Identification of Markers Associated With Development of Stroke in "Clinically Low-Risk" Atrial Fibrillation Patients

Abstract

Background Stroke and thromboembolic events may still occur in "clinically low-risk" atrial fibrillation (AF) patients as categorized by CHA2DS2-VASc score. Our aim was to assess the proportion of "clinically low-risk" patients using a nongender CHA2DS2-VASc (ie, CHA2DS2-VA) score of 0 to 1 among patients who experienced AF-associated stroke and to identify markers associated with stroke in "clinically low-risk" patients. Methods and Results We retrospectively recruited nonvalvular AF patients who experienced embolic stroke between 2013 and 2016 from 9 institutes in Korea. AF patients with CHA2DS2-VA score of 0 to 1 at the time of stroke were analyzed and compared with "clinically low-risk" AF patients without stroke. A total of 3033 subjects with AF-associated stroke were recruited. Of these, 583 patients (19.2%) had CHA2DS2-VA score of 0 to 1. On multivariate analysis, age (≥60 years), N-terminal pro B-type natriuretic peptide (≥300 pg/mL), creatinine clearance (<50 mL/min), and left atrial dimension (≥45 mm) were independently associated with stroke. With the combined application of these 4 factors (collectively, ABCD score) to the "clinically low-risk" patients, the c-index was 0.858 (95% CI 0.838-0.877; P<0.001). Conclusions The present study suggests a new insight into how additional use of markers can further refine stroke risk differentiation among AF patients initially classified as "clinically low-risk." Clinical Trial Registration URL: http://www.clinicaltrials.gov. Unique identifier: NCT03147911.

Keywords: ABCD score; atrial fibrillation; risk score; risk stratification; stroke, ischemic.

Figures

Figure 1

Distribution of AF patients with stroke event according to the ABCD score. A, Distribution of ABCD score in patients with CHA 2 DS 2‐VA score 0 or 1 is shown. B, Distribution of ABCD score in patients with CHA 2 DS 2‐VASc score 0 or 1 is shown. ABCD indicates age, NT‐proBNP, CCr, and dimension of the LA; AF, atrial fibrillation; CHA 2 DS 2‐VA, congestive heart failure, hypertension, age ≥75 years, diabetes mellitus, prior stroke or transient ischemic attack, vascular disease, and age 65 to 74; and CHA 2 DS 2‐VASc, congestive heart failure, hypertension, age ≥75, diabetes mellitus, prior stroke or transient ischemic attack, vascular disease, age 65 to 74 years, and sex category; CCr, creatinine clearance rate; LA, left atrium; NT‐proBNP, N‐terminal pro B‐type natriuretic peptide.

Figure 2

Receiver operating characteristic curve of the ABCD score for identifying a population with a truly low risk of stroke in AF patients. C‐index of ABCD score was 0.858 (95% CI 0.838–0.877) and its risk stratification in low‐risk group was superior to that of CHA 2 DS 2‐VA or CHA 2 DS 2‐VASc score. ABCD indicates age, NT‐proBNP, CCr, and dimension of the LA; AF, atrial fibrillation; CHA 2 DS 2‐VA, congestive heart failure, hypertension, age ≥75 years, diabetes mellitus, prior stroke or transient ischemic attack, vascular disease, and age 65 to 74 years; AUC, area under the curve; CHA 2 DS 2‐VASc, congestive heart failure, hypertension, age ≥75, diabetes mellitus, prior stroke or transient ischemic attack, vascular disease, age 65 to 74 years, and sex category.

Figure 3

Calibration of ABCD score. ABCD score categories were defined as low risk (score=0), moderate risk (score 1, 2), and high risk (score 3, 4). There were no significant differences between observed stroke event number (blue) and expected stroke event number (red). ABCD indicates age, NT‐proBNP, CCr, and dimension of the LA; AF, atrial fibrillation; CHA 2 DS 2‐VA, congestive heart failure, hypertension, age ≥75 years, diabetes mellitus, prior stroke or transient ischemic attack, vascular disease, and age 65 to 74 years; CCr, creatinine clearance rate; LA, left atrium; NT‐proBNP, N‐terminal pro B‐type natriuretic peptide.