The aim of this study was to compare coronary artery plaque burden, composition, distribution, and the degree of coronary artery stenosis in diabetic and nondiabetic patients with known or suspected coronary artery disease (CAD). The study group consisted of 594 patients with known or suspected CAD, including 122 diabetics, who underwent multidetector computed tomographic coronary angiography and traditional invasive coronary artery angiography. Coronary artery calcium scores were compared in different age subgroups. Noncalcified plaque, calcified plaque, and mixed plaque were analyzed by coronary segment on computed tomographic coronary angiography, as well as the degree of coronary stenosis on coronary artery angiography. Obstructive vessels were compared between the 2 groups. Total coronary artery calcium score was higher in patients with diabetes compared to those without (378.4 ± 613.0 vs 226.0 ± 408.4, p = 0.003). The percentage of patients with coronary artery calcium scores >400 among diabetics (22.1%) was higher than among nondiabetics (14.2%) (p = 0.032). Diabetics had a higher percentage of coronary segments with noncalcified plaque, calcified plaque, and mixed plaque than nondiabetics (35.3% vs 26.2%, p <0.001; 17.5% vs 11.6%, p = 0.017; and 9.8% vs 7.9%, p = 0.008). More diabetics had multivessel obstructive disease compared to nondiabetics (p <0.05). With longer duration of diabetes mellitus, the stenosed segments of coronary arteries increased accordingly. In conclusion, diabetics have more atherosclerotic plaque burden and more severe coronary atherosclerosis than nondiabetics. Most obstructive lesions were caused by mixed plaques in diabetics and nondiabetics.
Diabetes mellitus is considered a risk factor equivalent to known coronary artery disease (CAD). The risk for CAD is 2 to 5 times greater in patients with type 2 diabetes than in those free of the disease. Multidetector computed tomographic coronary angiography (CTCA) permits the noninvasive detection of coronary artery plaque and stenosis with good correlation to the gold standard, invasive coronary artery angiography (CAG). The added value of CTCA is that it provides high diagnostic accuracy in assessing the characterization of coronary atherosclerotic plaque, coronary artery wall, plaque morphology and distribution, and arterial luminal visualization. Previous studies of coronary artery plaque in diabetics used CTCA data alone. In our study, all patients underwent CTCA and CAG as the gold standard of luminal stenosis assessment. The purpose of this study was to compare coronary plaque burden, composition, distribution, and the degree of coronary artery stenosis in diabetic and nondiabetic patients with known or suspected CAD.
Methods
From January 1, 2009, to April 30, 2010, a total of 679 consecutive adult patients who had undergone CTCA and CAG were enrolled. Among them, 85 patients, including 60 who underwent percutaneous coronary intervention and 25 who underwent coronary artery bypass grafting, were excluded from the study. A total of 594 patients were retrospectively analyzed in this study, including 122 diabetic patients.
A history of CAD was defined as a history of diagnosed myocardial infarction or the presence of ≥1 angiographically documented coronary stenosis with luminal narrowing >50%. Suspected CAD was defined as atypical chest pain, chest distress, shortness of breath, or atypical ST-T change on electrocardiography. Type 2 diabetes mellitus was defined as a fasting plasma glucose level ≥7.0 mmol/L that was treated currently with dietary intervention, oral glucose-lowering agents, and/or insulin. Patients with allergic reaction to iodine contrast medium, renal insufficiency (creatinine clearance <60 ml/min), pregnancy, respiratory impairment, and unstable clinical status were prohibited from undergoing the examination. All patients provided informed consent for CTCA and CAG.
CTCA was performed using a 64-detector LightSpeed VCT scanner (GE Healthcare, Milwaukee, Wisconsin). All patients were in normal sinus rhythm at the time of CTCA. Patients with baseline heart rates >70 beats/min were administered oral β blockers as the preferred method for reducing the heart rate. After a scout x-ray of the chest was obtained, a timing bolus (using 10 to 20 ml of contrast) was performed to detect time to optimal contrast opacification in the axial image at a level immediately superior to the ostium of the left main coronary artery.
