Ihtisas Training and Research Hospital, Bursa, Turkey
¹¹ University of Pernambuco – UPE, Recife, Brazil
¹² Nucleus of Postgraduate and Research in Health Sciences of Faculty of Medical Sciences and Biological Sciences Institute (FCM/ICB), Recife, Brazil
¹³ Division of Cardiovascular Surgery of Pronto Socorro Cardiológico de Pernambuco – PROCAPE, Recife, Brazil
¹⁴ University of Connecticut/Hartford Hospital Evidence-Based Practice Center, Hartford, USA
¹⁵Department of Cardiology, Busan Paik Hospital, Inje University College of Medicine, Busan, South Korea
¹⁶Bristol Heart Institute, University of Bristol, School of Clinical Sciences, Bristol, United Kingdom
¹⁷Division of Cardiology, Department of Medical Sciences, Città della Salute e della Scienza Hospital, University of Turin, Turin, Italy
¹⁸Mayo Clinic Heart Rhythm Section, Cardiovascular Diseases, Mayo Clinic, Rochester, USA
¹⁹Department of Medico-Surgical Sciences and Biotechnologies, Sapienza University of Rome, Latina, Italy
²⁰Department of AngioCardioNeurology, IRCCS Neuromed, Pozzilli, Italy
²¹Department of Cardiology, Johns Hopkins Medical Institutions, Baltimore, USA
²²New York Presbyterian Hospital, Columbia University Medical Center, New York, 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

Subgroup	Studies (N)	WMD (95% CI)	I-squared and Heterogeneity-p-value and Effect-p-value respectively


Year of publication
>2000	41	−24.04 (−25.52 to −22.56)	91.1% and 0.001 and 0.001
≤2000	4	−60.67 (−65.22 to −55.62)	92.8% and 0.001 and 0.001

Geographic area
Asian	7		13.8% and 0.324 and 0.284
European	35	−3.88 (−10.98 to 3.21)	94% and 0.001 and 0.001
Africa	-	−30.05 (−31.59 to −28.50)	–
North American	3	–	0.0% and 0.401 and 0.001
South American	-	−12.23 (−16.39 to −8.08)	–
Australia	-		–

Design of study
Cohort	8	−29.32 (−31.25 to −27.40)	91.6% and 0.001 and 0.001
Case-control	37	−24.10 (−26.20 to −22.01)	93.8% and 0.001 and 0.001

Number of population
>300	2	−6.33 (−19.68 to 7.02)	0.0% and 0.689 and 0.353
≤300	43	−27.16 (−28.59 to −25.74)	93.7% and 0.001 and 0.001

Mean Age
>60 years	34	−27.90 (−29.34 to −26.46)	94.5% and 0.001 and 0.001
≤60 years	7	−0.76 (−9.25 to 7.12)	76.7% and 0.001 and 0.860

Male
>70%	8	−29.82 (−31.76 to −27.88)	85.8% and 0.001 and 0.001
≤70%	31	−16.15 (−18.44 to −13.86)	90.6% and 0.001 and 0.001

Diabetes mellitus
>30%	1	21.00 (−4.40 to 46.40)	–
≤30%	28	−22.68 (−24.24 to −21.12)	88.3% and 0.001 and 0.001

Hypertension
>70%	–	–	–
≤70%	29	−22.52 (−24.07 to −20.96)	88.4% and 0.001 and 0.001

History of MI
>20%	2	−11.74 (−15.35 to −8.13)	9.7% and 0.293 and 0.001
≤20%	3	−15.44 (−22.10 to −8.77)	31.1% and 0.234 and 0.001

Medication: Diuretic
>70%	–	–	–
≤70%	11	−28.43 (−30.31 to −26.56)	88.1% and 0.001 and 0.001

Medication: ACEI
>70%	–	–	–
≤70%	17	−25.60 (−27.33 to −23.88)	89.6% and 0.001 and 0.001

Medication: Statin
>70%	–	–	–
≤70%	18	−25.90 (−27.64 to −24.15)	88.4% and 0.001 and 0.001

Medication: Beta-Blocker
>70%	–	–	–
≤70%	17	−25.40 (−27.11 to −23.68)	89.3% and 0.001 and 0.001

Anti-coagulant status codes
1	9	−54.79 (−58.44 to −51.15)	93.4% and 0.001 and 0.001
2	3	1.69 (−17.11 to 20.53)	67.3% and 0.047 and 0.860
3	3	−3.15 (−17.55 to 11.23)	0.0% and 0.890 and 0.667
4	19	−25.27 (−27.00 to −23.53)	90.9% and 0.001 and 0.001
5	8	−10.84 (−14.41 to 7.24)	38.3% and 0.124 and 0.001
6	3	−6.34 (−21.47 to 8.77)	70.8% and 0.033 and 0.411

