Int J Cardiovasc Imaging DOI 10.1007/s10554-015-0587-0
ORIGINAL PAPER
Prevalence of coronary atherosclerosis in an Asian population: findings from coronary computed tomographic angiography Gyung-Min Park • Sung-Cheol Yun • Young-Rak Cho • Eun Ha Gil • Sung Ho Her • Seon Ha Kim • Min-Woo Jo • Moo Song Lee • Seung-Whan Lee • Young-Hak Kim • Dong Hyun Yang • Joon-Won Kang • Tae-Hwan Lim • Beom-Jun Kim • Jung-Min Koh • Hong-Kyu Kim • Jaewon Choe • Seong-Wook Park • Seung-Jung Park Received: 10 September 2014 / Accepted: 3 January 2015 Ó Springer Science+Business Media Dordrecht 2015
Abstract We sought to estimate the prevalence of coronary atherosclerosis by coronary computed tomographic angiography (CCTA) and to identify risk factors attributable to the development of coronary atherosclerosis in an asymptomatic Asian population. We analyzed 6,311 consecutive asymptomatic individuals aged 40 and older with no prior history of coronary artery disease (CAD) who voluntarily underwent CCTA evaluation as part of a general health examination. The mean age of study participants was 54.7 ± 7.4 years, and 4,594 (72.8 %) were male. After age and gender adjustment using the population census of the National Statistical Office, the prevalence of plaque was 40.5 % [95 % confidence interval (CI) 38.1–42.9], and significant CAD (diameter stenosis
Gyung-Min Park and Sung-Cheol Yun have contributed equally to this article. G.-M. Park E. H. Gil S. H. Her Department of Cardiology, Daejeon St. Mary’s Hospital, College of Medicine, The Catholic University of Korea, Daejeon, Korea S.-C. Yun M. S. Lee Department of Biostatistics, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea Y.-R. Cho Department of Cardiology, Dong-A University Hospital, Busan, Korea S. H. Kim Department of Nursing, College of Medicine, Dankook University, Cheonan, Korea M.-W. Jo Department of Preventive Medicine, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea
C50 %) was observed in 9.0 % (95 % CI 7.7–10.2). Individuals with significant CAD were significantly older than those without (59.2 ± 8.8 vs. 54.0 ± 7.1 years, p \ 0.001). Compared with individuals with no cardiovascular risk factors, there was a higher prevalence of significant CAD in individuals with diabetes mellitus [standardized rate ratio (SRR) 2.66; 95 % CI 1.93–3.68; p \ 0.001], hypertension (SRR 2.24; 95 % CI 1.69–2.97; p \ 0.001), or hyperlipidemia (SRR 1.65; 95 % CI 1.25–2.17; p \ 0.001). There was also a greater prevalence of significant CAD in individuals with an intermediate or high Framingham risk score (SRR 5.91; 95 % CI 2.34–14.95; p \ 0.001) or a high atherosclerotic cardiovascular disease risk score (SRR 8.04; 95 % CI 3.04–21.23; p \ 0.001). The prevalence of coronary atherosclerosis in this Asian population was not negligible and was associated with known cardiovascular risk factors and high-risk individuals. S.-W. Lee Y.-H. Kim (&) S.-W. Park S.-J. Park Department of Cardiology, Asan Medical Center, University of Ulsan College of Medicine, 388-1 Poongnap-dong, Songpa-gu, Seoul 138-736, Korea e-mail: [email protected] D. H. Yang J.-W. Kang T.-H. Lim Department of Radiology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea B.-J. Kim J.-M. Koh Department of Endocrinology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea H.-K. Kim J. Choe Department of the Health Screening and Promotion Center, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea
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Keywords Epidemiology Coronary computed tomographic angiography Atherosclerosis Coronary artery disease Introduction Although there have been advances in many medical fields over the past decades, coronary artery disease (CAD) remains the leading cause of death globally [1]. The prevalence of CAD in Asian countries has rapidly increased as a consequence of social and economic changes [2, 3], resulting in CAD becoming a major public health concern in these countries [4]. However, there are limited data on the prevalence of coronary atherosclerosis in Asian populations. Recently, with the advent of multidetector row computed tomography, coronary computed tomography angiography (CCTA) has proven effective in providing comprehensive information on coronary atherosclerosis, including the location, severity, and characteristics of atherosclerotic plaques [5]. Therefore, through a large cohort consisting of asymptomatic Korean individuals undergoing CCTA, we sought to estimate the prevalence of coronary atherosclerosis and to identify risk factors attributable to the development of coronary atherosclerosis in an Asian population. Methods Study population From January 2007 to December 2011, we enrolled 8,945 consecutive South Korean individuals aged 40 years and Fig. 1 Overview of the enrolled study population. CCTA coronary computed tomographic angiography, MI myocardial infarction, PCI percutaneous coronary intervention, ASD atrial septal defect, PDA patent ductus arteriosus, PFO patent foramen ovale, ESRD end stage renal disease
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older who had undergone self-referral CCTA evaluation as part of a general health examination in the Health Screening and Promotion Center at the Asan Medical Center. All subjects were made aware of the possible risks associated with CCTA and provided informed consent. A total of 6,922 (77.4 %) consented to participate in this study. Subjects with (1) a previous history of angina or myocardial infarction (MI); (2) abnormal resting electrocardiographic results, i.e., pathological Q waves, ischemic ST segments or T wave changes, or left bundle-branch blocks; (3) structural heart disease; (4) a prior history of open heart surgery; (5) a past history of percutaneous coronary intervention (PCI); (6) a previous cardiac procedure; or (7) renal insufficiency (creatinine [ 1.5 mg/dL) were excluded. Thus, 6,311 subjects were finally enrolled and analyzed (Fig. 1). This study was approved by the local Institutional Review Board of the Asan Medical Center, Seoul, Korea. All patients provided written informed consent. Basic demographic data from the subjects was acquired from a database maintained by the Health Screening and Promotion Center at the Asan Medical Center. Any medical history of angina, MI, stroke, structural heart disease, open heart surgery, PCI, previous cardiac procedure, diabetes mellitus, hypertension, or hyperlipidemia; family history of CAD; and smoking status were collected from a systemized questionnaire prior to general health examination. Diabetes mellitus was defined as a fasting plasma glucose concentration C126 mg/dL or a self-reported history of diabetes and/or treatment with dietary modification, or use of anti-diabetic medication. Hypertension was defined as blood pressure C140/90 mmHg or a selfreported history of hypertension and/or use of anti-hypertensive medication. Hyperlipidemia was defined as total
Int J Cardiovasc Imaging
cholesterol C240 mg/dL or use of an anti-hyperlipidemic treatment. In the general health examination, height, body weight, body mass index, waist circumference, and blood pressure were measured, and electrocardiogram (ECG) was performed. Moreover, fasting plasma glucose, glycated hemoglobin, uric acid, blood urea nitrogen, creatinine, total cholesterol, high-density lipoprotein cholesterol, low-density lipoprotein cholesterol, triglyceride, and high-sensitivity C-reactive protein concentrations were measured on the day of the examination after a fasting period of C12 h. For study participants aged 40–74 years, the Framingham risk score and atherosclerotic cardiovascular disease (ASCVD) risk score were calculated [6, 7]. With regard to the Framingham risk score, study participants were categorized as having either a low (\10 %), intermediate (10–20 %), or high ([20 %) 10 year risk for CAD. Participants with intermediate or high Framingham risk scores were defined as having a higher risk and were compared to those with a low risk [8]. In addition, participants with ASCVD risk scores of at least 7.5 % were defined as high risk and compared with those with a low risk (\7.5 %) [7]. Image acquisition and analysis CCTA was conducted using either single-source 64-slice CT (LightSpeed VCT, GE, Milwaukee, WI, USA) or dualsource CT (Somatom Definition, Siemens, Erlangen, Germany). Patients with no contraindication to b-adrenergic blocking agents and with initial heart rates [65 bpm received an oral dose of 2.5 mg bisoprolol (Concor, Merck, Darmstadt, Germany) 1 h before the CT examination. CT scanning was performed in the prospective ECG-triggering mode or the retrospective ECG-gating mode with ECGbased tube current modulation. Two puffs (2.5 mg) of isosorbidedinitrate (Isoket spray, Schwarz Pharma, Monheim, Germany) were sprayed into the patient’s oral cavity before contrast injection. During CCTA acquisition, 60–80 mL of iodinated contrast (Iomeron 400, Bracco, Milan, Italy) was injected at 4 mL/s, followed by a 40 mL saline flush. A region of interest was placed in the ascending aorta, and image acquisition was automatically initiated once a selected threshold (100 HU) had been reached using bolus tracking. A standard scanning protocol was used, and the tube voltage and tube current–time product were adjusted according to the patient’s body size as follows: 100 or 120 kVp tube voltage; 240–400 mAs per rotation (dual-source CT); and 400–800 mA (64-slice CT) tube current. The size-specific dose estimate was calculated by using the patient’s body diameter [9, 10]. The mean effective dose of our CT protocol was 7.6 mSv ± 5.1. All CCTA scans were analyzed using a dedicated workstation (Advantage Workstation, GE; or Volume Wizard, Siemens) by experienced cardiovascular
radiologists (D.H.Y., J.-W.K., and T.-H.L.). According to the guidelines of the Society of Cardiovascular Computed Tomography, a 16-segment coronary artery tree model was used [11]. A coronary artery calcium score (CACS) was measured as described [12], with categorized by scores of 0, 1–10, 11–100, 101–400, and [400 [13]. Plaques were defined as structures [1 mm2 within and/or adjacent to the vessel lumen, which could be clearly distinguished from the lumen and surrounding pericardial tissue. Plaques containing calcified tissue involving [50 % of the plaque area (density [130 HU) were classified as calcified, plaques with \50 % calcium were classified as mixed, and plaques without calcium were classified as non-calcified [14]. The contrast-enhanced portion of the coronary lumen was semi-automatically traced at the site of maximal stenosis and compared with the mean value of the proximal and distal reference sites [15]. Stenosis C50 % was defined as significant. Statistical analysis Categorical data were compared using Chi square statistics or Fisher’s exact test and presented as frequencies. Continuous variables were analyzed using the unpaired Student’s t test and presented as the mean ± SD. The prevalence rate was defined as the number of individuals with coronary atherosclerosis per 100 study participants. This rate was directly standardized to 10 year age and gender groups, using age and gender distributions from the 2010 South Korean population census [16]. The confidence interval (CI) for this standardized rate was estimated assuming a Poisson distribution of cases. To evaluate the effect of cardiovascular risk factors on the prevalence rate, standardized rates ratios (SRR) and associated 95 % CIs were also computed. All reported p values are two sided, and p values of \0.05 were considered statistically significant. Data manipulation and statistical analyses were conducted using SAS Version 9.1 (SAS Institute Inc., Cary, NC).
