As the CHADS 2 and CHA 2 DS 2 -VASc scores include similar risk factors for the development of coronary artery disease (CAD), they may provide crucial information regarding the severity of coronary artery lesions and the risk of thromboembolism. To increase the likelihood of determining CAD severity, we formulated the CHA 2 DS 2 -VASc-HS score comprising hyperlipidemia and smoking in addition to the components of the CHA 2 DS 2 -VASc score and male instead of female gender. We aimed to investigate whether these 3 risk scores can be used to predict CAD severity. A total of 407 consecutive patients who underwent coronary angiography were enrolled in the study. Presence of >50% stenosis in a coronary artery was assessed as significant CAD. Of the patients, 87 had normal coronary angiograms and served as group 1. The remaining 320 patients with coronary stenosis were further classified into 2 groups according to CAD with stenosis of <50% or ≥50%: 123 patients with mild CAD as group 2 and 197 patients with severe CAD as group 3. The CHADS 2 , CHA 2 DS 2 -VASc, and CHA 2 DS 2 -VASc-HS scores were significantly different among the 3 groups. The CHADS 2 , CHA 2 DS 2 -VASc, and CHA 2 DS 2 -VASc-HS scores correlated significantly with the number of diseased vessels (r = 0.406, p <0.001; r = 0.308, p <0.001; and r = 0.533, p <0.001, respectively) and the Gensini score (r = 0.383, p <0.001; r = 0.300, p <0.001; and r = 0.500, p <0.001, respectively). The CHA 2 DS 2 -VASc-HS score was found to be the best scoring scheme to predict CAD severity in the area under the curve comparison of these scoring systems. For prediction of severe CAD, the cut-off value of CHA 2 DS 2 -VASc-HS score was >2 with a sensitivity of 85.2% and a specificity of 57.5% (area under the curve 0.802, 95% confidence interval 0.760 to 0.839, p <0.001). In conclusion, our findings suggest that the CHADS 2 , CHA 2 DS 2 -VASc, and especially CHA 2 DS 2 -VASc-HS scores could be considered predictive of the risk of severe CAD.
The CHADS 2 score is a clinical predictor of the risk of stroke in patients with nonvalvular atrial fibrillation used to determine whether anticoagulation or antiplatelet therapy is required. It is simple and has been validated by many studies ; a high CHADS 2 score is indicative of greater stroke risk. In clinical use, the CHADS 2 score has been replaced by the CHA 2 DS 2 -VASc score, which provides better stratification of low-risk patients. Both the CHADS 2 and CHA 2 DS 2 -VASc scoring schemes are easily remembered and applied by physicians in clinical practice. As they include similar risk factors for the development or presence of coronary artery disease (CAD), we believed that they could also be used to predict CAD severity. We have also formulated a new score, termed the CHA 2 DS 2 -VASc-HS score, to increase the likelihood of determining CAD severity. This scoring system includes hyperlipidemia (HL) and smoking as other major risk factors for CAD, in addition to using male rather than female gender. In this study, we evaluated the CHADS 2 , CHA 2 DS 2 -VASc, and CHA 2 DS 2 -VASc-HS scores as multivariable risk assessment tools to identify those at high risk of severe CAD in patients who underwent diagnostic coronary angiography (CAG).
Methods
This was a single-center study in which a total of 407 consecutive patients who were admitted for diagnostic CAG were prospectively enrolled. All study patients were referred for CAG as outpatients because of the symptoms suggestive of CAD and/or abnormal noninvasive stress tests based on exercise electrocardiographic testing or myocardial perfusion imaging test. Patients who had acute coronary syndrome, acute heart failure, acute ischemic stroke or transient ischemic attack (TIA), previous coronary artery bypass surgery, and previous percutaneous coronary intervention were excluded from the study. Initially, 2 experienced cardiologists evaluated all angiograms in terms of coronary stenosis and assessed the Gensini score. Thereafter, 2 experienced cardiologists, without knowledge of patients’ CAD status, calculated the CHADS 2 , CHA 2 DS 2 -VASc, and CHA 2 DS 2 -VASc-HS scores.
For each patient, a detailed medical history, thorough clinical examination, standard 12-lead electrocardiogram, and conventional echocardiographic examination were performed based on the recommendations of the American Society of Echocardiography. Left ventricular ejection fraction was measured by echocardiography using a biplane modified Simpson’s method with the GE Vivid 7 (GE Healthcare, Milwaukee, Wisconsin). Blood samples were obtained by venipuncture on the same day of the procedure after a 12-hour overnight fast and drawn into standardized tubes that were delivered to the laboratory within a few minutes. Fasting blood glucose, total cholesterol, low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol, triglycerides, and renal function tests were performed using standard laboratory methods. LDL-C concentrations were calculated using the Friedewald formula.