AF
Chronic	12	−2.15 (−7.34 to 3.02)	35.6% and 0.106 and 0.414
Non-chronic	11	−21.73 (−24.45 to −19.01)	95.5% and 0.001 and 0.001

Type of AF
Paroxysmal	5	−5.29 (−11.24 to 0.64)	67.8% and 0.015 and 0.081
Persistent	3	−41.86 (−46.34 to −37.38)	97.4% and 0.001 and 0.001
Permanent	5	−4.55 (−11.58 to 2.46)	64.6% and 0.023 and 0.204

Cigarette smoking
>30%	9	2.31 (−4.14 to 8.77)	67.3% and 0.002 and 0.482
≤30%	17	−9.11 (−12.70 to −5.52)	46.6% and 0.018 and 0.001



Year of publication
>2000	All of studies: after 2000
≤2000

Geographic area
Asian	3	1.37 (1.16 to 1.58)	95.9% and 0.001 and 0.001
European	16	0.56 (0.51 to 0.61)	93.1% and 0.001 and 0.001
Africa	–	–	–
North American	–	–	–
South American	–	–	–
Australia	–	–	–

Design of study
Cohort	4	1.37 (1.14 to 1.60)	94.7% and 0.001 and 0.001
Case-control	15	0.57 (0.52 to 0.62)	93.6% and 0.001 and 0.001

Number of population
>300	2	0.90 (0.67 to 1.13)	0.0% and 0.666 and 0.001
≤300	17	0.59 (0.54 to 0.64)	94.9% and 0.001 and 0.001

Mean Age
>60 years	15	0.61 (0.56 to 0.66)	94.8% and 0.001 and 0.001
≤60 years	3	0.33 (0.13 to 0.54)	95.2% and 0.001 and 0.001

Male
>70%	4	0.67 (0.50 to 0.83)	95.6% and 0.001 and 0.001
≤70%	14	0.59 (0.54 to 0.64)	94.7% and 0.001 and 0.001

Diabetes mellitus
>30%	2	0.59 (0.53 to 0.65)	42.3% and 0.188 and 0.001
≤30%	14	0.60 (0.52 to 0.67)	95.8% and 0.001 and 0.001

Hypertension
>70%	–	–	–
≤70%	16	0.59 (0.55 to 0.64)	95.1% and 0.001 and 0.001

History of MI	Studies have not data about history of myocardial infarction

Medication: Diuretic
>70%	–	–	–
≤70%	8	0.57 (0.52 to 0.62)	95.5% and 0.001 and 0.001

Medication: ACEI
>70%	–	–	–
≤70%	10	0.60 (0.55 to 0.65)	96.4% and 0.001 and 0.001

Medication: Statin
>70%	–	–	–
≤70%	10	0.66 (0.61 to 0.72)	95.1% and 0.001 and 0.001

Medication: Beta-Blocker
>70%	–	–	–
≤70%	11	0.58 (0.53 to 0.63)	96.4% and 0.001 and 0.001

Anti-coagulant status codes
1	–	–	–
2	1	0.80 (0.26 to 1.33)	–
3	2	−0.07 (−0.31 to 0.16)	8.7% and 0.295 and 0.530
4	10	0.67 (0.62 to 0.73)	95.1% and 0.001 and 0.001
5	5	0.43 (0.33 to 0.53)	94.6% and 0.001 and 0.001
6	1	1.10 (0.75 to 1.45)	–

AF
Chronic	7	0.58 (0.53 to 0.63)	96.6% and 0.001 and 0.001
Non-chronic	3	0.85 (0.58 to 1.13)	88.6% and 0.001 and 0.001

Type of AF
Paroxysmal	1	1.70 (1.20. to 2.19)	–
Persistent	1	0.32 (−0.09 to 0.73)	–
Permanent	3	0.39 (0.28 to 0.51)	97.1% and 0.001 and 0.001

Cigarette smoking
>30%	8	0.68 (0.62 to 0.74)	94.7% and 0.001 and 0.001
≤30%	7	0.45 (0.36 to 0.54)	94.8% and 0.001 and 0.001



Year of Publication
>2000	11	29.31 (28.57 to 30.04)	88.6% and 0.001 and 0.001
≤2000	11	12.67 (11.49 to 13.85)	95.5% and 0.001 and 0.001