Results Population characteristics Table 1 shows the baseline characteristics of the study population. The mean age of the study participants was 54.5 ± 7.4 years, and 4,594 (72.8 %) were male. Diabetes mellitus, hypertension, hyperlipidemia, and current smoking were observed in 1,033 (16.4 %), 2,355 (37.3 %), 1,970 (31.2 %), and 1,443 (22.9 %) patients, respectively. The average Framingham and ASCVD risk scores were 8.1 ± 5.4 and 6.9 ± 6.5 %, respectively. Men in the
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Int J Cardiovasc Imaging Table 1 Characteristics of the study population Characteristics
Overall (n = 6,311)
Male (n = 4,594)
Female (n = 1,717)
Age (years)
54.5 ± 7.4
54.4 ± 7.3
54.6 ± 7.8
Body mass index (kg/m2)
24.6 ± 2.9
25.1 ± 2.7a
23.4 ± 3.0
Waist circumference (cm)
85.9 ± 8.2
88.0 ± 7.4a
80.4 ± 7.9 a
Systolic blood pressure (mmHg)
120.3 ± 13.2
121.7 ± 12.6
Diastolic blood pressure (mmHg)
76.9 ± 10.3
78.8 ± 9.8a
71.7 ± 10.0
Diabetes mellitus no. (%)
1,033 (16.4)
866 (18.9)a
167 (9.7)
Hypertension no. (%)
2,355 (37.3)
1,875 (40.8)a
480 (28.0)
Hyperlipidemia no. (%)
1,970 (31.2)
1,456 (31.7)
514 (29.9)
Current smoker no. (%)
1,443 (22.9)
1,398 (30.4)a
45 (2.6)
Previous stroke no. (%)
58 (0.9)
44 (1.0)
14 (0.8)
Family history of coronary artery diseaseb no. (%) Total cholesterol (mg/dL)
949 (15.0) 195.3 ± 34.3
662 (14.4)a 193.8 ± 33.9a
287 (16.7) 199.5 ± 35.3 122.2 ± 30.9
Low-density lipoprotein cholesterol (mg/dL)
121.3 ± 30.0
120.9 ± 29.7
High-density lipoprotein cholesterol (mg/dL)
53.4 ± 13.6
50.9 ± 12.3a
116.5 ± 13.9
60.1 ± 14.6 a
105.8 ± 60.5 100.3 ± 18.7
Triglyceride (mg/dL)
133.2 ± 83.1
143.4 ± 87.9
Fasting blood glucose (mg/dL)
105.1 ± 20.7
106.8 ± 21.2a
Glycated hemoglobin (%)
5.8 ± 0.8
5.8 ± 0.8
Creatinine (mg/dL)
0.9 ± 0.2
1.0 ± 0.1a
0.7 ± 0.1
Uric acid (mg/dL)
5.6 ± 1.4
6.0 ± 1.3a
4.4 ± 1.0
High-sensitivity C-reactive protein C2 mg/dL no. (%)
57 (0.9)
45 (1.0)
12 (0.7)
Framingham risk score
8.1 ± 5.4
9.6 ± 5.2a
4.0 ± 3.3
Low-risk group
4,375 (70.2)
2,781 (61.2)a
1,594 (94.2)
Intermediate-risk group
1,655 (26.5)
1,560 (34.3)a
95 (5.6)
High-risk group
205 (3.3)
201 (4.4)a
4 (0.2)
a
5.7 ± 0.7
Framingham risk stratification
a
Intermediate/high-risk group
1,860 (29.8)
1,761 (38.8)
Atherosclerotic cardiovascular disease risk score Atherosclerotic cardiovascular disease risk stratification
6.9 ± 6.5
8.4 ± 6.6a
3.0 ± 4.1
Low-risk group
4,122 (66.1)
2,592 (57.1)a
1,530 (90.4)
High-risk group
2,113 (33.9)
1,950 (42.9)a
163 (9.6)
99 (5.8)
Data are expressed as n (%) and mean ± SD a
p \ 0.05
b
Coronary artery disease in a first-degree relative of any age
cohort were, on average, older and had more comorbid conditions than women. Coronary atherosclerosis on CCTA in study population Table 2 shows coronary atherosclerotic findings by CCTA according to age. In the overall and male populations, the prevalence of coronary atherosclerosis increased with age. A similar trend but not multi-vessel disease was also observed in the female population. The mean CACS of the study participants was 42.1 ± 154.8. Atherosclerotic plaques were detected in 2,732 (43.3 %) individuals. Calcified, non-calcified, and mixed plaques
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were found in 1,844 (29.2 %), 1,200 (19.0 %), and 586 (9.3 %), respectively. Of the study participants, 521 (8.3 %) had significant CAD (diameter stenosis C50 %) by CCTA, and individuals with significant CAD were considerably older than those without (59.2 ± 8.8 vs. 54.0 ± 7.1 years, p \ 0.001). Significant stenosis in the left main (LM), left anterior descending (LAD), left circumflex, and right coronary arteries were observed in 26 (0.4 %), 350 (5.5 %), 169 (2.7 %), and 155 (2.5 %), respectively. One and multi-vessel disease were found in 382 (6.1 %) and 139 (2.2 %). Significant lesions in the LM or proximal LAD were also observed in 185 (2.9 %).
