Abstract
Background
It is unclear whether a prothrombotic state occurs in atrial fibrillation (AF) with
low stroke risk.
Methods
We studied 118 patients with AF with the Congestive Heart Failure, Hypertension, Age (≥ 75 years), Diabetes, Stroke/Transient Ischemic Attack/Systemic Embolism, Vascular Disease, Age (65-74 years), Sex (Female) (CHA2DS2-VASc) score of 1 in men or 2 in women vs 52 patients with AF with the CHA2DS2-VASc score of 0 in men or 1 in women. Plasma clot permeability (Ks), a measure of fibrin clot density, and clot lysis time (CLT), endogenous thrombin
potential (ETP), von Willebrand factor antigen, and plasminogen activator inhibitor-1
were evaluated in nonanticoagulated subjects.
Results
Patients with the CHA2DS2-VASc score of 1 (beyond sex), compared with those with 0, had lower Ks, prolonged CLT, increased ETP, von Willebrand factor antigen, and plasminogen activator
inhibitor-1 (all P < 0.001), without any sex-dependent differences. Heart failure (odds ratio [OR]:
10.28; 95% confidence interval [CI]: 2.32-45.41), age 65-74 years (OR: 4.37; 95% CI:
1.76-10.83), and hypertension (OR: 5.03; 95% CI: 1.81-13.94) were independently associated
with low Ks (the lowest quartile, ≤ 6.4 × 10−9 cm2), whereas only age 65-74 years (OR: 3.33; 95% CI: 1.59-6.96) significantly predicted
prolonged CLT (the top quartile, ≥ 108 minutes). Age 65-74 years (OR: 5.21; 95% CI:
2.12-12.80), heart failure (OR: 6.58; 95% CI: 1.49-29.06), and hypertension (OR: 4.33;
95% CI: 1.54-12.15) were independently associated with high ETP (the top quartile,
≥ 1681.3 nM × minutes).
Conclusions
A prothrombotic state (increased thrombin generation, denser fibrin clots, impaired
fibrinolysis, and endothelial injury) characterizes patients with AF with 1 additional
clinical stroke risk factor (beyond sex), with age 65-74 years being particularly
associated with prothrombotic indices.
Résumé
Contexte
La question de savoir si un état prothrombotique survient chez les patients atteints
de fibrillation auriculaire (FA) à faible risque d’accident vasculaire cérébral (AVC)
n’a pas été élucidée.
Méthodologie
Nous avons étudié 118 patients atteints de FA présentant un score CHA2DS2-VASc (insuffisance cardiaque congestive, hypertension, âge ≥ 75 ans, diabète, accident
vasculaire cérébral/ischémie cérébrale transitoire, maladie vasculaire, âge compris
entre 65 et 74 ans, sexe féminin) de 1 chez les hommes ou de 2 chez les femmes comparativement
à 52 patients atteints de FA et présentant un score CHA2DS2-VASc de 0 chez les hommes ou de 1 chez les femmes. La perméabilité du caillot plasmatique
(Ks), une mesure de la densité des caillots de fibrine, ainsi que le temps de lyse du
caillot (TLC), le potentiel endogène de thrombine (PET), et la concentration d’antigène
du facteur de von Willebrand et d’inhibiteur 1 des activateurs du plasminogène ont
été évalués chez les patients non traités par un anticoagulant.