Geographic area
Asian	8	30.31 (29.51 to 31.11)	77% and 0.001 and 0.001
European	14	15.91 (14.92 to 16.91)	96.2% and 0.001 and 0.001
Africa	–	–	–
North American	–	–	–
South American	–		–
Australia	–		–

Design of study
Cohort	All of studies are “case-control”
Case-control

Number of population
>300	All of studies are “number less than 300 population”
≤300

Mean Age
>60 years	11	15.79 (14.74 to 16.84)	94.2% and 0.001 and 0.001
≤60 years	6	13.01 (9.94 to 16.08)	90.1% and 0.001 and 0.001

Male
>70%	3	39.01 (33.37 to 44.65)	0.0% and 0.600 and 0.001
≤70%	9	19.98 (18.28 to 21.68)	90.9% and 0.001 and 0.001

Diabetes mellitus
>30%	–	–	–
≤30%	7	25.36 (23.30 to 27.42)	80.8% and 0.001 and 0.001

Hypertension
>70%	–	–	–
≤70%	7	25.36 (23.30 to 27.42)	80.8% and 0.001 and 0.001

History of MI	No Data

Medication: Diuretic	No Data

Medication: ACEI
>70%	No Data
≤70%

Medication: Statin
>70%			No Data
≤70%

Medication: Beta-Blocker
>70%	–	–	–
≤70%	4	27.17 (23.22 to 31.12)	89.1% and 0.001 and 0.001

Anti-coagulant status codes
1	14	14.70 (13.63 to 15.78)	93.6% and 0.001 and 0.001
2	–	–	–
3	1	39.16 (29.56 to 48.75)	–
4	3	27.83 (24.92 to 30.73)	85.5% and 0.001 and 0.001
5	4	29.83 (29.03 to 30.63)	97.8% and 0.001 and 0.001
6	–	–	–

AF
Chronic	8	24.21 (22.11 to 26.30)	96.7% and 0.001 and 0.001
Non-chronic	5	17.74 (14.40 to 21.08)	31.3% and 0.213 and 0.001

Type of AF
Paroxysmal	4	17.60 (13.57 to 21.63)	48.3% and 0.121 and 0.001
Persistent	–	–	–
Permanent	4	25.90 (23.39 to 28.40)	80.5% and 0.002 and 0.001

Cigarette smoking
>30%	3	39.01 (33.37 to 44.65)	0.0% and 0.600 and 0.001
≤30%	3	18.64 (16.00 to 21.27)	97.2% and 0.001 and 0.001



Year of Publication
>2000	9	6.38 (6.04 to 6.72)	99.8% and 0.001 and 0.001
≤2000	7	1.78 (1.36 to 2.20)	81.6% and 0.001 and 0.001

Geographic area
Asian	7	6.75 (6.32 to 7.17)	51.5% and 0.054 and 0.001
European	9	3.25 (2.91 to 3.59)	99.8% and 0.001 and 0.001
Africa	–	–	–
North American	–	–	–
South American	–		–
Australia	–		–

Design of study
Cohort	All of studies are “case-control”
Case-control

Number of population
>300	All of studies are “number less than 300 population”
≤300

Mean Age
>60 years	6	2.27 (1.93 to 2.61)	94.6% and 0.001 and 0.001
≤60 years	7	58.31 (55.83 to 60.80)	99.6% and 0.001 and 0.001

Male
>70%	1	2.80 (2.23 to 3.36)	–
≤70%	5	11.60 (9.55 to 13.66)	89.3% and 0.001 and 0.001

Diabetes mellitus
>30%	–	–	–
≤30%	4	15.25 (12.79 to 17.72)	69.6% and 0.020 and 0.001

Hypertension
>70%	–	–	–
≤70%	4	15.25 (12.79 to 17.72)	69.6% and 0.020 and 0.001

History of MI
>20%	1	15.55 (11.43 to 19.67)	–
≤20%	1	12.17 (8.38 to 15.95)	–

Medication: Diuretic	No Data

Medication: ACEI
>70%	–	–	–
≤70%	2	13.71 (10.92 to 16.50)	28.7% and 0.236 and 0.001

Medication: Statin
>70%	–	–	–
≤70%	18	13.71 (10.92 to 16.50)	28.7% and 0.236 and 0.001

Medication: Beta-Blocker
>70%	–	–	–
≤70%	4	15.25 (12.79 to 17.72)	69.6% and 0.020 and 0.001

