Prothrombotic State in Atrial Fibrillation Patients With One Additional Risk Factor of the CHA2DS2-VASc Score (Beyond Sex)

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 (K_s), 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 K_s, 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 K_s (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.