Résultats
Les patients ayant un score CHA2DS2-VASc de 1 (sans égard au sexe), comparativement à ceux chez qui ce score était de
0, affichaient un Ks moins élevé, un TLC plus long, et des valeurs plus élevées de PET et d’antigènes
du facteur de von Willebrand et d’inhibiteurs 1 des activateurs du plasminogène (p < 0,001 dans tous les cas), sans aucune différence liée au sexe. L’insuffisance cardiaque
(rapport des cotes [RC]: 10,28; intervalle de confiance [IC] à 95 % : de 2,32 à 45,41),
l’âge compris entre 65 et 74 ans (RC : 4,37; IC à 95 % : de 1,76 à 10,83) et l’hypertension
(RC : 5,03; IC à 95 % : de 1,81 à 13,94) étaient associés de manière indépendante
à une faible valeur de Ks (le quartile inférieur, ≤ 6,4 × 10−9 cm2), tandis que seul l’âge compris entre 65 et 74 ans (RC : 3,33; IC à 95 % : de 1,59
à 6,96) était associé de façon significative à l’allongement du TLC (le quartile supérieur,
≥ 108 minutes). L’âge compris entre 65 et 74 ans (RC: 5,21; IC à 95 % : de 2,12 à
12,80), l’insuffisance cardiaque (RC : 6,58; IC à 95 % : de 1,49 à 29,06) et l’hypertension
(RC : 4,33; IC à 95 % : de 1,54 à 12,15) étaient associés de manière indépendante
avec un PET élevé (le quartile supérieur, ≥ 1681,3 nM × minutes).
Conclusions
Un état prothrombotique (production accrue de thrombine, caillots de fibrine plus
denses, perturbation de la fibrinolyse et lésions endothéliales) caractérise les patients
atteints de FA qui présentent 1 facteur de risque d’AVC clinique additionnel (sans
égard au sexe), l’âge compris entre 65 et 74 ans présentant une association particulièrement
élevée avec les indices d’un tel état.
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References
- Stroke in paroxysmal atrial fibrillation: report from the Stockholm Cohort of Atrial Fibrillation.Eur Heart J. 2010; 31: 967-975
- Refining clinical risk stratification for predicting stroke and thromboembolism in atrial fibrillation using a novel risk factor-based approach: the Euro Heart Survey on Atrial Fibrillation.Chest. 2010; 137: 263-272
- Oral anticoagulation, aspirin, or no therapy in patients with nonvalvular AF with 0 or 1 stroke risk factor based on the CHA2DS2-VASc score.J Am Coll Cardiol. 2015; 65: 1385-1394
- Should atrial fibrillation patients with 1 additional risk factor of the CHA2DS2-VASc score (beyond sex) receive oral anticoagulation?.J Am Coll Cardiol. 2015; 65: 635-642
- 2016 ESC guidelines for the management of atrial fibrillation developed in collaboration with EACTS.Eur Heart J. 2016; 37: 2893-2962
- 2014 AHA/ACC/HRS guideline for the management of patients with atrial fibrillation: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines and the Heart Rhythm Society.J Am Coll Cardiol. 2014; 64: e1-e76
- 2018 Focused Update of the Canadian Cardiovascular Society Guidelines for the Management of Atrial Fibrillation.Can J Cardiol. 2018; 34: 1371-1392
- Atrial fibrillation and the hypercoagulable state: from basic science to clinical practice.Pathophysiol Haemost Thromb. 2003; 33: 282-289
- Inflammation in atrial fibrillation.J Am Coll Cardiol. 2012; 60: 2263-2270
- AssesSment of the left atrial appendage morphoLogy in patients aAfter ischaeMic Stroke—the ASSAM study protocol.Kardiol Pol. 2017; 75: 758-762
- Hemodynamic and hemorheologic determinants of left atrial spontaneous echo contrast and thrombus formation in patients with idiopathic dilated cardiomyopathy.Am Heart J. 1993; 125: 430-434
- Prethrombotic state in young very low-risk patients with atrial fibrillation.J Am Coll Cardiol. 2017; 69: 1990-1992
- Atrial fibrillation and hypercoagulability: dependent on clinical factors or/and on genetic alterations?.J Thromb Thrombolysis. 2003; 16: 155-161
- Relation of interleukin-6, C-reactive protein, and the prothrombotic state to transesophageal echocardiographic findings in atrial fibrillation.Am J Cardiol. 2004; 93 (A6): 1368-1373