Contrast media was injected via a 20-gauge trocar in the antecubital vein using a power injector (Stellant; Medrad, Indianola, Pennsylvania). Iohexol 350 mg I/ml (Omnipaque 350; GE Healthcare) or iopromide 370 mg I/ml (Ultravist 370; Bayer-Schering Pharma, Leverkusen, Germany) was injected at a speed of 4 to 5.5 ml/s. Contrast media was injected using a triple-phase-contrast protocol: iodinated contrast, followed by a mixture of 30% iodinated contrast and 70% saline, followed by a saline flush. Retrospective electrocardiographically gated helical contrast-enhanced computed tomographic coronary angiographic scans were performed from 20 mm above the level of the left main artery to 20 mm below the inferior myocardial apex.
The scan parameters were 64 × 0.625 mm collimation, gantry rotation time of 350 ms, tube voltage of 120 kV, electrocardiographically modulated tube current of 200 to 650 mA, and field of view of 250 mm. Images in the 75% RR interval were reconstructed; when there were artifacts in the coronary artery, images in 40% to 50% of the RR interval were reconstructed. The best RR interval image quality was chosen for interpretation.
Computed tomographic coronary angiographic images were evaluated on a 3-dimensional image analysis workstation (Advantage Workstation 4.3; GE Healthcare). All images were independently assessed by 2 experienced observers, who were blinded to patients’ clinical histories and coronary angiographic results. In the case of disagreement, a consensus decision was reached after a joint reading session. An overall Agatston score was recorded for each patient. A 16-segment scheme, as suggested by the American Heart Association, was used in the analysis of coronary arteries. All interpretable segments were evaluated for the presence of atherosclerotic plaque. The types of plaque included noncalcified plaque, calcified plaque, and mixed plaque. The noncalcified component of a plaque was defined as a lesion with radiodensity greater than that of neighboring soft tissue and lower than the luminal contrast. The calcified component of a plaque was defined as a lesion with a radiodensity greater than the luminal contrast. Plaques exhibiting <25% calcified component by volume on visual inspection were categorized as noncalcified plaque, 25% to 75% as mixed plaque, and >75% as calcified plaque.
The first and second diagonal branches were included in the left anterior descending coronary artery. The first and second obtuse marginal branches were included in the left circumflex coronary artery. The posterior left ventricular branch and posterior descending artery were included in the right coronary artery or left circumflex, which was determined according to whether the dominant type of coronary artery was right or left. In segments containing >1 plaque, the characteristics of the most stenotic plaque were recorded. Coronary artery stenoses were classified visually as obstructive (>50% luminal narrowing) or nonobstructive (≤50% luminal narrowing) by the blinded interpretation of the invasive coronary angiogram.
Continuous variables are expressed as mean ± SD and were compared using 2-sample Student’s t tests for independent samples. When not normally distributed, continuous variables are expressed as medians and were compared using nonparametric Mann-Whitney U tests. Categorical variables are presented as absolute values, and percentages were compared between groups using chi-square tests or Fisher’s exact tests as needed. A p value <0.05 was considered statistically significant. All statistical analyses were performed using SPSS version 14.0 (SPSS, Inc., Chicago, Illinois).
Results
The study population consisted of 594 patients (mean age 58.8 ± 10.0 years, 74.9% men), including 122 (25.8%) who had known type 2 diabetes and 472 who did not. Baseline characteristics of patients are listed in Table 1 . Hypertension is defined as a repeatedly elevated blood pressure ≥140/90 mm Hg. Hyperlipidemia refers to an elevation of lipids in the blood due to an increase in triglycerides, cholesterol, or both. All the patients were diagnosed with CAD or suspected CAD clinically and scheduled to undergo CAG to evaluate coronary stenosis.