Int J Cardiovasc Imaging Table 2 Coronary computed tomographic angiographic findings by age Age (years)
Number
CACS
Any plaque
Calcified plaque
Non-calcified plaque
Mixed plaque
Significant CAD
Multi-vessel disease
Significant CAD in the LM or proximal LAD
Overall 40–49
1,613
12.0 ± 56.0
50–59 60–69
3,338 1,095
34.9 ± 122.4 91.4 ± 213.8
265
186.1 ± 372.6
212 (80.0)
173 (65.3)
89 (33.6)
6,311
42.1 ± 154.8
2,732 (43.3)
1,844 (29.2)
1,200 (19.0)
C70 Total
420 (26.0)
248 (15.4)
191 (11.8)
77 (4.8)
60 (3.7)
11 (0.7)
21 (1.3)
1,405 (42.1) 695 (63.5)
908 (27.2) 515 (47.0)
621 (18.6) 299 (27.3)
283 (8.5) 177 (16.2)
232 (7.0) 159 (14.5)
60 (1.8) 44 (4.0)
80 (2.4) 57 (5.2)
49 (18.5) 586 (9.3)
70 (26.4) 521 (8.3)
24 (9.1) 139 (2.2)
27 (10.2) 185 (2.9)
Male 40–49
1,148
16.3 ± 65.3
50–59
2,487
43.8 ± 138.2
384 (33.4)
230 (20.0)
172 (15.0)
74 (6.4)
54 (4.7)
9 (0.8)
18 (1.6)
1,240 (49.9)
815 (32.8)
546 (22.0)
259 (10.4)
211 (8.5)
58 (2.3)
70 (2.8)
60–69
789
112.7 ± 240.6
556 (70.5)
413 (52.3)
241 (30.6)
158 (20.0)
134 (17.0)
42 (5.3)
48 (6.1)
C70
170
252.5 ± 438.5
146 (85.9)
124 (72.9)
60 (35.3)
36 (21.2)
50 (29.4)
21 (12.4)
21 (12.4)
4,594
56.4 ± 175.5
2,326 (50.6)
1,582 (34.4)
1,019 (22.2)
527 (11.5)
Total
449 (9.8)
130 (2.8)
157 (3.4)
6 (1.3)
2 (0.4)
3 (0.6) 10 (1.2)
Female 40–49
465
1.6 ± 13.7
36 (7.7)
18 (3.9)
19 (4.1)
3 (0.6)
50–59
851
8.7 ± 45.1
165 (19.4)
93 (10.9)
75 (8.8)
24 (2.8)
21 (2.5)
2 (0.2)
60–69
306
36.6 ± 101.6
139 (45.4)
102 (33.3)
58 (19.0)
19 (6.2)
25 (8.2)
2 (0.7)
9 (2.9)
95
68.8 ± 154.0
66 (69.5)
49 (51.6)
29 (30.5)
13 (13.7)
20 (21.1)
3 (3.2)
6 (6.3)
15.1 ± 67.1
406 (23.6)
262 (15.3)
181 (10.5)
59 (3.4)
72 (4.2)
9 (0.5)
28 (1.6)
C70 Total
1,717
Data are expressed as n (%) and mean ± SD CACS coronary artery calcium score, CAD coronary artery disease, LAD left anterior descending artery, LM left main
Prevalence of coronary atherosclerosis After adjusting for age and gender using the population census of the National Statistical Office, the prevalence of plaque was 40.5 % (95 % CI 38.1–42.9), significant CAD was observed in 9.0 % (95 % CI 7.7–10.2), multi-vessel disease was present in 2.2 % (95 % CI 1.7–2.8), and significant CAD in the LM or proximal LAD was found in 3.2 % (95 % CI 2.5–3.9). Age-adjusted atherosclerosis prevalence by gender was significant in men (Table 3). Age- and gender-adjusted atherosclerosis prevalence was associated with major cardiovascular risk factors. Compared with individuals with no cardiovascular risk factors, there was a considerably higher prevalence of significant CAD in those with diabetes mellitus (SRR 2.66; 95 % CI 1.93–3.68; p \ 0.001), hypertension (SRR 2.24; 95 % CI 1.69–2.97; p \ 0.001), or hyperlipidemia (SRR 1.65; 95 % CI 1.25–2.17; p \ 0.001). However, current smoking was not associated with a higher prevalence of significant CAD (SRR 1.74; 95 % CI 0.78–3.88; p = 0.176). According to Framingham risk score, 4,375 (70.2 %) individuals were classified as low risk and 1,860 (29.8 %) as higher risk (1,655 [26.5 %] in intermediate and 205 [3.3 %]) in high risk. Compared to low-risk individuals, those with a higher risk (intermediate or high Framingham
scores) had a significantly higher prevalence of plaque (SRR 1.87; 95 % CI 1.18–2.97; p = 0.007), significant CAD (SRR 5.91; 95 % CI 2.34–14.95; p \ 0.001), multivessel disease (SRR 8.74; 95 % CI 1.56–49.10); p = 0.014), and significant CAD in the LM or proximal LAD (SRR 6.26; 95 % CI 1.35–29.06; p = 0.019). By ASCVD risk score, 4,122 individuals (66.1 %) were categorized as low risk and 2,113 (33.9 %) as high risk. Individuals with high-risk ASCVD scores also had a significantly higher prevalence of plaque (SRR 2.13; 95 % CI 1.30–3.48; p = 0.003), significant CAD (SRR 8.04; 95 % CI 3.04–21.23; p \ 0.001), multi-vessel disease (SRR 13.63; 95 % CI 2.42–76.71; p = 0.003), and significant CAD in the LM or proximal LAD (SRR 7.94; 95 % CI 1.65–38.28; p = 0.010) than those with low-risk scores.
Discussion The age- and gender-adjusted prevalence of coronary atherosclerosis assessed by CCTA in this Asian population was 40.5 % for plaque, 9.0 % for significant CAD, 2.2 % for multi-vessel disease, and 3.2 % for significant CAD in the LM or proximal LAD. Older age, male gender, diabetes mellitus, hypertension, and hyperlipidemia were
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Int J Cardiovasc Imaging Table 3 Prevalence of coronary atherosclerosis by age, gender, major cardiovascular risk factors, and risk group
Plaque
Overall population (age- and gender-adjusted)
Men (age-adjusted)
Women (age-adjusted)
p ratea
p ratea
95 % CI
p ratea
SE
95 % CI
SE
p value
SE
95 % CI 26.4–34.1 \0.001
40.5
1.2
38.1–42.9
52.0
1.3
49.4–54.7
30.2
2.0
Significant CAD
9.0
0.6
7.7–10.2
11.3
0.7
10.0–12.7
6.9
1.0
4.8–8.9
\0.001
Multi-vessel disease
2.2
0.3
1.7–2.8
3.6
0.4
2.8–4.4
1.0
0.4
0.2–1.8
\0.001
Significant CAD in the LM or proximal LAD
3.2
0.4
2.5–3.9
4.2
0.4
3.3–5.0
2.4
0.6
1.2–3.5
0.011
Diabetes mellitus (age- and gender-adjusted)
Yes
No
p rate
a
SE
SRR
95 % CI
p rate
a
SE
95 % CI
95 % CI
p value
Plaque
52.7
3.7
45.4–59.9
38.5
1.3
35.9–41.0
1.37
1.17–1.60
\0.001
Significant CAD
19.0
2.7
13.6–24.3
7.1
0.6
6.0–8.3
2.66
1.93–3.68
\0.001
Multi-vessel disease
5.4
1.6
2.3–8.6
1.8
0.3
1.3–2.4
2.97
1.55–5.67
0.001
Significant CAD in the LM or proximal LAD
7.6
1.9
4.0–11.2
2.6
0.3
1.9–3.2
2.94
1.71–5.04
\0.001
SRR
95 % CI
p value
Hypertension (age- and gender-adjusted)
Yes
No
p ratea
SE
95 % CI
p ratea
SE
95 % CI
Plaque
50.7
2.1
46.5–54.8
35.2
1.8
31.8–38.7
1.44
1.27–1.63
\0.001
Significant CAD
13.0
1.2
10.7–15.4
5.8
0.6
4.5–7.1
2.24
1.69–2.97
\0.001
Multi-vessel disease
2.9
0.4
2.0–3.8
1.4
0.3
0.9–1.9
2.06
1.27–3.35
0.004
Significant CAD in the LM or proximal LAD
4.5
0.7
3.2–5.7
2.3
0.4
1.4–3.1
1.98
1.24–3.18
0.004
SRR
95 % CI
p value
Hyperlipidemia (age-and gender-adjusted)
Yes
Plaque Significant CAD Multi-vessel disease Significant CAD in the LM or proximal LAD
No
p rate
a
SE
95 % CI
p rate
48.1
2.2
43.8–52.5
12.1 2.9
1.2 0.6
5.0
0.8
Current smoking (age- and gender-adjusted)
Yes
Plaque Significant CAD
a
SE
95 % CI
37.1
1.5
34.1–40.1
1.30
1.15–1.46
\0.001
9.7–14.6 1.8–4.0
7.3 2.0
0.7 0.4
6.0–8.7 1.2–2.7
1.65 1.48
1.25–2.17 0.88–2.50
\0.001 0.142
3.3–6.6
2.3
0.3
1.7–3.0
2.13
1.39–3.28
0.001
No
p rate
a
a
SRR
95 % CI
p value
SE
95 % CI
p rate
SE
95 % CI
45.0
8.5
28.4–61.6
39.8
1.3
37.4–42.3
1.13
0.78–1.64
0.522
15.2
6.1
3.2–27.2
8.7
0.6
7.5–10.0
1.74
0.78–3.88
0.176
Multi-vessel disease
1.9
0.9
0.2–3.6
2.2
0.3
1.6–2.8
0.86
0.33–2.23
0.762
Significant CAD in the LM or proximal LAD
7.4
5.5
3.2
0.4
2.5–3.9
2.34
0.54–10.09
0.255
SRR
95 % CI
p value
Framingham risk classification (age- and gender-adjusted)
0–18.1
Intermediate/high risk group a
p rate
Low risk group
SE
95 % CI
p rate
a
SE
95 % CI
Plaque
62.4
14.4
34.1–90.6
33.3
1.3
30.8–35.8
1.87
1.18–2.97
Significant CAD
30.9
14.3
2.9–58.8
5.2
0.5
4.2–6.3
5.91
2.34–14.95
0.007 \0.001
Multi-vessel disease
12.2
10.1
0–31.9
1.4
0.4
0.6–2.2
8.74
1.56–49.10
0.014
Significant CAD in the LM or proximal LAD
13.4
10.1
0–33.1
2.1
0.4
1.3–3.0
6.26
1.35–29.06
0.019
ASCVD risk classification (age- and genderadjusted)
High risk group p rate
a
Low risk group a
SE
95 % CI
p rate
SE
95 % CI
SRR
95 % CI
Plaque
61.6
14.6
33.1–90.1
28.9
2.4
24.2–33.7
2.13
1.30–3.48
Significant CAD
29.5
14.2
1.6–57.4
3.7
0.4
2.9–4.5
8.04
3.04–21.23
123
p value
0.003 \0.001
Int J Cardiovasc Imaging Table 3 continued ASCVD risk classification (age- and gender-adjusted)
High risk group a
p rate
SE