Clinical and demographic characteristics including age, gender, diabetes mellitus (DM), hypertension (HT), HL, current cigarette smoking, family history of premature CAD, chronic heart failure, previous ischemic stroke or TIA, and peripheral artery disease (PAD) were obtained by medical history, physical examination, electrocardiographic findings, echocardiographic examination, laboratory data and digital and/or nondigital hospital records. Type 2 DM was defined as a previous diagnosis and/or fasting blood glucose ≥126 mg/dl or the use of antidiabetic medications. HT was defined as repeated measurements of systolic blood pressure ≥140 mm Hg, diastolic ≥90 mm Hg, or chronic treatment with antihypertensive medications. HL was considered to be LDL-C above the target level according to the National Cholesterol Education Program-3 recommendations or the use of lipid-lowering medications. Cigarette smoking was defined as smoking ≥10 cigarettes a day for at least 1 year without a quit attempt. Family history was defined as the presence of heart disease or sudden cardiac death in a male first-degree relative aged <55 years or in a female first-degree relative aged <65 years. Chronic heart failure was defined as reduced left ventricular ejection fraction (<40%). PAD was defined by the pathologic states that lead to stenosis of at least 50% in noncoronary artery circulation. Vascular disease was considered to be the presence of PAD. Stroke and TIA due to thromboembolism arising from carotid or vertebral arteries were only included in the scoring. Patients having stroke or TIA had severe carotid artery disease in this study.
CAG was performed using the Judkins technique. Significant CAD was diagnosed if there was ≥50% diameter stenosis in at least 1 major epicardial coronary artery. The severity of CAD was determined by the number of significantly diseased coronary arteries. Vessel disease was defined as the presence of ≥50% luminal diameter stenosis in at least 1 major coronary artery. Multivessel coronary disease was defined as the presence of ≥50% luminal diameter stenosis involving at least 2 major epicardial coronary arteries. Left main coronary artery narrowing of ≥50% was considered as 2-vessel disease. The Gensini score was calculated for each patient from the coronary angiogram by assigning a severity score to each coronary stenosis as 1 for 1% to 25% narrowing, 2 for 26% to 50%, 4 for 51% to 75%, 8 for 76% to 90%, 16 for 91% to 99%, and 32 for a completely occluded artery. The score is then multiplied by a factor according to the importance of the coronary artery. The multiplication factor is 5 for a left main coronary artery, 2.5 for proximal left anterior descending artery and proximal circumflex artery, 1.5 for a mid left anterior descending artery, and 1 for distal left anterior descending artery, mid or distal circumflex artery, and right coronary artery. The multiplication factor for any other branch is 0.5. The inter- and intraobserver correlation coefficients were 0.91 and 0.94, respectively.
The CHADS 2 nomenclature represents congestive heart failure (C), HT (H), age (A), DM (D), and stroke (S). The CHADS 2 score was calculated by assigning 1 point each for the presence of chronic heart failure, HT, age ≥75 years, and DM and by assigning 2 points for history of stroke or TIA. The CHA 2 DS 2 -VASc score is a modification of the CHADS 2 score and extends the latter by including additional common stroke risk factors including vascular disease (V), age 65 to 74 years (A), and female gender (as a sex category [Sc]). In the CHA 2 DS 2 -VASc score, age ≥75 years (A 2 ) is assigned 2 points. The CHA 2 DS 2 -VASc-HS score comprises HL and smoking in addition to the components of the CHA 2 DS 2 -VASc score and male gender instead of female gender ( Table 1 ). The maximum CHADS 2 , CHA 2 DS 2 -VASc, and CHA 2 DS 2 -VASc-HS scores were 6, 9, and 11, respectively.
| C | Congestive heart failure | 1 Point |
| H | HT | 1 Point |
| A 2 | Age >75 yrs | 2 Points |
| D | Diabetes mellitus | 1 Point |
| S 2 | Previous stroke or TIA | 2 Point |
| V | Vascular disease | 1 Point |
| A | Age 65–74 yrs | 1 Point |
| Sc | Sex category (male gender) | 1 Point |
| H | HL | 1 Point |
| S | Smoker | 1 Point |
The study was approved by the local ethics committee on the basis of strict maintenance of participant anonymity, and individual informed consent was obtained from all subjects.
