Association of inflammatory and hemostatic markers with stroke and thromboembolic events in atrial fibrillation: a systematic review and meta-analysis.
BACKGROUND
Atrial fibrillation (AF) increases the risk of stroke and thromboembolic events. Recently, biomarkers have been proposed as a practical tool to predict adverse outcomes in patients with AF. The prognostic value of inflammatory and hemostatic markers in AF has been widely studied; however, the results of previous studies have been inconclusive.


METHODS
We conducted a systematic review and meta-analysis to evaluate the association of inflammatory and hemostatic markers with stroke and thromboembolic events in patients with AF.


RESULTS
A total of 27 studies including 22,176 participants met our inclusion criteria for the systematic review. Our meta-analysis determined that elevated circulating plasminogen activator inhibitor-1 (PAI-1) and thrombin-antithrombin (TAT) were significantly associated with increased risk of stroke in patients with AF (standardized mean difference [SMD], 0.89; 95% confidence interval [CI], 0.20-1.59 and 1.43; 95% CI, 0.40-2.47, respectively). Higher levels of D-dimer were associated with increased subsequent thromboembolic event risk with a pooled hazard ratio of 2.90 (95% CI, 1.22-6.90) for cohort studies and an SMD of 0.93 (95% CI, 0.36-1.50) for case-control studies. There was also very limited evidence indicating that other biomarkers-such as interleukin-6, von Willebrand factor, P-selectin, and mean platelet volume-could predict adverse outcomes in AF.


CONCLUSIONS
In conclusion, increased circulating PAI-1 and TAT levels were significantly associated with subsequent stroke in patients with AF, and high levels of D-dimer were associated with thromboembolic events in AF. Further epidemiologic studies are needed to accumulate more evidence on the prognostic role of inflammatory and hemostatic markers in AF.
Department of Epidemiology, College of Preventive Medicine, Third Military Medical University, Chongqing, People's Republic of China; Evidence-based Medicine and Clinical Epidemiology Center, Third Military Medical University, Chongqing, People's Republic of China.
Na
N
Wu
Department of Cardiology, Southwest Hospital, Third Military Medical University, Chongqing, People's Republic of China.
Xinghua
X
Chen
Department of Epidemiology, College of Preventive Medicine, Third Military Medical University, Chongqing, People's Republic of China; Evidence-based Medicine and Clinical Epidemiology Center, Third Military Medical University, Chongqing, People's Republic of China.
Tongjian
T
Cai
Department of Epidemiology, College of Preventive Medicine, Third Military Medical University, Chongqing, People's Republic of China; Evidence-based Medicine and Clinical Epidemiology Center, Third Military Medical University, Chongqing, People's Republic of China.
Long
L
Wu
Department of Epidemiology, College of Preventive Medicine, Third Military Medical University, Chongqing, People's Republic of China; Evidence-based Medicine and Clinical Epidemiology Center, Third Military Medical University, Chongqing, People's Republic of China.
Ying
Y
Xiang
Department of Epidemiology, College of Preventive Medicine, Third Military Medical University, Chongqing, People's Republic of China; Evidence-based Medicine and Clinical Epidemiology Center, Third Military Medical University, Chongqing, People's Republic of China.
Mengxuan
M
Zhang
Department of Epidemiology, College of Preventive Medicine, Third Military Medical University, Chongqing, People's Republic of China; Evidence-based Medicine and Clinical Epidemiology Center, Third Military Medical University, Chongqing, People's Republic of China.
Yafei
Y
Li
Department of Cardiology, Southwest Hospital, Third Military Medical University, Chongqing, People's Republic of China.
Zhiyuan
Z
Song
Department of Cardiology, Southwest Hospital, Third Military Medical University, Chongqing, People's Republic of China. Electronic address: zhongli28@hotmail.com.
Li
L
Zhong
D000925:Anticoagulants / Q000627:therapeutic use; D000933:Antifibrinolytic Agents / Q000097:blood; D000990:Antithrombin III; D001281:Atrial Fibrillation / Q000097:blood* / Q000150:complications / Q000175:diagnosis* / Q000188:drug therapy / Q000401:mortality; D015415:Biomarkers / Q000097:blood; D005338:Fibrin Fibrinogen Degradation Products / Q000378:metabolism; D006801:Humans; D015850:Interleukin-6 / Q000097:blood; D063847:Mean Platelet Volume; D010447:Peptide Hydrolases / Q000097:blood*; D017395:Plasminogen Activator Inhibitor 1 / Q000097:blood*; D011237:Predictive Value of Tests; D011379:Prognosis; D019087:Selectins / Q000097:blood; D012680:Sensitivity and Specificity; D015842:Serine Proteinase Inhibitors / Q000097:blood*; D020521:Stroke / Q000097:blood* / Q000209:etiology; D013923:Thromboembolism / Q000097:blood* / Q000209:etiology; D014841:von Willebrand Factor / Q000378:metabolism
D000925:Anticoagulants; D000933:Antifibrinolytic Agents; D015415:Biomarkers; D005338:Fibrin Fibrinogen Degradation Products; D015850:Interleukin-6; D017395:Plasminogen Activator Inhibitor 1; D019087:Selectins; D015842:Serine Proteinase Inhibitors; C046193:antithrombin III-protease complex; C036309:fibrin fragment D; D014841:von Willebrand Factor; D000990:Antithrombin III; D010447:Peptide Hydrolases