Anti-coagulant status codes
1	9	1.90 (1.48 to 2.32)	90.6% and 0.001 and 0.001
2	–	–	–
3	1	2.80 (2.23 to 3.36)	–
4	2	13.71 (10.92 to 16.50)	28.7% and 0.236 and 0.001
5	4	8.18 (7.75 to 8.61)	99.9% and 0.001 and 0.001
6	–	–	–

AF
Chronic	2	2.93 (2.37 to 3.49)	97.3% and 0.001 and 0.001
Non-chronic	5	13.07 (10.71 to 15.43)	23.9% and 0.262 and 0.001

Type of AF
Paroxysmal	4	11.86 (8.98 to 14.75)	6.1% and 0.363 and 0.001
Persistent	1	15.50 (11.43 to 19.67)	–
Permanent	1	2.93 (2.37 to 3.49)	97.3% and 0.001 and 0.001

Cigarette smoking
>30%	1	2.80 (2.23 to 3.36)	–
≤30%	2	13.71 (10.92 to 16.50)	28.7% and 0.236 and 0.001



Year of Publication
>2000	23	4.92 (4.37 to 5.47)	98.6% and 0.001 and 0.001
≤2000	1	−71.00 (−104.1 to −37.80)	–

Geographic area
Asian	3	1.90 (0.42 to 3.38)	78.9% and 0.009 and 0.012
European	19	5.30 (4.71 to 5.89)	98.8% and 0.001 and 0.001
Africa	1	47.90 (29.57 to 66.22)	–
North American	–	–	–
South American	1	74.0 (46.63 to 101.36)	–
Australia	–		–

Design of study
Cohort	3	−0.27 (−1.16 to 0.61)	81.2% and 0.005 and 0.547
Case-control	21	8.04 (7.35 to 8.74)	98.6% and 0.001 and 0.001

Number of population
>300	1	−0.50 (−2.61 to 1.61)	–
≤300	23	5.29 (4.72 to 5.86)	98.6% and 0.001 and 0.001

Mean Age
>60 years	19	4.95 (4.38 to 5.53)	98.8% and 0.001 and 0.001
≤60 years	3	4.46 (2.38 to 6.54)	95.2% and 0.001 and 0.001

Male
>70%	8	5.42 (4.72 to 6.12)	99.5% and 0.001 and 0.001
≤70%	14	4.09 (3.19 to 4.99)	95.5% and 0.001 and 0.001

Diabetes mellitus
>30%	–	–	–
≤30%	15	4.70 (4.08 to 5.31)	99.0% and 0.001 and 0.001

Hypertension
>70%	–	–	–
≤70%	16	5.54 (4.93 to 6.15)	99.0% and 0.001 and 0.001

History of MI
>20%	1	−0.50 (−2.61 to 1.61)	–
≤20%	2	4.11 (1.41 to 6.82)	87.1% and 0.005 and 0.003

Medication: Diuretic
>70%	–	–	–
≤70%	7	5.24 (4.53 to 5.96)	99.0% and 0.001 and 0.001

Medication: ACEI
>70%	–	–	–
≤70%	8	5.25 (4.54 to 5.96)	98.9% and 0.001 and 0.001

Medication: Statin
>70%	–	–	–
≤70%	6	4.60 (3.87 to 5.34)	98.8% and 0.001 and 0.001

Medication: Beta-Blocker
>70%	–	–	–
≤70%	10	3.67 (3.02 to 4.33)	98.0% and 0.001 and 0.001

Anti-coagulant status codes
1	5	5.46 (2.88 to 8.03)	97.2% and 0.001 and 0.001
2	–	–	–
3	6	9.20 (7.99 to 10.42)	99.5% and 0.001 and 0.001
4	10	4.19 (3.50 to 4.87)	98% and 0.001 and 0.001
5	3	0.81 (−0.85 to 2.47)	91.4% and 0.001 and 0.342
6	–	–	–

AF
Chronic	6	5.94 (4.28 to 7.60)	99.4% and 0.001 and 0.001
Non-chronic	8	3.09 (1.94 to 4.23)	92.2% and 0.001 and 0.001

Type of AF
Paroxysmal	2	1.40 (−0.58 to 3.39)	2.1% and 0.312 and 0.166
Persistent	2	8.17 (6.10 to 10.25)	96.2% and 0.001 and 0.001
Permanent	5	6.13 (4.47 to 7.79)	99.5% and 0.001 and 0.001

Cigarette smoking
>30%	2	4.76 (2.68 to 6.84)	95.4% and 0.001 and 0.001
≤30%	15	5.41 (4.55 to 6.27)

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Platelets Cellular and Functional Characteristics in Patients with Atrial Fibrillation: A Comprehensive Meta-Analysis and Systematic Review

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