Table 3.
Blood-based biomarkers for stroke risk in AF.
| References | Design | Study population | n | % male; mean (SD) or median (IQR) age, years | Relevant outcome measures | Follow-up duration | Biomarker | Findings |
|---|---|---|---|---|---|---|---|---|
| Park et al. (52) | Prospective registry | AF | 10,978 | 63.6; 73.5 (11.8) | Stroke | 42.6 months | Platelet count (<100 × 109/L) | Lower platelet counts were associated with lower risk of stroke |
| Janion-Sadowska et al. (53) | Prospective cohort | AF on NOAC | 124 | 33.1; 70.3 (NA) | Stroke or TIA | 55 months | Platelet count (<100 × 109/L) | No association with stroke or TIA |
| Rivera-Caravaca et al. (54) | Prospective cohort | AF on OAC, attending clinic | 1,226 | 49.7; 76 (70–81) | Ischemic stroke | 6.5 years | Soluble fibrin monomer complex | No association with ischemic stroke |
| You and Tang (55) | Case-controlled study | Non-anticoagulated AF | 323 | 63.8; 75.2 (NA) | Ischemic stroke | NA (retrospective) | D-dimer | No association with ischemic stroke |
| Ancedy et al. (56) | Prospective cohort | Hospitalized AF | 122 | 46; 70 (14) | Composite of all-cause death and stroke; stroke | 5 years | vWF | Higher vWF levels were associated with greater risk of composite endpoint No association with stroke risk only |
| Hayashi et al. (57) | Prospective registry | AF | 1,013 | 71.6; 72.8 (9.7) | Stroke, TIA, or SE | 25 months | BNP | High BNP levels were associated with a 3.9-fold greater risk of stroke, TIA, or SE |
| Choi et al. (58) | Prospective cohort | AF | 352 | 57.4; 68.4 (12.1) | Composite of ischemic stroke and incidental LA thrombus | 35.4 months | Antithrombin III | No association with composite endpoint |
| MPV | High MPV levels were associated with a 6.4-fold greater risk of composite endpoint | |||||||
| Aulin et al. (59) | Sub-study of RCT | AF with at least 1 stroke risk factor | 6,187 | 63.7; 72 (67–77) | Stroke or SE | 2 years | IL-6 | Higher IL-6 levels were associated with greater risk of stroke or SE |
| CRP | No association with stroke or SE | |||||||
| Fibrinogen | No association with stroke or SE | |||||||
| Pignatelli et al. (60) | Prospective cohort | AF | 950 | 55.5; 73.3 (8.8) | Composite of stroke, TIA, MI, and coronary revascularization | 25.7 months | Serum NOX2-derived peptide | Higher serum NOX2-derived peptide levels were associated with greater risk of composite endpoint |
| Banerjee et al. (61) | Prospective cohort | AF | 5,912 | 62.9; 70.9 (NA) | Ischemic stroke or TE | 2.5 years | eGFR (MDRD) | Lower levels of renal function were associated with greater risk of ischemic stroke or TE |
| Roldan et al. (62) | Prospective cohort | AF on OAC, attending clinic | 1,172 | 49; 76 (71–81) | Stroke or TIA | 34 months | NT-proBNP | High NT-proBNP levels were associated with a 2.7-fold greater stroke or TIA risk |
| Apostolakis et al. (63) | Post-hoc analysis of RCT | AF | 4,576 | 66.5; 70 (9) | Stroke or SE | 10.8 months | CrCl, eGFR (MDRD, CKD-EPI) | Lower levels of renal function were associated with greater risk of stroke or SE |
| Krishnamoorthy et al. (64) | Prospective cohort | AF, attending clinic | 423 | 55.6; 72.7 (8.4) | Composite of stroke, acute MI, and all-cause mortality; Ischemic stroke | 19 months | vWF | Higher vWF levels were associated with greater risk of composite endpoint and Ischemic stroke |
| Soluble E-selectin | Higher soluble E-selectin levels were associated with greater risk of composite endpoint and Ischemic stroke | |||||||
