type 2 diabetes mellitus ( t2 dm ) is a major risk factor for cardiovascular disease and is associated with significant cardiovascular morbidity and mortality .
patients with t2 dm have increased risk of major adverse cardiac events ( mace ) .
acute coronary events are often caused by the rupture of unstable coronary atherosclerotic plaques and coronary stenosis [ 2 , 3 ] .
therefore , assessment of atherosclerotic plaque morphology and pathological features has become an important part of clinical investigation of coronary artery disease .
multidetector coronary computed tomography angiography ( ccta ) has been increasingly used in the evaluation of the coronary arteries . in an acute
setting , ccta is associated with 95% sensitivity and 90% specificity in diagnosing non - st - elevation myocardial infarction ( nstemi ) and unstable angina pectoris . the ability to detect not only coronary stenosis but also the nonobstructive coronary atherosclerotic plaques in a noninvasive fashion makes ccta imaging a potentially valuable tool for risk stratification . in recent years , ccta has been used to predict the prognosis or cardiac events in patients with suspected coronary artery disease [ 714 ]
. however , there has been limited information on the predictive value of ccta on the acute coronary events in patients with t2 dm . the purpose of this study is to investigate the ccta characteristics of the coronary plaques in patients with t2 dm . the sensitivity and specificity of ccta in predicting the acute coronary events in these patients are also evaluated .
the study was approved by the institutional ethics committee of our hospitals , and written informed consent was obtained from all participants . from february 2007 to november 2008 , 318 consecutive patients with t2 dm were referred to our department for coronary cta because of nonspecific chest pain , exertional dyspnea , or st - t depression or flattening on electrocardiogram ( ecg ) .
patients who had a previous coronary balloon angioplasty , stenting , or coronary artery bypass grafting were excluded .
other exclusion criteria were ( a ) heart rate above 90 beats / min or with atrial fibrillation or other arrhythmias ; ( b ) renal dysfunction ( serum creatinine  120  mmol / l ) ; ( c ) other chronic illnesses , such as severe respiratory insufficiency , hyperthyroidism ; ( d ) inability to give a written consent . in the end
the first 85 patients were scanned by philips brilliance 64-detector ct ( philips medical systems , eindhoven , the netherlands ) .
prior to the scans , beta - blocker was administered in patients whose heart beat was 70/min , and nitroglycerine ( 0.3  mg sublingually ) was used in all patients 15 minutes before the scans .
the scan parameters were 64  0.625  mm collimation , 120  kv tube voltage , 400600  mas tube current , 0.42  s rotation time , and 0.2 pitch .
data acquisition was completed within 4.15.9  sec with radiation dose of 13.916.8  msv ( median , 15.1  msv ) . in the remaining 65 patients ,
prospective ecg - gated scan was performed in 128-detector ct and heart rate was restricted within 6070 beats / min .
the scan parameters were 120  kv tube voltage , 200  mas tube current , collimation 128  0.625 , 0.180.27  sec rotation time , and 0.2 pitch .
scanning was completed within 3.96.8  sec with radiation dose of 3.164.14  msv ( median , 3.6  msv ) . a 5060  ml ( dependent on body mass index )
bolus of iodinated contrast agent ( iopamidol , 370  mg of iodine / ml ; bracco sine pharmaceutical corp . ltd . ,
shanghai , china ) was injected into the antecubital vein at a flow rate of 4 - 5  ml / sec .
the scanning range was from the tracheal bifurcation to 10  mm below the inferior cardiac apex .
the best quality images were chosen for evaluation and other phases or ecg - editing was performed if needed .
all initial data sets were transferred to a postprocessing workstation ( brilliance - workshop , philips medical systems , eindhoven , the netherlands ) for image analysis .
alternative image reconstruction methods for evaluation of coronary artery and plaques included maximum intensity projection , multiplanar reconstruction , curvature plane reconstruction , and volume rendering .
both observers were blinded to the medical histories , clinical diagnoses , and results of other investigations for all patients . in case of disagreement ,
noncalcified plaques are plaques with a lower density compared with the contrast - enhanced lumen ; calcified plaques are plaques with a higher density ; and mixed plaques are plaques with soft and calcified elements within a single plaque .
the measure was performed in axial and mpr images and 4 points were chosen randomly .
roi > 1.0  mm ( at least 3 contiguous pixels , area 1.03  mm ) and the smallest ct value were defined as the value of plaques ( figures 2 and 3 ) .
the coronary artery plaques were classified into 4 types [ 16 , 17 ] : type i , concentric lesions ; type ii , eccentric lesions with a wide base but smooth margin ; type iii eccentric lesions with a narrow base and rough surface ; type iv , long segment of irregular lesions .
number of diseased coronary vessels and segments , number and types of plaques , and grading of stenosis caused by plaques were evaluated .
the degree of stenosis was defined as the percentage of stenosis and adjacent normal vessel lumen : normal or mild ( < 50% ) , moderate ( 50%75% ) , and severe ( 75% ) stenosis .