Low risk group 95 % CI
a
p rate
SE
SRR
95 % CI
p value
95 % CI
Multi-vessel disease
11.9
10.1
0–31.6
0.9
0.2
0.4–1.3
13.63
2.42–76.71
0.003
Significant CAD in the LM or proximal LAD
12.9
10.1
0–32.6
1.6
0.3
1.0–2.2
7.94
1.65–38.28
0.010
a
Per 100 persons ASCVD atherosclerotic cardiovascular disease, CAD coronary artery disease, CI confidence interval, LAD left anterior descending artery, LM left main, SE standard error, SRR Standardized rate ratio
significantly associated with a higher prevalence of coronary atherosclerosis. Risk stratification using Framingham and ASCVD risk scores was also feasible to predict the prevalence of coronary atherosclerosis. CCTA has been widely used in the comprehensive evaluation of CAD, including lesion location, severity, and plaque characteristics [5]. However, little is known about coronary atherosclerosis assessed by CCTA in asymptomatic Asian individuals. Previous observational studies using CCTA in this population reported atherosclerotic plaque in 21.5–39.1 % of individuals and significant CAD in 5.2 % [5, 17]. Similar to previous studies, in our study, atherosclerotic plaques were identified in 2,732 (43.3 %) of individuals, and 521 (8.3 %) had significant stenosis on CCTA. After age and gender adjustment using the population census of the National Statistical Office, the overall prevalence of plaque and significant CAD were 40.5 % (95 % CI 38.1–42.9) and 9.0 % (95 % CI 7.7–10.2), respectively. Although it may be difficult to compare results across studies because of differences in methodology, the prevalence of significant CAD in our study was comparable to the rate calculated from pathological samples obtained at autopsy in Western countries (Table 4) [18]. These findings imply that coronary atherosclerosis is not uncommon in asymptomatic Asian populations. The prevalence of coronary atherosclerosis was significantly associated with major cardiovascular risk factors such as older age, male gender, diabetes mellitus, hypertension, and hyperlipidemia, which are traditionally derived from studies in Western countries [6]. These findings suggest that risk factors for CAD are applicable to all global populations regardless of ethnic differences [19] and thus efforts should be made to reduce known risk factors for the primary prevention of CAD. Interestingly, in our study, current smoking did not show an association with coronary atherosclerosis as in previous studies [20, 21], which may be due to the fact that our study did not specify the frequency or duration of smoking. Additional studies taking these factors into account are needed to reveal any associations between smoking and coronary atherosclerosis.
Coronary events occur after long periods of subclinical disease [22]. Mortality rates for CAD have fallen in the most developed countries [23], and these reductions are partially attributable to efforts aimed at the early identification of high-risk individuals and the reduction of risk factors [23, 24]. In this study, we showed an association between coronary atherosclerosis and risk groups stratified by Framingham and ASCVD risk scores [7, 8, 12]. Therefore, care of asymptomatic individuals should be focused on risk assessment using global risk scores and personalized modification of cardiovascular risk factors [25]. In the present study, we enrolled asymptomatic individuals undergoing self-referral CCTA evaluation. CCTA is not generally advocated as a screening tool in an asymptomatic population. However, there is still uncertain regarding the use of CCTA for subjects at high risk [26]. A recent cohort study showed that the CAD prevalence by CCTA in asymptomatic high-risk patients is high and CCTA could be an accurate screening tool for CAD due to its ability to detect non-calcifying plaques and to quantify plaque burden as well as coronary stenosis severity graduation [27]. In addition, a large international cohort study observed that CCTA provides incremental prognostic utility for prediction of mortality and non-fatal myocardial infarction for asymptomatic individuals with moderately high CACS (101–400) [28]. On the contrary, in the recent randomized trial which enrolled high-risk patients with diabetes based on age and diabetes duration, CAD screening with CCTA did not provide the incremental benefit over optimal medical therapy without any screening of CAD [29]. Therefore, further studies are needed to evaluate the role of CCTA in asymptomatic individuals with higher cardiac risk whose outcome might be improved through aggressive interventions. Limitations Our study has several limitations. First, it was conducted at a single center. All individuals voluntarily went to the hospital for a general health examination and were
123
123
210/5,438 (3.9)
0.220
asymptomatic. Therefore, there was a potential for selection bias. Second, calcified plaques and higher CACS may lead to overestimation of significant CAD [30]. Third, our study did not evaluate coronary atherosclerosis by functional tests such as exercise ECG, myocardial perfusion imaging, positive emission tomography scan, or stress echocardiography. A discrepancy has been observed between CCTA and functional tests [31]. Therefore, CCTA may overestimate the prevalence of CAD requiring treatment. Fourth, the napkin-ring sign, positive vessel remodeling, and low-attenuation plaque have been known as high-risk plaque features [32, 33]. However, the analysis of these characteristics in the present study was not performed. Therefore, in asymptomatic individuals, future studies to evaluate the clinical impact of these high-risk coronary atherosclerotic plaques are needed. Finally, advanced techniques have been developed to reduce the shortcomings of CCTA [34], such as the radiation hazard, use of iodinated contrast agents, and higher cost [35]. Although our study only enrolled volunteers, the performance of CCTA in asymptomatic individuals has not yet been justified.
0.742
Conclusions In this large observational study with asymptomatic Asian individuals, the prevalence of coronary atherosclerosis was not low and was significantly associated with major cardiovascular risk factors such as older age, male gender, diabetes mellitus, hypertension, hyperlipidemia, and higher risk by global risk assessment scores. These findings indicate that efforts should be made to reduce known cardiovascular risk factors to decrease the coronary atherosclerotic burden. These findings should be confirmed in large clinical trials.
0.541
399/4,424 (9.0)
1,291/14,059 (9.2)
52/1,622 (3.2) 451/6,046 (7.5) Total
1,501/19,497 (7.7)
Acknowledgments This study was supported by Grants from the Korea Healthcare technology R&D Project, Ministry of Health and Welfare, Republic of Korea (A102065, HI12C0630, and HI10C2020). Conflict of interest
Data are expressed as n (%)
0.698 25/306 (8.2) \0.001 159/1,095 (14.5) 60–69
699/6,367 (11.0)
0.001
134/789 (17.0)
569/4,641 (12.3)
130/1,726 (7.5)
0.291
0.613 18/1,778 (1.0)
62/1,934 (3.2) 0.079
6/465 (1.3)
21/851 (2.5)
0.410
488/5,011 (9.7) 0.083
234/4,407 (5.3) 54/1,148 (4.7)
211/2,487 (8.5)
0.518
550/6,945 (7.9) 50–59
252/6,185 (4.1) 60/1,613 (3.7)
232/3,338 (7.0)
40–49
This study p value Diamond and Forrester This study This study
Diamond and Forrester
p value
Men Overall Age
Table 4 Comparison between the prevalence of significant coronary artery disease in this and previous studies
Women
Diamond and Forrester
p value
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None.