| Characteristic | Diabetic Patients | Nondiabetic Patients | p Value |
|---|---|---|---|
| (n = 122) | (n = 472) | ||
| Men | 85 (69.7%) | 360 (76.3%) | 0.134 |
| Age (years) | |||
| Overall | 59.7 ± 9.6 | 58.6 ± 10.1 | 0.266 |
| Men | 58.3 ± 9.7 | 57.7 ± 10.2 | 0.988 |
| Women | 62.9 ± 8.7 | 61.5 ± 9.0 | 0.402 |
| Hypertension | 82 (67.2%) | 282 (59.8%) | 0.131 |
| Hyperlipidemia | 72 (59.0%) | 211 (44.7%) | 0.005 |
| Body mass index (kg/m 2 ) | 26.3 ± 3.4 | 26.1 ± 3.5 | 0.415 |
| (19.8–41.2) | (18.1–40.3) | ||
| Current smoker | 41 (33.6%) | 153 (32.4%) | 0.248 |
| Previous myocardium infarction | 14 (11.5%) | 49 (10.4%) | 0.726 |
| Typical angina pectoris | 35 (28.7%) | 134 (28.4%) | 0.548 |
| Atypical chest pain | 52 (50.8%) | 150 (36.4%) | 0.024 |
| Years with diabetes | 7.4 ± 6.1 | — | — |
| (0.17–30) |
Total coronary artery calcium scores (CACS) of diabetics were higher than those of nondiabetics (p = 0.003; Table 2 ). Significant differences were found in 27.5% of nondiabetics and 18% of diabetics with CACS of 0 (p = 0.032). There was no statistical difference in the proportion of CACS <400 in the 2 groups (p >0.05). The percentage of patients with CACS >400 among diabetics was higher than among nondiabetics (p = 0.032). Patients aged <70 years had no statistical difference of CACS between diabetic and nondiabetic groups, while in those aged >70 years with diabetes, higher CACS were found than among nondiabetics (p = 0.001; Table 3 ).
| CACS | Diabetic Patients | Nondiabetic Patients | p Value |
|---|---|---|---|
| Total | 378.4 ± 613.0 | 226.0 ± 408.4 | 0.003 |
| 0 | 22 (18.0%) | 130 (27.5%) | 0.032 |
| 1–99 | 32 (26.2%) | 144 (30.5%) | 0.356 |
| 100–399 | 29 (23.8%) | 110 (23.3%) | 0.914 |
| 400–999 | 27 (22.1%) | 67 (14.2%) | 0.032 |
| ≥1,000 | 12 (9.9%) | 21 (4.4%) | 0.019 |
| Age Group (Years) | Diabetic Patients | Nondiabetic Patients | p Value | ||
|---|---|---|---|---|---|
| n | CACS | n | CACS | ||
| <50 | 17 | 124.0 ± 300.1 | 88 | 89.5 ± 245.7 | 0.660 |
| 50–59 | 46 | 215.5 ± 277.8 | 170 | 178.2 ± 328.3 | 0.262 |
| 60–69 | 36 | 361.7 ± 480.7 | 145 | 249.9 ± 489.6 | 0.094 |
| ≥70 | 23 | 918.6 ± 1,031.8 | 69 | 373.3 ± 490.6 | 0.001 |
| Total | 122 | 378.4 ± 613.0 | 472 | 226.0 ± 408.4 | 0.003 |
After the exclusion of 119 coronary segments (1.3%) for nondiagnostic image quality (32 with small caliber, 87 with motion artifacts due to elevated heart rates), a total of 9,385 coronary segments were analyzed on CTCA. Atherosclerotic plaques were demonstrated in 116 diabetics (95.1%) and 412 nondiabetics (87.3%). As listed in Table 4 , there were statistically significant differences in the proportions of total plaque and calcified plaque between the 2 groups. Diabetics had a higher proportion of coronary segments with calcified plaque and total plaque than nondiabetics in the left main, left anterior descending, left circumflex, and right coronary arteries (all p values <0.05), while mixed plaque in the left anterior descending (14.9% vs 11.8%, p = 0.011) and right (10.8% vs 8.1%, p = 0.036) coronary arteries also had statistical significant differences.