the follow - up was conducted by structured telephone interviews with patients or the relatives who knew the patients ' conditions .
the follow - up questionnaires included the general health of the patients , use of medications , cardiovascular events including hospital admissions , coronary artery angiography or stenting , or coronary artery bypass grafting .
the acute coronary events were defined as acute coronary syndrome ( st - elevation or non - st elevation myocardial infarction , or unstable angina ) or sudden cardiac death ( study group ) .
patients with stable angina , or with angiographically identified coronary artery stenosis requiring elective coronary stenting or bypass grafting 6 months after ccta , were considered as having chronic coronary events   ( control group ) .
chi - square test was used to compare the categorical data between the study and control groups .
all statistical analyses were performed using the spss statistical package ( version 11.5 for windows , spss inc . , chicago , il , usa ) .
a total of 318 patients were recruited in this study but 150 completed the follow - up ( figure 1 ) .
the baseline characteristics of these patients are summarized in table 1 . during the follow - up period ,
acute coronary events occurred in 28 ( 18.7% ) patients , including acute myocardial infarction in 8 ( 5.3% ) ; unstable angina in 19 ( 12.7% ) ; and sudden death in 1 ( 0.7% ) . within the first 6 months of the follow - up , 15 patients with the acute coronary events had coronary stenting and 8 received coronary bypass grafting .
chronic coronary events occurred in 67 ( 44.7% ) patients , including stable angina pectoris in 58 , elective coronary stenting in 7 , and elective coronary bypass grafting in 2 .
the remaining 55 ( 36.7% ) patients were asymptomatic and free of coronary events during the follow - up .
a total of 420 segments were analyzed in study group and 1005 segments were analyzed in control group ( table 2 ) .
triple - vessel diseases were identified in 67.8% of the study group and in 68.6% of the control group ( p = 0.380 ) .
moderate - to - severe degree of coronary stenosis was found in 89.8% of the study group and in 88% of the control group ( p = 0.380 ) .
the numbers and characteristics of coronary plaques in the study and control groups are shown in table 3 . in the study group , there were 236 noncalcified , 315 mixed , and 87 calcified plaques . in the control group , the noncalcified , mixed , and calcified plaques were 48 , 596 , and 843 , respectively .
the proportion of calcified plaques in the study group was lower than in the control group ( 13.6% versus 53.2% , p < 0.01 ) .
the proportion of noncalcified plaques in the study group was higher than in the control group ( 37% versus 9.3% , p < 0.001 ) .
the numbers of different plaque types founded on ccta images are listed in table 4 . in the study group
, there was no statistically significant difference in the plaque types between patients with moderate or severe coronary stenosis ( p = 0.349 ) . in the control group ,
however , there was a statistically significant difference in the plaque types among different grades of stenosis in the control group ( p < 0.001 ) .
as shown in table 4 , there was no statistically significant difference in the proportion of type i plaques between the study and control groups ( p > 0.05 ) .
however , the proportion of type iii plaques in the study group was higher than in the control group , whereas the proportion of type ii and iv plaques was lower ( p < 0.01 ) . using type iii plaques to predict acute coronary events , the sensitivity and specificity were 76.2% and 63.8% , respectively .
the main findings of the present study are as follows : ( a ) the proportion of noncalcified and type iii plaques in patients with acute coronary events was higher than in patients with stable angina ; ( b ) the proportion of calcified plaques in patients with stable angina was higher than in patients with acute coronary events ; ( c ) the sensitivity and specificity of type iii plaques in predicting acute coronary events were 63.8% and 76.2% , respectively .
the sensitivity and specificity of type ii and iv plaques in predicting chronic coronary events were 91.5% and 79% , respectively .
these findings indicated that noninvasive ccta may be used to evaluate the unstable plaques that are prone to cause acs in patients with t2 dm .
previous studies have found that many coronary lesions in patients with coronary heart disease were nonobstructive , and the vessel with mild - to - moderate stenosis was responsible for cardiac events [ 20 , 21 ] .
the vulnerability of the intracoronary lesions is a key factor for acs in these patients with mild - to - moderate stenosis [ 20 , 21 ] .
acute coronary syndrome was often caused by rupture of coronary artery atherosclerosis plaques rather than lumen stenosis .
therefore , early detection of vulnerable or unsteady plaques is important in guiding prevention and treatment of acute cardiac events .
noncalcified plaques were unsteady and were commonly seen in patients with acute coronary syndromes [ 23 , 24 ] .
inconsistent with the previous reports , our study showed that there was little difference in the stenosis severity between patients with acute and chronic coronary events . on the other hand ,
the types of the coronary plaques on ccta seem to be related to the coronary events .
we also found that , in patients with acute coronary syndromes , there were more noncalcified plaques and fewer calcified plaques than in patients with stable angina .
these results suggest that , in patients with t2 dm , analysis of the stenosis severity alone on ccta is probably insufficient .