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ORIGINAL PAPER
Prevalence of coronary atherosclerosis in an Asian population: findings from coronary computed tomographic angiography Gyung-Min Park • Sung-Cheol Yun • Young-Rak Cho • Eun Ha Gil • Sung Ho Her • Seon Ha Kim • Min-Woo Jo • Moo Song Lee • Seung-Whan Lee • Young-Hak Kim • Dong Hyun Yang • Joon-Won Kang • Tae-Hwan Lim • Beom-Jun Kim • Jung-Min Koh • Hong-Kyu Kim • Jaewon Choe • Seong-Wook Park • Seung-Jung Park Received: 10 September 2014 / Accepted: 3 January 2015 Ó Springer Science+Business Media Dordrecht 2015
Abstract We sought to estimate the prevalence of coronary atherosclerosis by coronary computed tomographic angiography (CCTA) and to identify risk factors attributable to the development of coronary atherosclerosis in an asymptomatic Asian population. We analyzed 6,311 consecutive asymptomatic individuals aged 40 and older with no prior history of coronary artery disease (CAD) who voluntarily underwent CCTA evaluation as part of a general health examination. The mean age of study participants was 54.7 ± 7.4 years, and 4,594 (72.8 %) were male. After age and gender adjustment using the population census of the National Statistical Office, the prevalence of plaque was 40.5 % [95 % confidence interval (CI) 38.1–42.9], and significant CAD (diameter stenosis
Gyung-Min Park and Sung-Cheol Yun have contributed equally to this article. G.-M. Park E. H. Gil S. H. Her Department of Cardiology, Daejeon St. Mary’s Hospital, College of Medicine, The Catholic University of Korea, Daejeon, Korea S.-C. Yun M. S. Lee Department of Biostatistics, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea Y.-R. Cho Department of Cardiology, Dong-A University Hospital, Busan, Korea S. H. Kim Department of Nursing, College of Medicine, Dankook University, Cheonan, Korea M.-W. Jo Department of Preventive Medicine, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea
C50 %) was observed in 9.0 % (95 % CI 7.7–10.2). Individuals with significant CAD were significantly older than those without (59.2 ± 8.8 vs. 54.0 ± 7.1 years, p \ 0.001). Compared with individuals with no cardiovascular risk factors, there was a higher prevalence of significant CAD in individuals with diabetes mellitus [standardized rate ratio (SRR) 2.66; 95 % CI 1.93–3.68; p \ 0.001], hypertension (SRR 2.24; 95 % CI 1.69–2.97; p \ 0.001), or hyperlipidemia (SRR 1.65; 95 % CI 1.25–2.17; p \ 0.001). There was also a greater prevalence of significant CAD in individuals with an intermediate or high Framingham risk score (SRR 5.91; 95 % CI 2.34–14.95; p \ 0.001) or a high atherosclerotic cardiovascular disease risk score (SRR 8.04; 95 % CI 3.04–21.23; p \ 0.001). The prevalence of coronary atherosclerosis in this Asian population was not negligible and was associated with known cardiovascular risk factors and high-risk individuals. S.-W. Lee Y.-H. Kim (&) S.-W. Park S.-J. Park Department of Cardiology, Asan Medical Center, University of Ulsan College of Medicine, 388-1 Poongnap-dong, Songpa-gu, Seoul 138-736, Korea e-mail: [email protected] D. H. Yang J.-W. Kang T.-H. Lim Department of Radiology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea B.-J. Kim J.-M. Koh Department of Endocrinology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea H.-K. Kim J. Choe Department of the Health Screening and Promotion Center, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea
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Int J Cardiovasc Imaging
Keywords Epidemiology Coronary computed tomographic angiography Atherosclerosis Coronary artery disease Introduction Although there have been advances in many medical fields over the past decades, coronary artery disease (CAD) remains the leading cause of death globally [1]. The prevalence of CAD in Asian countries has rapidly increased as a consequence of social and economic changes [2, 3], resulting in CAD becoming a major public health concern in these countries [4]. However, there are limited data on the prevalence of coronary atherosclerosis in Asian populations. Recently, with the advent of multidetector row computed tomography, coronary computed tomography angiography (CCTA) has proven effective in providing comprehensive information on coronary atherosclerosis, including the location, severity, and characteristics of atherosclerotic plaques [5]. Therefore, through a large cohort consisting of asymptomatic Korean individuals undergoing CCTA, we sought to estimate the prevalence of coronary atherosclerosis and to identify risk factors attributable to the development of coronary atherosclerosis in an Asian population. Methods Study population From January 2007 to December 2011, we enrolled 8,945 consecutive South Korean individuals aged 40 years and Fig. 1 Overview of the enrolled study population. CCTA coronary computed tomographic angiography, MI myocardial infarction, PCI percutaneous coronary intervention, ASD atrial septal defect, PDA patent ductus arteriosus, PFO patent foramen ovale, ESRD end stage renal disease
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older who had undergone self-referral CCTA evaluation as part of a general health examination in the Health Screening and Promotion Center at the Asan Medical Center. All subjects were made aware of the possible risks associated with CCTA and provided informed consent. A total of 6,922 (77.4 %) consented to participate in this study. Subjects with (1) a previous history of angina or myocardial infarction (MI); (2) abnormal resting electrocardiographic results, i.e., pathological Q waves, ischemic ST segments or T wave changes, or left bundle-branch blocks; (3) structural heart disease; (4) a prior history of open heart surgery; (5) a past history of percutaneous coronary intervention (PCI); (6) a previous cardiac procedure; or (7) renal insufficiency (creatinine [ 1.5 mg/dL) were excluded. Thus, 6,311 subjects were finally enrolled and analyzed (Fig. 1). This study was approved by the local Institutional Review Board of the Asan Medical Center, Seoul, Korea. All patients provided written informed consent. Basic demographic data from the subjects was acquired from a database maintained by the Health Screening and Promotion Center at the Asan Medical Center. Any medical history of angina, MI, stroke, structural heart disease, open heart surgery, PCI, previous cardiac procedure, diabetes mellitus, hypertension, or hyperlipidemia; family history of CAD; and smoking status were collected from a systemized questionnaire prior to general health examination. Diabetes mellitus was defined as a fasting plasma glucose concentration C126 mg/dL or a self-reported history of diabetes and/or treatment with dietary modification, or use of anti-diabetic medication. Hypertension was defined as blood pressure C140/90 mmHg or a selfreported history of hypertension and/or use of anti-hypertensive medication. Hyperlipidemia was defined as total
Int J Cardiovasc Imaging
cholesterol C240 mg/dL or use of an anti-hyperlipidemic treatment. In the general health examination, height, body weight, body mass index, waist circumference, and blood pressure were measured, and electrocardiogram (ECG) was performed. Moreover, fasting plasma glucose, glycated hemoglobin, uric acid, blood urea nitrogen, creatinine, total cholesterol, high-density lipoprotein cholesterol, low-density lipoprotein cholesterol, triglyceride, and high-sensitivity C-reactive protein concentrations were measured on the day of the examination after a fasting period of C12 h. For study participants aged 40–74 years, the Framingham risk score and atherosclerotic cardiovascular disease (ASCVD) risk score were calculated [6, 7]. With regard to the Framingham risk score, study participants were categorized as having either a low (\10 %), intermediate (10–20 %), or high ([20 %) 10 year risk for CAD. Participants with intermediate or high Framingham risk scores were defined as having a higher risk and were compared to those with a low risk [8]. In addition, participants with ASCVD risk scores of at least 7.5 % were defined as high risk and compared with those with a low risk (\7.5 %) [7]. Image acquisition and analysis CCTA was conducted using either single-source 64-slice CT (LightSpeed VCT, GE, Milwaukee, WI, USA) or dualsource CT (Somatom Definition, Siemens, Erlangen, Germany). Patients with no contraindication to b-adrenergic blocking agents and with initial heart rates [65 bpm received an oral dose of 2.5 mg bisoprolol (Concor, Merck, Darmstadt, Germany) 1 h before the CT examination. CT scanning was performed in the prospective ECG-triggering mode or the retrospective ECG-gating mode with ECGbased tube current modulation. Two puffs (2.5 mg) of isosorbidedinitrate (Isoket spray, Schwarz Pharma, Monheim, Germany) were sprayed into the patient’s oral cavity before contrast injection. During CCTA acquisition, 60–80 mL of iodinated contrast (Iomeron 400, Bracco, Milan, Italy) was injected at 4 mL/s, followed by a 40 mL saline flush. A region of interest was placed in the ascending aorta, and image acquisition was automatically initiated once a selected threshold (100 HU) had been reached using bolus tracking. A standard scanning protocol was used, and the tube voltage and tube current–time product were adjusted according to the patient’s body size as follows: 100 or 120 kVp tube voltage; 240–400 mAs per rotation (dual-source CT); and 400–800 mA (64-slice CT) tube current. The size-specific dose estimate was calculated by using the patient’s body diameter [9, 10]. The mean effective dose of our CT protocol was 7.6 mSv ± 5.1. All CCTA scans were analyzed using a dedicated workstation (Advantage Workstation, GE; or Volume Wizard, Siemens) by experienced cardiovascular
radiologists (D.H.Y., J.-W.K., and T.-H.L.). According to the guidelines of the Society of Cardiovascular Computed Tomography, a 16-segment coronary artery tree model was used [11]. A coronary artery calcium score (CACS) was measured as described [12], with categorized by scores of 0, 1–10, 11–100, 101–400, and [400 [13]. Plaques were defined as structures [1 mm2 within and/or adjacent to the vessel lumen, which could be clearly distinguished from the lumen and surrounding pericardial tissue. Plaques containing calcified tissue involving [50 % of the plaque area (density [130 HU) were classified as calcified, plaques with \50 % calcium were classified as mixed, and plaques without calcium were classified as non-calcified [14]. The contrast-enhanced portion of the coronary lumen was semi-automatically traced at the site of maximal stenosis and compared with the mean value of the proximal and distal reference sites [15]. Stenosis C50 % was defined as significant. Statistical analysis Categorical data were compared using Chi square statistics or Fisher’s exact test and presented as frequencies. Continuous variables were analyzed using the unpaired Student’s t test and presented as the mean ± SD. The prevalence rate was defined as the number of individuals with coronary atherosclerosis per 100 study participants. This rate was directly standardized to 10 year age and gender groups, using age and gender distributions from the 2010 South Korean population census [16]. The confidence interval (CI) for this standardized rate was estimated assuming a Poisson distribution of cases. To evaluate the effect of cardiovascular risk factors on the prevalence rate, standardized rates ratios (SRR) and associated 95 % CIs were also computed. All reported p values are two sided, and p values of \0.05 were considered statistically significant. Data manipulation and statistical analyses were conducted using SAS Version 9.1 (SAS Institute Inc., Cary, NC).
