Abstract
It is unclear whether chronic kidney disease (CKD) increases thromboembolism in atrial fibrillation (AF). We conducted a retrospective cross-sectional analysis of 502 non-anticoagulated AF patients (median age, 66 (60–73) years, median CHA2DS2-VASc score, 3.0 (2.0–4.0)) with an estimated glomerular filtration rate (eGFR) ≥ 15 mL/min/1.73 m2. Endogenous thrombin potential (ETP), clot permeability (Ks), and clot lysis time (CLT), among others, were determined. Patients with stage 4 CKD (n = 87; 17.3%) had higher ETP and prolonged CLT compared with those with stage 3 CKD. In patients with stages 3 to 4 CKD (n = 180; 35.9%) N-terminal pro-B-type natriuretic peptide predicted low Ks (the lowest quartile, odds ratio [OR] per 100 pg/mL: 1.03, 95% confidence interval [CI]: 1.01–1.06) and prolonged CLT (the top quartile, OR per 100 pg/mL: 1.05, 95% CI: 1.02–1.08), but not high ETP. In the whole cohort, after adjustment for CHA2DS2-VASc score, stage 4 CKD, but not stage 3 CKD, predicted high ETP (OR: 9.06; 95% CI: 4.44−18.46) and prolonged CLT (OR: 3.58; 95% CI: 1.76–7.28), but not low Ks. compared to the reference eGFR category. This study is the first to demonstrate the prothrombotic and antifibrinolytic alterations in AF patients with stage 4 CKD, but not stage 3 CKD irrespective of clinical stroke risk factors.
Highlights
Chronic kidney disease (CKD) is associated with poor prognosis [1]
Our findings demonstrate that non-anticoagulated atrial fibrillation (AF) patients with stage 4 CKD, but not stage 3 CKD, display enhanced prothrombotic state, including increased thrombin formation and impaired fibrinolysis as compared to those with higher estimated glomerular filtration rate (eGFR)
We found that increased Endogenous thrombin potential (ETP) represents the most specific feature of the prothrombotic state in AF patients with impaired renal function, after adjustment for fibrinogen and CHA2DS2-VASc score risk factors
Summary
Chronic kidney disease (CKD) is associated with poor prognosis [1]. At the same time in patients with atrial fibrillation (AF) impaired renal function is independently related to stroke or systemic embolism [2]. The modified scoring systems in AF patients incorporating extra points for renal impairment to the congestive heart failure, hypertension, age (≥75 years), diabetes, stroke or transient ischemic attack (CHADS2) or the congestive heart failure, hypertension, age (≥75 years), diabetes, stroke or transient ischemic attack or systemic embolism, vascular disease, age (65–74 years), sex (female) (CHA2DS2-VASc) scores to enhance their clinical performance have been proposed, several studies assessing a clinical value of the modified scores yielded inconsistent findings [2,3,4,5,6]. Patients with AF have been reported to show increased fibrin clot density and decreased clot lysability [8]. These unfavorable fibrin clot properties, the so-called prothrombotic clot phenotype, have been found to be associated with N-terminal pro-B-type natriuretic peptide (NT-proBNP) and growth differentiation factor-15 [9,10]. It has been demonstrated that low plasma clot permeability and prolonged clot lysis can predict ischemic stroke or transient ischemic attack in AF during follow-up [11,12]
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