The CHADS2 score (congestive heart failure, hypertension, age >75 years, diabetes, and previous stroke/transient ischemic attack) is used for embolic risk stratification in patients with atrial fibrillation (AF). Although systemic inflammation is a known predictor of left atrial thrombus formation in patients with nonrheumatic AF, the relation between the CHADS2 score and systemic inflammation is unknown. A total of 165 patients with nonrheumatic AF were enrolled and analyzed. According to the CHADS2 score, the study patients were grouped into low- (score 0 to 1), intermediate- (score 2 to 3), or high- (score 4 to 6) risk categories. The plasma C-reactive protein levels, transesophageal echocardiographic findings, and cardiovascular events (death, stroke, and heart failure) were compared. Patients in the high-risk group had significantly greater C-reactive protein levels than those in the intermediate- and low-risk groups (0.80 mg/dl, range 0.21 to 1.50, vs 0.16 mg/dl, range 0.06 to 0.50, vs 0.08 mg/dl, range 0.04 to 0.21, p <0.01). Using transesophageal echocardiography, the incidence of left atrial spontaneous echo contrast and left atrial thrombus increased with an increasing CHADS2 score. During the follow-up period, the cardiovascular event-free survival was significantly lower in the high-risk group than in the intermediate- or low-risk groups. In conclusion, in patients with nonrheumatic AF, CHADS2 score is related to systemic inflammation, left atrial thrombus formation, and prognosis.
Atrial fibrillation (AF) is a common arrhythmia that represents an independent risk factor for systemic and cerebral embolism. Abnormalities of hemostasis, fibrinolysis, endothelium, and platelet function in patients with AF can increase the risk of stroke and thromboembolism. These prothrombotic states, in addition to left atrial (LA) blood stasis, can be associated with LA thrombus and spontaneous echo contrast. Furthermore, there is an apparent link between thrombogenesis and inflammation. In contrast, elevated levels of plasma markers of inflammation have been shown to predict an increased risk of cardiovascular events in patients with AF. We hypothesized that the plasma C-reactive protein (CRP) levels could be related to the clinical stroke risk stratification schema (CHADS2 score: congestive heart failure, hypertension, age >75 years, diabetes, and previous stroke/transient ischemic attack) and prognosis in patients with AF.
Methods
From October 2004 to December 2008, the study population was identified from a retrospective database of 218 consecutive patients with AF who underwent their first transesophageal echocardiographic and transthoracic echocardiographic examinations. Patients with rheumatic valvular heart disease (n = 13), prosthetic valves (n = 21), aortic dissection (n = 5), or infectious disease (n = 14) were excluded from the present study. A total of 165 patients (105 men, mean age 71 ± 10 years) were enrolled and analyzed.
An S3 probe was used for transthoracic echocardiography, and a T6H probe was used for transesophageal echocardiography with the Sonos 7500 system (Philips Ultrasound, Bothell, Washington).
The CHADS2 score was calculated for each patient by assigning 1 point each for age >75 years, hypertension, diabetes mellitus, and heart failure and 2 points for previous stroke or transient ischemic attack. Hypertension was diagnosed if the blood pressure was >140/90 mm Hg, or the patient had a known history of hypertension. Patients were diagnosed with diabetes if the fasting plasma glucose level was >126 mg/dl, the glucose level 2 hours after a 75-g oral glucose tolerance test was ≥200 mg/dl, or the patient had a known medical history of diabetes. Congestive heart failure was diagnosed according to the Framingham criteria. The study patients were grouped, according to the CHADS2 score into low- (score 0 to 1), intermediate- (score 2 to 3), or high- (score 4 to 6) risk categories.
Blood samples were taken within 1 week before the transesophageal echocardiographic examination. The serum CRP level was measured using latex nephelometry (LT Auto Wako CRP, Osaka, Japan). We used latex as the reagent and the Hitachi 7500 analyzer (Hitachi, Tokyo, Japan) as the measurement system. The lowest detection CRP limit for this test is <0.02 mg/dl. After the blood samples were taken, no medication, including anticoagulation therapy, was changed until the transesophageal echocardiographic examination had been performed.
Cardiovascular events were defined as death, stroke, and heart failure. Clinical information was obtained by either chart review or telephone interview.
The data are presented as the mean value ± SD or the median value with the interquartile range. Differences in clinical features and plasma marker levels between patients in each CHADS2 category were evaluated using an unpaired Student’s t test for normally distributed continuous variables, the Mann-Whitney U test for nonparametrically distributed continuous variables, and chi-square tests for categorical variables. Statistical analyses were done using the Statistical Package for Social Sciences, version 15.0 (SPSS, Chicago, Illinois). p Values <0.05 were considered statistically significant. Kaplan-Meier curves were used to estimate the time-to-time models (i.e., stroke, heart failure, acute coronary syndrome, and composite death).