Continuous data are presented as mean ± SD and/or median (minimum to maximum). The Kolmogorov-Smirnov test was used to evaluate whether the distribution of continuous variables was normal. One-way analysis of variance or Kruskal-Wallis tests were used to compare the 3 groups. Differences in continuous variables between 2 groups were determined by t test or Mann-Whitney U test. Correlation analysis was performed using Pearson or Spearmen tests. Categorical variables are summarized as percentages and compared with the chi-square or Fisher’s exact test. To predict cut-off value of Gensini score for CHADS 2 ≥2 and CHA 2 DS 2 -VASc ≥2 and indicate higher risk of thromboembolism, receiver operating characteristics (ROC) curve analysis was performed. The ROC curve was also used to demonstrate the sensitivity and specificity of CHA 2 DS 2 -VASc-HS score and its cut-off value for predicting severe CAD. The area under the curve (AUC) comparison of these scoring systems was performed using Delong method. A p value <0.05 was considered as significant. Statistical analyses were conducted using the Statistical Package for the Social Sciences (SPSS 17) for Windows (SPSS Inc., Chicago, Illinois) and MedCalc Statistical Software version 12.2 (MedCalc Software bvba, Ostend, Belgium).
Results
The study population consisted of 407 patients (mean age 61 ± 10 years, 113 women [28%]), of whom 87 had normal coronary arteries and were selected as the control group (group 1). The remaining 320 patients with coronary stenosis were further classified into 2 groups: 123 patients with CAD with stenosis of <50% as mild CAD group (group 2) and 197 patients with CAD with stenosis of ≥50% as severe CAD group (group 3). A comparison of the baseline demographics and characteristics of the 3 groups are presented in Table 2 . The CHADS 2 , CHA 2 DS 2 -VASc, CHA 2 DS 2 -VASc-HS, and Gensini scores were significantly different among the 3 groups and between each other. From group 1 to group 3, Gensini, CHADS 2 , CHA 2 DS 2 -VASc, and CHA 2 DS 2 -VASc-HS scores were significantly increased. The mean age, total cholesterol, LDL-C, creatinine and percent of DM, HT, HL, smoking, family history of CAD, left ventricular dysfunction, stroke or TIA, and PAD were highest in group 3 and significantly different among the groups. The gender distribution was similar among the groups, whereas high-density lipoprotein cholesterol levels were the lowest in group 3.
| Parameter | Group | p Value (1 vs 2) | p Value (1 vs 3) | p Value (2 vs 3) | ||
|---|---|---|---|---|---|---|
| 1 (n = 87) | 2 (n = 123) | 3 (n = 197) | ||||
| Age (yrs) | 57 ± 9 | 60 ± 10 | 63 ± 10 | 0.017 | <0.001 | 0.013 |
| CHADS 2 score | 0.70 ± 0.63 | 0.94 ± 0.76 | 1.45 ± 0.88 | 0.026 | <0.001 | <0.001 |
| 1 (0–2) | 1 (0–3) | 1 (0–4) | ||||
| CHA 2 DS 2 -VASc score | 1.19 ± 0.97 | 1.63 ± 1.22 | 2.14 ± 1.33 | 0.010 | <0.001 | 0.001 |
| 1 (0–4) | 2 (0–5) | 2 (0–5) | ||||
| CHA 2 DS 2 -VASc-HS score | 2.06 ± 0.94 | 2.49 ± 1.0 | 3.50 ± 1.2 | 0.002 | <0.001 | <0.001 |
| 2 (0–4) | 2 (0–5) | 4 (1–7) | ||||
| Gensini score | 0 ± 0 | 5.6 ± 2.6 | 40.4 ± 25.7 | <0.001 | <0.001 | <0.001 |
| 0 (0–0) | 6 (1–11) | 35 (5–136) | ||||
| Women | 26 (30) | 40 (33) | 47 (24) | 0.686 | 0.215 | 0.091 |
| DM | 13 (15) | 28 (23) | 78 (40) | 0.160 | <0.001 | 0.002 |