Results Population characteristics Table 1 shows the baseline characteristics of the study population. The mean age of the study participants was 54.5 ± 7.4 years, and 4,594 (72.8 %) were male. Diabetes mellitus, hypertension, hyperlipidemia, and current smoking were observed in 1,033 (16.4 %), 2,355 (37.3 %), 1,970 (31.2 %), and 1,443 (22.9 %) patients, respectively. The average Framingham and ASCVD risk scores were 8.1 ± 5.4 and 6.9 ± 6.5 %, respectively. Men in the
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Int J Cardiovasc Imaging Table 1 Characteristics of the study population Characteristics
Overall (n = 6,311)
Male (n = 4,594)
Female (n = 1,717)
Age (years)
54.5 ± 7.4
54.4 ± 7.3
54.6 ± 7.8
Body mass index (kg/m2)
24.6 ± 2.9
25.1 ± 2.7a
23.4 ± 3.0
Waist circumference (cm)
85.9 ± 8.2
88.0 ± 7.4a
80.4 ± 7.9 a
Systolic blood pressure (mmHg)
120.3 ± 13.2
121.7 ± 12.6
Diastolic blood pressure (mmHg)
76.9 ± 10.3
78.8 ± 9.8a
71.7 ± 10.0
Diabetes mellitus no. (%)
1,033 (16.4)
866 (18.9)a
167 (9.7)
Hypertension no. (%)
2,355 (37.3)
1,875 (40.8)a
480 (28.0)
Hyperlipidemia no. (%)
1,970 (31.2)
1,456 (31.7)
514 (29.9)
Current smoker no. (%)
1,443 (22.9)
1,398 (30.4)a
45 (2.6)
Previous stroke no. (%)
58 (0.9)
44 (1.0)
14 (0.8)
Family history of coronary artery diseaseb no. (%) Total cholesterol (mg/dL)
949 (15.0) 195.3 ± 34.3
662 (14.4)a 193.8 ± 33.9a
287 (16.7) 199.5 ± 35.3 122.2 ± 30.9
Low-density lipoprotein cholesterol (mg/dL)
121.3 ± 30.0
120.9 ± 29.7
High-density lipoprotein cholesterol (mg/dL)
53.4 ± 13.6
50.9 ± 12.3a
116.5 ± 13.9
60.1 ± 14.6 a
105.8 ± 60.5 100.3 ± 18.7
Triglyceride (mg/dL)
133.2 ± 83.1
143.4 ± 87.9
Fasting blood glucose (mg/dL)
105.1 ± 20.7
106.8 ± 21.2a
Glycated hemoglobin (%)
5.8 ± 0.8
5.8 ± 0.8
Creatinine (mg/dL)
0.9 ± 0.2
1.0 ± 0.1a
0.7 ± 0.1
Uric acid (mg/dL)
5.6 ± 1.4
6.0 ± 1.3a
4.4 ± 1.0
High-sensitivity C-reactive protein C2 mg/dL no. (%)
57 (0.9)
45 (1.0)
12 (0.7)
Framingham risk score
8.1 ± 5.4
9.6 ± 5.2a
4.0 ± 3.3
Low-risk group
4,375 (70.2)
2,781 (61.2)a
1,594 (94.2)
Intermediate-risk group
1,655 (26.5)
1,560 (34.3)a
95 (5.6)
High-risk group
205 (3.3)
201 (4.4)a
4 (0.2)
a
5.7 ± 0.7
Framingham risk stratification
a
Intermediate/high-risk group
1,860 (29.8)
1,761 (38.8)
Atherosclerotic cardiovascular disease risk score Atherosclerotic cardiovascular disease risk stratification
6.9 ± 6.5
8.4 ± 6.6a
3.0 ± 4.1
Low-risk group
4,122 (66.1)
2,592 (57.1)a
1,530 (90.4)
High-risk group
2,113 (33.9)
1,950 (42.9)a
163 (9.6)
99 (5.8)
Data are expressed as n (%) and mean ± SD a
p \ 0.05
b
Coronary artery disease in a first-degree relative of any age
cohort were, on average, older and had more comorbid conditions than women. Coronary atherosclerosis on CCTA in study population Table 2 shows coronary atherosclerotic findings by CCTA according to age. In the overall and male populations, the prevalence of coronary atherosclerosis increased with age. A similar trend but not multi-vessel disease was also observed in the female population. The mean CACS of the study participants was 42.1 ± 154.8. Atherosclerotic plaques were detected in 2,732 (43.3 %) individuals. Calcified, non-calcified, and mixed plaques
123
were found in 1,844 (29.2 %), 1,200 (19.0 %), and 586 (9.3 %), respectively. Of the study participants, 521 (8.3 %) had significant CAD (diameter stenosis C50 %) by CCTA, and individuals with significant CAD were considerably older than those without (59.2 ± 8.8 vs. 54.0 ± 7.1 years, p \ 0.001). Significant stenosis in the left main (LM), left anterior descending (LAD), left circumflex, and right coronary arteries were observed in 26 (0.4 %), 350 (5.5 %), 169 (2.7 %), and 155 (2.5 %), respectively. One and multi-vessel disease were found in 382 (6.1 %) and 139 (2.2 %). Significant lesions in the LM or proximal LAD were also observed in 185 (2.9 %).