| Hijazi et al. (65) | Sub-study of RCT | AF with at least 1 CHADS2 risk factor | 14,892 | 64.4; NA | Stroke or SE | 1.9 years | NT-proBNP | Higher NT-proBNP levels were associated with greater risk of stroke or SE |
| Highest quartile of NT-proBNP was associated with 2.4-fold greater risk of stroke or SE compared to lowest quartile | ||||||||
| Piccini et al. (17) | Sub-study of RCT | AF with at least 1 stroke risk factor | 14,264 | 60.7; 73 (NA) | Stroke or SE | 1.9 years | CrCl, eGFR (MDRD) | Lower levels of renal function were associated with greater risk of stroke or SE; every 10-mL/min decrease in CrCl resulted in 1.12-fold increase in risk; every 5 mL/min/1.73 m2 decrease in eGFR (MDRD) resulted in 1.09-fold increase in risk |
| Hijazi et al. (66) | Sub-study of RCT | AF with at least 1 stroke risk factor | 6,189 | 63.7; 72 (67–77) | Stroke | 2.2 years | NT-proBNP | Higher NT-proBNP levels were associated with greater stroke risk Highest quartile of NT-proBNP was associated with 2.4-fold greater risk of stroke compared to lowest quartile |
| Troponin I | Higher troponin I levels were associated with greater stroke risk Highest quartile of troponin I was associated with 2.0-fold greater risk of stroke compared to lowest quartile |
|||||||
| Roldan et al. (67) | Prospective cohort | AF on OAC, attending clinic | 930 | 51; 76 (70–81) | Stroke or TIA | 2 years | Troponin T | High troponin T levels were associated with a 2.4-fold greater stroke or TIA risk |
| IL-6 | No association with stroke or TIA | |||||||
| Ehrlich et al. (68) | Prospective cohort | AF | 278 | 63; 70 (11) | Composite of stroke, MI, SE, and all-cause death | 28 months | hsCRP | No association with composite endpoint |
| sCD40L | No association with composite endpoint | |||||||
| MMP-2 | Higher MMP-2 levels were associated with greater risk of composite endpoint | |||||||
| vWF | No association with composite endpoint | |||||||
| sVCAM-1 | Higher sVCAM-1 levels were associated with greater risk of composite endpoint | |||||||
| Roldan et al. (69) | Prospective cohort | AF on OAC, attending clinic | 829 | 50; 76 (70–80) | Composite of TE, acute MI, and acute HF | 27.6 months | vWF | High vWF levels were associated with a greater risk of composite endpoint |
| Ha et al. (70) | Prospective cohort | AF | 200 | 56; 68.9 (11.7) | Ischemic stroke | 15.1 months | MPV | Higher MPV levels were associated with greater ischemic stroke risk Highest tertile of MPV was associated with a 5.0-fold greater risk of ischemic stroke compared to lowest quartile |
| Sadanaga et al. (71) | Post-hoc analysis of prospective cohort | AF on OAC | 261 | 56; 74 (9) | Ischemic stroke, TIA, or SE | 24.7 months | BNP | High BNP levels were associated with a 5.3-fold greater risk of ischemic stroke, TIA, or SE |
| Sadanaga et al. (72) | Prospective cohort | AF on OAC | 269 | 57; 74 (9) | Ischemic stroke, TIA, or SE | 25.2 months | D-dimer | High D-dimer levels were associated with a 15.8-fold greater risk of ischemic stroke, TIA, or SE |
| Go et al. (73) | Sub-study of prospective cohort | AF | 10,908 | 57.2; 71.6 (NA) | TE | 3 years | eGFR (MDRD) | Lower levels of renal function were associated with greater TE risk |
| Pinto et al. (74) | Prospective cohort | Chronic AF | 373 | 63.5; 66.1 (7.4) | Ischemic stroke | 3 years | IL-1β | No association with ischemic stroke |
| TNF-α | Higher TNF-α levels were associated with greater ischemic stroke risk | |||||||