| HT | 42 (48) | 67 (55) | 138 (70) | 0.377 | 0.001 | 0.005 |
| HL | 20 (23) | 35 (29) | 94 (48) | 0.376 | <0.001 | 0.001 |
| Family history | 9 (10) | 31 (25) | 50 (25) | 0.007 | 0.012 | 0.972 |
| Smoker | 20 (23) | 28 (23) | 71 (36) | 0.970 | 0.014 | 0.013 |
| Stroke/TIA | 0 | 0 | 8 (4) | — | 0.112 | 0.026 |
| PAD | 0 | 5 (4) | 16 (8) | 0.078 | 0.004 | 0.154 |
| Congestive heart failure | 1 (1.1) | 8 (6.5) | 21 (10.7) | 0.084 | 0.006 | 0.208 |
| Left ventricular ejection fraction (%) | 60 ± 5 | 58 ± 7 | 53 ± 8 | 0.164 | <0.001 | <0.001 |
| Glucose (mg/dl) | 109 ± 27 | 114 ± 39 | 123 ± 47 | 0.579 | 0.092 | 0.473 |
| Creatinine (mg/dl) | 0.84 ± 0.2 | 0.92 ± 0.3 | 0.99 ± 0.3 | 0.056 | 0.001 | 0.530 |
| Total cholesterol (mg/dl) | 173 ± 38 | 181 ± 40 | 191 ± 37 | 0.378 | 0.002 | 0.05 |
| Low-density lipoprotein (mg/dl) | 104 ± 32 | 108 ± 34 | 119 ± 31 | 0.743 | 0.003 | 0.009 |
| High-density lipoprotein (mg/dl) | 41 ± 11 | 42 ± 11 | 38 ± 10 | 0.648 | 0.244 | 0.007 |
| Triglycerides (mg/dl) | 154 ± 83 | 152 ± 77 | 160 ± 83 | 0.986 | 0.869 | 0.705 |
When patients were divided into 4 subgroups according to the number of diseased vessels, each scoring system was found to be significantly different among the groups. A comparison of the groups revealed that as the number of diseased vessels increased, higher values were observed for each scoring system ( Table 3 ). The CHADS 2 , CHA 2 DS 2 -VASc, and CHA 2 DS 2 -VASc-HS scores correlated significantly with the number of significant diseased vessels (r = 0.406, p <0.001; r = 0.308, p <0.001; and r = 0.533, p <0.001, respectively). In addition, the CHADS 2 and CHA 2 DS 2 -VASc scores correlated significantly with the Gensini score (r = 0.383, p <0.001 and r = 0.300, p <0.001, respectively). The correlation between the CHA 2 DS 2 -VASc-HS and Gensini scores was greater than that between the CHADS 2 and CHA 2 DS 2 -VASc scores (r = 0.500, p <0.001).
| Score | Vessel Disease | p Value (for Trend) | |||
|---|---|---|---|---|---|
| 0 (n = 210) | 1 (n = 42) | 2 (n = 78) | 3 (n = 77) | ||
| CHADS 2 | 0.84 ± 0.72 | 0.98 ± 0.82 | 1.37 ± 0.81 | 1.79 ± 0.88 | <0.001 |
| 1 (0–3) | 1 (0–3) | 1 (0–3) | 2 (0–4) | ||
| CHA 2 DS 2 -VASc | 1.45 ± 1.15 | 1.57 ± 1.21 | 2.10 ± 1.32 | 2.51 ± 1.29 | <0.001 |
| 1 (0–5) | 1.5 (0–4) | 2 (0–5) | 2 (0–5) | ||
| CHA 2 DS 2 -VASc-HS | 2.31 ± 1.01 | 2.64 ± 1.06 | 3.46 ± 1.10 | 4.03 ± 1.14 | <0.001 |
| 2 (0–5) | 2 (1–5) | 3 (2–6) | 4 (1–7) | ||
The cut-off values of Gensini scores for CHADS 2 ≥2 and CHA 2 DS 2 -VASc ≥2 were 8.75 with a sensitivity of 76.2% and specificity of 61% (AUC 0.726, 95% confidence interval 0.675 to 0.778, p <0.001) and 8.75 with a sensitivity of 61.4% and specificity of 61.5% (AUC 0.648, 95% confidence interval 0.594 to 0.701, p <0.001), respectively, in the ROC curve analyses. For prediction of severe CAD, the cut-off value of CHA 2 DS 2 -VASc-HS score was >2 with a sensitivity of 85.2% and specificity of 57.5% (AUC 0.802, 95% confidence interval 0.760 to 0.839, p <0.001). When we analyzed the entire study population based on CHADS 2 , CHA 2 DS 2 -VASc, and CHA 2 DS 2 -VASc-HS scores, patients with CHADS 2 and CHA 2 DS 2 -VASc scores of ≥2 and CHA 2 DS 2 -VASc-HS score of ≥3 had significantly higher Gensini scores ( Table 4 ).
