The incidence of severe AS increased every year, but the incidence of CAD in patients with severe AS did not (Figure 5). Coronary angiography findings in patients with severe AS were as follows: 66.9% (n=384) normal angiogram; 22.5% (n=129) angiogram not significantly abnormal; 5.9% (n=34) CAD in one vessel; 3.3% (n=19) CAD in two vessels; and 1.4% (n=8) CAD in three vessels. The incidence of adverse events during the period of hospitalization to receive the surgery did not differ significantly between the significant CAD and non-significant CAD groups (13.1% vs. 9.6%).
In Logistic regression analysis, the independent predictor of the presence of CAD in severe AS patients was age (P=0.011; Table 3). Between 1995 and 2012, the incidence of severe AS in our hospital increased. Depending on the age of the patients, the incidence of CAD in severe AS patients also increased in this population (Figures 1A and 5). ROC curve analysis of our study population showed a better sensitivity (61%) for predicting critical coronary stenosis with an ideal cutoff value of 69.2 years (Figure 2).
The major risk factors for cardiovascular disease are old age, smoking, high BP, elevated serum cholesterol, and high plasma glucose. In multivariate analysis, we observed a significant interaction between the number of risk factors for cardiovascular disease and the incidence of CAD. An increased number of risk factors for cardiovascular disease have been associated with a higher incidence of significant CAD. If patients in our study had two or more risk factors for cardiovascular disease, the incidence of coronary artery stenosis increased significantly. If patients had four or more risk factors for cardiovascular disease, the rate of coronary artery stenosis was significantly higher (odds ratio=4.195, 95% confidence interval (CI)=2.142–8.214, P=0.005; Figure 6).
By ROC curve analysis, using two risk factors as the cutoff for cardiovascular disease risk was the most useful in predicting the incidence of significant CAD (Figure 7).
The main findings of our study in Korean patients with severe AS undergoing AVR are as follows: (1) the incidence of significant CAD was low, (2) the independent predictor of the presence of CAD was age, (3) that age significantly increased the incidence of significant CAD at 69.2 years, and (4) patients with a minimum of two risk factors for cardiovascular disease were more likely to also have significant CAD.
The presence of concomitant significant CAD in patients undergoing AVR worsens prognosis.5 Therefore, evaluation for the presence of significant CAD before AVR is necessary. Current updated guidelines suggest coronary angiography before valve intervention in patients with symptoms of angina, objective evidence of ischemia, decreased LV systolic function, history of CAD, or coronary risk factors (including men age ≥40 years and postmenopausal women) (Class I, Level of evidence C).23 CT coronary angiography is reasonable to exclude the presence of significant obstructive CAD in selected patients with a low/intermediate pretest probability of CAD (Class IIa, Level of evidence B). However, coronary angiography should still be carried out in all patients before AVR regardless of pretest probability of CAD due to the poor predictive value of angina pectoris and the lack of accuracy of available non-invasive tests.
Severe AS is generally caused by degenerative or rheumatic causes or infective endocarditis. In our study, 100% of patients with significant CAD had a degenerative etiology for their severe AS. The high incidence of AS was associated with old age in our study population. This study demonstrated the frequent association of valve stenosis with coronary and extracoronary (carotid and aorta calcification) atherosclerotic diseases. These results support the recent hypothesis that calcification in AS is a presentation of atherosclerosis, with the process of valve fibrosis and calcification resembling the different phases of arterial plaque formation and progression.27,28 Thus, the pathophysiology of degenerative aortic valve disease is similar to that of atherosclerosis, which may be responsible for the relationship between AS and increased incidence of coronary artery stenosis.29
In a previous study, bicuspid aortic valves progressed more rapidly into regurgitation or stenosis, which resulted in a higher occurrence of AVR, especially at a younger age.30 In the present study, 55% of patients with severe AS were found to have a bicuspid aortic valve, which is comparable with previous reports.30,31 However, in this study, the incidence of CAD in patients with tricuspid valves was higher than in patients with bicuspid valves. Therefore, the incidence of CAD seemed to be more related to the degeneration of the aortic valve, and the incidence of CAD increased depending on age.
Current updated guidelines suggest coronary angiography is indicated before valve intervention in patients with symptoms of angina, objective evidence of ischemia, decreased LV systolic function, history of CAD, or coronary risk factors (including men age ≥40 years and postmenopausal women).23 Guidelines do not currently suggest the number of coronary risk factors for predicting the presence of CAD. In general, the incidence of CAD increases progressively with the number of coronary risk factors. In our study population, conventional risk factors for CAD were more prevalent in the significant CAD group, including age, smoking, HTN, DM, and dyslipidemia. Previous studies found that the incidence of CAD increased progressively with an increase in the number of coronary risk factors, whereas the incidence was low in patients without angina or coronary risk factors undergoing routine coronary angiography before AVR.33 In our study population, if a patient had two or more risk factors for cardiovascular disease, the incidence of coronary artery stenosis increased significantly. If a patient had four or more risk factors for cardiovascular disease, the rate of incidence of coronary artery stenosis was even higher. By ROC curve analysis, using two risk factors for cardiovascular disease as a cutoff value to predict the incidence of significant CAD was the most useful.
According to a previous study, CAD has been reported in ≥50% of patients with AS ≥70 years of age and in ≥65% of patients ≥80 years of age.32 In our study population, ROC curve analysis showed a better sensitivity (61%) for predicting critical coronary stenosis with an ideal cutoff value of 69.2 years. Previous reports imply the rationalization of the diagnostic methods because of the limited value of age criteria in the ideal time of conventional coronary angiography.
The extent of CAD involvement in patients with severe AS predicts morbidity and mortality associated with AVR and is also important for the assessment of long-term prognosis.8,34 Thus, patients with severe AS scheduled for AVR should routinely undergo coronary angiography. The incidence of significant CAD in Korean patients with severe AS was low in this study and in some previous studies. Therefore, in patients with a low/intermediate pretest probability of CAD such as in Asian countries, CT coronary angiography is reasonable to exclude the presence of significant obstructive CAD in patients who are young or have few risk factors.
Patients included in this study were consecutively enrolled at a single center in Korea. We cannot assume these results represent other hospital patient populations in Korea or other Asian countries. We excluded patients with multiple valve disease and significant aortic regurgitation. However, in a previous study, it has been reported that patients with severe AS were associated with aortic regurgitation. So, we might have underestimated the incidence of patients with severe AS. However, we believe that the incidence of significant CAD in the general population and in patients with severe AS is quite similar in other Asian countries. Large-scale, multicenter studies will be needed to confirm these results.
The incidence of significant CAD in patients with severe AS was low in a Korean population; in our study, the overall incidence of angiographically significant CAD was 10.6%. Therefore, coronary angiography before AVR will be considered in patients with multiple risk factors for cardiovascular disease or in patients more than 69 years of age without risk factors for cardiovascular disease.
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