- Denser plasma clot formation and impaired fibrinolysis in paroxysmal and persistent atrial fibrillation while on sinus rhythm: association with thrombin generation, endothelial injury and platelet activation.Thromb Res. 2015; 136: 408-414
- Fibrin clot properties and their modulation in thrombotic disorders.Thromb Haemost. 2014; 112: 32-42
- Fibrinogen and fibrin in hemostasis and thrombosis.Arterioscler Thromb Vasc Biol. 2017; 37: e13-e21
- Fibrin clot permeability as a predictor of stroke and bleeding in anticoagulated patients with atrial fibrillation.Stroke. 2017; 48: 2716-2722
- The influence of type 2 diabetes on fibrin structure and function.Diabetologia. 2005; 48: 1198-1206
- Altered fibrin clot properties in patients with chronic heart failure and sinus rhythm: a novel prothrombotic mechanism.Heart. 2010; 96: 1114-1118
- The vulnerable blood. Coagulation and clot structure in diabetes mellitus.Hamostaseologie. 2015; 35: 25-33
- Elevated NT-proBNP is associated with unfavorably altered plasma fibrin clot properties in atrial fibrillation.Int J Cardiol. 2017; 243: 244-250
- Thrombin generation, a function test of the haemostatic-thrombotic system.Thromb Haemost. 2006; 96: 553-561
- Data management in thrombin generation.Thromb Res. 2013; 131: 3-11
- An international study on the standardization of fibrin clot permeability measurement: methodological considerations and implications for healthy control values.J Thromb Haemost. 2012; 10: 2179-2181
- Thrombin-activatable fibrinolysis inhibitor deficiency in cirrhosis is not associated with increased plasma fibrinolysis.Gastroenterology. 2001; 121: 131-139
- A history of early stent thrombosis is associated with prolonged clot lysis time.Thromb Haemost. 2012; 107: 513-520
- Applied Logistic Regression.2nd ed. John Wiley & Sons, Inc., Hoboken2000: 95
- Association of cardiac troponin I with prothrombotic alterations in atrial fibrillation.Kardiol Pol. 2018; 76: 1106-1109
- A biomarker-based risk score to predict death in patients with atrial fibrillation: the ABC (age, biomarkers, clinical history) death risk score.Eur Heart J. 2018; 39: 477-485
- Thrombin generation and fibrin clot structure.Blood Rev. 2007; 21: 131-142
- Hypercoagulability causes atrial fibrosis and promotes atrial fibrillation.Eur Heart J. 2017; 38: 38-50
- Transcatheter closure of atrial septal communication: impact on P-wave dispersion, duration, and arrhythmia in mid-term follow-up.Kardiol Pol. 2018; 76: 1465-1473
- Does von Willebrand factor improve the predictive ability of current risk stratification scores in patients with atrial fibrillation?.Sci Rep. 2017; 7: 41565
- Female sex as a risk factor for stroke in atrial fibrillation: a nationwide cohort study.J Thromb Haemost. 2012; 10: 1745-1751
- Is female sex a risk factor for stroke and thromboembolism in patients with atrial fibrillation? A systematic review and meta-analysis.QJM. 2014; 107: 955-967
- Antithrombotic properties of aspirin and resistance to aspirin: beyond strictly antiplatelet actions.Blood. 2007; 109: 2285-2292
- Atrial fibrillation patients do not benefit from acetylsalicylic acid.Europace. 2014; 16: 631-638
- Hypofibrinolysis in diabetes: a therapeutic target for the reduction of cardiovascular risk.Cardiovasc Diabetol. 2017; 16: 34
- Plasma fibrin clot structure and thromboembolism: clinical implications.Pol Arch Intern Med. 2017; 127: 873-881
Article info
Publication history
Published online: January 29, 2019
Accepted:
January 24,
2019
Received:
November 26,
2018
Footnotes
See editorial by Nattel and Lip, pages 547–549 of this issue.
See page 641 for disclosure information.
Identification
Copyright
© 2019 Canadian Cardiovascular Society. Published by Elsevier Inc. All rights reserved.