Results
Table 1 lists the clinical characteristics. Patients in the high-risk group were more likely to be older and more often had stroke risk factors. Aspirin and ticlopidine use were also significantly different statistically among the 3 groups. Patients in the high-risk group had significantly higher CRP levels than those in the intermediate- and low-risk group ( Figure 1 ). Table 2 lists the echocardiographic findings. The incidence of LA thrombus and spontaneous echo contrast increased with increasing CHADS2 score ( Figures 2 and 3 ) . In addition, the LA appendage velocity decreased with increasing CHADS2 score. Patients were followed up for a mean of 521 ± 489 days. Of the 165 patients, 8 died (3 cardiac and 5 noncardiac), 5 experienced stroke, and 12 experienced heart failure. Cardiovascular event-free survival (ie, death, congestive heart failure, and stroke) were significantly lower in patients in the high-risk group than in the intermediate- or low-risk group (log-rank test, p <0.0001; Figure 4 ).
| Variable | Risk Group | p Value | ||
|---|---|---|---|---|
| Low (n = 67) | Intermediate (n = 84) | High (n = 14) | ||
| Age (years) | 66 ± 9 | 74 ± 9 | 80 ± 5 | <0.01 |
| Men | 46 (69%) | 51 (61%) | 8 (57%) | 0.523 |
| Body mass index (kg/m 2 ) | 23 ± 3 | 23 ± 3 | 22 ± 2 | 0.470 |
| Smoker | 24 (36%) | 30 (36%) | 5 (36%) | 1.000 |
| Diabetes | 6 (9%) | 30 (36%) | 8 (57%) | <0.01 |
| Hypertension ⁎ | 26 (39%) | 68 (81%) | 13 (93%) | <0.01 |
| Hyperlipidemia † | 16 (24%) | 30 (36%) | 8 (57%) | 0.039 |
| Angiotensin-converting enzyme inhibitor/angiotensin II receptor blocker | 20 (30%) | 36 (43%) | 8 (57%) | 0.090 |
| Warfarin | 29 (43%) | 30 (36%) | 9 (64%) | 0.120 |
| Aspirin | 5 (7%) | 31 (37%) | 4 (29%) | <0.01 |
| Ticlopidine | 3 (4%) | 3 (4%) | 3 (21%) | 0.022 |
| Statin | 10 (15%) | 21 (25%) | 3 (21%) | 0.314 |
| Prothrombin time-international normalized ratio | 1.58 ± 0.64 | 1.62 ± 0.78 | 1.63 ± 0.60 | 0.811 |
⁎ Blood pressure >140/90 mm Hg or known history of hypertension.
† Total cholesterol >220 mg/dl, low-density lipoprotein cholesterol >140 mg/dl, or known medical history of hyperlipidemia.
| Variable | Risk Group | p Value | ||
|---|---|---|---|---|
| Low (n = 67) | Intermediate (n = 84) | High (n = 14) | ||
| Transthoracic echocardiography findings | ||||
| Left atrial dimension (cm) | 4.5 ± 0.9 | 4.5 ± 0.7 | 4.7 ± 0.5 | 0.154 |
| Intraventricular septum thickness (cm) | 1.1 ± 0.3 | 1.2 ± 0.2 | 1.2 ± 0.4 | 0.204 |
| Posterior left ventricular wall thickness (cm) | 1.1 ± 0.2 | 1.1 ± 0.2 | 1.1 ± 0.2 | 0.921 |
| Left ventricular diastolic dimension (cm) | 4.7 ± 0.8 | 4.7 ± 0.8 | 4.5 ± 0.9 | 0.538 |
| Left ventricular systolic dimension (cm) | 3.1 ± 0.8 | 3.3 ± 1.0 | 2.9 ± 1.1 | 0.106 |
| Ejection fraction (%) | 59.6 ± 11.9 | 55.4 ± 12.4 | 58.1 ± 11.5 | 0.158 |
| Transesophageal echocardiographic findings | ||||
| Left atrial thrombus | 2 (3%) | 9 (11%) | 4 (29%) | <0.01 |
| Spontaneous echo contrast | 11 (16%) | 30 (36%) | 10 (71%) | <0.01 |
| Left atrial appendage velocity (cm/s) | 36.7 ± 18.0 | 33.2 ± 20.9 | 26.4 ± 18.0 | 0.034 |
| Significant mitral regurgitation | 20 (30%) | 33 (39%) | 0 (0%) | 0.016 |
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