Int J Cardiovasc Imaging Table 2 Coronary computed tomographic angiographic findings by age Age (years)
Number
CACS
Any plaque
Calcified plaque
Non-calcified plaque
Mixed plaque
Significant CAD
Multi-vessel disease
Significant CAD in the LM or proximal LAD
Overall 40–49
1,613
12.0 ± 56.0
50–59 60–69
3,338 1,095
34.9 ± 122.4 91.4 ± 213.8
265
186.1 ± 372.6
212 (80.0)
173 (65.3)
89 (33.6)
6,311
42.1 ± 154.8
2,732 (43.3)
1,844 (29.2)
1,200 (19.0)
C70 Total
420 (26.0)
248 (15.4)
191 (11.8)
77 (4.8)
60 (3.7)
11 (0.7)
21 (1.3)
1,405 (42.1) 695 (63.5)
908 (27.2) 515 (47.0)
621 (18.6) 299 (27.3)
283 (8.5) 177 (16.2)
232 (7.0) 159 (14.5)
60 (1.8) 44 (4.0)
80 (2.4) 57 (5.2)
49 (18.5) 586 (9.3)
70 (26.4) 521 (8.3)
24 (9.1) 139 (2.2)
27 (10.2) 185 (2.9)
Male 40–49
1,148
16.3 ± 65.3
50–59
2,487
43.8 ± 138.2
384 (33.4)
230 (20.0)
172 (15.0)
74 (6.4)
54 (4.7)
9 (0.8)
18 (1.6)
1,240 (49.9)
815 (32.8)
546 (22.0)
259 (10.4)
211 (8.5)
58 (2.3)
70 (2.8)
60–69
789
112.7 ± 240.6
556 (70.5)
413 (52.3)
241 (30.6)
158 (20.0)
134 (17.0)
42 (5.3)
48 (6.1)
C70
170
252.5 ± 438.5
146 (85.9)
124 (72.9)
60 (35.3)
36 (21.2)
50 (29.4)
21 (12.4)
21 (12.4)
4,594
56.4 ± 175.5
2,326 (50.6)
1,582 (34.4)
1,019 (22.2)
527 (11.5)
Total
449 (9.8)
130 (2.8)
157 (3.4)
6 (1.3)
2 (0.4)
3 (0.6) 10 (1.2)
Female 40–49
465
1.6 ± 13.7
36 (7.7)
18 (3.9)
19 (4.1)
3 (0.6)
50–59
851
8.7 ± 45.1
165 (19.4)
93 (10.9)
75 (8.8)
24 (2.8)
21 (2.5)
2 (0.2)
60–69
306
36.6 ± 101.6
139 (45.4)
102 (33.3)
58 (19.0)
19 (6.2)
25 (8.2)
2 (0.7)
9 (2.9)
95
68.8 ± 154.0
66 (69.5)
49 (51.6)
29 (30.5)
13 (13.7)
20 (21.1)
3 (3.2)
6 (6.3)
15.1 ± 67.1
406 (23.6)
262 (15.3)
181 (10.5)
59 (3.4)
72 (4.2)
9 (0.5)
28 (1.6)
C70 Total
1,717
Data are expressed as n (%) and mean ± SD CACS coronary artery calcium score, CAD coronary artery disease, LAD left anterior descending artery, LM left main
Prevalence of coronary atherosclerosis After adjusting for age and gender using the population census of the National Statistical Office, the prevalence of plaque was 40.5 % (95 % CI 38.1–42.9), significant CAD was observed in 9.0 % (95 % CI 7.7–10.2), multi-vessel disease was present in 2.2 % (95 % CI 1.7–2.8), and significant CAD in the LM or proximal LAD was found in 3.2 % (95 % CI 2.5–3.9). Age-adjusted atherosclerosis prevalence by gender was significant in men (Table 3). Age- and gender-adjusted atherosclerosis prevalence was associated with major cardiovascular risk factors. Compared with individuals with no cardiovascular risk factors, there was a considerably higher prevalence of significant CAD in those with diabetes mellitus (SRR 2.66; 95 % CI 1.93–3.68; p \ 0.001), hypertension (SRR 2.24; 95 % CI 1.69–2.97; p \ 0.001), or hyperlipidemia (SRR 1.65; 95 % CI 1.25–2.17; p \ 0.001). However, current smoking was not associated with a higher prevalence of significant CAD (SRR 1.74; 95 % CI 0.78–3.88; p = 0.176). According to Framingham risk score, 4,375 (70.2 %) individuals were classified as low risk and 1,860 (29.8 %) as higher risk (1,655 [26.5 %] in intermediate and 205 [3.3 %]) in high risk. Compared to low-risk individuals, those with a higher risk (intermediate or high Framingham
scores) had a significantly higher prevalence of plaque (SRR 1.87; 95 % CI 1.18–2.97; p = 0.007), significant CAD (SRR 5.91; 95 % CI 2.34–14.95; p \ 0.001), multivessel disease (SRR 8.74; 95 % CI 1.56–49.10); p = 0.014), and significant CAD in the LM or proximal LAD (SRR 6.26; 95 % CI 1.35–29.06; p = 0.019). By ASCVD risk score, 4,122 individuals (66.1 %) were categorized as low risk and 2,113 (33.9 %) as high risk. Individuals with high-risk ASCVD scores also had a significantly higher prevalence of plaque (SRR 2.13; 95 % CI 1.30–3.48; p = 0.003), significant CAD (SRR 8.04; 95 % CI 3.04–21.23; p \ 0.001), multi-vessel disease (SRR 13.63; 95 % CI 2.42–76.71; p = 0.003), and significant CAD in the LM or proximal LAD (SRR 7.94; 95 % CI 1.65–38.28; p = 0.010) than those with low-risk scores.
Discussion The age- and gender-adjusted prevalence of coronary atherosclerosis assessed by CCTA in this Asian population was 40.5 % for plaque, 9.0 % for significant CAD, 2.2 % for multi-vessel disease, and 3.2 % for significant CAD in the LM or proximal LAD. Older age, male gender, diabetes mellitus, hypertension, and hyperlipidemia were
123
Int J Cardiovasc Imaging Table 3 Prevalence of coronary atherosclerosis by age, gender, major cardiovascular risk factors, and risk group
Plaque
Overall population (age- and gender-adjusted)
Men (age-adjusted)
Women (age-adjusted)
p ratea
p ratea
95 % CI
p ratea
SE
95 % CI
SE
p value
SE
95 % CI 26.4–34.1 \0.001
40.5
1.2
38.1–42.9
52.0
1.3
49.4–54.7
30.2
2.0
Significant CAD
9.0
0.6
7.7–10.2
11.3
0.7
10.0–12.7
6.9
1.0
4.8–8.9
\0.001
Multi-vessel disease
2.2
0.3
1.7–2.8
3.6
0.4
2.8–4.4
1.0
0.4
0.2–1.8
\0.001
Significant CAD in the LM or proximal LAD
3.2
0.4
2.5–3.9
4.2
0.4
3.3–5.0
2.4
0.6
1.2–3.5
0.011
Diabetes mellitus (age- and gender-adjusted)
Yes
No
p rate
a
SE
SRR
95 % CI
p rate
a
SE
95 % CI
95 % CI
p value
Plaque
52.7
3.7
45.4–59.9
38.5
1.3
35.9–41.0
1.37
1.17–1.60
\0.001
Significant CAD
19.0
2.7
13.6–24.3
7.1
0.6
6.0–8.3
2.66
1.93–3.68
\0.001
Multi-vessel disease
5.4
1.6
2.3–8.6
1.8
0.3
1.3–2.4
2.97
1.55–5.67
0.001
Significant CAD in the LM or proximal LAD
7.6
1.9
4.0–11.2
2.6
0.3
1.9–3.2
2.94
1.71–5.04
\0.001
SRR
95 % CI
p value
Hypertension (age- and gender-adjusted)
Yes
No
p ratea
SE
95 % CI
p ratea
SE
95 % CI
Plaque
50.7
2.1
46.5–54.8
35.2
1.8
31.8–38.7
1.44
1.27–1.63
\0.001
Significant CAD
13.0
1.2
10.7–15.4
5.8
0.6
4.5–7.1
2.24
1.69–2.97
\0.001
Multi-vessel disease
2.9
0.4
2.0–3.8
1.4
0.3
0.9–1.9
2.06
1.27–3.35
0.004
Significant CAD in the LM or proximal LAD
4.5
0.7
3.2–5.7
2.3
0.4
1.4–3.1
1.98
1.24–3.18
0.004
SRR
95 % CI
p value
Hyperlipidemia (age-and gender-adjusted)
Yes
Plaque Significant CAD Multi-vessel disease Significant CAD in the LM or proximal LAD
No
p rate
a
SE
95 % CI
p rate
48.1
2.2
43.8–52.5
12.1 2.9
1.2 0.6
5.0
0.8
Current smoking (age- and gender-adjusted)
Yes
Plaque Significant CAD
a
SE
95 % CI
37.1
1.5
34.1–40.1
1.30
1.15–1.46
\0.001
9.7–14.6 1.8–4.0
7.3 2.0
0.7 0.4
6.0–8.7 1.2–2.7
1.65 1.48
1.25–2.17 0.88–2.50
\0.001 0.142
3.3–6.6
2.3
0.3
1.7–3.0
2.13
1.39–3.28
0.001
No
p rate
a
a
SRR
95 % CI
p value
SE
95 % CI
p rate
SE
95 % CI
45.0
8.5
28.4–61.6
39.8
1.3
37.4–42.3
1.13
0.78–1.64
0.522
15.2
6.1
3.2–27.2
8.7
0.6
7.5–10.0
1.74
0.78–3.88
0.176
Multi-vessel disease
1.9
0.9
0.2–3.6
2.2
0.3
1.6–2.8
0.86
0.33–2.23
0.762
Significant CAD in the LM or proximal LAD
7.4
5.5
3.2
0.4
2.5–3.9
2.34
0.54–10.09
0.255
SRR
95 % CI
p value
Framingham risk classification (age- and gender-adjusted)
0–18.1
Intermediate/high risk group a
p rate
Low risk group
SE
95 % CI
p rate
a
SE
95 % CI
Plaque
62.4
14.4
34.1–90.6
33.3
1.3
30.8–35.8
1.87
1.18–2.97
Significant CAD
30.9
14.3
2.9–58.8
5.2
0.5
4.2–6.3
5.91
2.34–14.95
0.007 \0.001
Multi-vessel disease
12.2
10.1
0–31.9
1.4
0.4
0.6–2.2
8.74
1.56–49.10
0.014
Significant CAD in the LM or proximal LAD
13.4
10.1
0–33.1
2.1
0.4
1.3–3.0
6.26
1.35–29.06
0.019
ASCVD risk classification (age- and genderadjusted)
High risk group p rate
a
Low risk group a
SE
95 % CI
p rate
SE
95 % CI
SRR
95 % CI
Plaque
61.6
14.6
33.1–90.1
28.9
2.4
24.2–33.7
2.13
1.30–3.48
Significant CAD
29.5
14.2
1.6–57.4
3.7
0.4
2.9–4.5
8.04
3.04–21.23
123
p value
0.003 \0.001
Int J Cardiovasc Imaging Table 3 continued ASCVD risk classification (age- and gender-adjusted)
High risk group a
p rate
SE
Low risk group 95 % CI
a
p rate
SE
SRR