| IL-6 | Higher IL-6 levels were associated with greater ischemic stroke risk | |||||||
| IL-10 | No association with ischemic stroke | |||||||
| E-selectin | No association with ischemic stroke | |||||||
| P-selectin | No association with ischemic stroke | |||||||
| ICAM-1 | No association with ischemic stroke | |||||||
| VCAM-1 | No association with ischemic stroke | |||||||
| vWF | Higher vWF levels were associated with greater ischemic stroke risk | |||||||
| Ferro et al. (75) | Prospective cohort | AF | 231 | 48; 72.4 (10.3) | Composite of stroke and MI | 27.8 months | sCD40L | High sCD40L levels were associated with a 4.6-fold greater risk of composite endpoint |
| Nozawa et al. (76) | Prospective cohort | AF | 509 | 64.8; 66.6 (10.3) | Composite of clinically evident stroke, TIA, and SE | 2 years | D-dimer | High D-dimer levels were associated with a greater risk of composite endpoint |
| F1+2 | No association with composite endpoint | |||||||
| Platelet factor 4 | No association with composite endpoint | |||||||
| β-thromboglobulin | No association with composite endpoint | |||||||
| Conway et al. (77) | Prospective cohort | AF, attending clinic | 77 | 57; 68 (62–75) | Stroke | 6.3 years | IL-6 | High IL-6 levels were associated with a 2.9-fold greater stroke risk |
| CRP | No association with stroke | |||||||
| Vene et al. (78) | Prospective cohort | AF referred to clinic for initiation of OAC | 113 | 60; 70.2 (5.4) | Composite of stroke, MI, SE, peripheral vascular occlusion, and cardiovascular death | 44.3 months | D-dimer | Higher D-dimer levels were associated with greater risk of composite endpoint |
| tPA | Higher tPA levels were associated with greater risk of composite endpoint | |||||||
| F1+2 | No association with composite endpoint | |||||||
| TAT complexes | No association with composite endpoint | |||||||
| PAI-1 | No association with composite endpoint | |||||||
| Feinberg et al. (79) | Sub-study of prospective cohort | AF with at least 1 high-risk stroke factor | 1,531 | NA; 70 (NA) | Ischemic stroke or SE | 2 years | F1+2 | No association with ischemic stroke or SE |
| β-thromboglobulin | No association with ischemic stroke or SE | |||||||
| Fibrinogen | No association with ischemic stroke or SE | |||||||
| Factor V Leiden mutation | No association with ischemic stroke or SE |
AF, atrial fibrillation; BNP, B-type natriuretic peptide; CrCl, creatinine clearance; CRP, C-reactive protein; eGFR, estimated glomerular filtration rate; F1+2, prothrombin fragment F1+2; hsCRP, high-sensitivity C-reactive protein; ICAM-1, intercellular adhesion molecule-1; IL-10, interleukin-10; IL-1β, interleukin-1β; IL-6, interleukin-6; IQR, interquartile range; LA, left atrial; MDRD, Modification of Diet in Renal Disease Study; MI, myocardial infarction; MMP-2, matrix metalloproteinase-2; MPV, mean platelet volume; NA, not applicable or available; NOAC, non-vitamin K oral anticoagulants; NOX2, reduced nicotinamide adenine dinucleotide phosphate oxidase 2; NT-proBNP, N-terminal pro-B-type natriuretic peptide; OAC, oral anticoagulation; PAI-1, plasminogen activator inhibitor-1; RCT, randomized controlled trial; sCD40L, soluble CD40 ligand; SD, standard deviation; SE, systemic embolism; sVCAM-1, soluble vascular cell adhesion molecule-1; TAT, thrombin-antithrombin; TE, thromboembolism; TIA, transient ischemic attack; TNF-α, tumor necrosis factor-alpha; tPA, tissue plasminogen activator; vWF, von Willebrand factor.