evaluation of the plaque morphology and vulnerability on ccta seems to offer additional information on the future risk of acute coronary events .
the reliability of ccta in assessing coronary plaque stability has been under investigation in recent years [ 2528 ] .
the study of otaki et al .   showed the prognostic information of ccta enhances risk stratification and may improve medical therapy and/or behavioral changes that may enhance event - free survival .
an earlier study by motoyama et al .   demonstrated that ccta can be used to accurately assess plaque composition by measuring the ct value of the plaque on thin - ct images .
the lipid core was in the inner lining of the coronary lumen and was prone to rupture under the impact of blood flow .
the ruptured plaques will absorb platelets , leading to new clots formation and obstruction of coronary flow and causing acute coronary syndrome or sudden death . in the present study
, we have divided the coronary plaques into 4 types [ 16 , 17 ] .
the type iii plaques , those with an eccentric centre and rough surfaces , appear to be related to acute coronary events .
the predictive sensitivity and specificity of type iii plaques were 63.8% and 76.2% , respectively , for acute coronary events .
on the other hand , eccentric lesions with a wide base but smooth margin ( type ii plaques ) and long segment of irregular lesions ( type iv plaques ) represent relatively stable plaques and have 91.5% sensitivity and 79% specificity in predicting chronic coronary events .
achenbach and raggi   thought that the actual clinical utility of coronary cta for risk stratification purposes is very uncertain , especially when considering extending the currently available findings to a 
many trials [ 3336 ] which demonstrated a prognostic value of coronary cta were all retrospective analyses of individuals in whom ct was performed for a clinical reason , so most likely the populations mainly consisted of symptomatic patients . because of the low overall event rate , predicting acute coronary syndromes in asymptomatic individuals is substantially more difficult .
so ada 2013 guideline pointed that , for asymptomatic patients , it is not recommended for routine screening for cad , because this screening does not make sense to improve the outcomes as long as appropriate treatment for cad risks can be achieved . but similar to the detection and quantification of coronary calcium , one would expect that the detection and further characterization of noncalcified plaque should provide prognostic information concerning the occurrence of future acute coronary syndromes .
ostrom et al .   demonstrated that the presence of nonobstructive plaque in all three coronary arteries was associated with increased mortality ( risk ratio 1.77 when compared with individuals without any detectable plaque ) .
proposed that the burden of angiographic disease detected by cta provides both independent and incremental value in predicting all - cause mortality in symptomatic patients independent of age , gender , conventional risk factors , and cac .
so we should do more research to find unstable plaque or criminal vessels . a further concern
is the fact that ccta , as opposed to coronary calcium , requires the injection of contrast agent and is usually associated with substantially higher radiation exposure than calcium scans .
average effective doses for ccta are 12  msv , but they can easily reach 20  msv or more unless special measures to minimize the dose are implemented [ 33 , 39 ] . recently , numerous approaches to reduce the dose of ccta have been proposed and evaluated , and estimated effective doses , 3  msv [ 4043 ] in selected cases even 1  msv , can be achieved .
a potential limitation of the present study on the first 85 patients is that , in the earlier part of our study , retrospective ecg - gated helical ccta was performed using 64-detector ct . in the remaining 65 patients , prospective ecg - gated scan was performed using 128-detector ct .
the imaging quality of 128-detector ccta is generally superior to 64-detector ccta and the dose of radiation is also lower [ 5 , 31 ] .
so we need do more research to discover how predictive the ccta is versus traditional risk assessment .
ccta is a noninvasive modality to measure the severity of coronary stenosis and to assess the morphology of coronary plaques and provides potential prognostic information in t2 dm patients with suspected cad .
these data suggest morphology analysis on ccta may add value to coronary risk stratification in patients with t2 dm although more studies are needed .
these results may improve the risk stratification in patients evaluated by ccta and provide strategies for the individualized prevention programs .
 
 objectives . to analyze the predictive value of coronary computed tomography angiography on acute coronary artery events in patients with type 2 diabetes . methods . 
 coronary computed tomography angiography was performed in 250 type 2 diabetic patients . after a follow - up for 5 years 
 , 145 patients were excluded as they did not have any coronary events . 
 the remaining 95 patients were divided into study group and control group . according to their density and shape , 
 the coronary artery plaques were classified into 3 types and 4 types , respectively . 
 results . 
 there is no statistically significant difference in the degree of stenosis between two groups . 
 the proportion of calcified plaques in the study group was lower than in the control group . 
 the proportion of mixed - calcified plaques in the study group was higher than in the other . 
 type iii plaques have a 76.2% sensitivity and negative predictive value was 64.5% for acute coronary events ; type iv plaques have a sensitivity of 52.6% and positive predictive value of 63% for chronic coronary events . conclusions . 
 ccta may be used as a non - invasive modality for evaluating and predicting vulnerable coronary atherosclerosis plaques in patients with type 2 diabetes . 
1. Introduction
2. Subjects and Methods
3. Results
4. Discussion
5. Conclusions