95 % CI
p value
95 % CI
Multi-vessel disease
11.9
10.1
0–31.6
0.9
0.2
0.4–1.3
13.63
2.42–76.71
0.003
Significant CAD in the LM or proximal LAD
12.9
10.1
0–32.6
1.6
0.3
1.0–2.2
7.94
1.65–38.28
0.010
a
Per 100 persons ASCVD atherosclerotic cardiovascular disease, CAD coronary artery disease, CI confidence interval, LAD left anterior descending artery, LM left main, SE standard error, SRR Standardized rate ratio
significantly associated with a higher prevalence of coronary atherosclerosis. Risk stratification using Framingham and ASCVD risk scores was also feasible to predict the prevalence of coronary atherosclerosis. CCTA has been widely used in the comprehensive evaluation of CAD, including lesion location, severity, and plaque characteristics [5]. However, little is known about coronary atherosclerosis assessed by CCTA in asymptomatic Asian individuals. Previous observational studies using CCTA in this population reported atherosclerotic plaque in 21.5–39.1 % of individuals and significant CAD in 5.2 % [5, 17]. Similar to previous studies, in our study, atherosclerotic plaques were identified in 2,732 (43.3 %) of individuals, and 521 (8.3 %) had significant stenosis on CCTA. After age and gender adjustment using the population census of the National Statistical Office, the overall prevalence of plaque and significant CAD were 40.5 % (95 % CI 38.1–42.9) and 9.0 % (95 % CI 7.7–10.2), respectively. Although it may be difficult to compare results across studies because of differences in methodology, the prevalence of significant CAD in our study was comparable to the rate calculated from pathological samples obtained at autopsy in Western countries (Table 4) [18]. These findings imply that coronary atherosclerosis is not uncommon in asymptomatic Asian populations. The prevalence of coronary atherosclerosis was significantly associated with major cardiovascular risk factors such as older age, male gender, diabetes mellitus, hypertension, and hyperlipidemia, which are traditionally derived from studies in Western countries [6]. These findings suggest that risk factors for CAD are applicable to all global populations regardless of ethnic differences [19] and thus efforts should be made to reduce known risk factors for the primary prevention of CAD. Interestingly, in our study, current smoking did not show an association with coronary atherosclerosis as in previous studies [20, 21], which may be due to the fact that our study did not specify the frequency or duration of smoking. Additional studies taking these factors into account are needed to reveal any associations between smoking and coronary atherosclerosis.
Coronary events occur after long periods of subclinical disease [22]. Mortality rates for CAD have fallen in the most developed countries [23], and these reductions are partially attributable to efforts aimed at the early identification of high-risk individuals and the reduction of risk factors [23, 24]. In this study, we showed an association between coronary atherosclerosis and risk groups stratified by Framingham and ASCVD risk scores [7, 8, 12]. Therefore, care of asymptomatic individuals should be focused on risk assessment using global risk scores and personalized modification of cardiovascular risk factors [25]. In the present study, we enrolled asymptomatic individuals undergoing self-referral CCTA evaluation. CCTA is not generally advocated as a screening tool in an asymptomatic population. However, there is still uncertain regarding the use of CCTA for subjects at high risk [26]. A recent cohort study showed that the CAD prevalence by CCTA in asymptomatic high-risk patients is high and CCTA could be an accurate screening tool for CAD due to its ability to detect non-calcifying plaques and to quantify plaque burden as well as coronary stenosis severity graduation [27]. In addition, a large international cohort study observed that CCTA provides incremental prognostic utility for prediction of mortality and non-fatal myocardial infarction for asymptomatic individuals with moderately high CACS (101–400) [28]. On the contrary, in the recent randomized trial which enrolled high-risk patients with diabetes based on age and diabetes duration, CAD screening with CCTA did not provide the incremental benefit over optimal medical therapy without any screening of CAD [29]. Therefore, further studies are needed to evaluate the role of CCTA in asymptomatic individuals with higher cardiac risk whose outcome might be improved through aggressive interventions. Limitations Our study has several limitations. First, it was conducted at a single center. All individuals voluntarily went to the hospital for a general health examination and were
123
123
210/5,438 (3.9)
0.220
asymptomatic. Therefore, there was a potential for selection bias. Second, calcified plaques and higher CACS may lead to overestimation of significant CAD [30]. Third, our study did not evaluate coronary atherosclerosis by functional tests such as exercise ECG, myocardial perfusion imaging, positive emission tomography scan, or stress echocardiography. A discrepancy has been observed between CCTA and functional tests [31]. Therefore, CCTA may overestimate the prevalence of CAD requiring treatment. Fourth, the napkin-ring sign, positive vessel remodeling, and low-attenuation plaque have been known as high-risk plaque features [32, 33]. However, the analysis of these characteristics in the present study was not performed. Therefore, in asymptomatic individuals, future studies to evaluate the clinical impact of these high-risk coronary atherosclerotic plaques are needed. Finally, advanced techniques have been developed to reduce the shortcomings of CCTA [34], such as the radiation hazard, use of iodinated contrast agents, and higher cost [35]. Although our study only enrolled volunteers, the performance of CCTA in asymptomatic individuals has not yet been justified.
0.742
Conclusions In this large observational study with asymptomatic Asian individuals, the prevalence of coronary atherosclerosis was not low and was significantly associated with major cardiovascular risk factors such as older age, male gender, diabetes mellitus, hypertension, hyperlipidemia, and higher risk by global risk assessment scores. These findings indicate that efforts should be made to reduce known cardiovascular risk factors to decrease the coronary atherosclerotic burden. These findings should be confirmed in large clinical trials.
0.541
399/4,424 (9.0)
1,291/14,059 (9.2)
52/1,622 (3.2) 451/6,046 (7.5) Total
1,501/19,497 (7.7)
Acknowledgments This study was supported by Grants from the Korea Healthcare technology R&D Project, Ministry of Health and Welfare, Republic of Korea (A102065, HI12C0630, and HI10C2020). Conflict of interest
Data are expressed as n (%)
0.698 25/306 (8.2) \0.001 159/1,095 (14.5) 60–69
699/6,367 (11.0)
0.001
134/789 (17.0)
569/4,641 (12.3)
130/1,726 (7.5)
0.291
0.613 18/1,778 (1.0)
62/1,934 (3.2) 0.079
6/465 (1.3)
21/851 (2.5)
0.410
488/5,011 (9.7) 0.083
234/4,407 (5.3) 54/1,148 (4.7)
211/2,487 (8.5)
0.518
550/6,945 (7.9) 50–59
252/6,185 (4.1) 60/1,613 (3.7)
232/3,338 (7.0)
40–49
This study p value Diamond and Forrester This study This study
Diamond and Forrester
p value
Men Overall Age
Table 4 Comparison between the prevalence of significant coronary artery disease in this and previous studies
Women
Diamond and Forrester
p value
Int J Cardiovasc Imaging
None.
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